Clinical Cardiac Pacing, Defibrillation and Resynchronization Therapy 4th Edition: Expert Consult Premium Edition - Enhanced Online Features and Print

Clinical Cardiac Pacing, Defibrillation, and Resynchronization Therapy fourth edition KENNETH A. ELLENBOGEN, MD Kontos Professor of Medicine Chairman, Division of Cardiology Director, Clinical Electrophysiology Laboratory Medical College of Virginia Richmond, Virginia

G. NEAL KAY, MD Professor, Department of Medicine Director, Clinical Electrophysiology Section The University of Alabama at Birmingham Birmingham, Alabama

CHU-PAK LAU, MD Director, Cardiac Health Heart Centre Honorary Clinical Professor Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong, China

BRUCE L. WILKOFF, MD Director, Cardiac Pacing and Tachyarrhythmia Devices Robert and Suzanne Tomsich Department of Cardiovascular Medicine Institute Medical Information Officer Sydell and Arnold Miller Family Heart and Vascular Institute Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, Ohio

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

CLINICAL CARDIAC PACING, DEFIBRILLATION, AND RESYNCHRONIZTION THERAPY Copyright © 2011, 2007, 2000, 1995 by Saunders, an imprint of Elsevier Inc.

978-1-4377-1616-0

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier. com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data Clinical cardiac pacing, defibrillation, and resynchronization therapy / [edited by] Kenneth A. Ellenbogen … [et al.].—4th ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4377-1616-0 (hardcover : alk. paper)  1.  Cardiac pacing.  2.  Defibrillators.  I.  Ellenbogen, Kenneth A. [DNLM:  1.  Cardiac Pacing, Artificial.  2.  Cardiac Resynchronization Therapy.  3.  Defibrillators, Implantable.  4.  Pacemaker, Artificial. WG 168] RC684.P3C54 2011 617.4′120645—dc23 2011026279

Executive Publisher: Natasha Andjelkovic Developmental Editor: Janice M. Gaillard Publishing Services Manager: Patricia Tannian Project Manager: Sarah Wunderly Design Direction: Ellen Zanolle

Printed in United States of America Last digit is the print number:  9  8  7  6  5  4  3  2  1

Working together to grow libraries in developing countries www.elsevier.com | www.bookaid.org | www.sabre.org

To my wife and family, Phyllis, Michael, Amy, and Bethany, for their patience, support, and love. To my parents, Roslyn and Leon, who instilled in me a thirst for learning. To my students, teachers, and colleagues, who make each day an absolute delight. KAE

To my teachers, colleagues, and students, who have taught me about cardiac pacing. I am also indebted to the many members of the industry who have dedicated their professional careers to the design and improvement of pacing technology. These individuals have greatly improved the therapy that clinicians can offer to their patients, undoubtedly resulting in an improvement in their lives. Perhaps most important, this book is dedicated to my wife, Linda, for her patience and understanding during its preparation. GNK

To my wife and family, Carven, Yuk-Fai, and Yuk-Ming, for their understanding, support, and love. To my teachers, patients, and colleagues, who are my source of inspiration and encouragement. CPL

To my wife, Ellyn, children Jacob and Margaret, Benjamin and Kara, Ephram and Kay for their godly and inspirational patience and support. To my grandchildren, Isabelle and Tobias, for life, hope, and love. To my parents, Harvey and Glenna, for their unconditional love and insights. To Yeshua, the Messiah, for His salvation, and His sustaining covenant love. And for the inspiration of His words in Proverbs 15:2: “The tongue of the wise makes knowledge acceptable.” May the words of this book prove to be wise and useful to the student of cardiac pacing, defibrillation, and heart failure device therapy. BLW

CONTRIBUTORS Amin Al-Ahmad, MD Assistant Professor Department of Cardiovascular Medicine Stanford University School of Medicine Director, Cardiac Electrophysiology Laboratory Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices Angelo Auricchio, MD, PhD Professor of Cardiology University of Magdeburg Magdeburg, Germany Director, Clinical Electrophysiology Unit Fondazione Cardiocentro Ticino Lugano, Switzerland Basic Physiology and Hemodynamics of Cardiac Pacing Bryan Baranowski, MD Associate Staff Section of Cardiac Pacing and Electrophysiology Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio Imaging of Implantable Devices Gust Bardy, MD Clinical Professor of Medicine University of Washington Director, Seattle Institute for Cardiac Research Seattle, Washington Subcutaneous Implantable Cardioverter-Defibrillators Peter H. Belott, MD, FACC, FHRS Director of Electrophysiology Sharp Grossmont Hospital La Mesa, California Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation Janneke Berecki-Gisolf, MD, PhD Senior Research Fellow Monash University Accident Research Centre Melbourne, Victoria, Australia Pacing in Neurally Mediated Syncope Syndromes Paola Berne, MD Senior Fellow Department of Cardiology Electrophysiology Section Thorax Institute Hospital Clínic de Barcelona Barcelona, Spain ICD Therapy in Channelopathies Josep Brugada, MD, PhD, FESC Professor of Medicine Barcelona University Medical Director, Hospital Clínic de Barcelona Barcelona, Spain ICD Therapy in Channelopathies

Mina K. Chung, MD Associate Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, Ohio Imaging of Implantable Devices Joshua M. Cooper, MD Assistant Professor of Medicine University of Pennsylvania Attending Cardiac Electrophysiologist Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Engineering and Construction of Pacemaker and ICD Leads Ann M. Crespi, PhD Senior Principal Scientist Department of Battery Research Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators George H. Crossley III, MD Clinical Professor of Medicine University of Tennessee College of Medicine Chief, Cardiac Services Baptist Hospital Nashville, Tennessee Pacemaker, Defibrillator, and Lead Codes, and Headers J. Kevin Donahue, MD Associate Professor Department of Medicine, Biomedical Engineering, Physiology & Biophysics Case Western Reserve University Clinical Cardiac Electrophysiologist The MetroHealth System Cleveland, Ohio The Biologic Pacemaker Derek J. Dosdall, PhD Assistant Professor Department of Internal Medicine Division of Cardiology University of Utah School of Medicine Adjunct Assistant Professor Department of Bioengineering University of Utah Adjunct Assistant Professor Department of Animal, Dairy, and Veterinary Sciences Utah State University Salt Lake City, Utah Cardiac Electrical Stimulation Kenneth A. Ellenbogen, MD Kontos Professor of Medicine Chairman, Division of Cardiology Director, Clinical Electrophysiology Laboratory Medical College of Virginia Richmond, Virginia Pacing for Atrioventricular Conduction System Disease; Interventional Techniques for Device Implantation

vii

viii

Contributors

Andrew E. Epstein, MD, FAHA, FACC, FHRS Professor of Medicine University of Pennsylvania Chief, Cardiology Section Philadelphia VA Medical Center Philadelphia, Pennsylvania Troubleshooting of Implantable Cardioverter-Defibrillators Laurence M. Epstein, MD Associate Professor of Medicine Harvard Medical School Chief, Arrhythmia Service Director, Electrophysiology and Pacing Laboratory Brigham and Women’s Hospital Boston, Massachusetts Engineering and Construction of Pacemaker and ICD Leads Derek V. Exner, MD, MPH, FRCPC, FACC, FHRS Professor University of Calgary Canada Research Chair, Cardiovascular Clinical Trials Medical Director, Arrhythmia Program Libin Cardiovascular Institute of Alberta Calgary, Alberta, Canada Clinical Trials of Defibrillator Therapy Jeffrey M. Gillberg, MSEE Research Director Bakken Fellow Medtronic, Inc. Minneapolis, Minnesota Sensing and Detection Anne M. Gillis, MD, FRCPC Professor of Medicine University of Calgary Calgary, Alberta, Canada Pacing for Sinus Node Disease Andrew A. Grace, MBChB, PhD Research Group Head University of Cambridge Consultant Cardiologist Papworth Hospital Cambridge, United Kingdom Subcutaneous Implantable Cardioverter-Defibrillators Henry Halperin, MD, MA Carver Professor of Medicine Johns Hopkins School of Medicine Baltimore, Maryland Electromagnetic Interference and CIEDs Haris M. Haqqani, MBBS(Hons), PhD Senior Lecturer School of Medicine The University of Queensland Consultant Electrophysiologist The Prince Charles Hospital Brisbane, Queensland, Australia Engineering and Construction of Pacemaker and ICD Leads David Hayes, MD Medical Director, Affiliated Practice Network Mayo Clinic Mayo College of Medicine Rochester, Minnesota Ethical Issues

Margaret Hood, MBChB Cardiologist Auckland City Hospital Auckland, New Zealand Subcutaneous Implantable Cardioverter-Defibrillators Henry H. Hsia, MD Associate Professor of Medicine Stanford University School of Medicine Associate Director, Electrophysiology Laboratory Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices Raymond E. Ideker, MD, PhD Jeanne V. Marks Professor of Medicine Professor Departments of Biomedical Engineering and Physiology University of Alabama at Birmingham Birmingham, Alabama Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms Carsten W. Israel, MD Associate Professor of Medicine and Cardiology Department of Cardiology Division of Electrophysiology J. W. Goethe University Frankfurt, Germany Chief of Cardiology Evangelical Hospital Bielefeld Bielefeld, Germany Clinical Trials of Atrial and Ventricular Pacing Modes Bharat K. Kantharia, MD, FRCP, FAHA, FACC, FESC, FHRS Professor of Medicine Director, Cardiac Electrophysiology Training Program The University of Texas-Health Science Center at Houston Director, Cardiac Electrophysiology Laboratories Heart and Vascular Institute–Memorial Hermann Hospital Houston, Texas Approach to Pulse Generator Changes Karoly Kaszala, MD, PhD Assistant Professor of Cardiology Virginia Commonwealth University School of Medicine Director, Cardiac Electrophysiology Hunter Holmes McGuire VAMC Richmond, Virginia Electromagnetic Interference and CIEDs G. Neal Kay, MD Professor of Medicine Director, Cardiac Electrophysiology Section Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama Cardiac Electrical Stimulation Paul Khairy, MD, PhD, FRCPC Associate Professor Department of Medicine University of Montreal Canada Research Chair, Electrophysiology and Adult Congenital Heart Disease Director, Montreal Heart Institute Adult Congenital Center Montreal, Quebec, Canada Sensing and Detection



Daniel B. Kramer Teaching Fellow in Medicine Harvard Medical School Beth Israel Deaconess Medical Center Boston, Massachusetts Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories Steven P. Kutalek, MD Associate Professor of Medicine Director, Cardiac Electrophysiology Associate Chief, Division of Cardiology Drexel University College of Medicine Philadelphia, Pennsylvania Approach to Pulse Generator Changes Rachel Lampert, MD Associate Professor Yale University School of Medicine Attending Physician Yale New Haven Hospital New Haven, Connecticut Ethical Issues Chu-Pak Lau, MD Director, Cardiac Health Heart Centre Honorary Clinical Professor Department of Medicine University of Hong Kong Queen Mary Hospital Hong Kong, China Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring; Leadless Pacing Concepts Kathy L. Lee, MBBS, FRCP, FACC Honorary Clinical Assistant Professor Medical School University of Hong Kong Hong Kong, China Leadless Pacing Concepts Charles J. Love, MD Professor of Medicine Director, Cardiac Rhythm Device Services Division of Cardiovascular Medicine The Ohio State University Medical Center Columbus, Ohio Pacemaker Troubleshooting and Follow-up William H. Maisel, MD, MPH Associate Professor of Medicine Harvard Medical School Director, Pacemaker and ICD Service Beth Israel Deaconess Medical Center Boston, Massachusetts Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories Saman Nazarian, MD Assistant Professor of Medicine Johns Hopkins University School of Medicine Director, Ventricular Arrhythmia Ablation Service Johns Hopkins Hospital Baltimore, Maryland Electromagnetic Interference and CIEDs

Contributors

ix

Mark J. Niebauer, MD, PhD Assistant Professor Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Staff Physician Cleveland Clinic Cleveland, Ohio Defibrillation Testing, Implant Testing, And Relation to Empiric ICD Programming Marco V. Perez, MD Clinical Instructor Stanford University School of Medicine Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices Robert Andrew Pickett, MD Physician St. Thomas Research Institute St. Thomas Heart at Baptist Hospital Nashville, Tennessee Pacemaker, Defibrillator, and Lead Codes, and Headers Stephen M. Pogwizd, MD Featheringill Endowed Professor in Cardiac Arrhythmia Research Professor of Medicine, Physiology & Biophysics, and Biomedical Engineering Director, Center for Cardiovascular Biology Associate Director, Cardiac Rhythm Management Laboratory University of Alabama at Birmingham Birmingham, Alabama Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms Frits W. Prinzen, PhD Professor of Physiology Maastricht University Maastricht, the Netherlands Basic Physiology and Hemodynamics of Cardiac Pacing François Regoli, MD, PhD Attending Physician, Cardiologist Fondazione Cardiocentro Ticino Lugano, Switzerland Basic Physiology and Hemodynamics of Cardiac Pacing Dwight W. Reynolds, MD Professor of Medicine Chief, Cardiovascular Section University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation Michael P. Riley, MD, PhD Assistant Professor of Medicine Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Troubleshooting of Implantable Cardioverter-Defibrillators Anthony Rorvick, BS Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

x

Contributors

Elizabeth Vickers Saarel, MD Associate Professor University of Utah Director, Electrophysiology Primary Children’s Medical Center Salt Lake City, Utah Imaging of Implantable Devices

Warren M. Smith, MBChB Honorary Clinical Associate Professor in Medicine University of Auckland Cardiologist Auckland City Hospital Auckland, New Zealand Subcutaneous Implantable Cardioverter-Defibrillators

Leslie A. Saxon, MD Clinical Scholar and Chief Division of Cardiovascular Medicine Keck School of Medicine University of Southern California Los Angeles, California Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Bruce S. Stambler, MD Professor of Medicine Case Western Reserve University Cleveland, Ohio Pacing for Atrioventricular Conduction System Disease

Craig L. Schmidt, PhD Senior Director, Energy Systems Research Medtronic Energy and Component Center Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators Gerald A. Serwer, MD Professor of Pediatrics University of Michigan Attending Pediatric Cardiologist University of Michigan Congenital Heart Center Ann Arbor, Michigan Pediatric Pacing and Defibrillator Use Robert S. Sheldon, BSc, MD, PhD Professor of Cardiac Sciences University of Calgary Senior Vice President of Research Alberta Health Services Calgary, Alberta, Canada Pacing in Neurally Mediated Syncope Syndromes Richard B. Shepard Emeritus Professor, Cardiovascular Surgery University of Alabama at Birmingham Birmingham, Alabama Cardiac Electrical Stimulation Ira Shetty, MD Clinical Assistant Professor Loyola University Medical Center Maywood, Illinois Pediatric Pacing and Defibrillator Use Chung-Wah Siu, MD Clinical Assistant Professor Department of Medicine University of Hong Kong Hong Kong, China Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring Paul M. Skarstad, PhD Senior Director of Research (Retired) Medtronic Energy and Component Center Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

Marc Strik, MD PhD Student Department of Physiology Maastricht University Maastricht, the Netherlands Basic Physiology and Hemodynamics of Cardiac Pacing Michael O. Sweeney, MD Associate Professor of Medicine Harvard Medical School Cardiac Pacing and Defibrillation Cardiac Arrhythmia Service Brigham and Women’s Hospital Boston, Massachusetts Troubleshooting of Biventricular Devices Charles D. Swerdlow, MD, FACC, FAHA, FHRS Clinical Professor of Medicine Department of Cardiology Cedars Sinai Heart Institute David Geffen School of Medicine University of California Los Angeles Los Angeles, California Sensing and Detection Sandeep Talwar, MD, PhD, FRCP Senior Electrophysiology Fellow Division of Cardiology University of Utah Salt Lake City, Utah Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators Patrick J. Tchou, MD Associate Section Head, Cardiac Electrophysiology and Pacing Department of Cardiovascular Medicine Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio Defibrillation Testing, Implant Testing, And Relation to Empiric ICD Programming Hung-Fat Tse, MD William MW Mong Professorship in Cardiology Academic Chief, Cardiology Division Department of Medicine Queen Mary Hospital The University of Hong Kong Hong Kong, China Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring



Mintu P. Turakhia, MD, MAS Instructor of Medicine Stanford University School of Medicine Director of Cardiac Electrophysiology Veterans Affairs Palo Alto Health Care System Stanford, California Timing Cycles of Implantable Devices Darrel F. Untereker, PhD Vice President of Corporate Research and Technology Strategic and Scientific Operations Medtronic, Inc. Minneapolis, Minnesota Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators Niraj Varma, MA, DM, FRCP Consultant Cardiac Electrophysiologist Heart and Vascular Institute Cleveland Clinic Cleveland, Ohio Follow-up Monitoring of Cardiac Implantable Electronic Devices Gregory P. Walcott, MD Associate Professor of Medicine University of Alabama at Birmingham Birmingham, Alabama Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms Paul J. Wang, MD Professor of Medicine Stanford University School of Medicine Director, Cardiac Arrhythmia Service and Cardiac Electrophysiology Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices

Contributors

xi

Oussama Wazni, MD Assistant Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Director, Research Development Director, Out Patient Department, Cardiac Electrophysiology Cleveland Clinic Cleveland, Ohio Prevention and Management of Procedural Complications; Techniques and Devices for Lead Extraction Bruce L. Wilkoff, MD Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Director, Cardiac Pacing and Tachyarrhythmia Devices Medical Information Officer Heart and Vascular Institute Cleveland, Ohio Prevention and Management of Procedural Complications; Techniques and Devices for Lead Extraction Seth J. Worley, MD Section Chief for Research Lancaster General Health President and Medical Director Lancaster Heart and Stroke Foundation Lancaster, Pennsylvania Left Ventricular Lead Implantation; Interventional Techniques for Device Implantation Paul C. Zei, MD, PhD Clinical Associate Professor of Medicine Stanford University School of Medicine Director, Cardiovascular Medicine Outpatient Clinics Chief, Clinic Advisory Council Stanford University Medical Center Stanford, California Timing Cycles of Implantable Devices

PREFACE It all started with cardiac pacemakers in 1958, but now we have car-

diovascular implantable electronic devices (CIED). Investigations of the electrical stimulation of the heart began long ago, but the truly impressive technological developments of this technology over the past more than 60 years has been the result of intense collaborative efforts of physicians, engineers, allied professionals, and heart rhythm device manufacturers. When we began to collect the information to mentor heart rhythm device professionals for the initial 1995 edition of Clinical Cardiac Pacing we did not have a chapter on implantable defibrillators. We added implantable defibrillators in the second edition (2000), and in the third edition (2007) we added resynchronization therapy. Now we have a fourth edition. Although there is not a new form of therapy, there are still important changes in the technologies and our insights into how they are applied. There has been a huge increment in the evidence base of how and in whom these devices should be used, and a great maturation of the techniques of implantation and extraction of devices, and management of patients with specific conditions. Many new technologies are discussed, including leadless pacing, and the subcutaneous ICD. Our philosophy in putting together the fourth edition remains the same as that of our first three editions. We have planned this book to emphasize the science of cardiac pacing, implantable defibrillation, and cardiac resynchronization therapy, and to underline the importance of the fact that it is an interdisciplinary field. Physicians are part of a large web of health professionals who need increasing amounts of information about implantable devices. We have a web site with this edition that includes figures and movies not included in the paper version of our text, as well as much additional material. All of the figures from the text are included and available for download from this web site. We have sought to meet the needs of many with this textbook. Clinicians, scientists, nurses, technicians, and engineers will find the information in these pages practical, authoritative, and helpful in better understanding this therapy. We are excited about the opportunity to present this material in a comprehensive scientific manner, and in doing so we stand on the shoulders of giants in the field of heart rhythm devices. Sy Furman wrote the initial edition’s foreword, and for that affirmation we are extremely thankful. We are more in debt to his legacy of innovation, problem solving, always asking more questions, and, finally, his commitment to educating any and all who

demonstrate interest. He will always be greatly missed and remind us of our debt to all our colleagues, physicians, engineers, nurses, and technicians. We also owe a great debt of gratitude to Serge Barold and particularly to his singularly important text, Modern Cardiac Pacing, published in 1985 by the Futura Publishing Company. Each of us learned more about cardiac pacing from this textbook than from any mentor. It is hard to give credit to some and not others, but clearly there are so many others and also the giants that came before them. It is our hope that this edition will continue to mentor the next generation of heart rhythm professionals. We gratefully acknowledge the invaluable assistance and encouragement of Natasha Andjelkovic and Janice Gaillard of the Health Sciences Division of Elsevier for all their help in keeping the fourth edition on track. We owe a great debt of gratitude to our colleagues and fellows from the Medical College of Virginia and the McGuire Veterans Affairs Medical Center, the University of Alabama, The University of Hong Kong and Queen Mary Hospital, and the Cleveland Clinic for their patience and support in shouldering the extra workload that allowed us to finish our chapters and editing on time. Most important, we cannot thank enough our many contributors and their colleagues, who labored extensively, often taking time from family and other projects, to finish their chapters. This large group of individuals deserves all the credit and thanks for making the fourth edition possible. Our wonderful secretaries, Vera Wilkerson (Virginia Commonwealth University/Medical College of Virginia), Monica Crosby (Cleveland Clinic), Jenny To (The University of Hong Kong), and Dorothy Welch (University of Alabama) were invaluable for their contributions to help complete this project. This textbook is designed to be a functional tool and reference, helping clinicians, scientists, and engineers make the decisions that improve patients’ lives every day. It is our desire that this book serve as a valuable resource to all of these people for many years to come. Kenneth A. Ellenbogen, MD G. Neal Kay, MD Chu-Pak Lau, MD Bruce L. Wilkoff, MD

xiii

VIDEO CONTENTS Introduction Bruce L. Wilkoff, MD 9 Basic Physiology and Hemodynamics of Cardiac Pacing 1. 3D electroanatomical mapping in a patient with left bundle branch block QRS morphology 2. Animated 3D reconstruction of the left ventricular wall with myocardial strain 21 Permanent Pacemaker and Implantable CardioverterDefibrillator Implantation 3. Catheter Delivery of a Fixed Extended Screw in Lead to Coronary Sinus Os 4. Catheter Delivery of a Fixed Extended Screw in Lead 5. Removal of a Fixed Extended Screw in Lead in the Atrium 22 Left Ventricular Lead Implantation 6. Intracardiac View of Coronary Sinus Os and Thebesian Valve 7. Intracardiac View of the Thebesian Valve and Its Fenestrations 8. Intracardiac View of the Right Atrium from the IVC Including the Coronary Sinus Os and Thebesian Valve 9. Rotating Intracardiac View of the Right Atrium from the IVC Including the Coronary Sinus Os and Thebesian Valve 10. Intracardiac View of a White and Floppy Thebesian Valve 11. Intracardiac View of a Tattered Thebesian Valve 12. Intracardiac View of an Occlusive Balloon Inflation in the Coronary Sinus Os 13. Intracardiac View of Insertion and Occlusion of the Coronary Sinus with a Venography Catheter 14. Intracardiac View of a Double Coronary Sinus OS and Thebesian Valve 15. Intracardiac View of Coronary Sinus Os and Thebesian Valve with Only Free Access from Inferior Direction 16. Intracardiac View of Coronary Sinus Os and Tricuspid and Thebesian Valves with Attempted EP Catheter Access from Above 17. Intracardiac View of Coronary Sinus Os and Tricuspid and Thebesian Valves with Successful EP Catheter Access from Below 18. Intracardiac View of Coronary Sinus OS and Thebesian Valve with Attempted EP Catheter Access from Above 19. Intracardiac View of a Complicated Thebesian and Tricuspid Valve 20. Intracardiac View of Coronary Sinus Os with Early Branching 21. Intracardiac View of Coronary Sinus Os with Early Branching

22. Intracardiac View of Catheters in the Coronary Sinus and Through the Tricuspid Valve 23. Fluoroscopic Venogram of the Main Coronary Sinus and Mid-CS Valve 24. Fluoroscopic Advancement of a Decapolar EP Catheter into the Coronary Sinus 25. 3D image of the Cardiac Venous Anatomy 26. Occlusive Venography of Coronary Sinus LAO 30 27. Occlusive Venography of Coronary Sinus Anteroposterior Projection 28. Occlusive Venography of Coronary Sinus RAO 30 Projection 29. Sheath and Wire Subselected into Anterolateral Branch 30. Sheath and Wire Subselected into Posterior Vein Branch 31. Subvalvular Pouch Mimicking Coronary Sinus Os 32. True Coronary Sinus Venogram 33. Final Lead Position in Posterior-Lateral Branch 24 Approach to Pulse Generator Change 34. Abdominal ICD Pulse Generator with Subcutaneous Patch Electrode 35. Abdominal ICD Pulse Generator with Previously Cut and Capped Additional Electrode 36. Patient from Previous Case After Extraction and Reimplantation 37. Alternative Approach to an Occluded Subclavian Vein 38. Total Occlusion of the Left Subclavian Vein with Reconstitution via the Right Side 25 Prevention and Management of Procedural Complications 39. Transesophageal Echo of Large Right Atrial Vegetation on an ICD Lead 40. Transesophageal Echo of Large Right Atrial Vegetation on a Pacemaker Lead 41. Subclavian Vein Venography and Lead Fractures 26 Techniques and Devices for Lead Extraction 42. Needles-Eye-Snare Extraction of Fractured Ventriculo-Jugular Shunt 43. Fluoroscopy of Embolized Telectronics Accufix Wire 44. Laser Lead Extraction of Single Coil ICD Lead Special Presentation 45. ICD Implantation: Implantation and Management of Complications (PowerPoint presentation)

xvii

1 

Cardiac Electrical Stimulation G. NEAL KAY  |  DEREK J. DOSDALL  |  RICHARD B. SHEPARD

Pathologic cardiac conditions such as asystole, bradycardia, conduc-

tion block, and dyssynchronous contraction may lead to significant morbidity and mortality. One of the most influential and effective medical device therapies developed in the last century is the cardiac pacemaker and implantable cardioverter-defibrillator (ICD). The lives of millions of patients have been improved and extended through the use of pacing techniques that regulate heart rate and improve cardiac output. Direct electrical stimulation of excitable cardiac tissue causes a change in the transmembrane potential of resting cardiac cells. If the transmembrane potential is raised to a certain level, an action potential is initiated in the cells and spreads to adjacent working myocardial cells. The action potential induces mechanical contraction of the cardiac cells that spreads throughout the heart as a self-propagating wavefront. This chapter reviews the fundamental concepts of artificial electrical cardiac stimulation, including the cellular aspects of myocardial stimulation, the influence of external current on cardiac tissue, waveform and electrode considerations, clinical applications and considerations, and ongoing research regarding cardiac stimulation.

Concepts Related to Electrical Stimulation of the Heart STATIC ELECTRIC CHARGE AND ELECTRIC FIELDS Physical objects may acquire an electric charge when they have a net excess or deficit of electrons relative to the number of protons. When the number of electrons exceeds the number of protons, the object is said to have a negative charge, whereas a net deficit of electrons results in the object acquiring a positive charge. An electrically charged object is surrounded by an electric field such that charged objects act at a distance on other objects having similar or opposite charge. The strength of the electric field is related to the magnitude of its charge. A gravitational field also acts at a distance, but an electric field has an important difference, polarity. Thus, electric fields have directionality with the convention that field lines are drawn away from positively charged and toward negatively charged objects. The electric fields surrounding charged objects interact with each other such that the presence of two electrically charged objects results in a force that either attracts the two objects (if they have opposite charges) or repels the two objects (if they have the same qualitative charge). This attractive or repulsive force acts at a distance, not requiring that the charged objects be in contact, and the attractive or repulsive force (F) is given by Coulomb’s law:

F=k

Q1 Q2 r2

where Q1 and Q2 are the magnitude of the charges (measured in coulombs), r is the distance separating the charged objects, and k is a 1 constant equal to with ε being the permittivity of free space. 4πε According to Coulomb’s law, the force attracting or repelling charged objects increases with the magnitude of charge and decreases with the square of the distance that separates them. Potential Difference Voltage is the electrical potential energy possessed by a charge by virtue of its position in space. A charged object in space has potential energy

because of the forces that other charges exert on that object. When two charged objects repel one another, energy is required to move either object closer to the other, thereby increasing the potential energy. However, if the charged object is attracted to another charged object, potential energy will be converted into kinetic energy when either charge moves closer to the other. Thus, the force generated by the interaction of electrical charge is electromotive, tending to move charged objects. Voltage is the potential energy per unit charge for a charge in an electric force field. Thus, in order to move a charge from point A to point B, the work required (measured in joules) is calculated by multiplying the charge, Q, by the voltage difference between points A and B, VAB. Because voltage is potential energy per unit of charge, it is measured in terms of joules/coulomb, as follows:

1 volt = 1 joule/coulomb

When one refers to “voltage,” the reference is to a difference in potential between two points in space. Electric Current An electric current, I, is present when there is a movement of electric charge. Although electric charge may move through several mechanisms, for clinical purposes, electric charge is usually carried by the flow of electrons through a wire (e.g., pacemaker lead) or by the movement of ions in blood, interstitial fluid, across cell membranes, or within the cytoplasm of cells. By historical convention, current is considered to flow in the direction that positive charges would move. In reality, however, an electric current in a wire is carried by the movement of electrons that are negatively charged. For clarity in this chapter, current is stated in terms of electron or ion motion. Because electric current is the movement of charge, it is measured in terms of coulombs per second (It = dQ/dt), with 1 ampere of current equal to the movement of 1 coulomb/sec. The electromotive force for cardiac pacemakers or ICDs is determined by the chemistry of a battery. For lithium-iodine batteries at beginning of life, the chemical reaction generates approximately 2.8 volts of electromotive force. The total amount of charge that is available in the battery is measured in terms of the amount of current that can be provided for a given unit of time. For pacemaker or ICD batteries the amount of charge that can be stored in the battery is measured in terms of ampere-hours, with 1 A-hr equal to 3600 coulombs of charge. ELECTRIC CIRCUIT An electric circuit is an electric charge–conducting pathway that ends at its beginning. For electric circuits involved in myocardial stimulation by pacemakers or ICDs, the voltage difference in the circuit is provided by a battery. The difference in voltage generated by the battery results in a flow of charge (current) from the pulse generator through the conductors in the leads, electrodes, extracellular electrolytes, cell membranes with highly regulated transmission of charged ions in both directions through the membrane, and intracellular ions and charged molecules. As current flows through the complete electric circuit, the net voltage change must be zero (Kirchoff ’s voltage law). Thus, the electromotive force (voltage) generated by the battery (an increase in potential energy) must be completely dissipated (a decrease in potential energy) as current flows through all the elements of the circuit to end at the battery.

3

4

SECTION 1  Basic Principles of Device Therapy

Electric circuits in the clinical practice of pacing have multiple elements, including the pulse generator battery, the lead conductor(s), the electrodes, the myocardium, and blood within the great veins and cardiac chambers. All these elements introduce opposition to the flow of current. Series Circuit In a series circuit, or circuit module, the elements are connected so that current must flow sequentially through each element in the circuit. Thus, the current flowing through all elements in series is the same, with the voltage difference decreasing sequentially as it passes through each element in the circuit. Parallel Circuit In a parallel circuit, two or more elements are joined at each end to a common conductor (node in the circuit). Therefore, the potential difference is the same before each element and after each element, and current will flow from one of the common conductors to the other through any or all of the elements. The degree of current flow in each element is inversely related to the factors that oppose the flow of electric charge in that element. At any node (junction) in an electric circuit, the sum of currents flowing into that node is equal to the sum of currents flowing out of that node (Kirchoff ’s current law). Most biologic circuits are made of various combinations of series and parallel modules or subcircuits. For example, because of electrochemical effects, an electrode placed in the heart may act as a capacitor in parallel with a resistor, both in series with the lead joining the pulse generator to the electrode. ELECTRODE POLARITY All defibrillator and pacemaker electric circuits have both a positively charged electrode (the anode) and a negatively charged electrode (the cathode). The negatively charged cathode is typically the tip electrode on a pacing lead. Electrons from the pulse generator flow through the cathode-tissue interface and return to the anode, which may be located on a pacing lead or the pulse generator casing. The terminology used for electrode polarity may be confusing as applied to lead electrodes and the electrodes of a battery. The electrode in a battery at which oxidation occurs (e.g., oxidation of lithium to yield Li+ plus an electron, e−) is the battery anode. The battery anode, by continuing oxidation, furnishes electrons to the circuit external to it. Therefore, in contradistinction to the terminology used for pacing leads, the terminal of the battery where electrons are provided to the circuit is the battery anode. From the battery anode, electrons flow through the circuitry and eventually enter the pacemaker lead electrode that is in contact with the myocardium. This electrode, receiving electrons from the pulse generator and furnishing electrons to the tissue, is the lead cathode. The return electrode located in the heart or on the pulse generator casing is the lead anode. It collects electrons from the tissue and returns them through the pulse generator circuitry to the positive electrode of the battery, the battery cathode, where reduction occurs (e.g., I2 + 2e− yields 2I−). The consistency in the terminology is that, when oxidation occurs, it occurs at an anode, and in the circuitry, an anode connects to a cathode that subsequently connects to another anode, and so on. OPPOSITION TO FLOW OF ELECTRIC CURRENT In cardiac pacing and defibrillation, several elements in the electric circuit oppose the flow of electric current. As current flows through some of these elements, such as the conductor wires in the leads and pulse generator, the opposition to current flow results in energy being lost as heat. These elements are known as ohmic, and the opposition to current flow is called resistance (R). The instantaneous voltage developed across a perfect resistor is linearly proportional to the instantaneous current flow through the resistor. If a steady voltage across the

resistor is represented by V, the current by I, and an unchanging resistance by R, the relationship is expressed as follows in Ohm’s law:

V = IR

In reality, when all the elements of a cardiac pacing circuit are considered, these factors are much more complex than can be represented by Ohm’s law alone. These other factors include capacitance and inductance. For calculations involving a pulsed (e.g., pacemaker stimulus) or an alternating current (AC) circuit that contain reactive elements (e.g., electrodes in contact with electrolytes), the term impedance (Z) must be used in place of resistance. Impedance is a vector sum of resistance (R) and reactance (X). The following sections discuss the major components of reactance. CAPACITANCE As mentioned earlier, current can be carried in different ways. Electrolyte is used as a generic term for the electrically conductive extracellular and intracellular fluids near pacemaker or defibrillator electrodes and elsewhere in the heart and blood vessels. The electrolyte conducts ions but not electrons. The difference between the conduction of electric currents by electrolytic fluids and the flow of electrons over metal wires is crucial to pacing. Because a negatively charged pacing electrode in contact with the endocardium is surrounded by blood and interstitial fluid, positively charged ions move toward that electrode during a pacing stimulus. This results in the phenomenon of polarization, which develops rapidly and dissipates slowly after the end of the stimulus. The opposite effect occurs on the positively charged anode. This effect of ions moving to oppose the flow of electric current has the effect of a capacitor in the circuit. A capacitor is an object that stores energy in an electric field by holding positive charges apart from closely approximated negative charges. A capacitor requires a material or space between the layers of negative and positive charges that is normally nonconducting (the dielectric). A cell membrane, although leaky, acts as a capacitor by separating the negatively charged inside of the cell from the more positively charged outside. Cell membranes have very high capacitance per unit area of cell membrane. The interface between a pacing electrode and the charged electrolytes that surround the electrode at its surface in the myocardial tissue acts, in part, as a capacitor. The terms Helmholtz capacitor and Helmholtz capacitance are used in this chapter for capacitor-like effects that occur at pacemaker and defibrillator electrode-electrolyte interfaces. Capacitance (C) is the term that specifies, for a given voltage applied across a capacitor, how much electrical charge (Q) can be stored by the capacitor. If V represents a steady voltage applied across the capacitor, then Q = CV. (If E is used instead of V as the symbol for electric potential, the relationship may be expressed as Q = CE.) The unit for capacitance is the farad. One farad is the capacitance of a capacitor that, on being charged to 1 volt, will have stored 1 coulomb of charge. Again, a coulomb is the amount of charge delivered by 1 ampere flowing for 1 second. Coulombs delivered can be expressed as follows:

t

Q t = ∫ i t dt 0

in which Qt is the total charge delivered between time 0 and time t, and it is the instantaneous current at each time segment between time t 0 and time t. The integral ∫ i t dt is the net area under the instantaneous 0 current-versus-time plot. INDUCTANCE When an alternating current flows through a wire, a magnetic field surrounding the wire is induced. An inductor is an object that stores or releases energy in or from a changing magnetic field. The voltage difference across an inductor is proportional to the rate of change of current flowing through the inductor. Energy is stored during the formation of the magnetic field and is released when the magnetic field decreases or disappears. Inductance is the term that specifies the



1  Cardiac Electrical Stimulation

relationship between the voltage across an inductor and the rate of change of current traversing the inductor. The magnitude of the inductance can be represented by the symbol L. If Vt represents the instantaneous voltage across the inductor, and iL represents the instantaneous current flowing through the inductor, the relationship is given by the following equation: di L 1 t or i L = ∫ v t dt dt L 0 Note that the voltage across the inductor is directly proportional to the rate of change of current flowing through the inductor. Cell membrane currents have some of the current- and voltage-versus-time characteristics of an inductance in parallel with a capacitance.1 These inductancelike effects are related to the timing and magnitude of potassium ions moving into and out of the cell.2

vt = L

REACTANCE (CAPACITANCE AND INDUCTANCE) For reactive elements connected in series, net reactance is the scalar sum of inductive reactance (positive in the mathematical complex plane) and capacitive reactance (negative in complex plane). Pure reactance values depend on the rates of change of current and voltage, whereas pure resistance values do not. Phenomena of this type are caused by differences in the timing of the peaks (phase angles) of the voltages or currents in the various reactive components. These reactive effects can be important in biventricular pacing threshold measurements (see later discussion). The component of reactance that is most relevant to both pacing electrodes and cell membranes is capacitance, with inductance being much less important. For example, the cardiac action potential spreading throughout the heart generates a changing magnetic field that transiently stores a very small amount of energy. However, the changing magnetic field generated by spread of the action potential is so small that it is not clinically significant except in the research setting.3 For circuits with resistance R, capacitance C, and inductance L in series, where qt represents the charge accumulated across the capacitance at any time t, and where the current through these combined elements at time t is it, the voltage Vt at time t is described by the following equation: t idt qt di di ∫ 0 v t = i tR + + L or v t = i t R + +L C dt C dt t (remembering that q t = ∫ i t dt and that the voltage across a capacitor 0 qt at time t is ). C These equations indicate that, for an instantaneous current it, the instantaneous voltage across the series circuit is the sum of the effects at that instant in time of the resistance, capacitance, and inductance of the circuit. Note especially that the instantaneous effects are highly t related to the net amount of charge, q t = ∫ i t dt , that has accumulated 0 in the capacitor from time 0 to the instantaneous time t. The equations show that the capacitance effect on the voltage decreases as the capacitance increases. This has clinical relevance in that, for example, the polarization voltage that interferes with autosensing pulse generators decreases as the electrode capacitance increases.

(

)

Cellular Aspects of Myocardial Stimulation THE PHOSPHOLIPID BIMEMBRANE Living cells maintain or regenerate a difference in electric potential across the cell membrane. Excitable tissues such as myocardium respond to electrical stimulation of one or more cells with a wave of electrical depolarization—a transient reversal of the voltage gradient across the membrane—that can propagate from cell to cell. Excitable cells respond to a relatively small applied change in electric potential

5

Phospholipid

Lipid “tail” Phosphate “head” Ion channel

Figure 1-1  The phosphomembrane bilayer of a cardiomyocyte contains ion channels and structures that maintain distinct ion concentrations inside and outside of the cell. Charge pumps maintain an ion concentration gradient across the membrane while ion channels allow for charge in the form of ions to pass through the membrane. The ion current flow causes changes in transmembrane potential and cardiac activation.

difference across the cell membrane by triggering a series of biochemical and biophysical events (described later). These depolarization events result in myocyte contraction. Depolarization propagates along excitable cell membranes, as in the transmission of an action potential along a squid axon, and from myocyte to myocyte through gap junctions. CELL MEMBRANE CHARACTERISTICS Cell membrane characteristics are major determinants of tissue excitability. The membrane of the cardiac myocyte is composed principally of phospholipids, cholesterol, and proteins.4 The membrane phospholipids have a charged polar headgroup and two long hydrocarbon chains arranged as shown in Figure 1-1. The cell membrane comprises two layers of phospholipids with their hydrophobic aliphatic chains oriented toward the central portion of the bilayer membrane and their polar headgroup regions toward the outside boundaries of the membrane. Because the membrane is composed of two layers of phospholipids, the polar regions of the phospholipid molecules interface with the aqueous environments inside and outside the cell. The lipid-soluble hydrocarbon chains are forced away from the aqueous phase to form a nonpolar interior. DETERMINANTS OF THE RESTING TRANSMEMBRANE POTENTIAL Relatively large gradients of individual ion concentrations exist across the cardiac cell membrane.5 The gradient of sodium ions (Na+) across the membrane is approximately 145 millimoles per liter (mmol/L) outside to 10 mmol/L inside. In contrast, the potassium ion (K+) concentration outside the cell is approximately 4.5 mmol/L, whereas the inside concentration is 140 mmol/L. In the absence of a cell membrane, both Na+ and K+ would rapidly move in a direction determined by the concentration gradient. The diffusion force tending to move K+ out of and Na+ into the cell is proportional to the concentration gradients of those ions. The potential energy attributable to the diffusion force (PEd) tending to move K+ out of the cell is given by the following equation:   [K + ]   PEd = RT  ln  + i   [1-1]   [K ]o   where R is the gas constant, T is the absolute temperature, ln is the natural logarithm operator, [K+]i is the concentration of potassium ion inside the cell, and [K+]o is the concentration of potassium ion outside the cell. If the ratio of [K+]i to [K+]o is large, the potential energy across the membrane is large. For each ion species, the difference in concentration between the inside and the outside of the cell results in that ion’s contribution to the difference in electric potential across the cell membrane. In resting cardiac cells, the intracellular cytoplasm has a measured potential of about −90 millivolts (mV), relative to the extracellular

6

SECTION 1  Basic Principles of Device Therapy

fluid. This electric force tends to move positively charged ions such as K+ and Na+ to the inside of the cell and negatively charged ions such as chloride (Cl−) to the outside of the cell in proportion to the potential gradient. The potential energy attributable to the electric force (PEe) tending to move K+ into the cell is expressed as follows: PE e = zFVm



Na+

K+

A

Protein molecules embedded within the cell membrane have numerous functions, including those of being ion channels and signal transducers. The concept of ion channels was proposed in the 1950s by Hodgkin and Huxley.7 However, it was not until the introduction of the patch clamp technique by Neher and Sakmann in 1976 that the properties of these channels could be directly studied.8,9 There are two basic types of ion channels, distinguished by the factors that control opening and closing of the channel. Ion channels at muscle fiber end plates are chemically gated by specific transmitters. The opening of these channels is triggered by the binding of acetylcholine, and their closing is induced by its unbinding. In neuronal axons, conduction is mediated by faster, voltage-gated channels. These channels respond to differences in electric potential between the inside and outside of the

CACNA1C

INa/Ca

NCX1

0

i

Ion Channels

Ca2+

Probable gene SCN5A

ICa.L

Using known values for extracellular K+, Vm(K+) = −90 mV. When Equation 1-3 is solved using Na+ concentrations, a Vm(Na+) of +50 mV is obtained. Therefore, it is the equilibrium potential for potassium ion (not sodium ion) that is the major factor responsible for the resting transmembrane potential. This suggests that the resting membrane is more permeable to K+ than to Na+. To calculate the transmembrane potential when multiple ionic species exist in different concentrations across the membrane, the Goldman constant field equation (modified by Hodgkin and Katz6) is used: + + + + − − − RT   PK [K ]i + PNa [ Na ]i + PCl [Cl ]o + …  Vm =  ln  + + [1-4]  + + −  F   PK [K ] + PNa [ Na ] + PCl [Cl − ] + … where PK+, PNa+, and PCl− are the cell membrane permeabilities for the respective ions. At physiologic concentrations, this equation yields a transmembrane potential of −90 mV (the equilibrium potential for K+). Equation 1-4 describes how resting potentials vary as sodium and potassium ion concentrations are changed. Because there is a passive leak of charged ions through the membrane, the resting potential would not exist at the level of −90 mV unless it were actively maintained. This is accomplished by two active transport mechanisms that exchange Na+ ions for K+ and calcium (Ca2+) ions. One might ask: with all the potassium ions and other positively charged ions in the cell, and with a relatively small amount of negatively charged chloride ions in the cell, how can the interior of the cell be negative with respect to the outside? The answer is that an array of intracellular organic and inorganic anions inside the cell—molecules that do not cross the membrane—carry net negative charges sufficient to make the overall balance of charge negative.

K+

INa

 [K + ]  or, in log base 10 terms, Vm (K + ) = −61.5 log  + i  .  [K ]o 

o

Na+

[1-2]

where z here is the valence (the number of positive or negative electrical charges) of the ion, F is the Faraday constant (96,500 coulombs/ equivalent), and Vm is the transmembrane potential difference (transmembrane voltage, measured in millivolts). During equilibrium, the total of the potential energies from diffusion and electric forces is zero, and no net ionic movement occurs. Therefore, the sum of Equation 1-1 and Equation 1-2 may be set to zero. This yields the Nernst equation, which describes (in measurable electrical units) the potential that must exist for a single ionic species, here K+, to be in equilibrium across the membrane of a resting cardiac cell:  [K + ]  Vm (K + ) = −26.7 ln  + i  [1-3]  [K ]o 

o

Ca2+

IK1

KCNJ2

Ito1

KCND

Ito2

?

IKr

KCHNH2IKCNE2

IKs

KCHQ1IKCNE1

IKp

KCNK?

B Figure 1-2  Ion channels underlie cardiac excitability. A, Key ion channels (and electrogenic transporter) in cardiac cells. K+ channels (green) mediate K+ efflux from the cell; Na+ channels (purple) and Ca2+ channels (orange) mediate Na+ and Ca2+ influx, respectively. The Na+/ Ca2+ exchanger (red) is electrogenic, because it transports three Na+ ions for each Ca2+ ion across the surface membrane. B, Ionic currents and genes underlying the cardiac action potential: top, depolarizing currents as functions of time, and their corresponding genes; middle, ventricular action potential; bottom, repolarizing currents and their corresponding genes. (From Marban E: Cardiac channelopathies. Nature 415:213-218, 2002. ©Nature Publishing Group, http://www.nature.com.)

cell, across the membrane. Voltage-gated channels for sodium, potassium, and calcium appear to operate in similar ways, sharing many of the same structural features. In addition, each type of channel can be subdivided into several subtypes with different conductance or gating properties (Fig. 1-2). VOLTAGE-GATED CHANNELS Voltage-gated channels open in response to an applied electric potential. The source of this voltage can be an action potential propagated from an adjacent cell or the electric field of an artificial pacemaker electrode. If depolarization of the membrane exceeds a threshold voltage, an action potential is triggered, resulting in a complex cascade of ionic currents flowing across the membrane into and out of the cell. As a result of this flow of charge across the membrane, the potential gradient across the membrane changes in a characteristic pattern of events that produce the cardiac action potential (Fig. 1-3).

1  Cardiac Electrical Stimulation

50 Phase 1 Phase 2

–50

Phase 0

0 Threshold

Transmembrane potential (mV)



Phase 3

Phase 4 –100 100

200

300

400

500

Time (msec) Figure 1-3  Microelectrode recording of transmembrane potential (Vm) from left ventricular endocardium of human heart. In phase 0 (depolarization), sodium ions (Na+) rapidly enter the cell through fast channels. In phase 1, the initial repolarization is primarily the result of activation of a transient outward potassium ion (K+) current and inactivation of the fast Na+ current. In phase 2 (plateau), the net current is very small, although the individual Na+, Ca2+, and K+ currents are about an order of magnitude larger. Phase 3 (final repolarization) completes the cycle, with the Na+-K+ pump bringing the membrane potential to a stable point at which inward and outward currents are again in balance. During phase 4, the cell is polarized and gradually undergoes slow depolarization. (From Stokes K, Bornzin G: The electrode-biointerface [stimulation]. In Barold SS [ed]: Modern cardiac pacing. Mt. Kisco, NY, Futra, 1985, pp 33-78.)

Selective membrane-bound proteins (ion channels) determine the passive transmembrane flux of an individual ion species. The transmembrane currents determine or influence cellular polarization at rest, action potential depolarization and repolarization, conduction, excitation-contraction coupling, and myofibril contraction. The channels that regulate transmembrane conductance of Na+ and Ca2+ are voltage gated. The sodium channel is a large protein molecule composed of approximately 1830 amino acids.10 It contains four internally homologous repeating domains, believed to be arranged around a central water-filled pore lined with hydrophilic (“water-loving”) amino acids. It is estimated that there are 5 to 10 Na+ channels per square micrometer (µm2) of cell membrane. When an alteration changes the membrane potential to about −70 to −60 mV (the threshold potential), four to six positively charged amino acids move across the membrane in response to the change in electric field. This causes a change in the conformations of the channel proteins, resulting in opening of the channel. After a single Na+ channel changes to the open conformation, about 104 Na+ ions enter the cell. On depolarization of the membrane, the Na+ channels remain open for less than 1 millisecond (msec). After rapid depolarization of the membrane, the Na+ channel again changes to the closed conformation. In addition to the Na+ channel, specialized proteins are suspended in the cell membrane that have differential selectivity for K+, Ca2+, and Cl− ions, with much different time constants for activation and inactivation. SINOATRIAL AND ATRIOVENTRICULAR NODAL CELLS In contrast to Purkinje fibers and working myocardial cells, sinoatrial (SA) and atrioventricular (AV) nodal cells are characterized by no true resting potential. Following repolarization, the transmembrane potential of the nodal cells reach a minimum of approximately −60 mV. The SA and AV nodal cells have a slow, inward, depolarizing, combined Na+/K+ current known as the “funny” current (If ). These If channels open and cause the transmembrane potential to rise slowly until Ca2+ channels are activated and an action potential is generated. The rate of

7

this rise in transmembrane potential is affected by factors such as autonomic nervous stimulation and hormones. In these nodal structures, depolarization is primarily mediated by inward Ca2+ conductance through specialized Ca2+ channels. There are two types of Ca2+ channels in the mammalian heart. The L-type channels are the major voltage-gated pathway for entry of Ca2+ into the myocyte, and they are heavily modulated by catecholamines.11 The T-type channels contribute to spontaneous depolarization of the cell associated with automaticity (pacemaker currents). The pore of the Ca2+ channel has a functional diameter of about 0.6 nanometers (nm), larger than that of the Na+ channels (0.3-0.5 nm).12 The selectivity for Ca2+ is high, up to 10,000-fold greater than that for Na+ or K+. The key elements are high-affinity binding sites for Ca2+, positioned along a single file pore. “Elution” of a Ca2+ ion occurs when another Ca2+ ion enters and is selectively bound. In normal situations, the SA node has the most pronounced automaticity and highest spontaneous firing rate in the heart. If the SA node is not functioning properly, however, or if block develops between the SA node and the AV node, the AV node will display pacemaker activity at a slightly slower rate than the SA node. In the absence of a pacemaker signal from the AV node, Purkinje fibers will activate at an even slower rate than either the SA or the AV node. MAINTENANCE OF RESTING MEMBRANE POTENTIAL The resting membrane potential is maintained by the pumping of Na+ ions out of the cell and K+ ions into the cell. The Na+,K+—adenosine triphosphatase (ATPase) pump moves three Na+ ions out of the cell in exchange for two K+ ions moved into the cell.13-15 The basic unit of the Na+,K+-ATPase protein (pump) consists of one alpha (α-) and one beta (β-) subunit. The α-subunit is large (1016 amino acids) and spans the entire membrane, whereas the β-subunit is a smaller glycoprotein. There appear to be about 1000 pump sites/µm2 of cardiac cell membrane. The fully activated pump cycles about 50 to 70 times per second (interval of 15-20 msec/cycle). Similarly, the Na+-Ca2+ pump moves three Na+ ions out of the cell in exchange for one Ca2+ ion.16,17 Therefore, both transport mechanisms result in the net movement of one positive charge out of the cell, polarizing the membrane and maintaining a negatively charged interior. The function of both exchange mechanisms depends on the expenditure of energy in the form of high-energy phosphates and is susceptible to interruptions in aerobic cellular metabolism (e.g., during ischemia). THE CARDIAC ACTION POTENTIAL When the voltage gradient across the membrane of a myocyte decreases so that the inside of the cell becomes less negatively charged with respect to the outside of the cell, a critical transmembrane voltage difference is reached, the threshold voltage. At threshold, the cell membrane suddenly undergoes a further depolarization that is out of proportion to the intensity of the applied stimulus. This abrupt change in the potential across the membrane is the start of a cascade of inward and outward currents that together are known as an action potential.18 The cardiac action potential is an enormously complex event and consists of five phases19 (see Fig. 1-3): phase 0, the upstroke phase of rapid depolarization; phase 1, the overshoot phase of initial rapid repolarization; phase 2, the plateau phase; phase 3, the rapid repolarization phase; and phase 4, characterized by a slow, spontaneous depolarization of the membrane in cells with spontaneous pacemaker activity, until the threshold potential is again reached and a new action potential is generated. Phase 0: Rapid Depolarization The upstroke of the action potential is triggered by a decrease in the potential gradient across the membrane to the threshold potential of −70 to −60 mV. On depolarization of the membrane to the less negative threshold voltage, the Na+ channels open, resulting in an influx of

8

SECTION 1  Basic Principles of Device Therapy

positively charged ions (the inward Na+ current) and rapid reversal of membrane polarity. The rate of depolarization in phase 0 ranges from 800 volts per second (V/sec) in Purkinje cells to 200 to 500 V/sec in atrial and ventricular myocytes. In these cells, the inward Na+ current is primarily responsible for phase 0 of the action potential. In SA and AV nodal cells, where the inward Ca2+ current predominates, the upstroke velocity of phase 0 is much lower (20-50 V/sec). Phase 1: Initial Repolarization After voltage-dependent activation of the Na+ current in phase 0, the membrane potential rapidly changes from negative to positive. The increased conductance of Na+ is rapidly followed by voltage-dependent inactivation. Phase 1 is characterized by the transient outward K+ current (IKto). The outward movement of K+ is a major contributor to the various repolarization phases. It is complex and has a number of discrete pathways.20,21 Most K+ currents demonstrate rectification, that is, decreased K+ conductance with depolarization. The K+ currents include the instantaneous inward rectifier K+ current, the outward (delayed) rectifier K+ current, the transient outward currents, and ATP-, Na+-, and acetylcholine-regulated K+ currents. The initial repolarization, however, is mainly the result of activation of a transient outward K+ current and inactivation of the fast inward Na+ current.22 The transient outward K+ current has two components, one voltage gated and the other activated by a local rise in Ca2+. Phase 2: Plateau The net current during the plateau phase is apparently small, although the individual currents (inward Na+ and Ca2+ and outward K+) are each about an order of magnitude larger.23 Among the inward currents are the slowly activating Na+ current, a Ca2+ current, and an Na+-Ca2+ exchange current. Outward currents include a slowly activating K+ current (IKs), a Cl− current, a more rapidly activating K+ current (IKr), an ultra-rapidly activating K+ current (IKur), and the Na+-K+ electrogenic pump. During phase 2 of the action potential, the absolute refractory period, the cardiac cell cannot be excited by an electrical stimulus, regardless of its intensity. Phase 3: Final Repolarization Deactivation of inward Na+ and Ca2+ currents occurs earlier than for the K+ currents, favoring net repolarization of the membrane. When the membrane is sufficiently repolarized, an inward K+ rectifier current is progressively activated, resulting in a regenerative increase in outward currents and an increasing rate of repolarization. Repolarization is also accomplished by the function of the Na+,K+-ATPase pump. The membrane potential eventually becomes stable, so that inward and outward currents are again in balance and the resting potential reestablished. Between the end of the plateau phase and full repolarization, the cell is partially refractory to electrical stimulation. During this period, the relative refractory period, a greater stimulus intensity is required to generate an action potential than required after full recovery of the resting membrane potential. For clinical measurement of myocardial refractoriness, the effective refractory period, stimulation of the heart is usually performed at twice the threshold current, as determined during late diastole. Phase 4: Automaticity and the Conduction System Automaticity is the property of certain cells by which they are able to initiate an action potential spontaneously. It has been known for centuries that the heart can exhibit spontaneous contraction even when completely denervated. Leonardo da Vinci observed that the heart could “move by itself.”24 William Harvey reported that pieces of the heart could “contract and relax” separately.25 Many cells within the specialized conduction system have the potential for automaticity. Not all parts of the heart, however, possess this property. In fact, cells in different areas of the heart have different transmembrane potentials, thresholds, and action potentials. Fast responses are characteristic of ordinary working ventricular muscle cells and His-Purkinje fibers, with resting membrane potentials of −70 to −90 mV and rapid

conduction velocities. Normal SA and AV nodal cells have slow responses, with resting potentials of −40 to −70 mV and slow conduction velocities. Cells, or group of cells, with the fastest rate of spontaneous membrane depolarization during phase 4 are the first to reach threshold potential and initiate a propagated impulse. Therefore, cells with the steepest slope in phase 4 become the heart’s natural pacemaker. Ordinary working myocardial cells usually are not automatic. Normally, depolarization is initiated at the SA node.26,27 Figure 1-4 shows action potentials from different types of cardiac cells.28 Rather than maintaining a stable resting membrane potential, the repolarization of the action potential is followed by a slow depolarization from about −71 to −54 mV, the threshold required to initiate another action potential. This slow, spontaneous depolarization drives cardiac automaticity and is related to a specialized current (If ). In the case of AV nodal cells, the fast upstroke is carried predominantly by an inward Ca2+ current. Repolarization is caused by delayed activation of the K+ current. The balance of inward and outward currents determines the net “pacemaker” current and is finely regulated by both adrenergic and cholinergic neurotransmitters. In the presence of AV block or abnormal SA nodal function, AV junctional cells in the region of the proximal penetrating bundle usually assume the role of pacemaker at rates slower than that of the sinus node. In the absence of disease in the AV junction, the escape rhythm occurs with a frequency that is about 67% of the sinus rate.29

Artificial Electrical Stimulation of Cardiac Tissue Artificial lipid membranes in their pure form are electrical insulators. The myocyte cell membrane (sarcolemma) is much more complicated. Specialized protein molecules in the membrane allow it to be conductive.30,31 These proteins, either singly or in certain groupings, form channels that open and close for transport of specific ions through the membrane in response to particular stimuli. The channel proteins are the end stages of processes that provide both active and passive transport of ions and molecules through the membrane. When application of a pacemaker or defibrillator pulse produces a local electric field gradient, ion drift in the extracellular fluid at that site, as well as ion flow within the cell and within the membrane, are affected by the field. The field-induced ion drift cannot be uniform within and outside the cell because of the different drift properties of different ion types, different ion and protein concentrations within and without the cell, and the barrier impedance effect of connections between cells. The effect of the stimulus is to change the transmembrane voltage of nearby myocytes sufficiently so that depolarization begins in and spreads from these myocyte membranes. Propagation of the stimulus to nearby myocytes occurs because the local transmembrane depolarization changes the voltage gradient across adjacent membranes sufficiently to trigger depolarization of those membranes. To cause an action potential to spread throughout the whole heart, an electrical pulse must stimulate a minimum of approximately 50 closely coupled cardiac cells.5 The result is a self-regenerating action potential that progresses in a wavelike, relatively slow manner beyond the local effect of the pacemaker stimulus. Away from immediate vicinity of the electrode, transmission of depolarization and its velocity depend in part on the resistance and capacitance properties of the membrane, on the opening and closing of ion channels, and on ion flows through the sarcolemma. MYOCARDIAL CELL ELECTRICAL PROPERTIES A single Purkinje fiber typically has an internal resistance that is two to three times greater than that of blood. The specific membrane resistance of a Purkinje fiber is on the order of 104 ohms–square centimeter (Ω-cm2). The time constant of the surface membrane is on the order of 10 msec, and the membrane capacity is about 1 microfaraday (µF)/cm2. Gap junctions are intercellular channels that provide a



9

1  Cardiac Electrical Stimulation

Sinus node Atrial muscle AV node Common bundle Bundle branches Purkinje fibers Ventricular muscle R T

P

U

Q

S

Time (msec) 0 100 200 300 400 500 600 700 Figure 1-4  Action potentials from different cell types in the heart. Specialized pacemaker and conduction cell types have distinct action potential characteristics. Activation times for a normal heartbeat demonstrate the spread of activation throughout the whole heart. AV, Atrioventricular. (From Malmivuo J, Plonsey R: Bioelectromagnetism: principles and applications of bioelectric and biomagnetic fields. New York, 1995, Oxford University Press.)

SINGLE-CELL EXCITATION BY ELECTRICAL STIMULUS The basic principle underlying cardiac pacing is the ability of an externally applied voltage difference to generate a self-propagating wavefront of cardiac depolarization in the heart. This wavefront is the result of propagation of action potentials across the myocardium, a process that involves the opening and closing of ion channels in the membrane. In reality, an applied external electrical stimulus initiates cardiac excitation as a result of passive effects on the transmembrane potential. This is a result of a change in potential that is induced in the extracellular space. Because of the relatively high impedance between cells across the membrane and through the gap junctions compared with the lower impedance path through the extracellular space, relatively small amounts of current pass through the cell membrane. When an external stimulus is applied, the potential within the intracellular space does not vary appreciably over the length and width of a cardiac myocyte (Fig. 1-5). However, near the stimulating electrode, the extracellular stimulus causes a field gradient to develop in the extracellular space. The transmembrane voltage (Vm) is equal to the difference in potential inside the cell (Vi) minus the potential outside the cell in the extracellular space (Ve), so a change in extracellular potential with little change in intracellular potential across the length of the cell results in a net difference in Vm. This is represented as follows:

Vm = (Vi − Ve )

Thus, as considered along the length of a cardiac myocyte, one end has a more negative transmembrane potential than the other. This leads to a net hyperpolarization of the cell on one end and depolarization on the other end. The induced change in Vm has the capacity to open voltage-gated ion channels within the cardiac cell membrane. Voltagegated Na+ channels are opened by a decrease in Vm. If an external

Vi Vm+

Vm–

A

+

–

Ve Vm

Voltage

pathway for electrical communication between myocytes. Their diameter is about 2 nm and length about 12 nm. Gap conductance is voltage sensitive.32 Under pathologic conditions, such as severe hypoxia or ischemia, gap junctions will not function normally.

B

Vi Ve

Figure 1-5  Response of a cardiomyocyte to electric field. Relatively little current passes through the relatively high impedance cell membrane. A, Cardiomyocite exposed to extracellular electric field. The intracellular voltage (Vi) is relatively low impedance and thus does not vary from one side of the cell to the other while the extracellular voltage (Ve) drops from one end of the cell to the other. B, Transmembrane potential (Vm) is defined as Vm = Vi − Ve, so the left side of the cell is hyperpolarized by the external field while the right side of the cell is depolarized. If the extracellular field gradient is large enough, the rightsided portion of the cell may reach threshold and initiate an action potential that may activate the entire cell and spread to adjacent cells through gap junctions. (From Dosdall DJ, Fast VG, Ideker RE: Mechanisms of defibrillation. Annu Rev Biomed Eng. 12:233-258, 2010.)

10

SECTION 1  Basic Principles of Device Therapy

stimulus is strong enough to cause Vm on the depolarized side of the cell to rise above the threshold to activate the inward Na+ channels, the influx of Na+ ions rapidly leads to further depolarization of the cell and initiates an action potential. This action potential spreads to adjacent cells by passing ions through gap junctions and raising Vm in adjacent cells, and initiating an active response through the activation of Na+ channels. FACTORS DETERMINING CAPTURE BY AN ELECTRICAL STIMULUS In order for an electrical stimulus to stimulate (capture) myocardium, it must be applied with sufficient amplitude, for a sufficient duration (measured in milliseconds), at a time when the myocardium is electrically excitable. Many clinical factors determine whether a stimulus of given amplitude will result in capture, including proximity of the electrode to the myocardium, pathology of the underlying cardiac tissue, size and shape of the electrode, and effects of drugs and hormones, as well as electrolytes. For routine clinical practice, the most important factor is that the lead must be positioned close to well-functioning myocardium in a secure manner. (It is also important that the lead does not stimulate the diaphragm or the phrenic nerve, that it is at a site that results in good hemodynamic function, and that the location does not allow the electrode to bump other electrodes.) After adequate lead positioning, the strength-duration relation is the next most important consideration. CURRENT DENSITY, ELECTRIC FIELD GRADIENT, AND PROPAGATION OF DEPOLARIZATION There are two approaches to thinking about how an electrical stimulus induces a self-propagating wavefront of depolarization within myocardium. The current density approach considers the magnitude of current flowing through a given mass of myocardium between the stimulating electrodes and finds this to be the critical factor required to induce a regenerative wavefront of depolarization. From this point of view, the stimulation threshold is a function of current density (amperes/cm2) in the excitable myocardium underlying the electrode.33-36 The electric field approach holds that the critical factor affecting myocardial depolarization is the magnitude of the electric field gradient (volts/cm in viable tissue) that is induced in the myocardium beneath the stimulating electrode.37,38 These approaches are fundamentally the same in that there is a mathematical relationship between the electric field gradient and the current density at the stimulating electrode. Because reactance as well as resistance is present, Ohm’s law in this context must be stated in terms of impedance, as follows:

v = iz

[1-5a]

where v is the stimulus voltage, i is the current, and z is the impedance to current flow. Note that each of these is a vector. Also note that z varies with current density at the electrode (because of interface properties), with direction of current flow (anisotropy), and with domain (extracellular or intracellular). The total energy of the pacing stimulus is determined by the applied voltage, the current, and the duration of the stimulus, as follows:

t

J t = ∫ v t i t dt 0

[1-5b]

where Jt is the energy delivered (expressed in joules) from time zero to time t during the pulse, vt is the voltage, and it is the current at the electrode at instantaneous time t during the pulse. This equation indicates that the total energy delivered during the pulse is proportional to the area under a curve. The curve is formed in the vertical dimension by the instantaneous product of voltage and current applied to the electrode, and in the horizontal dimension by the time elapsing during the pulse. When the time t reaches the programmed pulse duration, the pulse ends. The area under the curve then represents the electrical energy transferred during the time span of the pulse. The equation can easily be solved in real time with a small digital computer, provided

that continuous phasic measurements of the voltage and current in the wire going to the electrode are available. (Note that this equation has blood flow and pressure energy analogs.39) For pacemakers in almost all clinical situations, it is more practical and very reasonable to calculate the energy delivered by a constantvoltage pulse through a pacemaker electrode by means of an approximation. The assumptions are that (1) the voltage during the pulse really is constant and (2) the current flowing is linearly related to the voltage. Because neither is quite true, the questions become (1) whether the information obtained proves useful and (2) to what degree it can be misleading. If the assumptions are close to being correct, the following equation can be approximately correct and useful: V V2 t= t, R R where J is the energy delivered, V is the “constant” voltage, I is the current, R is the resistance, and t is the stimulus duration. This equation indicates that the total energy delivered can be estimated by multiplying the voltage reading displayed on the pacing systems analyzer (PSA) by the current reading on the PSA and multiplying that product by the stimulus duration. Alternatively, the voltage reading can be squared, then divided by the resistance reading, and the quotient multiplied by the stimulus duration. The virtue in this calculation is that ordinary equipment can provide a quick, approximate determination of the total energy delivered per stimulus. In clinical practice, however, the usual range of good or acceptable values for pacing threshold current and voltage is known, and there is rarely a need to calculate the delivered energy. The stimulation threshold of isolated cardiac myocytes depends on their orientation within an electric field. The threshold is lowest when the myocytes are oriented parallel to the field and highest when the axis of the myocytes is perpendicular to the field.40 It is clear that myocardial stimulation may be induced with anodal or cathodal stimulation, or both, although with somewhat different characteristics. Various investigators have used several different parameters to express stimulation threshold, including current (mA), potential (V), energy (J), charge (Q), pulse width (t, msec), and voltage multiplied by stimulus duration (V-sec).41-47 For the purposes of this chapter, the myocardial stimulation threshold for pacing is defined as the minimum stimulus amplitude at any given pulse width required to consistently achieve myocardial depolarization outside the heart’s refractory period.48 Stimulation thresholds measured with a constant-voltage (CV) generator are stated in volts, and those of a constant-current (CI) generator are stated in milliamperes (mA). Note that a true constant-voltage generator may yield a slightly different stimulation threshold than the pseudoconstant-voltage generators in ordinary use. Why must an electrical pacing stimulus rely on propagation in myocardium rather than directly exciting the entire heart? With the magnitude of a stimulus generated by a pacemaker pulse generator, the electric field gradient and ion current density near the electrode are great enough to trigger an action potential only extremely close to the electrode. Unless propagation of the local depolarization occurs, no cardiac contraction will result. In contrast to cardiac pacing with direct production of only local depolarization and dependence on self-propagation of depolarization, defibrillation involves direct depolarization or hyperpolarization of a large portion of the heart. This is necessary to provide at least the minimum local voltage gradient required to produce depolarization over major portions of the myocardium. To do so requires a stimulus intensity that is much greater than that required for pacing49 (see Chapter 2 for a thorough discussion of defibrillation).

J = VIt = V

ELECTRIC POTENTIAL GRADIENTS AND CURRENTS FOR STIMULATION AND DEFIBRILLATION When the electric field exceeds approximately 1 V/cm in the extracellular space during diastole, myocardial stimulation (capture) results. The electric field must be achieved only in the area of several dozen



cells and may be achieved typically with less than 0.5 mA. When the electric field strength is increased to 6 V/cm, ventricular fibrillation may occur if the stimulus is applied during the vulnerable period (approximately the peak of the T wave). An area where the voltage gradient is at least 6 V/cm must be achieved at a distance of 1 cm from the electrode. To accomplish this, a current of approximately 20 mA is required to initiate ventricular fibrillation. This same field strength (6 V/cm) is also required to interrupt ventricular fibrillation (defibrillation). However, defibrillation requires the minimum field intensity to be approximately 6 V/cm at almost all points in the myocardium. In order to achieve this minimum electric field gradient at the same instant over the entire heart, a very large shock current, typically more than 10 A, must be applied. This current is thousands of times greater than the current required for pacing.49 When a pacemaker pulse is applied, electrically excitable myocytes respond with a wave of depolarization followed by repolarization in the myocardium. Depolarization of a small, local group of myocytes begins the self-propagating process. The initial depolarization adjacent to the electrode produces a potential gradient great enough at neighboring myocytes to result in their depolarization. The process is a self-regenerating mechanism that requires time to spread, and once established, it is largely independent of the distance from the stimulating electrode. Defibrillation is largely accomplished by providing an extremely large potential gradient between the defibrillation electrodes. This produces, at one instant within local myocardium everywhere in the heart, at least a 6 V/cm gradient. In contrast, pacing is accomplished by providing a gradient of approximately 1 V/cm or less at a local site and relies on self-propagation to spread the depolarization process throughout the myocardium. VIRTUAL ELECTRODE EFFECT Virtual electrodes are important because they can serve as sites that initiate or prevent depolarization of myocytes.50 Newton and Knisley51 defined virtual electrodes as “experimentally observed regions of large delta Vm that arise distant from the stimulating electrode.” “Delta Vm” (ΔVm) here represents the change in voltage difference across the myocyte membrane during application of the stimulation current. A virtual electrode can be described as a collection of charge predominately of one sign at a site away from a regular electrode. If, in an electrically neutral solution, ions of one charge sign are moved away by an electric field, a relative excess of ions of the other charge sign will be left or will move in the opposite direction. For example, if the regular electrode is paced with a negative-going stimulus, a site elsewhere in the tissue (i.e., not at this physical electrode) may become transiently positive and alter the transmembrane potentials of cells at that site.52-55 In cardiac tissue, a virtual electrode can occur as an effect of anisotropy after a defibrillation shock and can initiate refibrillation. A virtual electrode may also result from ion redistribution patterns in a nonanisotropic medium. In anisotropic tissue, charge redistribution produced by a physical electrode can have a “dog bone” shape.56 The virtual electrodes occur at sites where ions flow into or out of cells by crossing the cell membrane. An applied unipolar stimulation current flows into some cells while simultaneously flowing out of others, thus producing negative and positive virtual electrodes at different locations. In an anisotropic medium, a cathodal pulse produces a virtual electrode with a dog bone shape oriented perpendicular to cardiac fibers and containing a large ΔVm, and a pair of virtual electrodes containing negative ΔVm at locations along the fibers. Theoretical models have shown that this effect can be attributed to unequal tissue anisotropy in the intracellular and extracellular spaces; that is, intracellular current at a given location favors the longitudinal direction 10 to 1, whereas extracellular current favors the longitudinal direction only 3 to 1 (Knisley, personal communication, 2005). Knisley and Pollard57 studied the effects of electrode-myocardial separation on cardiac stimulation of rabbit hearts in conductive solution. The

1  Cardiac Electrical Stimulation

11

electrode-myocardial separation altered the spatial distribution of ΔVm and increased the pacing threshold. In regard to electrode-myocardial tissue separation, Shepard et al.,58 during 1980s transthoracic defibrillator implantation procedures, sewed the electrodes used for rate sensing onto the outer surface of the pericardium. Sensing voltages were normal. Pacing thresholds of these electrodes measured were high (3.7 ± 1.9 mA and 4.5 ± 2.19 V at 0.5msec stimulus duration), as would be expected both from current density considerations and from Knisley’s findings. The initial impedance was 1209 ± 383 Ω, and the chronic impedance was 1550 ± 358 Ω at a median follow-up time of 964 days. The thresholds had by then decreased to 3.8 ± 2.07 V and 2.7 ± 1.8 mA. The transpericardial distance from underlying myocardium did result in high initial pacing thresholds (and in the special distribution of ΔVm near the electrodes). However, the long-term tissue reaction of pericardium and underlying myocardium to the presence of these electrodes was not detrimental in terms of threshold evolution. Virtual electrodes normally exist near an electrode when a pacing pulse is applied. Nikolski and Sambelashvili,59 studying Langendorffperfused rabbit hearts, found that stimuli of magnitude five times threshold produced “make” or stimulus-onset excitation from virtual cathodes, whereas near-threshold stimuli produced “break” or stimulus-termination excitation from virtual anodes. In studying how cardiac tissue damage at an electrode results in a pacing threshold increase, Sambelashvili et al.60 found that the virtual electrode effect was destroyed by very strong (40 mA, 4 msec, biphasic, 240/min) pacing pulses applied for 5 minutes. Fluorescent optical mapping showed that decrease or loss of the virtual electrode polarization was associated with pacing threshold increase. Propidium iodide staining showed tissue damage within an area about 1 mm in diameter surrounding the electrode. Another view of the effect of strong stimuli as just described is that local tissue damage at a pacing electrode increases the distance from the electrode to normal myocytes. Because electric field strength and current density decrease with distance from the electrode, an increase in pacing stimulus amplitude applied to the electrode is necessary to restore the stimulus current density to the pacing threshold level of myocytes at the outer edge of the damaged tissue. ANODAL AND CATHODAL STIMULATION The polarity of a stimulus can be cathodal or anodal. In determining how an artificial electrical stimulus interacts with cardiac cells to initiate this self-propagating wavefront, the mechanism of excitation of cardiac tissue by an electrical stimulus depends on the polarity, strength, and duration of the stimulus. Cardiac excitation may occur immediately adjacent to the electrode by direct stimulation or at a distance from the electrode through virtual electrode effects. The two mechanisms by which electric current stimulates cardiac excitation close to electrodes are cathodal make and anodal break. Virtual electrodes cause cardiac excitation by cathodal break and anodal make phenomenon. Cathode make excitation occurs adjacent to a cathode from the high current density immediately surrounding the electrode. Current flows in the extracellular space and causes hyperpolarization and depolarization of opposite ends of the cell, as shown in Figure 1-5. Current also passes through the cell membrane and causes an increase in Vm that exceeds the threshold for fast Na+ channels to activate. Excitation spreads outward from the central excitation site in an elliptical shape because of tissue anisotropy (Fig. 1-6). Cathode make occurs on the rising edge of the stimulation pulse (Fig. 1-7, A). An anode tends to hyperpolarize cells immediately adjacent to the electrode, but virtual cathodes form on both sides of the central anode. Anode make excitation causes activation to spread on both sides of the central hyperpolarized region until the excitation merges into a single wavefront and spreads elliptically (Fig. 1-7, B). The threshold for stimulation with cathode make is typically higher than for anode make because the virtual cathodes that form at a distance from the central

12

SECTION 1  Basic Principles of Device Therapy

Cathodal make 0 – mV –100 Anodal break

0 + mV –100 Figure 1-6  Action potentials are initiated by cathodal and anodal excitation. Excitation make and break phenomena occur under and near electrodes. Cathodal make occurs when the excitation current directly excites the tissue under the electrode. Anodal break occurs under the excitation electrode on termination of the stimulating pulse. (From Antoni H: Electrical properties of the heart. In Reilly JP, editor: Applied bioelectricity: from electrical stimulation to electropathology. New York, 1998, Springer, p 160.)

0

3

6

anode are weaker and have less depolarizing power than the direct effects of a central cathode. Cathode break excitation occurs when the stimulating pulse is turned off (Fig. 1-7, C). While the stimulation pulse is turned on, the tissue under the stimulating electrode is depolarized, and the fast Na+ channels open and then become unexcitable. Propagation of the excitation is repressed somewhat by the virtual anodes on either side. On termination of the stimulating pulse, the virtual anodes disappear, and excitation spreads from the active tissue under the electrode to the hyperpolarized regions under the virtual anodes. Because the tissue under the virtual anodes was hyperpolarized, the Na+ channels are fully excitable, and the excitation wavefront spreads rapidly through the area previously covered by virtual anodes. Cathode make occurs at a lower threshold than cathode break and is not observed unless tissue is refractory when the stimulation pulse commences but becomes excitable during the pulse. If the tissue has recovered by the time the pulse turns off, cathode break may occur. If the tissue is unexcitable surrounding an anode at the beginning of a stimulation pulse, anode break excitation may result from a mechanism similar to that of cathode break. Excitation may be initiated by the termination of the excitation pulse (Fig. 1-7). Hyperpolarization directly below the anode causes the Na+ channels to become excitable. Depolarization from the virtual cathodes then rapidly propagates into the hyperpolarized region under the anode (Fig. 1-7, D). The virtual cathodes are relatively weak compared to the hyperpolarizing effect of the anode, but the activation spreads from the depolarized region into the hyperpolarized region because the cell membrane has a nonlinear response by which hyperpolarization decays more rapidly than does depolarization. Because anode break relies on virtual cathodes to initiate excitation in recently recovered tissue, however, this mechanism of excitation has the highest threshold of all, the make or break excitation mechanisms.

9

12

15

CM

A

AM

B

15 mV

–85 mV

CB

–185 mV

C

AB

D Figure 1-7  Computer simulation of four types of excitation with stimulating electrode (black rectangle). Cathode make (A), anode make (B), cathode break (C), and anode break (D) excitation are shown at various times; columns are time (t) in milliseconds. In A and B, t = 0 when the stimulation pulse turns on, and in C and D, t = 0 when the stimulation pulse is turned off. (From Wikswo JP, Roth BJ: Virtual electrode theory and pacing. In Efimov IR, Kroll MW, Tchou PJ, editors: Cardiac bioelectric therapy: mechanisms and practical implications. New York, 2009, Springer Science, pp 283-330.)



1  Cardiac Electrical Stimulation

Anode and cathode make and break phenomenon have been detected in computer models and verified in animal experiments.54,61 Optical mapping techniques with voltage-sensitive dye have been particularly useful in illuminating these mechanisms of stimulation.

Strength-Duration Relationships CHRONAXIE, RHEOBASE, ENERGY, AND PULSE DURATION THRESHOLDS





Irh

I=

[1-5c]

−t

threshold in terms of pulse duration can be misleading if the stimulus amplitude setting is omitted or unknown. In 1892, Hoorweg66 used a voltage source, a galvanometer, and lowleakage capacitors to conduct quantitative stimulation studies. He found that the voltage at which a capacitor must be charged to cause depolarization of nerves and muscles is an inverse function of the capacitance of the capacitor, as follows: Vc = aR + b / c



The intensity of an electrical stimulus (measured in volts or milliamperes) that is required to capture the atrial or ventricular myocardium depends on the duration of the stimulus.62,63 The historical background and the relations between the various electrical factors have been reviewed, further studied, and clearly stated by Blair,64 and by Geddes65 for electrode-electrolyte interface function and models. The interaction of stimulus amplitude and stimulus duration (pulse width) defines the strength-duration curve (Fig. 1-8). Lapique described this exponential relationship of stimulus intensity (current), I, and pulse duration, t, as follows:

1− e τ

where Irh is the rheobase current, e is the mathematical constant 2.718, and τ is the membrane time constant. The voltage or current amplitude required for endocardial stimulation has an exponential relation to the pulse duration, with a relatively flat curve at durations of longer than 1 msec and a rapidly rising curve at durations of less than 0.25 msec. Because of this fundamental property, a stimulus of short pulse duration must be of much greater intensity to capture the myocardium than a longer-duration pulse. Conversely, increasing the pulse width to longer than 1 msec has minimal influence on the intensity of the stimulus that is required for capture. Therefore, if one defines the stimulation threshold in terms of pulse amplitude without also specifying the pulse duration, important information is neglected. Similarly, specifying the capture

Threshold (V, µJ, µC)

x

Energy

4 x x

3

x x

x

x

x

x

x

Charge

x

2 Potential

Rheobase

1 Chronaxie 0 0

.2

.4

.6

.8

1.0

1.5

Pulse width (msec) Figure 1-8  Relationships between chronic ventricular canine constantvoltage strength-duration curves expressed in terms of potential ( V ), charge (µC), and energy (µJ) for a tined unipolar lead with an 8-mm2, polished, ring-tip electrode. Thresholds are measured at the point of gain of capture. Rheobase is the current or voltage threshold to the right that is independent of pulse width. Chronaxie is the pulse width at twice the rheobase. (From Stokes K, Bornzin G: The electrodebiointerface [stimulation]. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, pp 33-78.)

[1-6]

In this experimentally determined equation, Vc is the threshold voltage to which a capacitor of capacitance C must be charged to produce stimulation on discharge. R is the resistance of the circuit through which the capacitor is discharged, and a and b are coefficients that vary with the specimen (tissue) tested. Here, the experimentally determined constant a has the dimension amperes and the constant b has the dimension ampere-seconds. (The capacitance can be derived from the equation

C=

Q V

where C is the capacitance, Q is the charge on either conductor, and V is the magnitude of the potential difference across the capacitor; the capacitance has the dimension ampere-seconds [or coulombs] per volt; 1 coulomb per volt = 1 farad). Hoorweg determined that there was only one specific capacitance value for which the threshold charge was a minimum. He also determined that the threshold charge was a linear function of the stimulus duration, “intersecting the y-axis above zero.” However, Hoorweg did not have the capability to measure thresholds at very short pulse durations. In reality, the threshold charge increases toward infinity as the pulse duration approaches zero. In 1901, Weiss67 reported that the threshold charge required for stimulation increases linearly with stimulus duration. He called this relationship the “formule fondamentale.” If I represents the magnitude of the current, t is the stimulus duration, and a and b are constants determined by analyzing the data, Weiss found that: t

t

5

13

∫ Idt = at + b 0

[1-7]

Or, because ∫ idt = Q, the charge in the capacitor at threshold stimu0 lus duration t, Q = at + b. For a constant-current stimulus, this can be stated in words as threshold charge requirement = a amperes times t seconds + b, where b is a constant with dimensional units of ampereseconds. The values of the constants a and b vary with the tissue tested. The left-hand side of Equation 1-7 indicates that the charge delivered into the electrode is, for a constant current, the magnitude of the current multiplied by the duration of the current. The right-hand side states that the charge required to stimulate at threshold is a minimum of b ampere-seconds plus the product of the current level a and the stimulus duration t. Weiss67 noted that, for various stimulus durations tested, the quantity of charge required to initiate depolarization remained constant. The statement that the threshold charge requirement does not change with stimulus duration is true only within a limited range. The limitation leads to the concept of rheobase, as stated in 1909 by Lapique;68 when pulse duration is increased beyond a limited range, the current requirement does not decrease further. The charge delivered continues to increase as pulse duration is increased. Lapique called this minimum current the rheobase, or the lowest stimulus current that continues to capture the heart when the stimulus duration is made extremely long. In this situation, further increases in stimulus duration no longer reduce the magnitude of current required to stimulate the heart. Note from Equation 1-7 that the ratio a/b has the dimensions/ amperes divided by (ampere-seconds); this expression reduces in dimensions to the reciprocal of the stimulus duration. Lapique called the time seen in the a/b ratio the chronaxie, specified in seconds. Chronaxie time experimentally turns out to be approximately the threshold pulse duration at twice rheobase amplitude, and it has become defined

SECTION 1  Basic Principles of Device Therapy

as such; this is illustrated in Figure 1-8. Note again that rheobase is specified in terms of current, and chronaxie is specified in terms of time. Lapique69 determined that stimulation at the chronaxie pulse width approaches the minimum threshold energy. Therefore, the two most important reference points on a current or voltage strength-duration curve are rheobase and chronaxie. Obtaining a true rheobase typically requires pulse widths of 10 msec or greater. For clinical purposes, rheobase can be approximately measured at pulse widths of 1.5 to 2 msec. The value obtained may be slightly greater than the true rheobase. Therefore, the chronaxie stimulus duration obtained by setting the stimulus current at twice the approximate rheobase current and then finding the minimum stimulus duration that will result in capture is slightly low. In a time-saving, useful, and reasonable clinical sense, one may empirically set the stimulus duration at a value determined from experience, such as 0.4 to 0.5 msec and then determine the current and voltage thresholds. Safety factor allowances of current and voltage are then added or subtracted based on the patient’s current and projected clinical status (see later discussion). The goal is to find the combination of pacing threshold stimulus current, voltage, and pulse width that results in minimal charge drain from the pulse generator battery at normal pulse rates. Figure 1-8 shows that, for capture to be accomplished, the least charge was required at the shortest pulse duration (0.1 msec in the figure), but the least energy was required at about 0.3-msec stimulus duration. A very short pulse duration puts thresholds close to the steeply ascending limb of the voltage or current curve, where slight fluctuations can risk loss of capture. For this reason, Irnich70,71 recommended that chronaxie, or the pulse duration slightly to the left of chronaxie, is the most efficient pulse duration for both pacing and defibrillation. In most cases, the pulse duration at chronaxie or slightly greater appears to represent the best overall compromise between adequate safety and generator longevity. One also considers the expected stability or instability of the patient’s status, patient compliance, and follow-up arrangements, both short and long term. Pacing thresholds can also be specified in terms of only energy (microjoules, µJ) or only pulse duration (milliseconds). However, reliance on specifications in either of these units alone can be misleading. Doing so discounts that, regardless of the pulse duration or energy used, the heart cannot be stimulated unless the stimulus amplitude exceeds the rheobase current.72 For example, if rheobase is achieved with a pulse amplitude of 0.5 V and 10 msec, the pulse at this point on the strength-duration curve will have 5 µJ of energy (current × voltage × time) with a 500-Ω lead (1 mA × 0.5 V × 10 msec = 5 µJ). A 0.4-V, 20-msec pulse on a 500-Ω lead has 6.4 µJ of energy (28% greater than the “threshold” energy at 10 msec) but will not result in cardiac capture. Increasing the pulse duration to 100 msec at 0.4 V results in 32 µJ of energy (540% greater than “threshold” energy at 10 msec) but will still not capture the heart, for the same reason. No matter how far the pulse duration is extended (with increased energy), the myocardium will not be captured unless the stimulus amplitude is at least as great as the rheobase value. Therefore, calculation of the energy threshold at very long pulse durations does not provide clinically useful information.73 Coates and Thwaites74 studied the strength-duration curve in 229 patients with 325 leads. The mean atrial chronaxie (n = 101) was 0.24 ± 0.07 msec, and the mean ventricular chronaxie (n = 224) was 0.25 ± 0.07 msec. Mean atrial and ventricular rheobase values were 0.51 ± 0.2 V and 0.35 ± 0.14 V, respectively. Because the pulse generators were set at factory-nominal pulse durations of 0.45 to 0.50 msec, the authors concluded that pacing was suboptimal from the efficiency point of view. They pointed out that battery drain would be reduced by programming pulse duration to the chronaxie value and then programming the voltage to double the chronaxie value. In a study of excitability of rat atria during postnatal development up to 120 days, Gurjao de Godoy et al.75 found that atrial rheobase decreased with animal age and was altered by electric field orientation. Atrial chronaxie increased only with age. The clinician might keep in mind that the chronaxie is influenced not only by electrode material, size, and

stimulation mode, but also by clinically varying biochemical factors. Certainly, marked variations in pacing threshold, either up or down, do occur months and years after implantation in some children and adults.76 As stated earlier, on the left side of the chronaxie point of the strengthduration curve, the current and voltage rise rapidly as stimulus duration decreases. At pulse durations greater than chronaxie, the slope of the strength-duration curve gradually flattens. Small changes in stimulus amplitude are then less likely to result in loss of capture, especially if the threshold has increased because of a pathophysiologic condition. This increased safety comes at the cost of decreased battery life. PRACTICAL APPLICATION TO THRESHOLD MEASUREMENT To determine the strength-duration relationship, the clinician must measure the stimulation threshold at specific amplitudes and pulse durations. However, the result obtained varies somewhat with the method used. Usually the threshold, as measured at a specific stimulus duration (e.g., 0.5 msec), will be slightly higher when the stimulus amplitude is gradually being increased than being decreased. The threshold can also be measured by holding the output voltage constant and changing the stimulus duration. The stimulation threshold then is defined as the lowest-amplitude pulse duration that results in consistent capture of the myocardium. Only the threshold measured in this way can be clinically useful, as noted earlier. It also can be deceptive, because the strength-duration curve is not linear. For example, if the pulse duration threshold is 0.5 msec at an amplitude of 2 V, reprogramming the pacemaker stimulus to a pulse duration of 1 or even 1.5 msec would provide a very small margin of safety 10 9 8

Volts

14

7

D

6

2×V E

5 4

C

3 2

A

2×V 2 × PW

B

1 0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 2.0

Pulse duration (msec) Figure 1-9  Programming of pulse amplitude and pulse duration based on analysis of the strength-duration curve in a patient evaluated at the time of pulse generator replacement (6 years after lead implantation). The rheobase voltage was 1.4 V, and the chronaxie pulse width (PW) was 0.30 msec. Note that the stimulation threshold, determined by decreasing the stimulus amplitude at a constant pulse duration of 0.5 msec, was about 2 V (point A). Doubling of the PW on the relatively flat portion of the strength-duration curve (point B) provides little safety margin for ventricular capture. In contrast, consider a threshold value on the steeply ascending portion of the strength-duration curve (point C). Doubling of the pulse amplitude doubles the safety margin on this portion of the curve, but it lies very close to the curve (point D). An appropriate setting for the chronic pacing pulse might be achieved by doubling the pulse amplitude from point A to point E. Also note that a similar programmed setting would have been obtained had the pulse duration been tripled from point C. Thus, the shape of the strengthduration curve has an important influence on the choice of the amplitude and duration of the pacing pulse.



1  Cardiac Electrical Stimulation 1.0

Effect of Pacing Rate on Stimulation Threshold

0.8 0.7 0.6 0.5

Increment

0.4

Decrement

0.3 0.2 0.1 0.0 2250 2000 1750 1500 1250 1000

750

500

250

Cycle length (msec) Figure 1-10  Pacing thresholds determined by gradually incrementing and decrementing the pulse amplitude until gain and loss of capture, respectively, are demonstrated in a patient with complete atrioventricular block. The pacing threshold was determined at cycle lengths of 2000, 1500, 1000, 750, and 500 msec and with a constant pulse duration of 2.0 msec. To prevent variation in cycle length during incrementing and decrementing pulse amplitudes, a backup pulse was delivered at 25 msec. Note that the threshold values determined in this manner, with increments and decrements of the stimulus amplitude, are similar. Therefore, the Wedensky effect may be marginal when the pacing cycle length is maintained at a constant value.

(Fig. 1-9). Instead, doubling the stimulus amplitude to 4 V at a pulse duration of 0.5 msec would provide an adequate margin of safety. In contrast, consider that, in this same patient, the pulse duration threshold is 0.15 msec at a pulse amplitude of 3.5 V. Increasing the pulse width to 0.45 msec would also provide an adequate safety margin. The reason that a threefold increase in pulse width is not adequate in the first example but is acceptable in the second relates to the location of the threshold stimulus on the strength-duration curve. Consideration of programming the pulse generator to twice the voltage threshold found at the chronaxie pulse duration is only a starting point. Determination of the safety margin necessary for any particular patient depends on several physiologic factors, as discussed next. Capture Hysteresis (Wedensky Effect) The threshold stimulus amplitude measured by decreasing the voltage or current until loss of capture occurs is sometimes less than that determined by increasing the stimulus intensity from below threshold until gain of capture occurs. This hysteresis-like phenomenon is the Wedensky effect,77 the effect of subthreshold stimulation on the subsequent suprathreshold stimulation when the stimulus amplitude is being increased (Fig. 1-10). Langberg et al.78 observed no demonstrable capture hysteresis at pacing cycles longer than 400 msec. They concluded that the Wedensky effect was related to asynchronous pacing in the relative refractory period when incrementing the stimulus intensity, versus the synchronous late-diastolic stimulation when decrementing the stimulus amplitude until loss of capture. Swerdlow et al.79 showed in a study of 40 patients that cardiovascular collapse occurs at AC current levels less than the ventricular fibrillation current threshold. The continuous capture threshold for AC current is less than the capture threshold for a single ordinary pacing stimulus. The authors suggested that continuous capture at low levels of AC current requires a cumulative effect of subthreshold stimuli; this is a variation of the Wedensky effect. The safety standard for 60-hertz (Hz) current leakage longer than 5 seconds should be 20 microamperes (µA) or less to avoid intermittent capture.

Hook et al.80 reported a significant increase in ventricular pacing threshold in 10 of 16 patients at 400 msec and in 15 of 16 at 300 msec (relative to a pacing cycle length of 600 msec). The phenomenon was not observed at every trial (e.g., 12 of 72 trials at 400 msec). The patients were all candidates for ICDs, and 9 of 12 were receiving antiarrhythmic drugs. The leads were bipolar: a pair of epicardial corkscrews in 11 patients and endocardial screw-in lead in five patients. The atrial stimulation threshold has also been shown to vary as a function of pacing rate.81,82 Katsumoto et al.83 reported that 29 of 36 patients exhibited constant-current atrial pacing threshold energy and current variations as a function of pacing rate in the range of 60 to 120 beats per minute (bpm). The pacing was done with activated vitreous carbon electrodes. Kay et al.84 found significant human atrial threshold changes as a function of pacing rate (125-300 bpm) using constant-voltage stimulation. They found a significant increase in rheobase voltage (Fig. 1-11), chronaxie, and minimum threshold energy at pacing rates greater than 225 bpm using platinized (low-polarizing) unipolar electrodes. They also determined strength-interval curves and found no correlation between atrial effective refractory period and rheobase voltage, chronaxie, or rate-dependent changes in either of these values. They concluded that the phenomenon is probably related to the “opposing effects of decreasing cycle length on the action potential duration and the slope of the strength-interval curve. Thus, if the pacing interval shortens to a greater extent than the refractory period and pacing stimuli are delivered during the ascending limb of the strength-interval curve (the relative refractory period), the diastolic threshold will increase.”84 The increase in stimulation threshold with increasing stimulation rate probably has minimal implications for bradycardia pacing. It is important for antitachycardia pacing, however, because threshold must be measured at rates required to interrupt the arrhythmia. In addition, the safety factors used with antitachycardia pacemakers must be based on thresholds measured at the clinically appropriate rates, rather than during pacing at resting rates.

Strength-Interval Relationships Voltage and current stimulation thresholds vary as a function of the coupling interval of the stimulus to prior beats and to the stimulation frequency used for the basic drive train. Figure 1-12 shows a typical ventricular constant-current strength-interval curve. At relatively long extrastimulus coupling intervals (>270 msec), the intensity of the extrastimulus required for ventricular capture is relatively constant, approaching the rheobase value. At shorter extrastimulus coupling 4 Atrial pacing rheobase (V)

0.9

Rheobase (V)

15

3 2 1 0 125

150

175

200

225

250

275

300

Pacing rate (beats per min) Figure 1-11  Effect of pacing rate on atrial rheobase voltage in patients. The rheobase voltage increases significantly for pacing rates greater than 225 beats/min (values shown as mean ± SEM). (From Kay GN, Mulholland DH, Epstein AE, Plumb VJ: Effect of pacing rate on human atrial strength-duration curves. J Am Coll Cardiol 15:1618-1623, 1990.)

16

SECTION 1  Basic Principles of Device Therapy

9 8 7 Current (mA)

6 5

Distal unipolar cathodal

4

Bipolar

3

Proximal unipolar anodal

2 1 0

Because the purpose of a pacing stimulus is to produce high current density at the electrode-electrolyte interface in the heart, the ideal situation is to deliver a low current from a very small surface area of electrode. If high current density (current magnitude divided by the plane area of the myocardium touched by the electrode) can be obtained with a small, high-impedance electrode, the current drained from the battery will be less than with lower impedance. At pacing threshold, a certain current density exists. If the interface area is made smaller, the current can be reduced equivalently and the same current density maintained. Minimizing the current needed for stimulation requires an optimal combination of interface area, current density, surface material and structure of the electrode, and increased impedance from making the electrode interface area smaller. An increase in impedance made to reduce current drain from the battery should be accomplished by making changes in the electrode, not by increasing the resistance of the wires to and from the pacemaker. Opposition to Stimulus Current Flow

240

280

320

360

400

Delay (msec) Figure 1-12  Strength-interval curves. Unipolar distal cathodal, unipolar proximal anodal, and bipolar strength-interval curves during an acute study in a patient with a temporary bipolar lead (equal-sized cathode and anode). The bipolar and unipolar anodal refractory periods are equal and are shorter than the unipolar cathodal refractory period. (From Mehra R, Furman S: Comparison of cathodal, anodal, and bipolar strength-interval curves with temporary and permanent pacing electrodes. Br Heart J 41:468, 1979.)

intervals (<250 msec), the intensity of the extrastimulus must be increased for it to elicit myocardial capture. The exponential rise in amplitude required for capture at short coupling intervals is the result of encroachment into the refractory period of the myocardium. During the relative refractory period, corresponding to the repolarization phase of the action potential, the myocardium can be induced to generate a new action potential if the stimulus has sufficient intensity. During the absolute refractory period, corresponding to the plateau phase of the action potential, no depolarization can be achieved, regardless of the stimulus intensity. The strength-interval curve of atrial and ventricular myocardium is shifted to the left at shorter basic drive cycle lengths. Therefore, the effective refractory period, which is usually measured at a pulse duration of 2 msec and an amplitude that is twice that of the late-diastolic threshold, decreases as a function of the pacing cycle length. At relatively slow pacing rates (<200 bpm), minimal interaction occurs between the strength-duration and strength-interval curves. As discussed previously, however, at rapid pacing rates (>225 bpm), pacing stimuli during the basic drive may encounter the relative refractory period. If the stimulus amplitude becomes subthreshold, 2 : 1 capture of the myocardium results.

Factors Opposing Pacemaker Current Flow When an electrical stimulus is applied to a pacing lead in contact with the heart, factors opposing current flow include the electrical resistance of the pacemaker lead wires, the impedance of the electrode-tissue interface, and characteristics of ion movement in the myocardium. All these are important to both the efficiency of stimulation and the longevity of a pacemaker or ICD battery. CONDUCTOR RESISTANCE AND CONDUCTION LOSSES Energy dissipation in the lead from the pulse generator to the electrode is proportional to the square of the current. To minimize charge drain from the battery, low lead resistance and low current are desirable.

The resistance of the wire leading from the pulse generator to the stimulating electrode—the cathode—is typically in the range of 50 to 150 Ω. The resistance of the pathway leading to the anode may be 50 to 150 Ω, or it may be lower, as in some unipolar pacing systems. For some practical purposes, one can consider the electrode and the tissue to act as resistances, rather than having a combination of reactive and resistive elements (i.e., impedance). Measuring the ratio of peak or average voltage to peak or average current when a pulse is applied provides useful information about load on the pulse generator and expected battery life. An increase in resistance calculated from voltage/current ratios may indicate a lead fracture, poor lead contact in the connector block, or an electrode that is not in good contact with tissue or blood. Very low impedance values may indicate an insulation defect. The absence of gross change from normal lead resistance does not rule out a broken lead or an insulation defect. An insulation defect can act as a shunt to ground. Its effect depends on its magnitude and location. A broken wire can separate and produce an extremely high measured lead resistance (e.g., 1800 Ω). However, the broken ends may remain in contact or in intermittent contact. If the ends are in continuous contact, lead resistance may not increase significantly. Intermittent contact can cause erratic pacing, sensing, or lead resistance measurements. Impedance at Electrode-Tissue Interface The resistance (ohmic polarization) of the stimulating electrode is inversely and exponentially proportional to the size of the electrode and the temperature and conductivity of the tissue.85,86 For practical purposes, in vivo temperature and conductivity are essentially constant. Decreasing the geometric surface area of the electrode, as illustrated in Figure 1-13, is a way to increase the current density at the electrode for any given level of output current from the pulse generator. Size reduction alone, however, has the negative effect of increasing polarization impedance. In effect, the Helmholtz capacitance at the interface is decreased by reducing the area of the electrode. One remembers from the equation 1 t v t = ∫ i tdt C 0 that the voltage vt across the Helmholtz capacitance at the electrode is proportional to the accumulated charge and inversely proportional to the capacitance. If the electrode contact area with the tissue is made smaller to increase the current density and nothing else is changed, the capacitance will be decreased. For a given applied charge, that action will increase the Helmholtz capacitance voltage, because of the inverse relationship between the voltage and the capacitance. For a given electrode material (as a first approximation), capacitance (C) is a function of the interface surface area (Ai):

C = eA i /d

[1-8]



1  Cardiac Electrical Stimulation

Ohmic pacing impedance (Ω × 102)

100 (N = 48 models, 323 canines) 50

10 5

The total reactance in a simple series circuit is the scalar sum of the inductive and capacitive reactances, each of which varies with the frequency content of the applied signal. Impedance also varies with signal frequency content; it is the vector sum of reactance and resistance. Impedance has a magnitude and a phase angle, both dependent on the rates of change of the applied voltage. The phase angle represents the difference in timing of sinusoidal current flow peaks compared with sinusoidal voltage peaks when a sinusoidal voltage is applied to a circuit. A voltage or current pulse of any shape can be broken down mathematically into combinations of sinusoidal components. In a simple series circuit, where R is the resistance and X is the sum of the capacitive and inductive reactances, the magnitude of impedance Z is defined as follows:

1 .1

.5 1.0 5.0 10 Geometric surface area (mm2)

50 100

Figure 1-13  Leading-edge ohmic polarization or electrode resistance of chronic canine ventricular leads (12 weeks after implantation) measured with a Medtronic Model 5311 pacing systems analyzer as a function of the unipolar cathode’s geometric surface area. Each data point was obtained from a population of animals testing one lead design. The study included 323 animals and 48 lead models.

where e is the dielectric constant of the Helmholtz double layer and d is its thickness. Because e and d are essentially constants in vivo, the capacitance of the electrode varies as a function of the interface surface area. How does one obtain a very large surface area to contact the tissue and not use a large-diameter electrode? Initially, this was accomplished by making the electrodes porous.87-89 Microporous electrodes, such as activated carbon or platinized platinum, have a higher real surface area.90,91 The capacitance of microporous surfaces is greater than that of porous surfaces and still greater than that of polished surfaces. Fractal-surface electrodes have been best at meeting the requirements of very small geometric areas and large Helmholtz interface areas at the same time. Another approach to the problem of decreasing polarization is to use a material that supplies its own majority charge carriers. An example is the silver–silver chloride (Ag/AgCl) electrode in chloride solution. The majority carrier, in this case Cl−, cannot be depleted; Cl− evolves at the cathode and is formed at the anode. Therefore, voltage across the electrode interface has a waveshape (waveform) essentially identical to that of the applied constant current, and the electrode is “nonpolarizing.” Unfortunately, no clinically usable, nonpolarizing (charge-carrier supplying) electrode material seems available for permanent implantation. Ag/AgCl electrodes, for example, are not used for permanent pacing because the anode erodes and the AgCl eventually dissolves from the cathode.92,93 The ideal, practical stimulating electrode is made of a corrosionresistant, biocompatible material with small geometric size and very high interface surface area, which gives it the characteristics of very high capacitance and a lower polarization voltage. Impedance Impedance can be defined as the vector sum of all forces opposing the flow of current in an electric circuit. Pure inductors and pure capacitors have no energy losses. They store or release energy in or from an electric field (capacitor) or a magnetic field (inductor). They also change the time relationships between varying voltage and current. The effects can be quantified in terms of reactance. Capacitive and inductive reactances oppose each other. If a sine-wave voltage is applied to a pure capacitance, the current peaks occur 90 degrees earlier than the voltage peaks. If a sine-wave voltage is applied to a pure inductance, the current peaks occur 90 degrees later than the voltage peaks.

17

Z = R2 + X2

[1-9]

for a single R-X series combination. For various combinations of reactance and resistive elements in parallel and in parallel-series combi­ nations, each component of impedance (Z1, Z2, Z3, . . . ) used in determining the total impedance must be treated as a vector quantity. Serial and parallel connection calculations using such vector components cannot be accurately performed by ordinary scalar, algebraic, Ohm’s law manipulations.94 Right ventricular (RV) and coronary sinus (CS) catheters connected to a single pulse generator output socket represent impedances in parallel. Reactance is positive for inductance (i.e., when a sine wave voltage is applied, the voltage leads the current, as seen on an oscilloscope screen) and negative for capacitance (when a sine wave voltage is applied, the voltage lags the current). Reactance and Charge Movement at Electrode-Electrolyte Interface The electrode and the tissue act not as pure resistances but as reactances that change the time relationships between voltage and current when a pacemaker or defibrillator pulse is applied. The only elements of almost-pure resistance in the pacemaker circuit external to the pulse generator are the lead wires. When the pacing pulse begins, several events occur almost immediately. Electron motion in the lead wires and electrodes must result in ion motion in the interstitial fluid. The electric field between the electrodes results in (1) reversible or irreversible oxidation-reduction processes occurring at the interface between the electrode and the electrolyte, and/or (2) the electrode-tissue interface’s acceptance of current without charge crossing the interface. In the latter case, the interface acts as a capacitor. Figure 1-14 shows the result is the sequence of events. The leading-edge voltage/current ratio is referred to as ohmic polarization. The increasing charge on the Helmholtz capacitor results in increasing opposition to further current inflow. The figure shows this as polarization overvoltage. The rates of voltage and current change depend on rates of ion movement within the electrolyte. These in turn depend on the mass and charge of ion species, species interactions and concentrations, and the applied electric field. The result is that lead wire current and voltage are not linearly related. The circuit is reactive. The vector combination of this reactance and the resistive elements (e.g., lead wires) make up the impedance faced by the pulse generator output. CHARGE CONDUCTION AND TRANSMEMBRANE POTENTIAL CHANGES IN CARDIAC PACING AND DEFIBRILLATION The directed motion of electric charge is the result of electric field gradients. Currents at pacemaker or defibrillator electrodes and within the heart can be considered in several categories, including (1) ion movement currents external to cells, within cells, and across cell membranes, and (2) charge separation currents that bring opposing charges to the electrode-electrolyte interface and membrane intracellularextracellular interfaces, without charge actually crossing the interface.

18

SECTION 1  Basic Principles of Device Therapy

Pulse generator pulse

Polarization effect

ELECTRICAL CHARGE MOVEMENT IN WIRES AND IN TISSUE

Vp

Leading edge

Trailing edge

Vo

Whether contraction of a myocyte occurs when a pacemaker pulse is applied is a function of several factors: (1) the amplitude, waveform, and duration of ion flow in the extracellular tissue resulting from the electric field gradient produced by the pulse; (2) the state of the preexisting voltage difference from the outside to the inside of the cell (degree of polarization or depolarization of the cell membrane); and (3) the biochemical state of the cell. Irnich104,105 discussed fundamental laws of electrostimulation in 1990, then three myocardial stimulation theorems in 2002, introduced by George Weiss 100 years earlier: (1) the pacing threshold, as measured by the voltage-time product of the stimulus, is a linear function of the pulse duration; (2) there is a minimum of the delivered threshold energy requirement that depends on the pulse duration; and (3) pulse shape plays no role in electrostimulation. The third theorem is a concept with clinically apparent limitations and requires some interpretation,106,107 as discussed later. Electron Flow versus Ion Flow

Time (pulse width) Figure 1-14  The effect of polarization (upper diagram) has been separated from the capacitively coupled constant-voltage pacing pulse (lower diagram) to help clarify the electrical manifestation of electrode polarization. At the leading edge of the pulse, polarization is essentially zero. With time (pulse duration), the voltage resulting from polarization (sometimes called polarization overvoltage, Vp) increases. When the pacing pulse is shut off, polarization overvoltage decays exponentially as a result of diffusion. (From Stokes K, Bornzin G: The electrodebiointerface [stimulation]. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, pp 33-78.)

The latter currents are capacitive, charging the Helmholtz capacitor at the electrode and changing the voltage difference across the cell membrane before it depolarizes. In 1969, Otto Schmidt95 described biologic information processing using the concept of “interpenetrating domains.” In the heart, two domains of charge flow exist: extracellular and intracellular. The two domain pathways are different in their anisotropic characteristics, and they are interwoven. Current passes from one domain to the other through cell membranes. Bidomain theory and studies are based on the concept that at every point in the heart, there are two electric potential vectors, one intracellular and one extracellular. Mathematically, each domain is continuous and occupies the entire domain. Membrane current leaves one domain and enters the other at the same coordinates. The analytical and experimental work from these concepts has provided insight about depolarization wavefront passage over the myocardium, current flow directions in relation to wavefront direction, and virtual electrode formation.96-99 Roth99 showed that stimulation of myocytes by application of a defibrillation shock can result in transmembrane voltage (Vm) changes by four mechanisms: (1) direct polarization of the tissue, as described by cable theory (see later discussion); (2) production of virtual anodes and cathodes, as described by bidomain models with unequal anisotropy ratios of the intracellular and extracellular spaces; (3) polarization of the tissue secondary to change in orientation of cardiac fibers (curving); and possibly, (4) polarization of individual cells or groups of cells because of a sawtooth electric potential effect. Sawtooth alterations in potential may result from resistive discontinuities introduced by intercellular gap junctions. Plonsey and Barr100 predicted the occurrence of sawtooth effects in 1986. Under what circumstances and to what degree, if any, the sawtooth effect might become important in fibrillation or defibrillation is uncertain.101-103

An interface between ion drift current and electron drift current occurs at the electrode-electrolyte interface. In pacemaker and defibrillator leads and electrodes connected to the negative output socket of the pulse generator, current flow consists of a net drift of electrons through the negative lead toward the electrode surface. In contrast, in the extracellular fluid, the current flow is ion drift. The motion of an individual ion is random, with the drift imposed by the electric field superimposed on the random motion. Drift velocity is proportional to the magnitude of charge on the ion, the mean time between collisions with other ions divided by the mass of the ion, and the electric field strength and direction. In addition, ions interact with each other. For a pacemaker electrode in the heart, all these properties, together with the Helmholtz double-layer capacitance effect, mean that current flow in the lead wires going to the electrodes does not vary instantaneously in proportion to the applied voltage. CAPACITANCE AND POLARIZATION When an electric field is applied to an electrode, the interface with the surrounding tissue stores electric charge separated by charge sign, thereby acting as a capacitor. A capacitor requires a finite amount of time to charge or discharge to any specified voltage. The relationship between the voltage across a pure capacitor at any time t, when i represents the instantaneous current flow and the capacitance has magnitude C (measured in farads), is t 1 v t = = ∫ i t dt C 0 and the instantaneous current i entering or leaving the capacitor is dv it = C dt where dv/dt represents the rate of change of the voltage across t the capacitor. The amount of charge stored, ∫ i t dt , is directly propor0 tional to the net area under the curve of instantaneous current entering and leaving the capacitor plotted against time. Note also that, for a given amount of charge, the voltage across the capacitor is inversely proportional to the capacitance. A perfect capacitor with no energy loss in storage or discharge is described by these equations. Neither cell membranes nor man-made capacitors are perfect capacitors. In nonperfect capacitors, some energy is dissipated in the capacitor during storage or discharge. Pacemaker and defibrillator electrodes act as imperfect capacitors by means of the Helmholtz double-layer effect (described later). The capacitance of canine myocytes in isosmotic solution is about 175 picofarads (pF). Cell membrane capacitance is about 0.01 microfarad (µF) per square millimeter of membrane surface area.108 The



1  Cardiac Electrical Stimulation

Input current from pulse generator cathode Lead resistance

Helmholtz doublelayer capacitance

Electrode interface with electrolyte in adjacent myocardium

Tek Output current to pulse generator anode Myocardial bulk impedance

T Trig’d

19

M Pos: 1.980ms

2

1

Faradic charge Warburg transfer resistance diffusion impedance Figure 1-15  Equivalent circuit representation of an electrodeelectrolyte interface, including the Helmholtz capacitance and the Warburg impedance. (Modified from Rodman JE: Solution, Surface and solid state assembly of porphyrins [PhD thesis]. Cambridge, University of Cambridge, 2000, Fig 4.6.)

capacitance of pacemaker electrodes has been reported to range from 0.2 µF/mm2 (smooth surface) to 40 µF/mm2 (fractal-surface electrode). The area of pacemaker tip electrodes is usually in the range of 4 to 10 mm2. Therefore, the capacitance might be 200 µF or more. The time constant for a 200-µF capacitor C discharging through a 500-Ω resistor R is R × C, or 100 msec. This means that the voltage across the capacitor, or across an ideal electrode-electrolyte interface, if the capacitance were a truly constant 200 µF and the interface impedance 500 Ω, would on discharge decrease from its maximum level to 37% of maximum in 100 msec. Figure 1-15 shows the Helmholtz capacitance and Warburg impedance in a schematic representation of a typical pacing configuration. These effects are caused by the electrode/tissue interface and the conversion of electric charge from electron flow to ion flow. Figure 1-16 demonstrates the decay of the Helmholtz capacitance following a constant current pulse. After termination of the pacing pulse, the voltage decays slowly toward baseline, but does not reach it before the second pulse is delivered. If the impedance between the positive and negative sockets of the pulse generator were made to go to very high impedance when the pacemaker pulse ends, almost no current would flow in the catheter wires between pulses. The Helmholtz capacitor at the electrode would discharge mainly through resistive components in the electrode-electrolyte interface. In that case, when the constant-current stimulus stops, the voltage measured across the catheter pins would keep the same polarity and would decay slowly rather than go to zero precipitously. Figure 1-16 also illustrates this decay by an electronic circuit simulation during pacing of a fibroblast cell culture through a bipolar cardiac catheter. The top trace shows a biphasic constant-current pulse with 3 msec between the end of the initial, negative phase and the beginning of the positive phase. The duration of each phase is 1 msec. The pulse generator circuit here goes to a high impedance rather than a low impedance when each phase ends. The bottom trace shows the voltage response. At the end of each phase, the voltage measured at the pulse generator terminals initially goes rapidly toward zero but, partway toward zero, it begins to change only slowly. This is the effect of the Helmholtz capacitor discharging into the surrounding electrolyte, and it is a function of the rates of ion movement at that time during the discharge cycle. BIPHASIC STIMULUS EFFECT Of great interest is the effect of decreasing the delay time between the end of the first and the beginning of the second phase. Compare Figure 1-16 with Figure 1-17. When the stimulus is biphasic with almost no delay (here about 10 µsec) between phases, the slow decay of voltage

Ch1 500mV

Ch1

Ch2 500mVBw 1 msec

Figure 1-16  Slow decay of pacing catheter lead voltage between biphasic stimulus phases. The plot shows current (top trace) and induced voltage (lower trace) from a Bloom stimulator delivered between the pacing tip of an Endotak catheter and a “hot can” electrode in saline. At the end of each phase, the voltage measured at the pulse generator terminals initially goes rapidly toward zero but then, partway toward zero, it begins to change only slowly. This is the effect of discharge of the Helmholtz capacitor into the surrounding electrolyte. This voltage response between phases is a function of the rates of ion movement in the electrolyte.

at the end of the first phase is aborted by the beginning of the second, opposite-polarity phase. The amplitude and duration of the voltage decay after the second phase are each less when the second phase occurs immediately rather than being delayed by 3 msec. In practical terms, because of Helmholtz effects, electrical activity continues to occur at and near the electrode after the stimulating pulse stops. Details of the activity depend on the stimulus (uniphasic or biphasic), delay time between phases, characteristics of each phase, and the action of the pulse generator output circuit when the stimulus stops (high impedance, low impedance, or recharge pulse). The electrical activity also depends on the characteristics of the electrode (e.g., geometric vs. electrical surface area), the ionic solution, and the tissue. Tek

Stop

M Pos: 1.980ms

2

1

Ch1 500mV

Ch2 500mVBw 1 msec

Ch1

Figure 1-17  Effect of near-zero delay between phases on voltage response to biphasic constant-current pulse. This plot was made under the same conditions as Figure 1-16, except that the delay between phases was decreased from 3 msec to approximately 100 µsec. When the stimulus is biphasic with almost no delay between phases, the slow decay of voltage at the end of the first phase is aborted by the beginning of the second, opposite-polarity phase.

20

SECTION 1  Basic Principles of Device Therapy

Cc

CAPACITANCE, POLARIZATION, AND TRUE IMPEDANCE When using an ordinary pacing systems analyzer, one thinks of impedance as a voltage/current ratio. If reactance is present, as it is at a pacemaker or defibrillator electrode because of the Helmholtz capacitance effect, the voltage/current ratio as seen on the PSA can be deceptive (see Biventricular Pacing). Because of the charging and discharging of the Helmholtz capacitor at the electrode-electrolyte interface, the applied voltage and resultant current are not linearly related. Therefore, the circuit is reactive, and impedance rather than resistance is the correct measure of opposition to current flow (see earlier discussion). There are practical problems in easily measuring true impedance during implantation procedures. In most clinical circumstances, however, the voltage/current ratio provides a reasonable estimate of the load into which the pulse generator is working, which is a major factor in determining current drawn from the battery.

T–

Rw –

Rc Rt

IPG Ca i0 T+

Rw+ Ra

CHARGE GROUPING AND POLARIZATION When an electrical stimulus is applied to the heart, the negatively charged cathode in contact with the myocardium attracts positively charged ions in the extracellular space. Likewise, the positively charged anode attracts negatively charged ions. This grouping phenomenon is known as polarization. The word “polarization” in this chapter has the following meanings: 1. The grouping and subgrouping by charge sign of electrons in the metal, and of ions in the electrolyte, at and near pacemaker or defibrillator electrodes, resulting in the formation of two or more electric charge layers and voltage gradients during the application of a pacemaker or defibrillator stimulus, and their subsequent decline after cessation of the stimulus. 2. The charge separation across a cell membrane, measurable as a voltage gradient between the inside and the outside of the cell. 3. The opposition to current flow within a battery, which results, when current is being drawn from the battery, in a decrease in the voltage available at its terminals. CAPACITANCE EFFECT OF HELMHOLTZ DOUBLE LAYER About 1879, Helmholtz suggested that a layer of ions (inner Helmholtz layer) is attracted to the surface of a charged electrode, and that this layer is bounded on its nonelectrode side by a layer of oppositely charged ions (outer Helmholtz layer) in the solution.109 This interface acts as a capacitor. Helmholtz assumed for this model that no electron transfer reactions occur at the electrode and that the electrode environment is only an electrolyte. These (and more complicated charge redistributions) occur because of attraction and repulsion interactions between an electrode held at a given electric potential (e.g., 2 V negative during 0.5-msec pacemaker pulse) and the ions and charged molecules in the interstitial fluid. The charge placed on the electrode, by electrostatic attraction, forces the accumulation of a polarized water layer and a second layer of hydrated, oppositely charged ions adjacent to the electrode surface. The oppositely charged ions come from the electrolyte. The interface at the electrode becomes an electrical double layer. This is in effect a charged capacitor.110 However, the actual interface is not a simple double layer. The Helmholtz model does not take into account other factors, such as absorption on the surface, thermal buffeting, and interaction between solvent dipole moments and the electrode. Models more complicated than the Helmholtz include the Gouy-Chapman and Gouy-Chapman-Stern.111 These models have dissimilar shapes for the plot of electric potential variation with distance from the electrode. The layers have relatively high dielectric constants and form an interface that behaves electrically like a capacitor (Cc and Ca in Fig. 1-18). In a semiconductor or in localized regions of an electrolyte, an excess of positive or of negative

Figure 1-18  Simplified equivalent circuit for cardiac pacemaker. T− and T+ are, respectively, the negative (cathode) and positive (anode) terminals of the implanted pulse generator (IPG; in a unipolar device, T+ is inside the can). The direction of current flow is shown with i0. RW− is the resistance of the conductor wire leading to the distal tip of the lead (cathode), whereas RW+ is that of the wire leading to the bipolar lead’s proximal ring electrode or the unipolar pulse generator’s can. Rt is the resistance of the tissue between the bipolar lead’s two electrodes, or the lead tip to the pulse generator can in a unipolar system. Rc is the ohmic polarization of the cathode, whereas Ra is that of the bipolar anode or unipolar generator can. Cc is the capacitance of the cathode, and Ca is that of the anode (can). The equivalent circuit is the same for unipolar and bipolar systems, but the values for some of the components differ.

charge may be present. If the excess is of positive charge carriers, the positive carriers are the majority carriers and the negative charge carriers the minority carriers. An excess of negative carriers makes these the majority and the positive carriers the minority. The second layer of the double layer is formed of hydrated ions and more water (Fig. 1-19). In physiologic electrolytes, the ions include Na+ and Cl− in major concentrations (majority carriers). Other ions present in lower concentrations (minority carriers) include hydronium (H3O+), hydroxyl (OH−), and phosphate (HPO42−). The ions attracted to or repelled from the electrode during the electrical stimulation pulse make up a separation of charge in the tissue electrolyte. When the pacemaker pulse is applied as a negative voltage to the electrode, electrons accumulate in the electrode. Reversible reactions may form metal-oxide complexes on the surface of the electrode. A primary water layer forms on the electrode. Positive ions surrounded by water molecules—a water shell—make a secondary water layer. This accumulation of positive ions in the electrolyte near the electrode unbalances local electrolyte charge neutrality. Secondary ion rearrangements occur in great complexity, with several names for the various processes. When the pacemaker pulse stops, the ions, being no longer attracted to or repelled from the electrode (depending on the polarity of the electrode and of the ions), are forced by their charges to rearrange themselves back toward their original, more electrically neutral positions (determined by random motion) in the electrolyte near the electrode. Ion rearrangement is not as fast as the transmission of an electric potential in a wire. The result is that, after a pacemaker or defibrillator pulse stops, the Helmholtz capacitor acts as if it were a temporary battery of declining voltage discharging itself into the tissue. The decaying voltage gradient in the tissue persists long enough to be detected by a pacemaker or defibrillator and may be great enough to interfere with sensing in autocapture devices in some situations. Other factors being equal, the voltage decay duration is greater and the polarization voltage is less when the electrode surface area is great versus small.



1  Cardiac Electrical Stimulation

+ H3O + Na – Cl + Na

– OH

+ Na

+ Na

A

B

C

Figure 1-19  Hypothesized structure of the Helmholtz double layer. At the left is an uncharged cathodic electrode interface. When the electrode is charged, a layer of surface hydration develops (region A). Region B contains a second, more loosely held hydration layer with hydrated ions. Based on electrostatic considerations, layer B has a high dielectric constant, approaching that of pure water. It has a thickness of less than 10 Å. Region C represents bulk solution. (From Stokes K, Bornzin G: The electrode-biointerface [stimulation]. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, p 63.)

ELECTRODE-ELECTROLYTE INTERFACE PROCESSES At equilibrium, an electrode in a solution will have, relative to a reference electrode, a potential that depends on the composition of the electrode, the composition of the solution, and other factors such as temperature.112 When a pacemaker pulse is applied, the electrode is forced to a different electric potential. This new potential forces ion flow to occur in the vicinity of the electrode. Ion secondary rearrangements occur distally. The net ion drift near the electrode is in a direction that will produce a new equilibrium, a balance of charge across the interface. At least two types of processes involving ion flow occur at the interface between a pacemaker or defibrillator electrode and tissue. First, oxidation-reduction reactions, which can be reversible or irreversible, involve electron movement across the interface and constitute faradic current. The second process, nonfaradic current, occurs without transfer of electrons across the interface. It consists of electron flow in or out of the electrode itself and a flow of ions in various layers or “clouds” toward or away from the interface. This nonfaradic process is similar to charging or discharging an electrical capacitor, but at an electrode in electrolyte, there is directed electron drift in or out of the electrode and directed ion drift within the electrolyte. The ion flow and the electron flow each constitute an electric current, yet no charge crosses the interface. Away from the electrode in the body of the electrolyte, the electric potential gradient causes ions to move away from or toward the electrode region, depending on their charge. Ion mobility characteristics, concentration gradients, and temperature gradients also affect ion movement. In the heart the process is more complicated than in an electrolyte solution alone, because of the anisotropic properties of the extracellular and intracellular domains. Faradic Current Flow Faradic current is so named because Michael Faraday (1791-1867) quantitatively described the effects of electric current through an electrolyte in 1834, stating that “the chemical decomposing action of a current is constant for a constant quantity of electricity, notwithstanding the greatest variations in its sources, in its intensity, in the size of

21

the electrodes used, in the nature of the conductors (or nonconductors) through which it is passed, or in other circumstances.”113 If one thinks of an electrode-electrolyte interface as resembling a variable resistor and variable capacitor in parallel, faradic current flow would be flow—electron transfer—through the resistor. Whether electron transfer across the interface occurs depends on the properties of the electrode and the electrolyte and on the applied electric pulse characteristics. The current crossing the interface when one is charging a battery is faradic current produced by oxidation-reduction reactions. Capacitive Current Flow This mechanism is not a transfer of electrons in one direction or the other across the electrode-electrolyte interface. Capacitance current flow is the accumulation of charge on the electrode at the interface balanced by a corresponding accumulation of charge of net opposite sign in the electrolyte adjacent to the interface. Charge flows in the lead, and in the electrolyte, but not across the interface. The flow of charge into the capacitor is measurable current in a pacemaker lead, even though in a perfect capacitor, no charge crosses the interface. The resulting arrangement of ion groupings at and near the electrode-electrolyte interface can be very complicated.114 The accumulation of charge separated by charge sign at the interface defines the Helmholtz double-layer capacitance.115 Energy is stored as an electrostatic field that exists between the positive and negative charge layers. When a pacemaker pulse is applied to an electrode in the heart, the charge movement into or out of the Helmholtz capacitance—both electrons in the electrode and ions in the electrolyte—is an electric current, even though no charged particle necessarily crosses the interface. At a pacemaker electrode, the capacitance is not constant. It is dependent on current density, electrolyte composition, and the area and other surface characteristics (e.g., fractal surface) of the electrode material.116 Because of the minute distances separating positive and negative charge layers at an electrode in electrolyte, the capacitance is high, ranging from about 0.2 to 40 mF/mm2 of geometric area of the electrode.117 The fractal-surface electrode has a much higher capacitance than a smooth-surface electrode. dv states that the current i entering or leaving The equation it = C dt a capacitor at time t varies directly as the magnitude of the capacitance (C, measured in farads) multiplied by the rate of change of the voltage difference across the capacitor. Because a constant-voltage pulse is nominally a rectangular wave, its rate of change is small except when the pulse is being turned on or off. Therefore, current flow into the capacitor (i.e., into the pacemaker electrode-electrolyte interface, Helmholtz capacitance) occurs very rapidly during the leading edge of a nominal constant-voltage pacemaker pulse. Then, as charge accumulates at the electrode-electrolyte interface, the accumulating negative charge collection at the electrode surface slows the rate of further accumulation. It does so because the accumulating negative charge opposes the inflow of additional negative charge. Finally, unless the pacemaker output voltage were to be raised during the pulse, no further accumulation can occur. The voltage across the capacitor becomes equal and opposite to the constant-voltage pulse that had been driving current flow into the lead. Note that the Helmholtz capacitance is influenced by the current density at the electrode, the types and numbers of ions in the electrolyte, the material and surface of the electrode, the temperature, and other factors. Relation of Electrode-Tissue Interface Capacitance to Polarization Voltage 1 t Note that in the expression vt = ∫ i tdt , describing the voltage that C 0 occurs across a capacitor when current flows into it, the developed voltage varies inversely as the capacitance (C, measured in farads). If

22

SECTION 1  Basic Principles of Device Therapy

both sides of this equation are multiplied by C, the equation becomes t t Cvt = ∫ i t dt . The amount Qt of stored charge at any time t is ∫ i t dt . 0 0 Therefore, Cvt = Qt, and vt = Qt/C. That is, for a given amount of charge put into the defibrillator or pacemaker electrode, the voltage across the interface will be decreased if the surface area of the electrode (and therefore the capacitance) is increased. This voltage is the polarization voltage. During its decay time after the stimulation pulse has ended, the polarization voltage can interfere with autosensing of capture. For a given stimulus voltage, the greater the polarization voltage at the electrode-tissue interface, the lesser the voltage gradient elsewhere in the tissue between the cathode and the anode. A fractal-surface electrode, with its high capacitance,117 has, for the same charge flow in and out, a lesser potential difference across the electrode-electrolyte interface than a smooth-surface electrode. Therefore, the fractal surface is preferred. No electrode is completely free of charge transfer across the interface between its surface and the electrolyte. Some current flow across the interface does occur by means of electron transfer through oxidationreduction reactions. At a pacemaker electrode, these reactions, if reversible, may be desirable. Irreversible charge transfer results either in corrosion or in electrochemical reactions in the tissue. For present-day implantable pacemaker electrodes, if the pulse duration is short, or if the pulse is biphasic with a sufficiently short time between balanced phases, the charge transfer reactions do not normally result in gross corrosion or gross tissue changes. Therefore, those reactions that do occur must be largely reversible.118 Ideal and Non-Ideal Electrodes To avoid corrosion and deposition of toxic products in the adjacent tissue, electrodes that undergo irreversible reactions only minutely are highly desirable for pacemakers and defibrillators. Michael Faraday worked out the quantitative relationship between electrode-electrolyte chemical changes and the total amount of charge passed through the electrode into the electrolyte.119 Electrodes that under the conditions of use produce irreversible electrochemical reactions by means of these faradic currents entering or leaving the electrolyte are non-ideal electrodes. Equal back-and-forth transfer of electrons from an inert electrode to an electrolyte occurs naturally and is an equilibrium situation. When an external voltage is applied, electrodes that then do not produce irreversible chemical reactions are so-called ideal electrodes. Although metal oxide films form on the electrodes, occurrence of other oxidation-reduction reactions and corresponding electron transfer through the interface do not occur or are minimal in ideal electrodes. In this sense, no real electrode can be completely “ideal” in all circumstances. If the magnitude and duration of polarization secondary to occurrence of the electric pulse is brief, electrochemical reactions occurring at the electrode may reverse. If the charge redistribution time is long, the effects of charge redistribution on the electrode and on the tissue may become irreversible. When biphasic pulses are used, minimal postpulse polarization persists, provided the time between phases is in the microsecond range. If the time between phases is increased into the millisecond range, the duration and amplitude of persisting polarization increases (see Figs. 1-16 and 1-17). OPTIMIZING IMPEDANCE FOR MINIMUM BATTERY CONSUMPTION The effects of high impedance on the pacing system vary with the cause and location. The manner of resistance distribution in the system can produce different effects, increasing or decreasing the efficiency of the stimulating pulse. To clarify these issues, one needs to examine the leads and the electrode-tissue interface impedance and conduction losses. A clinically useful electrode does not waste energy in mini–heat production or in undesirable chemical reactions, and it also has a low pacing threshold. Therefore, the electrode should have minimal energy

loss in the lead wires, minimal energy loss in moving ions in the electrolyte during charge and discharge of the Helmholtz capacitance, and high current density at the electrode, allowing depolarization of the membranes of nearby myocytes with less lead current than would otherwise be needed. All these factors influence the impedance as seen at the pulse generator. Note that fibrous tissue formation around an electrode does not necessarily increase the impedance but does increase the pacing threshold. (For further discussion of these issues, see Clinical Aspects of Myocardial Stimulation by Pacemakers.)

Impedance in the Extracellular Electrolyte WARBURG IMPEDANCE In 1899, Warburg described an effect of ion motion caused by a voltage difference between two electrodes in an electrolyte as an “impedance.” The Warburg impedance is an effect of ion diffusion activity under the influence of the potential gradient at the interface between electrode and electrolyte. It is said that “a Warburg impedance can be difficult to recognize because it is nearly always associated with a charge transfer resistance and a double layer capacitance.”120 The Helmholtz capacitance concept is based on the separation of charges in the electrode from charges in the electrolyte at angstromdimension levels. Warburg developed his impedance concept to model the effects of diffusion. When a sine-wave voltage is applied across an electrolyte, this impedance manifests itself as a 45-degree phase shift between the voltage and the current if the current density is infinitely low. The Warburg impedance magnitude becomes small compared with other impedances at the electrode-electrolyte interface as the electrolyte concentration is made greater and as the stimulation frequency increases.121 Ovadia and Zavitz122 made an impedance spectroscopy study of the interface between a platinum electrode and a metabolically active, perfused living heart. Three impedance spectral components were found: the Warburg impedance, a thin-film impedance, and a single high-angle constant-phase impedance. The impedance spectrum was not single-valued and was not stable in time. Figure 1-15 shows one equivalent circuit representation of an electrode-electrolyte interface, including the Helmholtz capacitance and Warburg impedance (modified from Rodman123). The Helmholtz capacitance–Warburg impedance effects can become especially important in explaining some of the threshold measurements and seeming contradictions found during biventricular pacing procedures,124,125 as discussed later. CAPACITANCE AND ELECTRIC POTENTIAL GRADIENTS RELATED TO MEMBRANE DEPOLARIZATION IN PACING AND DEFIBRILLATION The cell membrane does charge and discharge similar to a nonlinear capacitor. Ions under both electric gradient and biochemical-signaling control traverse the membrane as if it were both a variable and a highly ion species–selective resistor connected in parallel with a variable capacitor. When a negative-going pacemaker stimulus reaches the membrane, the stimulus reverses the voltage gradient across the membrane, beginning processes that in effect discharge the capacitor. Krassowska and Neu126 pointed out that the response of the cell to an external field is a two-stage process. The initial polarization proceeds with the cellular time constant (magnitude <1 µsec). The actual change of physiologic state proceeds with the membrane time constant (several milliseconds). The membrane resistance changes as ion channels open and close (see Fig. 1-2). The membrane capacitance may vary with ion concentrations and with stimulating voltage and frequency.127 Membrane capacitance and resistance determine the membrane time constant. An ordinary pacemaker stimulus can reverse the membrane potential to threshold levels only locally. The voltage gradient produced in the tissue by a pacemaker electrode decreases to below-threshold



1  Cardiac Electrical Stimulation

values with distance from the electrode. In order to depolarize much more myocardium at once than a pacemaker does, a defibrillator electrode must have a much greater voltage gradient between its electrodes. To initiate fibrillation during the vulnerable period or to defibrillate, an extracellular electric field of approximately 6 V/cm in a large volume of tissue is required, whereas for pacing, a local electric field of only about 1 V/cm in a small volume is necessary. Ideker et al.49 noted that, because the potential gradient decreases rapidly with distance from the stimulating electrode, a current about 40 times greater than the diastolic pacing threshold is required to generate an electric field of 6 V/cm approximately 1 cm from the stimulating electrode. To generate the 6-V/cm field over the entire ventricular myocardium, a current thousands of times greater than the low milliampere level necessary for pacing is required. The difference in voltage and current requirements for pacing and for defibrillation can be described using a “lumped” and distributed systems analogy. A line of cars is stopped at a traffic light. When the light changes from red to green, the front car moves, which prompts the next car to move. The motion propagates back down the line of cars in the manner of a string of myocytes undergoing sequential depolarization, or a line of falling dominoes; this is an analogy for pacing. Defibrillation is analogous to all the cars being connected by an iron rod. Much force would be required to move the whole string of cars at once, even though the force required for each individual car is relatively little. Similarly, to depolarize most of the ventricles at once, a very large voltage is needed to obtain the small transmembrane voltage gradient reversal that is required at each distant myocyte.

Cathodal and Anodal Stimulation, Constant Voltage, Constant Current, Monophasic and Biphasic Stimulation ANODAL AND CATHODAL STIMULATION Generally speaking, anodal stimulation is associated with properties that are less desirable than those of cathodal stimulation. If the stimulating electrode is a unipolar cathode, the strength-interval curve has a shape that is similar to a strength-duration curve. The shape of the typical anodal strength-interval curve is somewhat different from that of a cathodal curve (Fig. 1-20). Given equal-sized electrodes, the 8.0 7.0 6.0

mA

5.0 4.0 3.0 2.0 1.0

Anodal Cathodal

0.0 190 210 230 250 270 290 310 330 350 370 390 410 S1-S2 coupling interval Figure 1-20  Anodal and cathodal ventricular strength-interval curves are demonstrated in a patient with atrioventricular block, using unipolar constant-current stimuli. The anodal threshold is slightly higher than the cathodal threshold at coupling intervals greater than 250 msec. At coupling intervals of less than 210 msec, the anodal threshold is about equal to the cathodal threshold. In some patients, the anodal threshold may not decrease (“dip”) to a value that is lower than the cathodal threshold.

23

anodal stimulation threshold is generally somewhat greater than that for cathodal stimulation at long coupling intervals. With progressively more premature coupling intervals, there is a dip in the anodal curve to threshold values lower than those of the cathodal curve. At still more premature coupling intervals, the anodal curve rises steeply, as observed with cathodal stimulation.128 The “dip” phenomenon is not always seen.129 If the electrodes of a bipolar lead are of equal size, or if the anode is smaller than the cathode, it is possible to stimulate earlier in the cardiac cycle, in the relative refractory period, than with unipolar cathodal stimulation. This may occur because the threshold for anodal stimulation with electrodes of equal size is lower than for cathodal stimulation in the strength-interval curve at shorter pulse widths. Anodal stimulation generating tachyarrhythmias in ischemic or electrolyte-unbalanced hearts is well documented.130,131 This is one of several reasons that implantable bipolar leads are designed with considerably larger anodes than cathodes. In fact, it is commonly believed that the bipolar anode needs to be large enough that anodal stimulation is prevented. It is unlikely that this actually prevents anodal stimulation, however, because most pulse generators are set at outputs much higher than threshold. Even a 50-mm2 anode probably can reach threshold at a stimulus intensity well below 5 V and 0.5 msec. It is likely that delivery of the stimulation pulse with many bipolar leads at times actually results in capture of the myocardium at both the cathode and the anode. Therefore, the size relationship between cathode and anode probably has greater significance than currently known. Many newer bipolar leads have smaller anodes because the cathodes are smaller. The anode/cathode ratio should be maintained, and the designs should be supported with strength-interval tests. Bipolar pacing with equal-sized electrodes has been common in temporary pacing and in implanted epicardial systems, in which two unipolar leads are often used for bipolar pacing. The clinician should keep in mind the arrhythmogenic possibilities of such combinations in addition to their occasional advantages. For example, if two epicardial leads have been used in the past for bipolar pacing, with one electrode on the right ventricle and the other at an easily available site on the left ventricle, the hemodynamic result compared with unipolar pacing could have been better or worse. The sequences of contraction of the left ventricle periphery, septum, and right ventricle are hemodynamically important. Another reason that anodes should be relatively large is to preclude unacceptable corrosion rates. Platinum, for example, does not corrode under the cathodic current densities used in pacing, but anodic potentials can cause corrosion. To preclude significant corrosion, the proximal electrode (anode) of a transvenous bipolar pacing lead is made large enough to ensure that current density is low in that electrode. Careful examinations of explanted platinum polished distal tips (cathodes) have often revealed rough surfaces that are the result of corrosion. One explanation for the occurrence of corrosion at the distal tip electrode is that it is a cathode only during the stimulation pulse. Some pulse generators also have a fast-recharge pulse immediately after the stimulus to neutralize the afterpotential. Because the polarity of the fast recharge is then reversed, this portion of the pulse is actually anodal. Therefore, as “cathode” size decreases, current density increases and corrosion can rise to eventually unacceptable levels. Nonetheless, excellent canine performance has been reported with electrodes as small as 0.6 mm2 in geometric surface area.132 If the electrode is porous or fractal, the surface area of the electrolyte interface is actually large despite the small volume encompassed by the geometric surface. This can reduce current density and interface voltage at the electrodeelectrolyte interface to a level below that required for corrosion by the fast-recharge pulse.

Unipolar and Bipolar Stimulation All pacing systems require both a cathodal and an anodal electrode to complete the electric circuit from the pulse generator to, through, and from the myocardium back to the pulse generator. Therefore, all

SECTION 1  Basic Principles of Device Therapy

pacemakers are bipolar with respect to the body, but not the heart. Ordinary terminology defines a bipolar system as one that has two electrodes in contact with myocardium. A unipolar system has only one electrode in contact with myocardium. The effects of unipolar and bipolar configurations on sensing are profound, as covered in Chapter 2, and the engineering aspects are equally important, as discussed in Chapter 3. In an ordinary unipolar pacing system, one electrode—the cathode—is in contact with myocardium. The metal case of the pulse generator is the anode. Bipolar leads may have higher stimulation thresholds than unipolar leads if the two electrodes are of equal size. In this case, the output voltage delivered by the pulse generator is divided equally between the two electrodes, causing the measured threshold to be higher. The voltage required to force threshold current through two small electrodes is greater than that required for one small electrode. By making the cathode relatively small and the anode relatively large, the overall impedance can be kept at about the same value as for the cathode alone. The threshold current can be delivered with little increase in the driving voltage. Making the anode large makes it a relatively poor stimulating electrode, thereby reducing the arrhythmogenic potential of anodal stimulation, compared with a bipolar lead with equal-sized electrodes. To produce bipolar thresholds that are statistically equivalent to unipolar leads, the anode must be at least three times larger than the cathode.133 It has become standard practice in the design of pacing leads to ensure that the anode area is at least 4.5 times larger than the geometric surface area of the cathode. Bipolar electrode spacing can also be important, especially for sensing (see Chapter 2). It is generally accepted, for example, that as the electrodes are moved closer together, the signal-to-noise ratio, resistance to crosstalk, and median frequency of the sensed signal increase, whereas signal amplitude may decrease. If the spacing is too close, transvenous electrode pairs can have high stimulation thresholds, because current can be shunted between the two electrodes, producing a partial short circuit. In his classic thesis, De Caprio134 determined that the optimal bipolar spacing (for sensing) was about 8 mm.

Constant-Current versus Constant-Voltage Stimulation A constant-current generator delivers a current pulse that is rectangular in shape. That is, the trailing edge (Ite) of the pulse equals the leading-edge (Ile) current in amplitude and the pulse is flat on top. The current delivered by a constant-current pulse generator is independent of pacing impedance to the limits of the power source (Fig. 1-21). If impedance decreases, the pulse generator output voltage automatically decreases to keep the current constant. In the presence of a highresistance circuit, such as one with a lead partial fracture, the limits of the power source can be reached. In this case, the pulse generator does not generate enough voltage to maintain a preset level of current. The result is delivery of a lower current than programmed. Although under normal operating conditions the current waveform of a constant-current pulse generator is rectangular, the resultant voltage waveform is not. It would be rectangular if the circuit beyond the pulse generator were purely resistive. However, because of the reactance in the circuit, capacitive in nature at the electrode-electrolyte interface, the initial leading-edge voltage (Vle) rises rapidly, then more slowly to a larger, trailing-edge voltage (Vte), as shown in Figure 1-22. At the end of the pulse, an immediate drop in voltage equal to Vle is observed, followed by an exponential decay back to baseline. The voltage rise during the pulse, called the overvoltage, is caused by an increase in pacing impedance due to electrode polarization, and the afterpotential is caused by the gradual dissipation of that polarization. At present, probably all implantable pulse generators are capacitively coupled devices of approximately constant voltage. Because the pulse generator output comes from a capacitor, the voltage delivered

Voltage at 10 mA

18 16

Voltage at 5 mA

14 Volts and milliamperes

24

12 10

Current at 10 mA Voltage at 2 mA

8 6

Current at 5 mA

4

Current at 2 mA

Voltage at 1 mA

2 Current at 1 mA 100

1000

10,000

Resistance (ohms) Figure 1-21  The effects of pacing impedance on constant-current leading-edge waveform amplitudes using a Medtronic Model 5880A external pulse generator. Current is independent of impedance until the battery is “saturated.” This occurs when the voltage cannot increase any more to keep the current constant. (From Barold SS, Winner JA: Techniques and significance of threshold measurement for cardiac pacing. Chest 70:760, 1976.)

decreases as charge is delivered from the capacitor to the electrode in the heart. The fully charged capacitor in the output circuit of the pulse generator delivers a set leading-edge voltage (Fig. 1-23). This results in continuing charge transfer from the capacitor to the heart during the duration of the pulse. The difference in voltage at the beginning and end of the pulse is directly proportional to the amount of charge transferred out of the capacitor: Vle − Vte = Q*/C pg



in which Vle is the leading-edge voltage of the pulse, Vte is the trailingedge voltage, Q* is the amount of charge removed from the capacitor

Delivered voltage

Resultant voltage

5V

Resultant current 20mA

5V

Delivered current 20mA Constant voltage

Constant current

Figure 1-22  Voltage and current waveforms from a capacitively coupled, constant-voltage implantable pulse generator, the Medtronic Model 7000A (left), and the constant-current mode output of an external research stimulator, Medtronic Model 1356 (right). A unipolar lead with a polished platinum, 8-mm2 ring tip is used with a 900-mm2 titanium anode in 0.18% NaCl solution. The voltage across the lead is measured against a 100-mm2 Ag/AgCl electrode to eliminate the anode’s polarization from the waveform. (From Stokes K, Bornzin G: The electrodebiointerface [stimulation]. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, pp 33-78.)



25

1  Cardiac Electrical Stimulation 40

32

Volts and milliamperes

28 24

2 1 .8 .6 .4

.1

16

8

x x

2 1 .8 .6 .4

x x

.3

.5 .8 1.0 2.0

x x

x

Chronic

x x

x x

Peak (3 weeks)

x x

x

x

Implant

.2

.2

Leading edge

20

Threshold (volts)

Threshold (mA)

36

12

10 8 6 4

10 8 6 4

.1

.3

.5 .8 1.0 2.0

Pulse width (msec) Trailing edge Leading edge

Voltage

4

Current

Trailing edge

0

Figure 1-24  Logarithmic plots of canine ventricular constant-current (left) and constant-voltage (right) strength-duration curves for a passively fixed, atraumatic, unipolar lead with a polished platinum, 8-mm2 ring tip at various times after implementation (three different animals). (From Stokes K, Bornzin G: The electrode-biointerface [stimulation]. In Barold SS, editor. Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, p 41.)

100

1000

high-impedance lead than for a low-impedance lead. Also, the rate of charge delivery decreases as the pulse generator capacitor output voltage decreases. This means that the voltage droop line is not a straight line, although it may appear so when the impedance is very high. The output voltage pulse becomes almost rectangular (i.e., Vle − Vte is very small) when the impedance of the lead-heart-lead circuit into which the pulse generator capacitor is discharging is very high. If the impedance is low, the pulse waveform droop is steeper. If it is very low (<200 Ω), the capacitor may not be able to maintain even an approximate constant voltage. Constant-current thresholds are related to constant-voltage thresholds by impedance. However, impedance is not constant during the pulse. It increases with polarization. Therefore, constant-current strength-duration curves can have slightly different shapes than constant-voltage curves. Most modern endocardial leads (e.g., iridium oxide, fractal, platinized platinum, or “activated” carbon surfaces) have relatively low-polarizing electrodes. These tend to have a lower-voltage rheobase and a somewhat higher chronaxie than highly-polarizing electrodes135 (Figs. 1-24 and 1-25). In fact, a nonpolarizing electrode made from Ag/AgCl has the same shape strength-duration curve for constant-voltage stimulation as for constant-current stimulation

10,000

Resistance (ohms) Figure 1-23  Effect of pacing impedance on capacitively coupled, constant-voltage leading-edge and trailing-edge waveform amplitudes. The leading-edge voltage remains constant as a function of pacing impedance at values of 200 Ω or greater (Medtronic Model 5950 pulse generator). The trailing edge of the voltage waveform changes slightly with impedance up to about 1000 Ω. Current falls significantly with increasing impedance. Any constant-voltage source may no longer be constant at very low pacing impedances, because the battery becomes unable to supply enough current to maintain a steady voltage. These very low impedance values are not likely to be encountered clinically in a properly functioning pacing system. (From Barold SS, Winner JA: Techniques and significance of threshold measurements for cardiac pacing. Chest 70:760, 1976.)

(measured in coulombs), and Cpg is the capacitance of the capacitor (measured in farads). Obviously, what is delivered through the lead wire to the pulse generator is not truly a constant-voltage pulse. The change in voltage over the pulse duration (“droop”) is directly proportional to the total charge delivered (Q*) during the pulse. For a given leading-edge voltage, the charge delivered will be less for a

2.0

2.0

1.5 Polished platinum

1.0

0.5

Cl 0.0

0.5

1.0

Pulse width (msec)

1.5

Ag/AgCl 1.0

0.5

CV

0.0

A

Threshold (V)

Threshold (V)

1.5

CV Cl

0.0 2.0

0.0

B

0.5

1.0

1.5

2.0

Pulse width (msec)

Figure 1-25  Constant-current (CI) compared with constant-voltage (CV) canine ventricular strength-duration curves for passively fixed, atraumatic electrodes. A, Polarizing, 8-mm2, polished ring-tip electrode. B, Nonpolarizing, Ag/AgCl, 8-mm2 electrode.

26

SECTION 1  Basic Principles of Device Therapy

1.4 *

Threshold (V/cm)

1.2

M B

2.52.5

1.0

2.5 *

0.8

55

5

0.6

10

20

0.4

1010

electrode, together with the present and future states of the myocardium, determine the pacing margin of safety. This margin is the difference between the stimulus magnitude delivered by the pulse generator and the magnitude, now and in the future, required for myocardial stimulation. The electrodes normally are the major factor in determining the impedance into which the pulse generator delivers its stimuli. In addition, the electrodes, along with the pulse generator circuitry, determine the sensing characteristics of the pacing system.140 Size, material, surface structure, and biologic response of the tissue to the particular electrode material are critical factors in electrode design. These factors are reviewed in the following sections, along with some effects of shape, spacing, fixation methods, and material.

0.2

SIZE OF THE STIMULATING ELECTRODE (GEOMETRIC SURFACE AREA)

0.0 0

5

10

15

20

Duration (msec) Figure 1-26  Monophasic (M) and biphasic (B) strength-duration curves obtained in strips of frog ventricular myocardium superfused with a solution containing 3 mmol/L of potassium. At pulse duration of 20 msec, there is no significant difference in the rheobase threshold. Note that the M waveform produces a lower threshold than the B waveform at pulse durations of 5 msec or less. Therefore, although the M and B waveforms have a similar rheobase, chronaxie is less with M than with B stimuli. (From Knisley SB, Smith WM, Ideker RE: Effect of intrastimulus polarity reversal on electric field stimulation thresholds in frog and rabbit myocardium. J Cardiovasc Electrophysiol 3:239, 1992.)

(see Fig. 1-25). Therefore, polarization affects the value of the constantvoltage stimulus chronaxie. This accounts for most of the differences in shape between constant-voltage and constant-current strengthduration curves.

Monophasic and Biphasic Waveforms A biphasic defibrillator stimulus, compared with a monophasic stimulus, has a lower voltage threshold for atrial and ventricular defibrillation.136 Knisley et al.137 studied the effect of biphasic and monophasic stimuli on excitation thresholds in rabbit and frog ventricles (Fig. 1-26). At very long pulse durations (20 msec), there was no difference in the stimulation threshold for monophasic versus biphasic waveforms. Therefore, reversal of waveform polarity during a long stimulus did not affect rheobase voltage. At shorter pulse durations (2.5 msec), the threshold voltage was significantly greater for biphasic than for monophasic waveforms. Therefore, the chronaxie pulse duration was significantly increased by an intrastimulus polarity reversal during shorter stimuli. The energy requirements for pacing and defibrillation are different for monophasic stimuli compared with biphasic stimuli. The energy requirement for pacing is greater with biphasic stimuli. For defibrillation, however, biphasic stimuli decrease the energy requirements required. Overlapping biphasic waveforms for pacing the atria in single-lead DDD pacing have been studied. One object was the reduction of atrial pacing thresholds and, consequently, reduction of the incidence of diaphragmatic stimulation compared with monophasic pacing under the same conditions.138 This configuration uses unipolar anodal and cathodal pulses delivered to two closely spaced, floating atrial electrodes so that the pulses of opposite polarity overlap. Phrenic stimulation remains a problem.139

Design Features of Pacing Electrodes That Affect Performance The performance of any pacing electrode is one of the major deter­ minants of the pacing threshold. Stimulation characteristics of the

Stimulation threshold varies as an inverse function of the size or geometric surface area of the stimulating electrode.37,141-143 Irnich38 stated that, in theory, the chronic stimulation threshold of a spherical electrode should decrease as its radius (geometric surface area) decreases to a certain value. With further decreases below that value, the chronic threshold should begin to increase. Therefore, the electric field strength E necessary for stimulation is a nonlinear function of the electrode radius r and of the potential V applied to a spherical electrode. Stimulation threshold increases during the first several weeks after lead implantation. This increase in threshold is related to the development of a conductive but nonexcitable fibrotic capsule that forms around the electrode and separates it from normal, excitable myocardium37,38,144,145 (Fig. 1-27). The fibrous capsule is a biologic response to the presence of a foreign body, in this case the electrode. With perhaps rare exceptions, the fibrous capsule is not a response to the electrical stimulus.146 In reality, if r is the electrode radius and d is the approximate mean thickness of the fibrotic capsule, r + d describes the dimensions of the effective or “virtual electrode,” as defined by Furman et al.147 If the stimulus voltage is held constant, the field strength varies as a function of the thickness of the nonexcitable capsule. Higher voltages must be applied to maintain the intensity of the field at the interface of the virtual electrode and the excitable myocardium. Therefore, chronic thresholds (for steroid-free electrodes) must be higher than the values at implantation. This theory was modeled by Irinch,37 as follows140: 2 V r  E=  [1-10] r  (r + d)  Equation 1-10 is lacking a crucial parameter required by the strength-duration relationship—stimulus duration. According to Irnich, the equation is based on measurements taken at a pulse duration of 1 msec. Holding everything else constant, the capsule thickness is the same for a large electrode radius as for a small one. If, for

Figure 1-27  Schematic representation of a simple collagenous capsule around an electrode, which separates it from excitable tissue. The length of the arrow in the left panel indicates the radius (r) of the spherical electrode. In effect, the fibrous tissue becomes a “virtual electrode” with radius r + d (arrow in right panel), where d is the thickness of the fibrous tissue (stippled area). (From Stokes K, Bornzin G: The electrode-biointerface [stimulation]. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, Futura, 1985, pp 33-78.)



1  Cardiac Electrical Stimulation

example, two electrodes of different radii (0.5 and 5 mm) develop a 1-mm-thick capsule (d), the electrode with the smaller actual radius will be associated with a greater percentage increase (r + d vs. r) with the formation of the virtual electrode (300% vs. 20%, respectively). This helps to explain the observation that smaller electrodes have lower acute thresholds but develop a greater rise in threshold over time.86,89 There is a point (r = d) at which chronic threshold reaches a minimum. According to Equation 1-10, when d is greater than r, thresholds increase. Therefore, there is a theoretical minimum spherical electrode radius at which thresholds must reach their minimum value. Irnich found this to be 0.72 mm for polished electrodes. In reality, because currently used electrodes are not polished and are not spherical, the relationship between stimulation threshold and electrode radius is more complex. Electrode size is more meaningful when it is discussed in terms of not only geometric surface area but also electrical surface area, which can be vastly increased by having a fractal surface. EFFECTS OF MAXIMIZING ELECTRODE SURFACE AREA Maximizing the electrical surface area of the electrode has the effect of increasing the Helmholtz capacitance. For a given stimulus amplitude expressed in terms of charge delivered, the voltage across the capacitance will decrease as the magnitude of the capacitance increases (V = Q/C; see earlier discussion). This means that increasing the Helmholtz capacitance decreases the polarization voltage, provided the delivered charge is kept the same. A very small-diameter electrode

A

27

with a large surface area (due to its fractal structure) can have a high Helmholtz capacitance and a high current density at the electrodetissue interface. The result is an electrode with high impedance and a lower threshold current requirement. Sensing performance may be good or not so good, depending on the electrode and pulse generator design (see later discussion). ELECTRODE SURFACE STRUCTURE (INTERFACE SURFACE AREA) Based on animal studies, electrodes with pores that allow tissue ingrowth have thinner fibrous capsules and somewhat lower chronic thresholds than electrodes with solid or polished surfaces.148-151 These claims have been somewhat controversial when applied to humans.152-155 Pore structures of certain dimensions are known to promote rapid tissue ingrowth156 (Fig. 1-28). Activated-carbon electrodes are reported to have porosity on the order of 10 nm.157 It has been argued that microporosity provides rapid stability of the electrode at its interface with the myocardium and prevents electrode motion that otherwise may result in tissue irritation and high chronic stimulation thresholds. The importance of microporosity among the many other factors involved in electrode mechanical stability is uncertain. RELATIONSHIP OF ELECTRODE SIZE AND SENSING PERFORMANCE The amplitude of the electrogram sensed by the amplifier of the pulse generator is less than the amplitude of the available signal in the

B

C Figure 1-28  Electron micrographs of microporous electrode surfaces. A, Activated carbon surface of Siemans Model 412S/60 electrode at about 8000× magnification. B, Medtronic Model 4011 platinized surface at 6900× magnification. C, Polished platinum surface of Medtronic Model 6971 at 7000× magnification. The polished platinum surface has little microstructure. Its actual microscopic surface area is similar to its apparent or geometric surface area (8 mm2). The platinized platinum surface (B) is composed of particles so small that they absorb visible light, and the surface appears black. The true surface area of the interface is many orders of magnitude greater than the geometric surface area. (From Seeger W: A scanning electron microscopic study on explanted electrode tips. In Aubert AE, Ector H, editors: Pacemaker leads. Amsterdam, 1985, Elsevier Science, pp 417-432.)

SECTION 1  Basic Principles of Device Therapy

myocardium. The attenuation of the signal is related to the ratio of the source impedance (of the electrode-myocardial interface) and the input impedance of the sensing amplifier. The higher the source impedance, the more the signal amplitude is attenuated for a given input impedance. Signal attenuation can be greatly minimized by increasing the input impedance of the sense amplifier, so that the ratio of input impedance to source impedance is very large.

Clinical Aspects of Myocardial Stimulation by Pacemakers STABILITY OF STRENGTH-DURATION CURVES AND THE DISTORTING EFFECT OF POLARIZATION None of the relationships published in the last 100 years has exactly duplicated the capacitively coupled, constant-voltage strength-duration curves that have been measured empirically with various types of electrodes. This may be caused, in part, by the confounding effect of polarization, which varies significantly with electrode size, shape, surface finish, and material. Another problem, however, is that the voltage and current strength-duration relationships, typically plotted on linear coordinates, are really logarithmic158 (see Fig. 1-24). When plotted in this manner, the strength-duration curve for constantcurrent stimuli is now seen to be a straight line up to rheobase, whereas the constant-voltage line turns upward, as seen at stimulus duration 2 msec in Figure 1-24. The effect of polarization on reducing current flow in constant-voltage pacing does not occur with constant-current pacing, because with the latter the pulse generator develops whatever voltage is necessary to force the set level of current into the circuit. The slope of the strength-duration curves for passively fixed, atraumatic leads does not change with time after implantation (see Fig. 1-24). The acute, peak, and chronic mean thresholds of five ventricular and three atrial, passively fixed, atraumatic leads in 77 canines had a (log10) slope of about 0.60 ± 0.07 V/msec.158 The correlation coefficient for these relationships was typically more than 0.99 at pulse durations of less than 0.5 msec for polished electrodes and at durations of less than 1.0 msec for low-polarizing designs. Traumatic electrodes, such as those with active fixation, typically had a lower slope immediately after implantation, which shifted to about the same 0.60-V/msec value within days as the acute trauma to the electrode-tissue interface healed. Because strength-duration curves are typically plotted on linear rather than logarithmic coordinates, changes in voltage and current threshold after implantation are usually seen as a shift upward and to the right. In most cases, because it is related to the slope of the curve (the tissue’s time constant), chronaxie does not change significantly with time. However, Cornacchia 159 showed that the administration of propafenone shifted both the strength-duration curve and the chronaxie to the right. The pacing threshold also increased. Some older pulse generator designs attempted to compensate for the gradual decline in stimulus voltage that results from battery depletion by automatic “stretching” of the pulse duration to maintain the stimulus energy at an almost constant value. Although this feature was designed to prevent loss of capture, increasing the pulse duration from a programmed value of 0.5 msec adds little to the pacing safety margin, because it approaches an essentially flat portion of the strengthduration curve. In fact, although this automatic increase in pulse duration was added in the name of safety, it is a wasteful use of battery energy. Preventing the decrease in output voltage of the pulse generator, while giving adequate warning of the depleted state of the battery, is a better solution. The pulse-duration increase method did temporarily prolong pacing capture, although inefficiently. This was valuable for patients who were far away from medical care for a short time. It also did provide a warning in that both transtelephonic checking devices and clinical devices measure the actual pulse width. Newer pulse generators have abandoned this approach to compensating for battery depletion in favor of automatic regulation of stimulus voltage. They maintain constant stimulus amplitude despite declining battery voltage.

THRESHOLD CHANGES AS A FUNCTION OF TIME AFTER LEAD IMPLANTATION It is well known that stimulation thresholds change as a function of time after lead implantation, typically rising to a peak value after several weeks.160-163 With older polished electrodes, some patients had thresholds that evolved over longer periods, up to 6 months.164 Luceri et al.165 observed that, after the acute rise in stimulation threshold, 43% of 120 patients had stable chronic thresholds for up to 8 years; 17% had chronic thresholds that decreased at a rate of 5% per year, and 19% had thresholds that rose at a rate of 14% per year; 20% had thresholds that varied widely around a stable mean. Modern pacing electrodes have a porous or microporous surface structure. Most also elute a glucocorticosteroid. As shown in Figure 1-29, the technological progression from polished to porous to microporous to steroid-eluting electrodes has significantly reduced the evolution of stimulation threshold as a function of time after implantation.166 In fact, as can be determined from the follow-up data available, the thresholds of porous and microporous steroid-eluting leads do not change significantly with increasing time after implantation.167-170 The reasons for threshold changes as a function of time and electrode design are to be found in the foreign body response to the electrodes. ELECTRODE-TISSUE INTERFACE AND FOREIGN BODY RESPONSE The body’s response to an implanted device has been relatively well characterized.171 Figure 1-30 shows schematically what typically occurs at an implantation site as a function of time. If one analyzes the tissues adjacent to canine ventricular endocardial atraumatic electrodes as a function of time after implantation, the evolution depicted in Figure 1-30 is typically observed (with one exception). In the first 1 to 3 days, there is no evidence of cellular inflammation, and thresholds do not change significantly. This lack of a cellular response in the first few days is an exception to the classic view of surgical wound inflammation. In a surgical wound, polymorphonuclear leukocytes (PMNs) normally are present during this period to scavenge necrotic debris and bacteria.

2

Threshold (V)

28

1

x x 3

x

1

x

x

xx

x

4

2 x 3 x 4 5 6

xx

0 0

2

4

8

12

Implantation time (wk) Figure 1-29  Canine ventricular voltage thresholds at 0.5 msec for 8-mm2 unipolar, transvenous, tined leads as a function of time after implantation. 1, Polished platinum ring-tip (manufacturer A); 2, polished platinum ring-tip (manufacturer B); 3, porous-surface platinum hemisphere (manufacturer C); 4, porous-surface titanium hemisphere (manufacturer B); 5, platinized Target Tip (manufacturer B); 6, steroid-eluting titanium porous-surface electrode (manufacturer B).



1  Cardiac Electrical Stimulation

Implantation of lead Myocardial membrane changes Increased local perfusion Increased endothelial permeability

Edema/fibrinolysis PMN cellular infiltration Macrophages and granulation tissue Exocytosis

Chemotaxis

H2O2 O2 radicals Enzymes

Fibroblasts Collagen capsule

Necrosis Myofibril disarray

More macrophages High stimulation threshold

Figure 1-30  Schematic representation of the inflammatory process and foreign body response to lead implantation. This has been correlated approximately with time after implantation of a cardiac pacemaker lead, based on histologic studies of canine electrode-tissue sites. PMN, Polymorphonuclear neutrophil; H2O2, hydrogen peroxide.

The classic view of inflammation holds that the initial event is dilation of blood vessels and alteration in the vascular endothelium, resulting in increased permeability. This increased perfusion and permeability of the blood vessel walls allows plasma to leak into the surrounding tissue, producing edema. Because plasma and serum are more conductive than myocardium, pacing impedance decreases almost immediately after lead implantation. After 2 to 3 days, a mixed cellular inflammation begins to appear in the tissues surrounding the electrode, and the stimulation threshold begins to rise. Tissue inflammation reaches its peak in about 1 week, with clearly evident interstitial edema and cellular necrosis. Pacing impedance typically reaches its minimum value at the inflammatory peak (about 1 week after implantation), after which it increases as the edema resolves. The stimulation threshold may or may not reach its peak at the same time as the nadir of pacing impedance. After the early, mixed cellular reaction, the inflammatory response is characterized by a gradual accumulation of macrophages that reach the electrode surface, adhere, and become activated. The major function of the macrophage is to dispose of dead or foreign cells and particles by the process of endocytosis116,172 (Fig. 1-31, A). With a large foreign object, such as a pacing electrode, the process of endocytosis is impossible. In this case, the macrophage tries to destroy the large foreign body by the process of exocytosis, the extracellular release of enzymes and oxidants (Fig. 1-31, B). Macrophages spread over the electrode surface, often differentiating into foreign body giant cells. Their lysosomes migrate to the membrane surface, releasing hydrolytic enzymes and oxidants into the surrounding tissue and onto the electrode surface. Additional macrophages settle on the foreign body giant cells and are activated. Myocytes adjacent to the electrode-tissue interface are bathed in a “soup” of inflammatory mediators resulting from exocytosis. These mediators of the inflammatory response dissolve the subcellular collagen beams, struts, and nets that hold the myocytes in the normal orderly array of myocardium.173 After 3 to 4 weeks (for a stable, biocompatible device), the more global inflammatory response has essentially resolved, with the

EXOCYTOSIS

ENDOCYTOSIS Phagocyte

29

Phagocyte

Particle

Lysosome

Lysosome

Device

Activation

Membrane invagination

Adhesion activation

Lysosomal release extra membrane

Vacuole

Enzymes H2O2

Lysosomal release within membrane

O2

A

Etc.

B

Figure 1-31  Endocytosis and exocytosis. A, Schematic representation of phagocytosis by endocytosis. A small particle attaches to the macrophage’s membrane. The membrane invaginates, encapsulating the particle in a membrane-lined vacuole. The vacuole and lysosome migrate toward each other, and their membranes fuse. The particle is then destroyed by lysosomal enzymes and oxidants. B, Schematic representation of the process of “frustrated phagocytosis” by exocytosis, or the acute foreign body response on the device surface, which results in lysosomal release of inflammatory mediators on the device surface and into the adjacent tissue.

30

SECTION 1  Basic Principles of Device Therapy

development of a collagenous capsule surrounding the electrode. If the electrode is biocompatible and stable relative to the myocardium, few significant visible histologic changes occur in the adjacent tissues after this period. Thresholds may subsequently decrease, remain stable, or increase, depending on the intensity of the chronic foreign body response at the electrode-tissue interface. Chronic atraumatic polished electrodes typically have a layer of foreign body giant cells on their surface (Fig. 1-32, A). These are covered by a layer (or layers) of macrophages that can be surprisingly thick. This cellular component of the capsule is not an acute, transient phenomenon but has been observed on electrodes up to 13 years after implantation in Stoke’s canine studies. These cells are covered by a layer of collagen that is oriented along the surface of the electrode. The myocytes adjacent to the collagen layers are disarrayed and are interspersed with collagen fibers that are radially oriented with respect to the surface of the electrode. There may also be circular “holes” in this layer of disoriented myocytes, which appear to be infiltrated with fatty material. Groups of macrophages with fused membranes (foreign body giant cells) enveloping bundles of myocardial fibers adjacent to the electrode were observed 1 to 4 weeks after implantation. The presence of this fatty infiltration, its location, and its severity depend on the stability, myocardial location, and shape of the electrode relative to the vector of myocardial contraction. Outside the disarrayed myofiber zone, one finds normally oriented myocardium. Therefore, it is clear that the concept of a simple fibrous capsule (Irnich’s “d”) separating the electrode surface from viable myocardium does not completely describe this complex biologic response and its effect on pacing. PASSIVELY FIXED LEADS Porous and Microporous Electrodes Electrodes with pores 10 to 100 µm in diameter allow the formation of collagen because of chronic inflammation. Therefore, in a sense,

macroporous electrodes promote inflammation. In addition, the chronic capsule surrounding porous electrodes can be associated with significant myofibrillar disarray (Fig. 1-32, B). Despite these factors, porous electrodes are associated with a relatively thin collagenous capsule. Histologic study of the chronic tissue reaction surrounding porous electrodes has shown that inflammatory cells are usually not found on the surface of the electrode. Rather, the active cellular component of the fibrous capsule is located within the pores. Similarly, microporous electrodes tend to have few cells on their surfaces with well-healed interfaces (Fig. 1-32, C). Target Tip design electrodes show an active cellular component deep in the grooves of the electrode (Fig. 1-32, D). The smooth outer surface interfaces directly with collagen. Steroid-Eluting Electrodes It has long been recognized that systemically administered glucocorticosteroids decrease both acute and chronic stimulation thresholds. In the early days of cardiac pacing, sometimes one or more of the several mercury cells in the pulse generators would internally short circuit and fail suddenly, causing loss of capture. In these cases, intravenous hydrocortisone was an effective emergency measure for temporarily regaining and maintaining capture on the way to the operating room. Initially, the threshold-lowering effect of systemic glucocorticoid therapy was thought to be caused by effects on the myocyte membrane and sodium and potassium “retention.”174 Steroid-eluting leads, in which dexamethasone sodium phosphate or acetate is gradually released from a reservoir within or around the electrode, have become standard for permanent pacing. It has been conclusively demonstrated that steroid elution decreases chronic thresholds. Despite the clear clinical benefits of steroid elution on the evolution of stimulation thresholds, however, the mechanism of this effect is not well understood.175 Although steroid-eluting, porous electrodes tend to have thinner capsules than polished-platinum electrodes, these capsules surrounding steroid-eluting leads can be difficult

A

B

C

D

Figure 1-32  Optical micrographs of chronic electrode-tissue interfaces. A, Capsule surrounding a polished electrode (upper left) has a relatively thick layer of activated phagocytic cells, including foreign body giant cells on the surface and macrophages further out. Collagenous material encapsulates these cells, with fibrous stringers extending outward into the myocardium. B, Myofibrillar disarray is seen between the collagenous capsule and normal myocardium. The capsule surrounding a porous electrode (upper right) appears to be thinner. However, the active cellular component of the capsule and some of the collagen have been removed with the electrode to facilitate trimming of the tissues. C, Microporous (Target Tip) electrode-tissue interface is shown at lower left. Note the thin, fibrous capsule over the external surfaces and at the ridges. D, Some macrophages are seen deep in the Target Tip electrode’s grooves at higher magnification.



1  Cardiac Electrical Stimulation

to differentiate from those steroid-free electrodes in blind analyses. The capsule surrounding a steroid-eluting lead is characterized by minimal cellularity between the collagen and the electrode surface and minimal myofibrillar disarray. EFFECT OF GLUCOCORTICOIDS ON EVOLUTION OF PACING THRESHOLDS Glucocorticosteroids are known to stabilize the membranes of phagocytes, such as the macrophage, through interaction with surface receptors, inhibiting release of lysosomal contents.176 It has been shown, however, that dexamethasone and its derivatives have no significant electrical effects on myocyte membranes.177,178 The salutary effect of systemic glucocorticoids on stimulation threshold probably results from inhibition of the release of inflammatory mediators from the cellular components of the fibrous capsule. When steroid therapy is discontinued, the release of inflammatory mediators resumes, and stimulation thresholds once again increase. The same phenomenon minimizes inflammation (foreign body response) on and adjacent to the surface of a steroid-eluting electrode. Acute stabilization of macrophage membranes on the electrode surface reduces or minimizes lysosomal release, thereby minimizing myofibrillar disarray and myocyte membrane damage. Chronic steroid elution suppresses the slow, insidious leakage of inflammatory mediators, thereby preventing threshold increase, without the risk of systemic side effects. MECHANICAL INSTABILITY AT MYOCARDIUMELECTRODE INTERFACE Mechanically unstable electrodes can provoke a significant pathologic response in the myocardium. Consider, for example, a transvenous corkscrew electrode that “rocks” at the interface with the endocardium because the lead behind it is too stiff. In some cases, large pockets of activated macrophages may develop on either side of the helix, resulting in the formation of a “preabscess.” In other cases, thick collagenous capsules form and then differentiate into cartilage and, if the instability is severe enough, into bone. Because active-fixation myocardial electrodes interfere with the contractile motion of the adjacent myofibers, myocardial degeneration with fatty infiltration may result in patterns that are clearly related to this mechanical interference. For example, the center of a myocardial helix may fill in with fatty “cells.” A myocardial pin may also provoke myocardial degeneration and fatty infiltration. Therefore, mechanical instability at the electrode-myocardium interface can produce marked histologic and physiologic effects that result in deterioration of the stimulation threshold. A particularly notable example of a lead with a high potential for exit block was an active-fixation lead that used an electrically inactive helix and a platinum-iridium electrode. The presence of a stiff, metal, J-shaped retention wire increased the stiffness effect of this lead. It had an exit block rate of about 10%.

TABLE

1-1 

31

SECOND-ORDER EFFECTS OF ELECTRODE DESIGN Spatial and Size Relationships between Electrode Pairs As previously established, within clinically relevant limits, porous and microporous electrode size and shape per se have no significant effects on the chronic stimulation thresholds (at least with steroid-free electrodes). Nonetheless, the size and shape of the electrode can still be important factors under certain circumstances. For example, a small displacement can affect the performance of a smaller electrode because its high-density field influences relatively few cells.179,180 A larger electrode is not as threshold efficient, but perforation is less likely, and small displacements have less effect on lead performance. The ring-tip electrode design is essentially a small electrode made into a large shape.181 This allows high electric field strength coverage of a larger number of myocardial cells, while affording a lower probability of perforation than a lead with a smaller tip. Although myocardial screws, barbs, and hooks are traumatic to the underlying myocardium, these electrodes all have points that serve as sources of high field strength. Therefore, myocardial electrodes of this design can still have good chronic performance, assuming that the lead is not so stiff as to apply undue force on the electrode-myocardium interface. Electrode Fixation The most efficient electrode design has poor long-term performance if it is mechanically unstable, resulting in both high stimulation thresholds and histopathologic evidence of excessive trauma. For chronically stable, steroid-free electrodes in canines, however, there was no correlation between the mechanism of fixation and the chronic stimulation threshold (Table 1-1). Given similar geometric surface areas, there were comparable chronic canine ventricular thresholds with tined, flanged, screw-in, and hook-in polished electrodes, whether endocardial or myocardial. These results were confirmed by human studies in both the atrium and ventricle.182-184 Therefore, the hypothesis that fixation remote from the electrode stimulation site is necessary for low chronic thresholds does not appear to be valid.185,186 It has not been established whether this is also true for steroid-eluting electrodes. However, a variety of leads are available that combine active fixation and steroid elution. The long-term pacing thresholds of these leads are much lower than those for similar models without steroid elution. Electrode Materials To minimize inflammation and its subsequent effects on stimulation threshold, electrodes for permanent pacing should be biocompatible and resistant to chemical degradation. Many materials, such as platinum, titanium, titanium oxide, titanium nitride, carbon, tantalum pentoxide, iridium, and iridium oxide, have been shown to be acceptable for use as pacing electrodes.187-189 Even silver, which is toxic in neurologic tissue and is certainly not corrosion resistant, has been used successfully in the heart as an electrode.190 Titanium and tantalum have been known to acquire a surface coating of oxides, which some argue may impede charge transfer at the electrode interface. To prevent this,

Chronic (12-Week) Unipolar Canine (Constant-Voltage) Thresholds of Polished Platinum Electrodes at 0.5 msec vs. Fixation Mechanism

Model No. 6901 6950 6961 6971 4016 6959 6955 4951 6917

Insertion Fixation Endocardial flange Endocardial long tines Endocardial short tines Endocardial medium tines Endocardial helix Endocardial helix Endocardial helix Epicardial hook Epicardial helix

Electrode Location and Shape Endocardial cylinder Endocardial cylinder Endocardial ring Endocardial ring Myocardial helix Endocardial ring Myocardial helix Myocardial hook Myocardial helix

Surface Area (mm2) 11 11 8 8 10 13 10 10 12

Stimulation Threshold (V) 1.9 ± 0.77 1.6 ± 0.48 1.8 ± 0.69 1.5 ± 0.57 1.1 ± 0.30 1.3 ± 0.42 1.6 ± 0.51 1.5 ± 0.44 1.4 ± 0.53

From Stokes K, Bornzin G: The electrode-biointerface (stimulation). In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, 1985, Futura, p 40. *P <.05 considered statistically significant.

n 11 4 9 8 6 8 10 10 17

P vs. Model 6971* 0.2 >0.5 0.35 — 0.1 0.4 >0.5 >0.5 >0.5

32

SECTION 1  Basic Principles of Device Therapy

titanium has been coated with platinized platinum or vitreous carbon. Others accept the concept that the oxide layer acts as the dielectric of a capacitor, so that no charge is transferred across the dielectric during stimulation. In that situation, current continues to enter and leave each side of the capacitor (see earlier discussion of Helmholtz capacitance). In any case, titanium oxide electrodes are highly corrosion resistant, and these combinations have been found to have excellent long-term performance as pacing electrodes.190-194 Some theories have held that the foreign body reaction is a response to the electrode material.195,196 As a result, many attempts have been made to improve thresholds through the use of more biocompatible materials. For example, some claim that pyrolytic carbons are more biocompatible and produce lower chronic thresholds than platinum.94,197-199 Besides having a different composition, these electrodes are also microporous. When similar electrodes are polished, we have found that the chronic canine thresholds are not significantly different from those observed with polished platinum electrodes. Proper electrode material selection certainly is necessary to prevent unacceptable toxic responses or corrosion. At this point, however, apparently no biocompatible electrode composition significantly improves thresholds. Not all conductive materials are suitable for use as electrodes. Certain materials, such as zinc, copper, mercury, nickel, and lead, are associated with toxic reactions in the myocardium and are unsuitable for use in permanent pacing leads.182 Stainless steel materials are highly varying in composition and microstructure, with great variation between production lots. Electrodes made from one lot may be acceptable, whereas those made from another lot may corrode unacceptably. Because some of the corrosion products may be inflammatory or toxic, high thresholds occasionally occur with these materials. Therefore, stainless steel materials are no longer used for implantable electrodes. The polarity of the electrode may also have an important influence on its chemical stability. For example, Elgiloy, a non-noble and highly polarizing metal alloy, was used in the past as a cathode. It could not be used as an anode because it is susceptible to significant corrosion. Although Elgiloy had other excellent qualities, it is no longer used as a pacemaker electrode. The materials presently used for permanent pacing electrodes include platinum-iridium, titanium (oxide), platinum- or carboncoated titanium, platinized platinum, vitreous carbon, and iridium oxide. The platinized platinum, “activated” carbon, and iridium oxide electrodes are associated with a reduced degree of polarization. A negligible degree of corrosion occurs with these materials. The vitreous carbon electrodes have been improved by roughening the surface, a process known as activation that increases the surface area of the interface, thereby reducing polarization. Fractal coating of the distal electrode also has been introduced as a method for reducing electrode polarization. This technique involves coating the distal electrode with a microscopic granular structure that produces a complex surface. Electrode Location (Epicardial, Endocardial, Intramyocardial) As shown previously in canine ventricles for electrodes without steroid elution, the type of fixation (as opposed to the location of the electrode) has no effect on stimulation thresholds, in that epicardially applied corkscrews, transvenous corkscrews, and passively fixed endocardial electrodes all tend to have about the same chronic thresholds. Most epicardial or myocardial pacing leads are used in pediatric patients, in whom threshold complications are relatively common.200,201 It is generally perceived that epicardial and myocardial electrodes without steroid elution have less desirable threshold performance than endocardial leads. One reason that the performance of epicardial and myocardial leads has lagged behind that of endocardial passively fixed leads is the mechanical limitations involved. Epicardial and transvenous active-fixation leads are significantly more complex and are more difficult to design with all the attributes necessary for low, chronic stimulation thresholds. Nonetheless, there is no inherent reason that transvenous active-fixation or myocardial electrodes should not perform as well as or better than endocardial systems.

The first transvenous steroid-eluting active-fixation lead, the Medtronic Model 5078 (Medtronic, Minneapolis), was bipolar, with an electrically inactive, fixed helix surrounding a 5.8-mm2 porous, platinized cathode. This lead had excellent electrical performance in both the atrium and the ventricle.202-205 However, difficulties with helix distortion and entrapment in some cases resulted in the abandonment of the design. Active-fixation steroid-eluting leads provide significantly reduced pacing thresholds compared with standard active-fixation leads. Active-fixation electrode thresholds tend to be slightly higher than those of passive-fixation steroid-eluting electrodes.206 Steroid elution has also been applied to epicardial leads; with a significant reduction in long-term pacing threshold compared with steroid-free leads.207 PHARMACOLOGIC EFFECTS ON CARDIAC STIMULATION Several types of antiarrhythmic drugs have been demonstrated to increase stimulation thresholds in both humans and animals. Type 1 drugs decrease Na+ conductance and decrease the rate of rise of the action potential. Therefore, it should be no surprise that these agents can increase the threshold for pacing. Type 1A drugs, such as quinidine208 and procainamide,209 may result in increased thresholds, especially when administered in high doses.210 Type 1C drugs, such as encainide, flecainide, and propafenone, have been associated with increased pacing thresholds.211-215 The increase in stimulation threshold with these drugs has been demonstrated to correlate with the change in QRS duration. In addition to the type 1 agents, propranolol has been shown to result in an increase in pacing threshold when administered intravenously.216 Amiodarone, lidocaine, tocainide, and verapamil reportedly have minimal effects on pacing threshold, although we have seen one patient with congenital heart disease in whom amiodarone reproducibly increased the pacing threshold to the point of exit block.217 METABOLIC EFFECTS ON CARDIAC STIMULATION Stimulation Thresholds Stimulation thresholds may rise during sleeping or eating, factors associated with withdrawal of sympathetic tone and increased vagal tone.218,219 In contrast, factors associated with increased sympathetic tone, such as exercise or assumption of the upright posture, are associated with a decrease in threshold. The myocardial stimulation threshold is increased by several metabolic abnormalities, including hypoxemia, hypercarbia, metabolic alkalosis, and metabolic acidosis. In the presence of respiratory or cardiac arrest, the pacing threshold may increase by well over 100%, resulting in loss of capture despite the use of a conventional safety margin. Because of this observation, antitachycardia pacing devices, such as pacemakers and ICDs, are often designed to deliver high-intensity stimuli during anti-tachycardia pacing or after a high-energy shock. In patients undergoing implantation of an ICD, Khastgir et al.220 were unable to demonstrate an increase in pacing threshold 10 and 60 seconds after defibrillation. Ventricular fibrillation was electrically induced, however, and defibrillation was promptly performed under controlled circumstances in this study. PHYSIOLOGIC AND PHARMACOLOGIC EFFECTS ON PACING In the presence of a primary respiratory arrest, pacing stimuli may not capture the myocardium until adequate ventilation and pH balance are restored. Therefore, careful attention to respiration and pH must be maintained during anesthesia in patients with implanted pacemakers to ensure continued myocardial capture. Ischemia produces variable effects on stimulation threshold, depending on the location of the pacing electrode relative to the ischemic myocardium. In the presence of acute myocardial ischemia, the resting membrane potential decreases



1  Cardiac Electrical Stimulation

(cells become partially depolarized), the action potential upstroke velocity decreases, and the action potential duration dramatically shortens. In the presence of metabolic blockade with 2,4-dinitrophenol, Delmar221 noted an upward shift in the strength-duration curve, indicating an increase in the current required for capture at all pulse durations. Therefore, if the stimulating electrode is located in an ischemic region, the stimulation threshold would be expected to increase. With further ischemia and infarction, the myocardial threshold may rise dramatically. This may be seen clinically in patients who develop an acute inferior myocardial infarction (MI) with right ventricular (RV) infarction; in such patients, a previously implanted pacemaker may suddenly lose capture. However, if the stimulating electrode is located in a nonischemic region (e.g., right ventricle), activation of the sympathetic nervous system may reduce the pacing threshold. Hyperkalemia has been shown to increase the stimulation threshold when the serum K+ concentration exceeds 7 mEq/L.222,223 In contrast, in the presence of hypokalemia, intravenous (IV) K+ may decrease the pacing threshold and restore capture of a subthreshold pulse.224 In addition, the reduced excitability during hyperkalemia can be corrected by IV calcium.225 Hyperglycemia in the range of 600 mg/dL may increase stimulation thresholds by as much as 60%.226 Therefore, patients who have diabetes or renal failure—conditions associated with the potential for altered glucose metabolism and electrolyte abnormalities—may need a larger safety margin than other patients. Hypothyroidism has also been demonstrated to increase pacing thresholds, an effect that is reversible with thyroxine replacement.227,228 As stated previously, glucocorticosteroids decrease stimulation thresholds and have been used to treat exit block both acutely and chronically.229 Endogenous and synthetic catecholamines are effective in lowering pacing thresholds.230,231 The effect of IV epinephrine or isoproterenol is to decrease the stimulation threshold initially, followed by an increase. IV or sublingual isoproterenol has been demonstrated to reverse high pacing thresholds related to antiarrhythmic drug toxicity.232

Biventricular Pacing Optimal clinical outcomes with permanent pacing require that the hemodynamic effects of the pacing site and the timing of atrial and ventricular contraction be carefully considered. As a result, cardiac resynchronization pacemakers and ICDs typically use electrodes in the coronary venous system to allow left ventricular (LV) stimulation. Implantation of permanent pacing leads in the cardiac veins is the predominant method for chronic LV stimulation.233 Although epicardial LV pacing using standard myocardial leads remains an effective method for biventricular pacing for the treatment of congestive heart failure, it requires a more extensive operation than a transvenous approach. Transvenous stimulation of the left ventricle requires placement of the lead into a branch of the cardiac venous circulation, usually a posterolateral vein. The electrical properties of chronic stimulation of both the right and left ventricles are complex. The com­ plexity of dual ventricular stimulation has been reported in canine studies.234 The initial clinical approach to cardiac resynchronization therapy (CRT) involved the use of a pulse generator with an atrial output circuit and a single ventricular output circuit. Thus, a pacing stimulus could be delivered in a series configuration to the right ventricle as the anode and the left ventricle as the cathode (or vice versa). Such a configuration had the advantage of having very high impedance because both the anode and the cathode were small, tip electrodes of the RV and LV leads. This approach was limited by the inability to time RV and LV stimuli separately and the marked prolongation of the intracardiac electrogram, which resulted from recording both RV and LV activation during sensing. Such a configuration was not acceptable for ICDs because oversensing of both RV and LV activation occurred in the combined electrogram. The next configuration used clinically involved splitting the current between the RV and the LV electrodes in a shared-cathodal

33

configuration. This configuration was limited by reduced current density at both the RV and the LV tip electrode resulting from the parallel circuit design and inability to separate timing of RV and LV stimulation. In addition, the ventricular electrogram was a composite of RV and LV activation, leading to double counting when the interventricular conduction time was prolonged. Pacing impedance in the ventricular split, bipole configuration was much higher than for either electrode alone. The anode was programmable to be either the pulse generator casing (unipolar split-cathodal configuration) or the ring electrode on the RV lead (bipolar split-cathodal configuration). The magnitude of the current flowing to either ventricular electrode was determined by the impedance of the two leads. The apparent pacing threshold in the left ventricle was dramatically affected by this splitcathodal configuration. For example, Mayhew et al.125 found that, when the unipolar LV (coronary venous) threshold was measured using the coronary venous tip electrode as the cathode and the pulse generator casing as the anode, the mean threshold was 0.7 ± 0.5 V at 0.5-msec pulse duration. Splitting the cathode between the LV tip and the RV tip electrodes increased the apparent LV threshold to 1.0 ± 0.8 V. When the anode was changed from the pulse generator casing to the RV ring electrode, the apparent LV threshold further increased to 1.3 ± 0.9 V. Therefore, a split-cathodal configuration greatly increased the apparent pacing threshold, compared with pacing the coronary venous lead alone. A further observation with the split-cathodal pacing configuration is that the impedance measured with a PSA does not behave as predicted by the simple application of Ohm’s law. For example, when the bipolar pacing configuration was used with the RV ring electrode as the anode,125 the pacing impedance was measured to be 705 Ω in the right ventricle and 874 Ω in the left ventricle. Using a split-cathodal bipolar configuration, the measured impedance was 516 Ω, higher than would be predicted by Ohm’s law, with both ventricles stimulated in parallel (390 Ω). The higher-than-predicted impedance is explained by the size and shape of the combined cathodes being different from those for either electrode alone. The combined-cathodal configuration results in a Warburg resistance and capacitance. Combining electrodes of similar size essentially doubles the cathodal surface area. Because the electrode resistance of a hemispherical electrode is about proportional to the square root of the electrode surface area, doubling the size of the cathode by combining the RV and LV electrodes decreases the Warburg resistance by a factor of 1/ 2. This helps to explain why the measured impedance using a split-cathodal configuration is not halved, as would be predicted by doubling the size of electrodes joined in parallel. Combining electrodes in parallel also increases the voltage droop during a constant-voltage pulse. Coronary venous pacing leads tend to result in higher impedance compared with endocardial RV leads (based on a lower volume of blood surrounding the electrode), and this further tends to shunt current from the higher-impedance electrode to the lower-impedance electrode when both ventricles are stimulated in parallel. This factor serves to increase the apparent LV threshold with the split-cathodal configuration. Current CRT devices use separate RV and LV output circuits, with multiple options for programming the stimulation vector. Thus, the left ventricle can be stimulated by a single electrode in the cardiac venous system or in the bipolar configuration with two electrodes in the cardiac veins. In addition, the unipolar configuration can be used with a single electrode in the cardiac venous system and the oppositepolarity electrode being the RV ring, the pulse generator casing, or another, more proximal electrode of a quadripolar LV lead. The polarities of the LV electrodes can also be reversed. With these multiple options for pacing the left ventricle, the undesirable effects of the older, split-cathodal pacing configuration have been overcome in newer CRT devices. However, because of the additional output circuit, there is additional battery drain with these newer devices. Another feature of CRT devices involves the use of bipolar or even quadripolar cardiac venous leads. These leads differ from traditional right atrial or RV leads in that the surface area of the two cardiac venous electrodes is often similar. Therefore, when the leads are

34

SECTION 1  Basic Principles of Device Therapy

programmed to the bipolar pacing configuration, the impedance is much higher than with unipolar pacing, because current flows between two small electrodes rather than between one small and one large electrode. In addition, the bipolar pacing threshold (measured in volts) is often considerably higher than the unipolar configuration, because the current delivered with higher impedance is reduced. The important clinical advantage of multiple electrode LV pacing leads and independent output circuits with programmable polarity options is the much better chance of finding a cardiac venous site that offers a low stimulation threshold while minimizing the chances of phrenic nerve stimulation.

Automated Capture Features To ensure ventricular capture and allow programming of a low margin of safety, newer pacemakers use algorithms that automatically detect ventricular capture. Based on the measured stimulation threshold, the amplitude of the pacing stimulus is automatically adjusted to provide a programmed margin of safety. The Autocapture feature of St. Jude Medical (St. Paul, Minn.) pacemakers automatically adjusts the amplitude of the stimulation pulse by detecting capture in the ventricle from the evoked ventricular electrogram (the evoked response). The St. Jude pacemakers may use either a bipolar or a unipolar ventricular pacing lead with low polarization properties for the distal electrode. The presence or absence of ventricular capture is determined by sensing of the evoked response from the tip electrode. These devices automatically determine the evoked response gain and sensitivity levels by delivering five paired ventricular pulses of 4.5 V at a minimum pulse duration of 0.5 msec or the programmed value. The first of the paired pulses measures the evoked response, and the second pulse is delivered within 100 msec of the first (i.e., during physiologic refractory period of myocardium) to determine the level of polarization. If the evoked-response (ER) amplitude is greater than 2.5 mV, the measured lead polarization is less than 4.0 mV, and the ratio of the ER/ER sensitivity is greater than 1.8 : 1, the device will automatically determine that the safety margin is acceptable and recommend Autocapture as a programmed feature. The Autocapture feature uses unipolar pacing from the tip electrode and determines capture on a beat-to-beat basis. If a ventricular stimulus is not followed by a detectable evoked response, a second test pulse is given at a value 0.25 V greater than the last threshold measurement, known as the automatic pulse amplitude (APA). If a pulse is not followed by detectable capture, a backup pulse is delivered within 80 to 100 msec at an amplitude of 4.5 V. If two consecutive APA pulses are not followed by an evoked response, the threshold is measured to determine whether the APA needs adjustment. Specifically, the pulse is incremented 0.25 V above the last APA. If capture is not confirmed, the APA is repeated in 0.125-V increments until two consecutive captured events occur. For these devices, all lossof-capture pulses are immediately followed by a backup pulse. A potential complicating factor with detection of the evoked response is differentiating fusion from capture. In the DDD(R) pacing mode, precisely timed intrinsic conduction can result in false detection of loss of capture. To differentiate true loss of capture from fusion, the atrioventricular (AV) delay is incremented by 100 msec after two consecutive loss-of-capture events to search for intrinsic conduction. If intrinsic conduction is indeed present during this extension of the AV delay, the backup pulse is eliminated. On the other hand, if subsequent backup pulses or APA increments are required due to loss of capture, the paced or sensed AV delay is shortened to either 50 or 25 msec, respectively. This sequence can complicate the interpretation of electrocardiographic tracings with irregular AV delays. However, knowledge of the function of the Autocapture algorithm allows recognition that this is a normal phenomenon. Automatic capture algorithms have also been applied by most other manufacturers. The Sorin Group pacemakers (Milan, Italy) detect the evoked response on the tip electrode of a unipolar lead, provided that the polarization properties of the electrode are favorable. Boston Scientific pacemakers (Natick, Mass.) use a lower-capacitance output

capacitor to minimize the afterpotentials on the ventricular lead as a method for improving detection of the evoked response. The smalleroutput capacitor increases the droop of the pacing pulse, but the afterpotential is greatly reduced. The smaller-output capacitor may have the effect of slightly increasing the apparent stimulation threshold, an effect that is usually measurable only when the pacing threshold exceeds 2.5 V. Other manufacturers offer variants of the automatic capture algorithm that do not deliver backup pulses on a beat-to-beat basis but provide automatic determination of pacing threshold at programmed intervals during the day. These devices determine the pacing threshold and adjust the pacing amplitude to provide a programmed margin of safety. In general, automatic capture algorithms function quite effectively and may reduce the risk of loss of capture due to fluctuations in pacing threshold caused by drugs, metabolic derangement, or lead dislodgment. The capability for reducing the programmed margin of safety is effective for prolonging battery life and may reduce the frequency of clinic follow-up visits. The Medtronic Ventricular Capture Management feature determines a strength-duration threshold at a programmable interval (nominally, once per day). After the amplitude threshold is determined at a pulse duration of 0.4 msec, the pulse amplitude is doubled and a pulse duration threshold is measured. The permanent ventricular stimulation amplitude is then automatically reprogrammed using a programmable amplitude safety margin (usually twice the threshold) or a programmable minimum amplitude, whichever is higher. The nominal values for ventricular capture management are a safety margin of twice the threshold with a pulse duration of 0.4 msec and a minimum ventricular amplitude of 2.5 V. During measurement of the pacing threshold, each test pulse is followed by a backup pulse 110 msec later to ensure that a pacing pause does not occur. If the automatically measured ventricular stimulation threshold is greater than 2.5 V at 0.4 msec, the ventricular output is automatically programmed to 5.0 V and 1.0 msec. The Medtronic Atrial Capture Management feature is designed to periodically measure the atrial stimulation threshold and adapt the atrial output to a programmable amplitude safety margin. This feature does not use the evoked potential to determine the presence or absence of atrial capture. Rather, the pacemaker searches for evidence that atrial test pulses reset the sinus node (Atrial Chamber Reset Method) or observes the ventricular response to determine whether a captured atrial test pulse is conducted to the ventricles through the AV conduction system. The Atrial Capture Management feature performs an atrial amplitude threshold at 0.4-msec pulse duration and after loss of capture is detected (defined as two of three test pulses indicating loss of capture); the amplitude setting is increased until atrial capture is confirmed. Because this feature does not rely on detection of the evoked response, there is no restriction on the type of atrial lead that can be used. This feature will not measure thresholds if the sinus rate is consistently faster than 87 bpm.

Adequate Margin of Safety A pacemaker must be programmed with a safety factor that allows for changes in pacing threshold. The clinician needs to know how much thresholds actually change in the acute to chronic period, as well as chronically on an hour-to-hour and day-to-day basis. Settings as low as 2.5 V and 0.5 msec at implantation appear to ensure capture for most adult patients with modern microporous, steroid-eluting leads. Higher values should be used with older-technology leads. Some patients have large variations in threshold. The factors involved in estimating how great a margin of safety to allow in programming are the (1) presently measured threshold, (2) probability of a catastrophe if pacing ceases, (3) patient’s ability to recognize intermittent loss of capture if occurring, (4) pharmacologic milieu, and (5) frequency of pacing threshold monitoring. In most patients, a 1.5 : 1 or 2 : 1 ratio of output voltage (Vo) to threshold voltage (Vthr), or output current to threshold current, provides a reasonable safety factor. The balance over



LONG-TERM AND DIURNAL VARIATIONS IN PACING THRESHOLD McVenes et al.241 found no significant threshold changes in adult canines using then-modern chronic atrial or ventricular leads as a function of eating, sleeping, or exercise. This finding is supported by Kadish et al.,242 who found no changes in chronic human pacing thresholds during a 24-hour period in four of five patients studied. Although in one patient the threshold at 0.6 msec changed from 1 to 1.5 V between 3 and 6 pm, these investigators concluded that “ventricular pacing thresholds do not show substantial diurnal variability.”242 Grendahl and Schaanning243 also found minimal variation in pacing threshold during the day, after meals, or during sleeping or physical activity.184 Shepard et al.76 reviewed 4942 pacing threshold measurements in 257 patients with 312 non-steroid-eluting leads at up to 295 months after implantation. The median in-use time was 17 months. Of the measurements, 1053 were in children younger than 12 years. At stimulus durations of 0.5 ± 0.04 msec, for thresholds measured 1 month or more after implantation, the mean threshold was 1.2 ± 0.66 V for endocardial electrodes and 2.8 ± 1.39 V for epicardially applied electrodes. Highest mean thresholds were in the 6- to 12-year-old age group. In patients with five or more measurements after 3 months of use, an increase in pacing threshold occurred after 3 months in 24%. An additional 21% had at least one threshold that exceeded the post3-months individual patient mean by three standard deviations. Other clinical events possibly related to threshold increases included a doubling of the threshold in a child during two successive summers, when mild cold–like symptoms began. The effects of various drugs on thresholds have been reported, but neither the test protocols nor the results have been consistent.244 Therefore, minimal literature appears to support the statistical validity of any particular safety factor.

35

On the basis of the earlier report of Preston et al.,239 Barold et al.245 suggested that Vo/Vthr must be at least 1.75 to ensure an adequate safety margin, assuming a 50% increase in energy at threshold throughout the day. Ohm et al.177,246 studied threshold evolution as a function of implant duration for an 8-mm2 polished platinum ring electrode and found that this lead had a peak threshold of 2.2 ± 0.75 V at a pulse duration of 0.5 msec measured 2 weeks after implantation. Assuming an output setting of 5 V and 0.5-msec pulse duration, the average patient had a Vo/Vthr of 2.3 : 1 during the peak threshold time. The 98th percentile patient (mean ± 2 standard deviations) had a Vo of 5 V and a Vthr of 2.2 ± 0.75 V, or a safety margin of about 1.35 : 1 at peak threshold. Unpredictable or unusual situations (e.g., myxedema) may occur that justify greater safety factor ratios.247 The important clinical point is that, for patients who are always or intermittently dependent on pacing to stay alive, a much greater pacing safety factor reduces the risk of otherwise unexplained sudden death. PROGRAMMING VOLTAGE VERSUS PULSE WIDTH FOR MAXIMUM PULSE GENERATOR LONGEVITY A common clinical concern for programming of the pulse generator to optimize battery longevity relates to whether it is more useful to program the amplitude or the duration of the output pulse. Based on examination of the strength-duration relationship, it is more efficient to reduce the Vo of the pulse, because the current drain varies as the square of voltage. Figure 1-33 illustrates the effect of doubling the Vthr (at a constant pulse width) or tripling the threshold pulse width (without changing voltage) on current drain. In this example, the rheobase voltage was determined to be 1 V and the chronaxie duration was 0.3 msec. The stimulation threshold was 4 V at a pulse duration of 0.1 msec or 2 V at 0.3 msec. Tripling the pulse duration at 4 V to 0.3 msec provided an adequate (2 : 1) safety margin with a current of 8 mA per pulse (4.8 µA continuous current) and a stimulus energy of 9.6 µJ. Similarly, doubling the Vthr at a pulse duration of 0.3 msec from 2 to 4 V yielded an identical current drain (8 mA/pulse, or 4.8 µA) and safety factor. If the patient had a higher threshold, for example 2 V at 1 msec, doubling of the voltage or tripling of the pulse width would still give the same current drain (12 µA), but the safety factor would be significantly different. Tripling the pulse width would provide a marginal (at best) safety margin, because threshold is approaching rheobase on the flat portion of the strength-duration curve. It would be necessary to double the voltage in this case to ensure a 2 : 1 safety margin. The foremost consideration for programming voltage and pulse duration is patient safety.

22 20 18

Volts, µJ

years is that of safety factor beyond threshold versus how long the pulse generator can be used. Again, clinical factors and patient reliability in checking need to be considered. Children may experience a higher rate of exit block because of their active inflammatory responses. In all patients, but especially children, use of steroid-eluting electrodes is recommended whenever possible.235-237 In a study reporting on 4953 threshold measurements made up to 20 years after implantation, long-term thresholds and threshold variations of non-steroid-eluting electrodes were found to be greater in children than in adults.76 The safety factors provided during the peak threshold phase are highest for steroid-eluting porous electrodes and lower for (in descending order) microporous electrodes, porous electrodes, and polished-tip electrodes, based on data represented in Figure 1-29. There may also be situations in which the patient’s pacemaker must be set at the maximum output at implantation (e.g., if the patient will not be available for follow-up). In these cases, an acceptable balance of safety margin and battery longevity might be obtained with a setting of 2.5 V and 0.5 msec for a steroid-eluting electrode, or a setting of up to 5 V and 0.5 msec with other leads. These numbers are at best only general guides. It is much better to arrange, by whatever means possible, for actual follow-up threshold measurements, both acutely and chronically. Modern perception of the range of chronic circadian threshold variation is based mainly on the work of Sowton and Norman238 (mid1960s), Preston et al.239 (late 1960s), and Westerholm240 (1971). The first two studies used constant-current generators and reported thresholds in terms of energy. Because the computed energy “thresholds” could have been a reflection of changes in impedance, the actual variation in voltage threshold cannot be determined from these studies. Westerholm, who reported both voltage and energy data, noted substantial circadian variations in both parameters. In all these studies, the leads were primarily epicardial/myocardial with polished electrodes. These human data, however, may be of marginal relevance to modern constant-voltage generators and porous, steroid-eluting electrodes.

1  Cardiac Electrical Stimulation

Energy (2× voltage)

16 14 12

Energy (3× PW)

10 8

Energy (threshold)

6 4

Threshold (V)

2 0

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 PW (msec) Figure 1-33  Effect on current drain and safety margin of programming the stimulus voltage to twice the threshold (at a constant pulse duration) or programming the pulse width (PW) to three times the threshold value (at the threshold voltage). See text for discussion.

36

SECTION 1  Basic Principles of Device Therapy

Summary Myocardial stimulation is the fundamental principle underlying artificial cardiac pacing. Perhaps the most important concept for programming of an implantable pacing system is a thorough understanding of the strength-duration relationship. Pulse generators allow the clinician to program both the pulse amplitude (in volts) and the pulse duration (in milliseconds). The stimulation threshold is a function of both these parameters. The exponential shape of the strength-duration curve must always be considered when programming the output pulse to ensure an adequate margin of safety between the delivered stimulus and the capture threshold. For example, pulse durations of 1 msec and greater are located on the flat portion of the strength-duration curve, whereas pulse durations of less than 0.15 msec are on the steeply rising portion of the curve. The practical importance of these facts can be appreciated by considering two points on the strength-duration curve shown in Figure 1-9. If the clinician determines the threshold to occur at point A (2 V and 0.5 msec) by decrementing the stimulus voltage at a constant pulse duration, programming of the pulse duration to 1 msec (point B) would provide very little margin of safety. Similarly, if the threshold is measured to be at point C (3.5 V and 0.15 msec) by decrementing the pulse duration at a constant voltage, doubling of the stimulation voltage to 7 V (point D) also would provide a poor safety margin. When one considers the shape of the strength-duration curve, a more appropriate programmed setting would be provided by doubling the threshold voltage at a pulse duration of 0.5 msec (point E, 4 V and 0.5 msec). As a general rule, if the threshold is determined by decrementing the stimulus voltage, an adequate margin of safety can be assumed by doubling the voltage if the pulse duration used was greater than 0.3 msec. The two most important points on the strength-duration curve (rheobase and chronaxie) are easily estimated with modern pulse generators (see Fig. 1-8). Rheobase can be estimated by decrementing the output voltage at a pulse duration of 1.5 to 2 msec. Chronaxie can then be estimated by determining the threshold pulse duration at twice the rheobase voltage. If instead the threshold is determined by decrementing the pulse duration, an adequate safety margin can be assumed by tripling the pulse duration only if the threshold is 0.15 msec or less. If the rheobase and chronaxie are measured, doubling of the threshold voltage at the chronaxie pulse duration provides an excellent method for programming a pacing system. In most circumstances, however, experienced clinicians will measure the pacing threshold at an initial stimulus duration of 0.4 or 0.5 msec, then make decisions based on their knowledge of the patient’s problems and medications. What constitutes an adequate safety factor depends on knowledge of the patient’s status. How dependent on the pacemaker is the patient? How medically stable is the patient? What medicines that can influence the pacing threshold is this patient taking? Have important threshold variations been seen, or are they anticipated in this patient after the initial stabilization period? Are there problems with the leads? How old is the pulse generator, and what is the known history of this pulse generator and attached leads in other patients? These factors determine clinical judgments about voltage and current safety, frequency of pacing and medical status monitoring, and early or late replacement of the pulse generator and leads. When programming the pulse generator at implantation, the clinician must also consider the acute to chronic evolution of the stimulation threshold. Because an acute rise in threshold typically occurs during the first several weeks after lead implantation, voltage and pulse duration may need to be programmed to higher values than needed for chronic pacing. The physician should reevaluate the stimulation threshold after the acute rise (and sometimes subsequent fall). For

most patients, the pacing system can be programmed to chronic output settings at a follow-up evaluation about 6 weeks after lead implantation. Although these recommendations may not be as applicable to patients receiving a steroid-eluting lead, caution is still warranted. The importance of drug and electrolyte effects on the strengthduration curve should also be appreciated. For patients requiring antiarrhythmic therapy, the stimulation threshold should be measured a number of times after drug initiation to ensure an adequate margin of safety for pacing. Similarly, patients who are more likely to experience alterations in electrolyte concentration (e.g., patients with renal failure, patients taking potassium-wasting diuretics) may need their pace­ makers to be programmed with a greater margin of safety. Perhaps most important, the degree to which the heart depends on pacing to sustain life or to prevent severe symptoms must be factored into the choice of a programmed margin of safety. For pacemakerdependent patients, a pacing pulse at least 2.5 times the chronic capture threshold is usually recommended. In contrast, patients unlikely to experience severe symptoms should failure to capture occur may have their pacemaker programmed to a lower margin of safety, perhaps twice the threshold. The effect of pacing rate on the stimulation threshold should also be considered for patients who require antitachycardia pacing, with the pacing threshold measured at all rates likely to be used. In the presence of high impedance caused by lead fracture, the current output of a constant-voltage pulse generator decreases. Loss of capture can occur. If lead insulation failure occurs, the impedance as seen by the pulse generator may decrease because of current shunting to noncardiac tissue. This results in an increase in the current from the pulse generator without a change in the nominal output voltage. This change may not be detected early if threshold is determined only by the voltage required for pacing capture. Measuring the voltage/current ratio allows detection of the nominal impedance and alterations in lead insulation or in wire continuity. Because some wire fractures intermittently make and break contact, a normal impedance measurement does not always ensure that the lead is intact. Pacing impedance is determined by four factors: (1) resistance in the conductor wire pathways, (2) polarization at the electrode-tissue interfaces, (3) resistance (small geometric size for high resistance) at the electrode-tissue interface, and (4) impedance/resistance of the tissues between the electrodes. The first two factors are energy inefficient, decreasing the current available for stimulation, whereas the third factor decreases current drain without decreasing the efficiency of stimulation. An ideal electrode would have, among other attributes, high resistance and high capacitance (low polarization voltage) at the electrode-tissue interface. Pacing with a monophasic stimulus is more energy efficient than pacing with a bipolar stimulus. The pacing threshold is greater at normal stimulus durations for biphasic stimuli than uniphasic stimuli with the same total duration. For successful defibrillation, biphasic stimuli are more energy efficient. A biphasic stimulus with proper characteristics reduces the postpulse ion rearrangements. Biphasic stimuli also may reverse continuing local and undesirable chemical processes at the electrode.

Conclusion Electrical stimulation, not only of the heart but also of other types of tissue (e.g., brain), is being used clinically more and more. Increasing knowledge of fundamental factors in electrical stimulation and practical developments for particular clinical circumstances is ongoing. Such knowledge will help cardiologists, as well as physicians and surgeons of other disciplines, make good decisions and expand the range of patient care.



1  Cardiac Electrical Stimulation

37

REFERENCES 1. Huxley AH, Sir: Regarding Kenneth Stewart Cole, July 10, 1900-April 18, 1984. In Huxley AH, Sir: Biographical memoirs, Washington, DC, 1996, National Academies Press, pp 24-45. http://books.nap.edu/html/biomems/kcole.html. 2. Cole KS: Membranes, ions and impulses: a chapter of classical biophysics. Berkeley, 1968, University of California Press, pp 173, 204. 3. Koch H: Recent advances in magnetocardiography. J Electrocardiol 37(suppl):117-122, 2004. 4. Guyton AC, Hall JE: Transport of substances through the cell membrane. In: Guyton AC, Hall JE, editors. The textbook of medical physiology, Philadelphia: W.B. Saunders Company; 2005:40-51. 5. Antoni H: Electrical properties of the heart. In Reilly JP, editor: Applied bioelectricity: from electrical stimulation to electropathology, New York, 1998, Springer, pp 148-193. 6. Hodgkin AL, Katz B: The effect of sodium ions on the electrical activity of the giant axon of the squid. J Physiol (Lond) 108:37, 1949. 7. Hodgkin AL, Huxley AF: A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (Lond) 117:500-544, 1952. 8. Neher E, Sakmann B, Steinbach JH: The extracellular patch clamp: method for resolving currents through individual open channels in biological membranes. Plugers Arch Eur J Physiol 375:219, 1978. 9. Neher E, Sakmann B: The patch clamp technique. Sci Am 266: 44-51, 1992. 10. Ebihara L: The sodium current. In Rosen MR, Janse MJ, Wit AL, editors: Cardiac electrophysiology: a textbook, Mt Kisco, NY, 1990, Futura, pp 63-74. 11. Hartel HC, Duchatelle-Gourdon I: Structure and neural modulation of cardiac calcium channels. J Cardiovasc Electrophysiol 3:567-578, 1992. 12. Tsien RW: Calcium channels in the cardiovascular system. In Rosen MR, Janse MJ, Wit AL, editors: Cardiac electrophysiology: a textbook, Mt Kisco, NY, 1990, Futura, pp 75-89. 13. Thomas RC: Electrogenic sodium pump in nerve and muscle cells. Physiol Rev 52:563-594, 1972. 14. Glitsch HG: Electrogenic Na pumping in the heart. Annu Rev Physiol 44:389-400, 1982. 15. Gadsky DC: The Na/K pump of cardiac cells. Annu Rev Biophys Bioeng 13:373-398, 1984. 16. Mullins IJ: The generation of electric currents in cardiac fibers by Na/Ca exchange. Am J Physiol 236:C103-C110, 1979. 17. Hilgemann DW: Numerical approximations of sodium-calcium exchange. Prog Biophys Mol Biol 51:1-45, 1988. 18. Carmeliet E: The cardiac action potential. In Rosen MR, Janse MJ, Wit AL, editors: Cardiac electrophysiology: a textbook, Mt Kisco, NY, 1990, Futura, pp 55-62. 19. Hoffman BF, Cranefield PF: Electrophysiology of the heart. New York, 1960, McGraw-Hill. 20. Binah O: The transient outward current in the mammalian heart. In Rosen MR, Janse MJ, Wit AL, editors: Cardiac electrophysiology: a textbook, Mt Kisco, NY, 1990, Futura, pp 93-106. 21. Joho RH: Toward a molecular understanding of voltage-gated potassium channels. J Cardiovasc Electrophysiol 3:589-601, 1992. 22. Coraboeuf E, Carmeliet E: Existence of two transient outward currents in sheep cardiac Purkinje fibers. Pflugers Arch 392:352359, 1982. 23. Cohen IS, Datyner N: Repolarizing membrane currents. In Rosen MR, Janse MJ, Wit AL, editors: Cardiac electrophysiology: a textbook, Mt Kisco, NY, 1990, Futura, pp 107-116. 24. Bottazzi F: Leonardo as physiologist. In Bottazzi F: Leonardo da Vinci, London, 1964, Leisure Arts, pp 373-387. 25. Harvey W: De Motu Cordis. [The movement of the heart and blood]. Translated by D Whiteridge. Oxford, 1976 (1628), Blackwell. 26. Keith A, Flack M: The form and nature of the muscular connections between the primary divisions of the vertebrate heart. J Anat Physiol 41:172-189, 1907. 27. Irisawa H: Comparative physiology of the cardiac pacemaker mechanism. Physiol Rev 58:461-498, 1978. 28. DiFrancesco D: The hyperpolarization-activated current, If, and cardiac pacemaking. In Rosen, MR, Janse ML, Wit AL, editors: Cardiac electrophysiology: a textbook, Mt Kisco, NY, 1990, Futura, pp 117-132. 29. Urthaler F, Isobe JH, James TN: Comparative effects of glucagon on automaticity of the sinus node and atrioventricular junction. Am J Physiol 227:1415-1421, 1974. 30. Bean RC: Protein-mediated mechanisms of variable ion conductance in thin lipid membranes. Membranes 2:409-477, 1973. 31. Haydon DA, Hladky SB: Ion transport across thin lipid membranes: a critical discussion of mechanisms in selected systems. Q Rev Biophys 5:187-282, 1972. 32. Jongsma HJ, Rook MB: Biophysics of cardiac gap junction channels. In Zipes DP, Jalif J, editors: Cardiac electrophysiology: from cell to bedside, ed 3, Philadelphia, 2000, Saunders, pp 119-125. 33. Furman S, Parker B, Escher DJW: Decreasing electrode size and increasing efficiency of cardiac stimulation. J Surg Res 11:105, 1971. 34. Furman S, Hurzler P, Parker B: Clinical thresholds of endocardial cardiac stimulation: a long-term study. J Surg Res 19:149, 1975.

35. Angello DA, McAnulty JH, Dobbs J: Characterization of chronically implanted ventricular endocardial pacing leads. Am Heart J 107:1142-1145, 1984. 36. Geddes LA, Bourland JD: The strength-duration curve. IEEE Trans Biomed Eng 32:458-459, 1985. 37. Irnich W: Considerations in electrode design for permanent pacing. In Thalen HJT, editor: Cardiac Pacing, In Proceedings of the IVth International Symposium on Cardiac Pacing. Assen, The Netherlands, 1973, Van Gorcum, pp 268. 38. Irnich W: Engineering concepts of pacemaker electrodes. In Schaldach M, Furman S, editors: Advances in pacemaker technology, New York, 1975, Springer-Verlag, pp 241. 39. Shepard RB: Invited letter concerning: the effect of extraanatomic bypass on aortic root impedance in open chest dogs. Should the vascular prosthesis be compliant to unload the left ventricle? J Thorac Cardiovasc Surg 104:1175-1177, 1992. 40. Bardou AL, Chenais J-M, Birkui PJ, et al: Directional variability of stimulation threshold measurements in isolated guinea pig cardiomyocytes: relationship with orthogonal sequential defibrillating pulses. Pacing Clin Electrophysiol 13:1590-1595, 1990. 41. Preston TA, Fletcher RD, Lucchesi BR, Judge RD: Changes in myocardial thresholds: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235-242, 1967. 42. Katsumoto K, Niibori I, Takamatsu T, Kaibara M: Development of glassy carbon electrode (Dead Sea scroll) for low energy cardiac pacing. Pacing Clin Electrophysiol 9(6 pt 2):1220-1224, 1986. 43. Mond H, Stokes KB, Helland J, et al: The porous titanium steroid eluting electrode: a double blind study assessing the stimulation threshold effects of steroid. Pacing Clin Electrophysiol 11:214219, 1988. 44. Hill WE, Murray A, Bourks JP, et al: Minimum energy for cardiac pacing. Clin Phys Physiol Meas 9:41-46, 1988. 45. Breivik K, Ohm O-J, Engedal H: Acute and chronic pulse-width thresholds in solid versus porous tip electrodes. Pacing Clin Electrophysiol 5:650-657, 1982. 46. Irnich W: The chronaxie time and its practical importance. Pacing Clin Electrophysiol 3:292-301, 1980. 47. Barold SS, Stokes KB, Byrd CL, McVenes R: Energy parameters in cardiac pacing should be abandoned. Pacing Clin Electrophysiol 20:112-121, 1996. 48. Furman S, Hurzler P, Parker B: Clinical thresholds of endocardial cardiac stimulation: a long-term study. J Surg Res 19:149, 1975. 49. Ideker RE, Zhou X, Knisley SB: Correlation among fibrillation, defibrillation, and cardiac pacing. Pacing Clin Electrophysiol 18:512-525, 1995. 50. Roth BJ: Virtual electrodes made simple: a cellular excitable medium modified for strong electrical stimuli. Rochester, Mich, 2002, Department of Physics, Oakland University. http:// sprojects.mmi.mcgill.ca/heart/pages/rot/rothom.html. 51. Newton JC, Knisley SB: Review of mechanisms by which electrical stimulation alters the transmembrane potential. J Cardiovasc Electrophysiol 10:234-243, 1999. 52. Knisley SB: Transmembrane voltage changes during unipolar stimulation of rabbit ventricle. Circ Res 77:1229-1239, 1995. 53. Srinivasan R, Roth BJ: A mathematical model for electrical stimulation of a monolayer of cardiac cells. Biomed Eng Online 3:1, 2004. 54. Wikswo JP, Jr, Lin SF, Abbas RA: Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation. Biophys J 69:2195-2210, 1995. 55. Efimove IR, Gray RA, Roth BJ: Virtual electrodes and deexcitation: new insights into fibrillation induction and defibrillation. J Cardiovasc Electrophysiol 11:339-353, 2000. 56. Knisley SB, Pollard AE, Fast VG: Effects of electrode-myocardial separation on cardiac stimulation in conductive solution. J Cardiovasc Electrophysiol 11:1132-1143, 2000. 57. Knisley SB, Pollard AE: Effects of electrode-myocardial separation on cardiac stimulation in conductive solution. J Cardiovasc Electrophysiol 11:1132-1143, 2000. 58. Shepard RB, Epstein AE, Kirklin JK, et al: Use of epipericardial rate-sensing/pacing electrodes in defibrillator implantation (avoid intra-pericardial scarring pretransplantation). Pacing Clin Electrophysiol 15:575, 1992. 59. Nikolski VP, Sambelashvili AT: Mechanisms of make and break excitation revisited: paradoxical break excitation during diastolic stimulation. Am J Physiol Heart Circ Physiol 282:H565-H575, 2002. 60. Sambelashvili AT, Nikolski VP, Efimov IR: Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage. Am J Physiol Heart Circ Physiol 286:H2183H2194, 2004. 61. Roth BJ: A mathematical model of make and break electrical stimulation of cardiac tissue by a unipolar anode or cathode. IEEE Trans Biomed Eng 42:1174-1184, 1995. 62. Dressler L, Gruse G, von Knorre GH, et al: The optimization of the pulse delivered by the pacemaker. Pacing Clin Electrophysiol 2:282, 1979. 63. Chaptal AP, Ribot A: Statistical survey of strength-duration threshold curves with endocardial electrodes and long-term behavior of these electrodes. In Meere C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp, pp 21-22.

64. Blair HA: On the quantity of electricity and the energy in electrical stimulation. J Gen Physiol 19:951-964, 1936. 65. Geddes LA: Historical evolution of circuit models for the electrode-electrolyte interface. Ann Biomed Eng 25:1-14, 1997. 66. Hoorweg JL: Condensatorentladung und auseinandersetzung mit du Bois-Reymond. Pflugers Arch 52:87-108, 1892. 67. Weiss G: Sur la possibilité de render comparable entre les appareils cervant à l’excitation électrique. Arch Ital Biol 35:413, 1901. 68. Lapique L: Definition experimentale de l’excitabilité. C R Soc Bil 67:280, 1909. 69. Lapique L: La chronaxie et ses applications physiologiques. Paris, 1938, Hermann et Cie. 70. Irnich W: Elektrotherapie des herzens. Berlin, 1976, Fachverlag Schiele & Schon. 71. Irnich W: The chronaxie time and its practical importance. Pacing Clin Electrophysiol 3:292, 1980. 72. Bernstein AD, Parsonnet V: Implications of constant energy pacing. Pacing Clin Electrophysiol 6:1229-1233, 1983. 73. Barold SS, Stokes KB, Byrd CL, McVenes R: Energy parameters in cardiac pacing should be abandoned. Pacing Clin Electrophysiol 20:112-121, 1996. 74. Coates S, Thwaites B: The strength-duration curve and its importance in pacing efficiency. Pacing Clin Electrophysiol 23:1273-1277, 2000. 75. Gurjao de Goday CM, de Magalhaes Galvao K, de Almeida Bacarin T, Franco GR: The effects of electrode position on the excitability of rat atria during postnatal development. Physiol Meas 23:649-659, 2002. 76. Shepard RB, Kim J, Colvin EC, et al: Pacing threshold spikes months and years after implant. Pacing Clin Electrophysiol 14:1835-1841, 1991. 77. Wedensky NE: Uber die Beziehungzwischen Reizung und erregung im Tetanus. St Petersburg, 1887, Ber Akad Wiss, 54:96. 78. Langberg JJ, Sousa J, El-Atassi R, et al: The mechanism of pacing capture hysteresis in humans [abstract]. Pacing Clin Electrophysiol 15:577, 1992. 79. Swerdlow CD, Olson WH, O’Connor ME, et al: Cardiovascular collapse caused by electrocardiographically silent 60-Hz intracardiac leakage current. Circulation 99:2559-2564, 1999. 80. Hook BC, Perlman RL, Callans JD, et al: Acute and chronic cycle length dependent increase in ventricular pacing threshold. Pacing Clin Electrophysiol 15:1437-1444, 1992. 81. Plumb VJ, Karp RB, James TN, Waldo AL: Atrial excitability and conduction during rapid atrial pacing. Circulation 63:11401149, 1981. 82. Buxton AE, Marchlinski FE, Miller JM, et al: The human atrial strength-interval relation: Influence of cycle length and procainamide. Circulation 79:271-280, 1989. 83. Katsumoto K, Niibori T, Watanabe Y: Rate dependent threshold changes during atrial pacing: Clinical and experimental studies. Pacing Clin Electrophysiol 13:1009-1019, 1990. 84. Kay GN, Mulholland DH, Epstein AE, Plumb VJ: Effect of pacing rate on human atrial strength-duration curves. J Am Coll Cardiol 15:1618-1623, 1990. 85. Lindemans FW, Denier van der Gon JJ: Current thresholds and luminal size in excitation of heart muscle. Cardiovasc Res 12:477, 1977. 86. Irnich W, Gebhardt U: The pacemaker-electrode combination and its relationship to service life. In Thalen HJTh, editor: To pace or not to pace: controversial subjects in cardiac pacing, The Hague, 1978, Martin Nijhoff, pp 209. 87. Parsonnet V, Zucker IR, Kannerstein ML: The fate of permanent intracardiac electrodes. J Surg Res 6:285, 1966. 88. Thalen HJTh, Van den Berg JW: Threshold measurements and electrodes of the cardiac pacemaker. Acta Pharmacol Nederl 14:227, 1966. 89. Akyurekli Y, Taichman GC, White DL, et al: Myocardial responses to sutureless epicardial lead pacing. In Meere C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp. 90. Stokes K, Bornzin G: The electrode-biointerface (stimulation). In Barold SS, editor: Modern cardiac pacing, Mt Kisco, NY, 1985, Futura, pp 33-78. 91. Amundson DC, McArthur W, Moshaffafa M: The porous endocardial electrode. Pacing Clin Electrophysiol 2:40, 1979. 92. Stokes KB, Frohlig G, Bird T, et al: A new bipolar low threshold steroid eluting screw-in lead [abstract]. Eur J Card Pacing Electrophysiol 2:A89, 1992. 93. Greatbatch W: Metal electrodes in bioengineering. CRC Crit Rev Bioeng 5:1, 1981. 94. Horowitz P, Hill W: Section 1.18: Frequency analysis of reactive circuits. In Horowitz P, Hill W: The art of electronics, Cambridge, 1980, Cambridge University Press, pp 25-29. 95. Schmidt OH: Biological information processing using the concept of interpenetrating domains. In Leibovic KN, editor: Information processing in the nervous system, New York, 1969, Springer-Verlag, pp 325-331. 96. Geselowitz DB, Miller WT, 3rd: A bidomain model for anisotropic cardiac muscle. Ann Biomed Eng 11:191-206, 1983. 97. Sepulveda NG, Roth BJ, Wikswo JP, Jr: Current injection into a two-dimensional anisotropic bidomain. Biophys J 55:987-999, 1989.

38

SECTION 1  Basic Principles of Device Therapy

98. Ashihara T, Trayanova NA: Asymmetry in membrane responses to electric shocks: insights from bidomain simulations. Biophys J 87:2271-2282, 2004. 99. Roth BJ: The bidomain model: two dimensional propagation in cardiac muscle. In Zipes DP, Jalife J, editors: Cardiac electrophysiology: from cell to bedside, ed 3, Philadelphia, 2000, Saunders, pp 268-270. 100. Plonsey R, Barr RC: Inclusion of junction elements in a linear cardiac model through secondary sources: application to defibrillation. Med Biol Eng Comput 24:137-144, 1986. 101. Roth BJ, Krassowska W: The induction of reentry in cardiac tissue: the missing link—how electric fields alter the transmembrane potential. Chaos 8:204-220, 1998. 102. Sharma V, Tung T: Theoretical and experimental study of sawtooth effect in isolated cardiac cell-pairs. J Cardiovasc Electrophysiol 12:1164-1173, 2001. 103. Sharma V, Tung L: Spatial heterogeneity of transmembrane potential responses of single guinea-pig cardiac cells during electric field stimulation. J Physiol 542:477-492, 2002. 104. Irnich W: The fundamental law of electrostimulation and its application to defibrillation. Pacing Clin Electrophysiol 13(11 pt 1):1433-1447, 1990. 105. Irnich W: George Weiss’ fundamental law of electrostimulation is 100 years old. Pacing Clin Electrophysiol 25:245-248, 2002. 106. Thakor NV, Ranjan MS, Rajasekhar MS, et al. Effect of varying pacing waveform shapes on propagation and hemodynamics in the rabbit heart. Am J Cardiol 79:36-43, 1997. 107. Huang J, Ken-Knight BH, Walcott GP, et al: Effects of transvenous electrode polarity and waveform duration on the relationship between defibrillation threshold and upper limit of vulnerability. Circulation 96:1351-1359, 1997. 108. Wagner B: Electrodes, leads, and biocompatibility. In Webster J, editor: Design of cardiac pacemakers, Piscataway, NJ, 1995, IEEE Press, pp 138. 109. Moor WJ: Physical chemistry. Englewood Cliffs, NJ, 1972, Prentice-Hall, pp 510. 110. Von Helmholtz H: The modern development of Faraday’s conception of electricity, delivered before the Fellows of the Chemical Society in London on April 5, 1881. 111. Bockris JO’M, Reddy AKN, Gamboa-Aldeco M: Modern electrochemistry 2A: fundamentals of electrodics, ed 2. New York, 2000, Kluwer Academic/Plenum, pp 885. 112. Bockris JO’M, Reddy AKN, Gamboa-Aldeco M: Modern electrochemistry 2A: fundamentals of electrodics, ed 2. New York, 2000, Kluwer Academic/Plenum, pp 1047-1049, 1122-1123. 113. Faraday M: On electrical decomposition. Philosoph Trans R Soc, 1834. 114. Bockris JO’M, Reddy AKN, Gamboa-Aldeco M: Modern electrochemistry 2A: fundamentals of electrodics, ed 2. New York, 2000, Kluwer Academic/Plenum, pp 771-1033. 115. Bockris JO’M, Reddy AKN, Gamboa-Aldeco M: Modern electrochemistry 2A: fundamentals of electrodics, ed 2. New York, 2000, Kluwer Academic/Plenum, pp 873-882. 116. Ragheb T, Geddes LA: Electrical properties of metallic electrodes. Biol Eng Comput 28:182-186, 1990. 117. Wagner B: Electrodes, leads, and biocompatibility. In Webster J, editor: Design of cardiac pacemakers, Piscataway, NJ, 1995, IEEE Press, pp 138. 118. Lilly JC, Hughes JR, Ellsworth CA, et al: Noninjurious electric waveform for stimulation of the brain. Science 121:468, 1955. 119. Bockris JO’M, Reddy AKN, Gamboa-Aldeco M: Modern electrochemistry 2A: fundamentals of electrodics, ed 2. New York, 2000, Kluwer Academic/Plenum, pp 1455. 120. Recognizing a Warburg impedance: Research Solutions & Resources (Dr Bob Rodgers). http://www.consultrsr.com/ resources/eis/warburg1.htm. 121. Bockris JO’M, Reddy AKN, Gamboa-Aldeco M: Modern electrochemistry 2A: fundamentals of electrodics, ed 2. New York, 2000, Kluwer Academic/Plenum, pp 1133. 122. Ovadia M, Zavitz DH: Impedance spectroscopy of the electrodetissue interface of living heart with isoosmotic conductivity perturbation. Chem Phys Lett 390:445-453, 2004. 123. Rodman JE: Solution, surface and solid state assembly of porphyrins [PhD thesis]. Cambridge, 2000, University of Cambridge, Fig 4.6. 124. Rho RW, Patel VV, Gerstenfeld EP, et al: Elevations in ventricular pacing threshold with the use of the Y adapter: implications for biventricular pacing. Pacing Clin Electrophysiol 26:747-751, 2003. 125. Mayhew M, Johnson P, Slabaugh J, et al: Electrical characteristics of a split cathodal pacing configuration. Pacing Clin Electrophysiol 26:2264-2271, 2003. 126. Krassowska W, Neu JC: Response of a single cell to an external electric field. Biophys J 66:1768-1776, 1994. 127. Lu C-C, Kabakov A, Maarkin V: Membrane transport mechanisms probed by capacitance measurements with megahertz voltage clamp. Proc Natl Acad Sci USA 92:11220-11224, 1995. 128. Mehra R, Furman S: Comparison of cathodal, anodal, and bipolar strength-interval curves with temporary and permanent pacing electrodes. Br Heart J 41:468-476, 1979. 129. Kay GN: Basic aspects of cardiac pacing. In Ellenbogen KA, editor: Cardiac Pacing, Cambridge, MA, 1992, Blackwell Scientific. 130. Preston TA: Anodal stimulation as a cause of pacemakerinduced ventricular fibrillation. Am Heart J 86:366-372, 1973. 131. Bilitch M, Cosby RS, Cafferry EA: Ventricular fibrillation and competitive pacing. N Engl J Med 276:598-604, 1967.

132. Stokes K, Bird T, Taepke R: A new low threshold, high impedance microelectrode. In Antonioli GE, Reufeut AE, Ector H, editors: Pacemaker leads, Amsterdam, 1991, Elsevier, pp 543-548. 133. Bird T, Stokes KB: Ventricular electrode spacing and anode size [abstract 205]. Rev Eur Technol Biomed 3:63, 1990. 134. De Caprio V: Endocardial electrograms from transvenous pacemaker electrodes [PhD thesis in biomedical engineering]. 1977, Polytechnic Institute of New York. 135. Garberoglio B, Inguaggiato B, Chinaglia B, Cerise O: Initial results with an activated pyrolytic carbon tip electrode. Pacing Clin Electrophysiol 6:440, 1982. 136. Jones JL, Jones RE, Balasky G: Improved cardiac cell excitation with symmetrical biphasic defibrillation waveforms. Am J Physiol 253:H1418-H1424, 1987. 137. Knisley SB, Smith WM, Ideker RE: Effect of intrastimulus polarity reversal on electric field stimulation thresholds in frog and rabbit myocardium. J Cardiovasc Electrophysiol 3:239-254, 1992. 138. Tse HF, Lau CP, Leung SK, et al: Single lead DDD system: a comparative evaluation of unipolar, bipolar and overlapping biphasic stimulation and the effects of right atrial floating electrode location on atrial pacing and sensing thresholds. Pacing Clin Electrophysiol 19:1758-1763, 1996. 139. Izquierdo R, Rodrigo G, Pelegrin J, et al: Single lead DDD pacing using electrodes with longitudinal and diagonal atrial floating dipoles. Pacing Clin Electrophysiol 25:1692-1698, 2002. 140. Ripart A, Fletcher R: Sensing. In Ellenbogen KA, Kay GN, Wilkoff B, editors: Clinical cardiac pacing, Philadelphia, 1992, Saunders. 141. Barold SS, Ong LS, Heinle RA: Stimulation and sensing thresholds for cardiac pacing: Electrophysiologic and technical aspects. Prog Cardiovasc Dis 24:1, 1981. 142. Barold SS, Ong LS, Heinle RA: Stimulation and sensing thresholds for cardiac pacing: electrophysiologic and technical aspects. Prog Cardiovasc Dis 24:1, 1981. 143. Smyth NPD, Tarjan PP, Chernoff E, et al: The significance of electrode surface area and stimulating thresholds in permanent cardiac pacing. J Thorac Cardiovasc Surg 71:559, 1976. 144. Parsonnet V, Zucker IR, Kannerstein ML: The fate of permanent intracardiac electrodes. J Surg Res 6:285, 1966. 145. Thalen HJT, Van den Berg JW: Threshold measurements and electrodes of the cardiac pacemaker. Acta Pharmacol Nederl 14:227, 1966. 146. Akyurekli Y, Taichman GC, White DL, et al: Myocardial responses to sutureless epicardial lead pacing. In Meere C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp. 147. Furman S, Hurzler P, Parker B: Clinical thresholds of endocardial cardiac stimulation: a long-term study. J Surg Res 19:149, 1975. 148. Wilson GJ, MacGregor DC, Bobyn JD, et al: Tissue response to porous-surface electrodes: basis for a new atrial lead design. In Moore C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp. 149. Amundson D, McArthur W, MacCarter D, et al: Porous electrode-tissue interface. In Moore C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Monstreal, 1979, PaceSymp. 150. Amundson DC, McArthur W, Moshaffafa M: The porous endocardial electrode. Pacing Clin Electrophysiol 2:40, 1979. 151. MacGregor DC, Wilson GJ, Lixfeld W, et al: The porous surface electrode: a new concept in pacemaker lead design. J Thorac Cardiovasc Surg 78:281, 1979. 152. Breivik K, Ohm O-J, Engedahl H: Acute and chronic pulse-width thresholds in solid versus porous tip electrodes. Pacing Clin Electrophysiol 5:650, 1982. 153. Berman ND, Dickson SE, Lipton IM: Acute and chronic clinical performance comparison of porous and solid electrode design. Pacing Clin Electrophysiol 5:67, 1982. 154. Freud GE, Chinaglia B: Sintered platinum for cardiac pacing. Int J Artif Organs 4:238, 1981. 155. MacCarter DM, Lundberg KM, Corstjens JP: Porous electrodes: concept, technology and results. Pacing Clin Electrophysiol 6:427, 1983. 156. MacGregor DC, Pilliar RM, Wilson GJ, et al: Porous metal surfaces: a radical new concept in prosthetic heart valve design. Trans Am Soc Artif Intern Organs 22:646, 1976. 157. Elmqvist H, Schuller H, Richter G: The carbon tip electrode. Pacing Clin Electrophysiol 6:436, 1983. 158. Stokes KB, Bornzin G: The electrode-biointerface (stimulation). In Barold SS, editor: Modern cardiac pacing, Mt Kisco, NY, 1985, Futura, pp 33-78. 159. Cornacchia O, Maresta A, Nigro P, et al: Effect of propafenone on chronic ventricular pacing threshold in patients with steroideluting (capture) and conventional leads. Eur J Card Pacing Electrophysiol 2:A88, 1992. 160. Pearce JA, Bourland JD, Neilsen W, et al: Myocardial stimulation with ultrashort duration current pulses. Pacing Clin Electrophysiol 5:52-58, 1982. 161. Meyers GH, Parsonnet V: Engineering in the heart and blood vessels. New York, 1989, Wiley-Interscience. 162. Hurzeler P, Furman S, Escher DJW: Cardiac pacemaker current thresholds versus pulse duration. In Silverman HT, Miller IF, Salkind AJ, editors: Electrochemical bioscience and bioengineering, Princeton, NJ, 1973, Electrochemical Society, pp 124. 163. Barold SS, Winner JA: Techniques and significance of threshold measurement for cardiac pacing. Chest 70:760, 1976. 164. Brownlee WC, Hirst R: Six years experience with atrial leads. Pacing Clin Electrophysiol 9(6 pt 2):1239-1242, 1989.

165. Luceri RM, Furman S, Hurzeler P, et al: Threshold behavior of electrodes in long-term ventricular pacing. Am J Cardiol 40:184, 1977. 166. Bornzin GA, Stokes KB, Wiebusch WA: A low-threshold, lowpolarization platinized endocardial electrode [abstract]. Pacing Clin Electrophysiol 6:A-70, 1983. 167. Elmqvist H, Schuller H, Richter G: The carbon tip electrode. Pacing Clin Electrophysiol 6:436, 1983. 168. Mond H, Stokes KB: The electrode-tissue interface: the revolutionary role of steroid elution. Pacing Clin Electrophysiol 15:95107, 1992. 169. Ohm O-J, Breivik K: Pacing leads. In Gomez FP, editor: Cardiac pacing, electrophysiology, tachyarrhythmias, Madrid, 1985, Editorial Group, pp 971-985. 170. Hoff PI, Breivik K, Tronstad A, et al: A new steroid-eluting electrode for low-threshold pacing. In Gomez FP, editor: Cardiac pacing, electrophysiology, tachyarrhythmias, Mt Kisco, NY, 1985, Futura, pp 1014-1019. 171. Anderson JM: Inflammatory response to implants. ASAIO Trans 34:101-107, 1988. 172. Henson PM: Mechanisms of exocytosis in phagocytic inflammatory cells. Am J Pathol 101:494-514, 1980. 173. Robinson TF, Cohen-Gould L, Factor SM: Skeletal framework of mammalian heart muscle: arrangement of inter- and pericellular connective tissue structures. Lab Invest 29:482-498, 1983. 174. Preston TA, Judge RD: Alteration of pacemaker threshold by drug and physiologic factors. Ann NY Acad Sci 167:686-692, 1969. 175. Stokes KB, Anderson J: Low threshold leads: the effect of steroid elution. In Antonioli GE, editor: Pacemaker leads, Amsterdam, 1991, Elsevier, pp 537-542. 176. Sibille Y, Reynolds HY: Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis 141:471-502, 1990. 177. Benditt DG, Kriett JS, Ryberg C, et al: Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes. Int J Cardiol 22:67-73, 1989. 178. Stokes KB, Kriett JM, Gornick CA, et al: Low-threshold cardiac pacing electrodes. In Frontiers of Engineering in Health Care: Proceedings of the Fifth Annual Conference IEEE Engineering in Medicine and Biology Society, 1983. 179. Irnich W: Considerations in electrode design for permanent pacing. In Thalen HJT, editor: Proceedings of the IVth International Symposium on Cardiac Pacing, Assen, The Netherlands, 1973, Van Gorcum, pp 268. 180. Irnich W: Engineering concepts of pacemaker electrodes. In Schaldach M, Furman S, editors: Advances in pacemaker technology, New York, 1975, Springer-Verlag, pp 241. 181. Mond H, Sloman JG, Cowling R, et al: The small tined pacemaker lead: absence of displacement. In Meere C, editor: Proceedings of the VI World Symposium on Cardiac Pacing, Montreal, 1979, PaceSymp, pp 29-35. 182. Baker JH, Shepard RB, Plimb VJ, Kay GN: Effects of fixation mechanism and electrode material on atrial stimulation threshold: long-term evaluation in 338 patients [abstract]. Pacing Clin Electrophysiol 15:54, 1992. 183. Cornacchia D, Jacopi F, Fabbri M, et al: Comparison between active screw-in and passive leads for permanent transvenous ventricular pacing [abstract]. Pacing Clin Electrophysiol 6:A56, 1983. 184. EI Gamal M, Van Gelder L, Bonnier J, et al: Comparison of transvenous atrial electrodes employing active (helicoidal) and passive (tined J-lead) fixation in 116 patients [abstract]. Pacing Clin Electrophysiol E 6:205, 1983. 185. Kay GN, Anderson K, Epstein AE, Plumb VJ: Active fixation atrial leads: randomized comparison of two lead designs. Pacing Clin Electrophysiol 12:1355-1361, 1989. 186. Rasor NS, Spickler JW, Clabaugh JW: Comparison of power sources for advanced pacemaker applications. In Proceedings of the 7th Intersociety Energy Conversion Engineering Conference, Washington, DC, 1972, American Chemical Society, p 752. 187. Hirshorn MS, Holley LK, Hales JR, et al: Screening of solid and porous materials for pacemaker electrodes. Pacing Clin Electrophysiol 4:380, 1981. 188. Schaldah M: New pacemaker electrodes. Trans Am Soc Artif Intern Organs 17:29, 1971. 189. Helland J, Stokes KB: Nonfibrosing cardiac pacing electrode. US Patent No 4033357. February 17, 1976. 190. Elmqvist H, Schuller H, Richter G: The carbon tip electrode. Pacing Clin Electrophysiol 6:436, 1983. 191. Thuesen L, Jensen PJ, Vejby-Christensen H, et al: Lower chronic stimulation threshold in the carbon-tip than in the platinum-tip endocardial electrode: a randomized study. Pacing Clin Electrophysiol 12:1592-1599, 1989. 192. Bornzin GA, Stokes KB, Wiebush WA: A low threshold, low polarization, platonized endocardial electrode. Pacing Clin Electrophysiol 6:A70, 1983. 193. Mugica J, Duconge B, Henry L, et al: Clinical experience with new leads. Pacing Clin Electrophysiol 11:1745-1752, 1988. 194. Djordjevic M, Stojanov P, Velimirovic D, et al: Target lead-low threshold electrode. Pacing Clin Electrophysiol 9:1206-1210, 1986. 195. Amundson DC, McArthur W, Moshaffafa M: The porous endocardial electrode. Pacing Clin Electrophysiol 2:40, 1979. 196. Timmis GC, Helland J, Westveer DC, et al: The evolution of low threshold leads. Clin Prog Pacing Electrophysiol 1:313, 1983.



197. Berman ND, Dickson SE, Lipton IM: Acute and chronic clinical performance comparison of porous and solid electrode design. Pacing Clin Electrophysiol 5:67, 1982. 198. Freud GE, Chinaglia B: Sintered platinum for cardiac pacing. Int J Artif Organs 4:238, 1981. 199. Kay GN, Anderson K, Epstein AE, Plumb VJ: Active fixation atrial leads: randomized comparison of two lead designs. Pacing Clin Electrophysiol 12:1355-1361, 1989. 200. Stokes KB: Preliminary studies on a new steroid eluting epicardial electrode. Pacing Clin Electrophysiol 11:1797-1803, 1988. 201. Hamilton R, Gow R, Bahoric B, et al: Steroid-eluting epicardial leads in pediatrics: improve epicardial thresholds in the first year. Pacing Clin Electrophysiol 14:2066, 1991. 202. Stokes KB, Frohling G, Bird T, et al: A new bipolar low threshold steroid eluting screw-in lead. Eur J Card Pacing Electrophysiol 2:A89, 1992. 203. Schwaab B, Frohling G, Schwerdt H, et al: Long-term follow-up of a bipolar steroid eluting pacing lead with active and passive fixation. In Antoniolo GE, editor: Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 361-364. 204. Schwaab B, Frohling G, Schwerdt H, et al: Long-term follow-up of three microporous active fixation leads in atrial position. In Antoniolo GE, editor: Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 365-368. 205. Schwaab B, Frohling G, Schwerdt H, et al: Atrial and ventricular pacing characteristics of a steroid eluting screw-in lead. In Antoniolo GE, editor. Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 383-388. 206. Menozzi C: Comparison between latest generation steroideluting screw-in and tined leads: Long term follow-up. In Antoniolo GE, editor: Pacemaker leads 1997, Bologna, 1997, Monduzzi Editore, pp 389-394. 207. Nurnberg JH, Schopper H, Busscher U, et al: Retrospective comparison of epicardial steroid-eluting and conventional leads for pacing after corrective surgery in congenital heart disease. Pacing Clin Electrophysiol 20:1193, 1997. 208. Wallace AG, Cline RE, Sealy WC, et al: Electrophysiologic effects of quinidine. Circ Res 19:960-969, 1966. 209. Gay RJ, Brown DF: Pacemaker failure due to procainamide toxicity. Am J Cardiol 34:728-731, 1974. 210. Moss AJ, Goldstein S: Clinical and pharmacological factors associated with pacemaker latency and incomplete pacemaker capture. Br Heart J 31:112, 1969. 211. Hellestrand KJ, Burnett PJ, Milne JR, et al: Effect of the anti­ arrhythmic agent flecainide acetate on acute and chronic pacing thresholds. Pacing Clin Electrophysiol 6:892, 1983. 212. Salel AF, Seagren SC, Pool PE: Effects on encainide on the function of implanted pacemakers. Pacing Clin Electrophysiol 12:1439, 1989. 213. Montefoschi N, Boccadamo R: Propafenone induced acute variation of chronic atrial pacing threshold: a case report. Pacing Clin Electrophysiol 13:480-483, 1990. 214. Huang SK, Hedberg PS, Marcus FI: Effects of antiarrhythmic drugs on the chronic pacing threshold and the endocardial R

1  Cardiac Electrical Stimulation wave amplitude in the conscious dog. Pacing Clin Electrophysiol 9:660, 1986. 215. Bianconi L, Boccadamo R, Toscano S, et al: Effects of oral propafenone therapy on chronic myocardial pacing threshold. Pacing Clin Electrophysiol 15:148-154, 1992. 216. Kubler W, Sowton E: Influence of beta-blockade on myocardial threshold in patients with pacemakers. Lancet 2:67, 1970. 217. Irnich W, Gebhardt U: The pacemaker-electrode combination and its relationship to service life. In Thalen HJT, editor: To pace or not to pace: controversial subjects in cardiac pacing, The Hague, 1978, Martin Nijhoff, pp 209. 218. Gay RJ, Brown DF: Pacemaker failure due to procainamide toxicity. Am J Cardiol 34:728-731, 1974. 219. Preston TA, Fletcher RD, Lucchesi BR, Judge RD: Changes in myocardial threshold: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235, 1967. 220. Khastgir T, Lattuca J, Aarons D, et al: Ventricular pacing threshold and time to capture postdefibrillation in patients undergoing implantable cardioverter-defibrillator implantation. Pacing Clin Electrophysiol 14:768-772, 1991. 221. Delmar M: Role of potassium currents on cell excitability in cardiac ventricular myocytes. J Cardiovasc Electrophysiol 3:474486, 1992. 222. Gettes LS, Shabetai R, Downs TA, et al: Effect of changes in potassium and calcium concentrations on diastolic threshold and strength-interval relationships of the human heart. Ann NY Acad Sci 167:693-705, 1969. 223. Lee D, Greenspan K, Edmands RE, et al: The effect of electrolyte alteration on stimulus requirement of cardiac pacemakers. Circulation 38:124, 1968. 224. Walker WJ, Elkins JT, Wood LW, et al: Effect of potassium in restoring myocardial response to a subthreshold cardiac pacemaker. N Engl J Med 271:597, 1964. 225. Surawicz B, Chelbus H, Reeves JT, et al: Increase of ventricular excitability threshold by hyperpotassemia. JAMA 191:71-76, 1965. 226. Westerholm CJ: Threshold studies in transvenous cardiac pacemaker treatment. Scand J Thorac Cardiovasc Surg 8(suppl):1, 1971. 227. Schlesinger Z, Rosenberg T, Stryjer D, et al: Exit block in myxedema, treated effectively by thyroid hormone replacement. Pacing Clin Electrophysiol 3:737-739, 1980. 228. Basu D, Chatterjee K: Unusually high pacemaker threshold in severe myedema: decrease with thyroid hormone therapy. Chest 70:677-679, 1976. 229. Nagatomo Y, Ogawa T, Kumagae H, et al: Pacing failure due to markedly increased stimulation threshold 2 years after implantation: successful management with oral prednisolone—a case report. Pacing Clin Electrophysiol 12:1034-1037, 1989. 230. Haywood J, Wyman MG: Effects of isoproterenol, ephedrine, and potassium on artificial pacemaker failure. Circulation 32(suppl II):110, 1965. 231. Katz A, Knilans TK, Evans JJ, Prystowsky EN: The effects of isoproterenol on excitability, supranormal excitability and

39

conduction in the human ventricle [abstract]. Pacing Clin Electrophysiol 14:710, 1991. 232. Levick CE, Mizgala HF, Kerr CR: Failure to pace following high dose anti-arrhythmic therapy: reversal with isoproterenol. Pacing Clin Electrophysiol 7:252-256, 1984. 233. Daubert C, Ritter P, Cazeau S, et al: Permanent biventricular pacing in dilated cardiomyopathy: Is a totally endocardial approach technically feasible? Pacing Clin Electrophysiol 19:699, 1996. 234. McVenes R, Stokes K: Alternative pacing sites: how the modern technology deals with this new challenge. In Antonioli GE, editor. Pacemaker leads 1997, Bologna, 1997, Monduzi Editore, pp 223-228. 235. Hurzeler P, Furman S, Escher DJW: Cardiac pacemaker current thresholds versus pulse duration. In Silverman HT, Miller IF, Salkind AJ, editors: Electrochemical bioscience and bioengineering, Princeton, NJ, 1973, Electrochemical Society, pp 124. 236. Stokes KB, Church T: The elimination of exit block as a pacing complication using a transvenous steroid-eluting lead. Pacing Clin Electrophysiol 10:748, 1987. 237. Till JA, Jones S, Rowland E, et al: Clinical experience with a steroid eluting lead in children [abstract]. Circulation 80:389, 1989. 238. Sowton E, Norman J: Variations in cardiac stimulation thresholds in patients with pacing electrodes. In Digest of the 7th International Conference on Medical and Biological Engineering, 1967, Stockholm. 239. Preston TA, Fletcher RD, Luchesi BR, et al: Changes in myocardial threshold: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235-242, 1967. 240. Westerholm C-J: Threshold studies in transvenous cardiac pacemaker treatment. Scand J Thorac Surg Suppl 8(suppl):1-35, 1971. 241. McVenes R, Lahtinen S, Hansen N, Stokes K: Physiologic and drug induced changes in cardiac pacing and sensing parameters [abstract 324]. Eur J Card Pacing Electrophysiol 2:A86, 1992. 242. Kadish A, Kong T, Goldberger J: Diurnal variability in ventricular stimulation threshold and electrogram amplitude [abstract]. Eur J Card Pacing Electrophysiol 2:A86, 1992. 243. Grendahl H, Schaanning CG: Variations in pacing threshold. Acta Med Scand 187:75-78, 1970. 244. Barold S: Effect of drugs on pacing thresholds. In Antonioli GE, Aubert AE, Ector H, editors: Pacemaker leads 1991, New York, 1991, Elsevier, pp 73-86. 245. Barold SS, Ong LS, Heinle RA. Stimulation and sensing thresholds for cardiac pacing: Electrophysiologic and technical aspects. Prog Cardiovasc Dis 24:1, 1981. 246. Ohm O-J, Breivik K: Pacing leads. In Gomez FP, editor: Cardiac pacing, electrophysiology, tachyarrhythmias, Madrid, 1985, Editorial Group, pp 971-985. 247. Basu D, Chatterjee K: Unusually high pacemaker threshold in severe myedema: decrease with thyroid hormone therapy. Chest 70:677-679, 1976.

40

2 

SECTION 1  Basic Principles of Device Therapy

Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms GREGORY P. WALCOTT  |  STEVEN M. POGWIZD  |  RAYMOND E. IDEKER

E

lectrical defibrillation is the only practical means for halting ventricular fibrillation (VF). Although it has been known for more than a century that application of an electric shock directly to the myocardium causes VF, and that the heart can be returned to normal rhythm by subsequent application of a shock of greater magnitude,1-3 knowledge of the mechanisms underlying the process of defibrillation was slow in developing. Only the introduction of novel techniques for the analysis of action potentials and activation sequences has allowed greater insight into the physiology of both fibrillation and defibrillation.4-8 It is hoped that this insight will result in a higher success rate for external defibrillation and improved design of implantable cardioverter-defibrillators (ICDs). A large part of current research is dedicated to determining the underlying reason for the success or failure of a defibrillating shock. VF is maintained by multiple activation fronts that are constantly moving in a pattern of reentry. Characteristics of the activation pattern and action potential are believed to be important determinants of whether a shock will successfully defibrillate the heart. A successful defibrillating shock is believed to extinguish most of these activation fronts, permitting the resumption of coordinated responsiveness.9-13 For the defibrillating shock to be completely successful, this must be accomplished without creating an environment that promotes susceptibility to reinitiation of fibrillation.9,10 It has been established that successful defibrillation requires that the shock results in adequate distribution of the potential gradient (a surrogate for local current flow) throughout the ventricular myocardium.14-16 Fundamentally, defibrillation is believed to be realized through an electrical pulse that causes an alteration in the transmembrane potential of myocytes. It most likely requires a rapid induction of changes in the transmembrane potential of the myocytes in a critical mass of myocardium (75%-90% of myocardium in dogs).13,14,16 Because this represents a large mass of tissue, depolarization must be achieved at a considerable distance from the stimulating electrode. To gain an understanding of this complex far-field process, various mathematical models have been generated and predictions of computer simulations compared with physiologic findings. Both discontinuities in the anisotropic properties of the extracellular and intracellular domains, as described by the bidomain model,17,18 and highly resistive discontinuities in the intracellular space (e.g., collagenous septa), as described in the secondary source model,19-21 may contribute to the far-field changes in the potential gradient that halt the activation fronts of fibrillation; these are discussed later. The mechanisms underlying degeneration into fibrillation in failed shocks remain incompletely understood. Residual wandering wavelets,22 nonuniform refractoriness,23 and areas of low potential gradient, in which critical points (centers of reentrant circuits) form,15 may be the sources of propagating wavefronts that can result in fibrillation through reentry. Centrifugal propagation from ectopic foci induced by the defibrillation shock may also play a role, especially in the atrium.10 This chapter expands on the subjects just mentioned, discussing characteristics of VF important to understanding defibrillation and characteristics of shock that lead to successful defibrillation, such as waveform shape and electrode configuration. A shock is traced from its origin at the defibrillation electrodes to its distribution through the

40

heart, with a discussion of its effect on the transmembrane potential and how it leads to the successful cessation of fibrillation.

Fibrillation Understanding defibrillation requires an understanding of fibrillation. Knowing the basic characteristics of VF and whether it is maintained by reentrant or focal activity, as well as the characteristics of the action potential and the excitability of the fibrillating tissue, helps to define the therapy that will be successful in stopping the arrhythmia. Ventricular fibrillation has been characterized as progressing through four stages, based on high-speed cinematography of electrically induced fibrillation in dog hearts24 (Fig. 2-1). A brief undulatory, or tachysystolic, stage lasting only 1 to 2 seconds occurs first. It is characterized by three to six undulatory contractions that resemble a series of closely occurring systoles and involve the sequential contraction of large areas of the myocardium. This is followed by a second stage of convulsive incoordination (15-45 seconds) during which more frequent waves of contraction sweep over smaller regions of the myocardium. Because the contractions in each region are not in phase, the ventricles are pulled in a convulsive manner. It is during this stage of fibrillation that the ICD shocks are given, about 10 to 20 seconds after the onset of fibrillation. In the third stage of tremulous incoordination, the independently contracting areas of the ventricular surface become even smaller, giving the heart a “trembling” appearance. Tremulous incoordination lasts for 2 to 4 minutes, before the fourth and final stage of atonic fibrillation occurs. Atonic fibrillation develops within 3 to 5 minutes after the onset of fibrillation and is characterized by the slow passage of feeble contraction wavelets over short distances. With time, the number of quiescent areas increases. Ischemia plays a role in the development of the third and fourth stages, because the fibrillating heart remains in the second stage if the coronary arteries are perfused with oxygenated blood.25,26 Driving the mechanical activity of the heart during fibrillation is the electrical activity of the myocardium. The electrical activity of the heart during fibrillation has been studied using both extracellular and optical recordings. Several groups have suggested that fibrillation is maintained by reentry. In most cases, reentry appears to be caused by “wandering wavelets” of activation, activation fronts that follow continually changing pathways from cycle to cycle. In some studies, the activation sequence appears moderately repeatable from cycle to cycle, following approximately the same pathway.27-29 Occasionally, a spiraling pattern of functional reentry emanates from the same region for several cycles. Sometimes, the central core of these spiral waves meanders across the heart.5 At other times, new reentrant activation fronts are generated when one front interacts with another during its vulnerable period. Study of VF suggests that there is a level of organization to the seemingly random patterns of wandering wavelets. Two competing hypotheses have been proposed to explain this organization. The “mother rotor” hypothesis was first proposed by Lewis30 in 1925 and revived in 1996 by Gray and Jalife.31 This hypothesis proposes that a single, stationary reentrant circuit (or mother rotor), located in the fastestactivating region of the heart, “drives” VF by giving rise to activation fronts that propagate throughout the remainder of the myocardium.29



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

41

CELLULAR ACTION POTENTIAL AND EXCITABLE GAP DURING FIBRILLATION y y

W

y

y

X

B

A

C

D

E

F

Figure 2-1  Spread of waves in analysis of motion pictures obtained during four stages of fibrillation described by Wiggers. A, Spread of wavefront during initial, undulatory stage. B, Theoretical passage of impulses from point x to form a wavefront at y. C through F show the appearance of contraction waves in the small rectangular area W from A, magnified. C, Undulatory stage; D, convulsive stage; E, tremulous stage; F, atonic stage. (From Wiggers CJ: Studies of ventricular fibrillation caused by electric shock: cinematographic and electrocardiographic observations of the natural process in the dog’s heart—its inhibition by potassium and the revival of coordinated beats by calcium. Am Heart J 5:351-365, 1930.)

These wavefronts propagate away from this fast-activating region, encounter areas of unidirectional block, and break up into smaller, slower-moving waveforms that resemble Wiggers’ wandering wavelets. Experiments best demonstrating the “mother” rotor have been performed in small hearts, from guinea pigs or rabbits. Studies of larger hearts have shown areas of faster and slower activation across the heart, but the existence of a single reentrant rotor that drives fibrillation has not been clearly demonstrated.32,33 In contrast to the mother rotor hypothesis is the “restitution” hypothesis. Restitution properties of the heart have been recognized for many years. Restitution in the heart refers to the relationship between the duration of an action potential in a particular cell and the duration of the previous diastolic or resting interval. If the previous diastolic interval (DI) is short, the current action potential duration (APD) will also be short. If the previous DI is long, the current APD will be long. For a regular rhythm, the preceding DI is constant and, therefore, so is the duration of the subsequent APD. The relationship between an APD and the previous DI is often described graphically as a plot of APDn versus DIn-1 (Fig. 2-2). The steepness of the restitution curve is an important characteristic of this curve, especially at short DIs. If this slope is greater than 1, then, at a constant cycle length, a single perturbation in DI will cause the ensuing APDs and DIs to oscillate, with the oscillations progressively increasing until the site is refractory at the time of the next cycle, causing conduction block and VF initiation. During VF, it is hypothesized that, when the slope of the restitution curve is greater than 1, oscillations in DI and APD increase until block occurs and wavefronts break up. Figure 2-2 shows an example of a restitution curve recorded from the right ventricle of a pig. The relationship between a DI and the subsequent APD is well defined during paced rhythm but less well defined during VF. Understanding how VF is maintained may help develop new therapies that will make fibrillation easier to stop. If VF is maintained by a mother rotor, targeting of electrical therapy, either shocks or pacing, to the region that contains the dominant reentrant circuit may be successful in halting VF. If VF is started and maintained primarily by the DI restitution properties of the heart, drugs that decrease the slope of the restitution curve, especially at short coupling intervals, may be successful in halting VF.

In the past few years, knowledge of the characteristics of the action potentials during fibrillation has increased greatly. This is a direct result of the introduction of techniques for recording action potentials in whole hearts, either in vivo31 or in perfused, isolated hearts.4-6,10,31 During fibrillation, the action potentials are altered: the APD is decreased; the action potential upstroke is slowed (decreased firstorder derivative, dV/dt) and of decreased magnitude; the plateau phase is abbreviated; and DIs are abbreviated or absent (Fig. 2-3). During the first few seconds of VF (or atrial fibrillation), the activation rate is quite rapid; the mean cycle length of VF in patients undergoing defibrillator implantation was 213 ± 27 msec.6 DIs are rarely seen during early fibrillation, and the upstroke of most action potentials occurs before the transmembrane potential has returned to baseline from the previous action potential. The demonstration of an excitable gap in fibrillating atrial tissue,34 as well as evidence of an excitable gap in fibrillating ventricular tissue,35 suggests that there are periods late in the action potential in the fibrillating myocardium during which an electrical stimulus can capture a portion of the fibrillating myocardium. Knowledge of an excitable gap provides an opportunity to stimulate the tissue just in front of a fibrillating wavefront, to cause wavefront block. As described in Chapter 1, the electrical activity of the heart is controlled ultimately by ion channels located in the cell membrane of the myocyte. It has been established that both the voltage-gated fast channels (sodium [Na+]) and slow channels (Na+ and calcium [Ca2+]) are active during the first few seconds of VF.8 The fast-channel activity is indicated by the rapidity of the upstroke of the action potential (phase

200 180 160 APD60 (msec)

y

140 120 100 80 60 40 0

20

40

60

80

100

DI (msec) Figure 2-2  Restitution curve recorded from right ventricle of pig. Dynamic action potential duration APD60 restitution relationship during pacing and ventricular fibrillation (VF) in one animal. (APD60 is the action potential duration at 60% of return to resting membrane voltage.) Open circles represent data from pacing, and solid squares represent data throughout 60 seconds of VF. Data were recorded from the anterior right ventricle using a floating microelectrode. The heart was stimulated using decremental pacing at an initial pacing rate of 1 pulse every 450 msec. The stimulus-to-stimulus interval was progressively shortened until either the heart was refractory to the stimulation or VF was induced. Note that the open circles form an exponential relationship between the diastolic interval (DI) and APD60, whereas the relationship between DI and APD60 is not well defined during VF. (From Huang J, Zhou X, Smith WM, Ideker RE: Restitution properties during ventricular fibrillation in the in situ swine heart. Circulation 110:3161-3167, 2004.)

42

SECTION 1  Basic Principles of Device Therapy

I II III

MAP 250 msec ECM Figure 2-3  Recording during ventricular fibrillation in a human. Leads I, II, and III are body surface electrocardiograms. Note that there is no period of diastole between action potentials. MAP, Right ventricular monophasic action potentials; ECM, local bipolar electrogram. (From Swartz JF, Jones JL, Fletcher RD: Characterization of ventricular fibrillation based on monophasic action potential morphology in the human heart. Circulation 87:1907-1914, 1993.)

0) during early fibrillation and its sensitivity to administration of the Na+ channel blocker, tetrodotoxin. As fibrillation proceeds, the upstrokes of the action potentials become increasingly slower, with a decreased dV/dtmax, but the action potentials remain sensitive to tetrodotoxin until 1 to 5 minutes after initiation of fibrillation. A transition then occurs in which the action potential upstrokes become insensitive to tetrodotoxin. This suggests that the propagation of the action potential is no longer mediated primarily by the fast voltage-gated Na+ channels and may be mediated by slow voltage-gated Ca2+ channel activity in the later stages of fibrillation.4 The activation complexes recorded from the ventricular myocardium remain active only as long as the coronary arteries are perfused with oxygenated blood, suggesting that ischemia may be responsible for the loss of fast-channel activation during prolonged VF.26

Defibrillation As previously mentioned, application of a powerful electrical shock to the heart is the only reliable means of stopping fibrillation. Successful defibrillation can reflect either the immediate cessation of all activation fronts or the cessation of activation fronts after two to three cycles,11,36 followed by coordinated beating of the heart. Unsuccessful defibrillation can reflect a failure to inhibit the fibrillating activation fronts or the resumption of fibrillating activation fronts after their initial inhibition. WAVEFORMS, CURRENT STRENGTH, AND DISTRIBUTION DURING DEFIBRILLATION The two most common waveform shapes used clinically are the monophasic and biphasic waveforms. In monophasic waveforms, the polarity of the shock is unchanged at each electrode for the entire duration of the electrical shock. In biphasic waveforms, the polarity of the shock reverses at each electrode partway through the defibrillation waveform. Many studies, in both animals and humans, have shown that biphasic waveforms can defibrillate with less current and energy than monophasic waveforms, in both internal and transthoracic defibrillation configurations.37-40 Within each type, waveforms can be described as truncated exponential or damped sinusoidal shapes. ICDs use truncated exponential biphasic waveforms. Most external defibrillators have used damped sinusoidal monophasic waveforms, but because of the inductor necessary to shape the waveform, these defibrillators tend to be large and heavy. More recently, smaller, lighter external defibrillators have been developed that use truncated exponential biphasic waveforms similar to those used in ICDs. Damped sinusoidal biphasic waveforms are used in external defibrillators in Russia; similar to truncated exponential biphasic waveforms, these show improved efficacy over monophasic waveforms.41,42

However, not all biphasic waveforms are superior to monophasic waveforms, For example, if the second phase of the biphasic waveform becomes much longer than the first phase, the energy required for defibrillation increases and can eventually rise to a level greater than the energy required to defibrillate with a monophasic waveform (with duration equal to the first phase of the biphasic waveform).40,43,44 The optimum duration of the two phases of the biphasic waveform depends on the electrode impedance and the defibrillator capacitance.45-48 Several groups have shown that defibrillation efficacy for square waveforms follows a strength-duration relationship similar to that for cardiac stimulation;49,50 as the waveform becomes longer, the average current at the 50% success point (the current when one half of delivered shocks will succeed) becomes progressively less, approaching an asymptote called the rheobase.51 On the basis of this observation, some suggest that cardiac defibrillation can be mathematically modeled using a resistor-capacitor (RC) network to represent the heart45,51-53 (Fig. 2-4). As empirically determined, the time constant for the parallel RC network is 2.5 to 5 msec.45,47,53 In one version of the model,53 a current waveform is applied to the RC network. The voltage across the network is then calculated for each time point during the defibrillation pulse. The relative efficacies of different waveform shapes and durations can be compared by determining the current strength that is necessary to make the voltage across the RC network reach a particular value, called the defibrillation threshold. Several observations can be made from this model. First, for square waves, as the waveform duration becomes longer, the voltage across the network increases, approaching an asymptote, or rheobase. For truncated exponential waveforms, however, the model voltage rises, reaches a peak, and then, if the waveform is long enough, begins to decrease (see Fig. 2-4). Therefore, the model predicts that monophasic exponential waveforms should be truncated at a time when the peak voltage across the RC network is reached. Current or energy delivered after that point is wasted. In support of this prediction, strength-duration relationships measured in both animals53 and humans54 do not approach an asymptote but rather reach a minimum and remain constant as the waveform lengthens. This minimum occurs over a range of waveform durations and does not extend indefinitely. Schuder et al.55 showed that, if the duration of a waveform becomes too long, defibrillation efficacy decreases. Second, the model predicts that the heart acts as a low-pass filter.52 Therefore, waveforms that rise gradually should have better efficacy than waveforms that turn on immediately. This prediction has been shown to hold true for external defibrillation,56 internal atrial defibrillation,57 and internal ventricular defibrillation.58 Ascending ramps defibrillate with a greater efficacy than do descending ramps.58,59 Third, several groups have suggested that the optimal first phase of a biphasic waveform is the optimal monophasic waveform.46,53 If so, what does the model predict as the “best” second phase of a biphasic waveform? Empirically, the role of the second phase apparently is to return the model voltage response back to zero as quickly as possible, thereby maximizing the increased efficacy of the biphasic waveform over that of the monophasic waveform with the same duration as phase 1 of the biphasic waveform. If the network voltage does not reach zero, or if it overshoots zero, efficacy is lost. Swerdlow et al.47 showed in humans that the “best” phase 2 of a biphasic waveform returns the model response close to zero. Together, these models allow the clinician to choose optimal capacitor sizes for truncated exponential biphasic waveforms, the waveforms most often used in ICDs. The capacitor must be large enough to be able to raise the network voltage to its threshold value and still hold enough charge to drive the network voltage back to zero. For a 40-Ω interelectrode impedance and a network time constant of 2.8 msec, the minimum capacitor that can accomplish this has a capacitance of 75 microfarads (µF). These models can also help in choosing shock parameters, including phase duration for biphasic waveforms. Shock duration should be varied depending on defibrillation lead impedance; patients with low impedance should receive short-duration shocks, whereas patients

Model response

15.0 10.0 5.0 0.0 0

5

10

B

20

25

30

Time (msec) Leading-edge current

C

15

Model response

22 16 12 6 2 4 8 0

D

5

10

15

20

Time (msec)

Figure 2-4  Parallel resistor-capacitor (RC) network representation of heart. Responses of RC network to monophasic and biphasic truncated exponential waveforms with a time constant of 7 msec. The parallel RC network has a time constant of 2.8 msec. A, Input monophasic waveforms. The leading-edge current of the input waveform was 10 A. The waveforms were truncated at 1, 2, 3, 4, 5, 6, 8, and 10 msec.  B, Model response, V(t). Initially, as the waveform lengthens, V(t) increases until it reaches a maximum at about 4 msec, after which it begins to decrease. C, Input biphasic waveforms. The leading-edge current was 10 A. Phase 1 was truncated at 6 msec. Phase 2 was truncated after 1, 2, 3, 4, 5, 6, 7, and 8 msec. D, Model response does not change polarity until the phase 2 duration is longer than 2 msec. (From Walcott GP, Walker RG, Cates AW, et al: Choosing the optimal monophasic and biphasic waveforms for ventricular defibrillation. J Cardiovasc Electrophysiol 6:737-750, 1995.)

with high impedance should receive longer-duration shocks. Initially, the concept of “tilt” was used to vary shock phase durations with impedance. Tilt is defined as the quotient of the leading-edge voltage minus the trailing voltage at the end of the shock divided by the voltage at the beginning of the shock, expressed as a percentage. For example, a shock with starting voltage of 500 V and ending voltage of 100 V has a tilt of 80%. If tilt is held constant, shock duration varies linearly with shock impedance. Compared with model predictions (Fig. 2-5), fixedtilt waveforms are too short for patients with low impedance and too

long for patients with higher impedance. One defibrillator manufacturer has developed a reference table that gives waveform phase durations as a function of patient impedance using a model similar to the one previously presented.60,61 Their model uses “model time constants” of 2.5, 3.5, and 4.5 msec. It is recommended that the 3.5-msec constant be used first. If the defibrillation threshold for the 3.5-msec waveform is unsatisfactory, using the 4.5-msec constant is likely to be more effective than 2.5 msec. Waveforms that are too short tend to fail; waveforms that are too long tend to waste shock energy yet still defibrillate. The location of the defibrillation electrodes affects the magnitude of the shock necessary to defibrillate the heart. Typically, 200 to 360 J of energy are necessary for successful defibrillation, with the defibrillation electrodes located on the body surface, during transthoracic defibrillation with a damped sinusoidal monophasic waveform. Although less energy is required for a truncated exponential biphasic waveform,62 only about 4% to 20% of the current that is delivered to transthoracic defibrillation electrodes ever reaches the heart.63,64 Indeed, when the defibrillation electrodes are placed in the heart itself, usually only 20 to 34 J of energy is required, and the requirement may be as low as only a few joules when large, contoured epicardial electrodes are used.40,65 The strength of the shock also varies for different locations on or in the heart; epicardial patches defibrillate with a lower shock energy than transvenous electrode configurations.66 Although defibrillation efficacy is usually described by some measure of defibrillation shock “strength” (energy, voltage, or current), little insight into the mechanisms of defibrillation can be obtained from these measures. Knowing how the current (or voltage) of a defibrillation shock is distributed over the heart allows greater understanding of how defibrillation occurs. Several studies have measured the potential gradient distribution throughout the heart during a defibrillation shock.14,67,68 The potential gradient is a measure of the spatial variation of shock voltage across the heart. The potential gradient is measured in volts per centimeter (V/cm) of tissue. In a region with a high potential gradient, the difference in voltage between a given point and an area 1 cm distant from that point is high. Regions of low potential gradient have a measured voltage that is similar to that of nearby points. These studies show an uneven potential distribution for most electrode configurations, with areas of high potential gradient near the defibrillation electrodes and areas of low potential gradient in regions distant from the defibrillating electrodes. It has been hypothesized that a minimum potential gradient must be attained for successful defibrillation to occur, and that this requirement is independent of the current applied or the electrode configuration.15,16 After a shock that fails to defibrillate VF, the site of earliest activation immediately after the 65%

10 9 Waveform duration (msec)

A

43

2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

Leading-edge current



8 50%

τm = 4.5 msec

7 6 5

τm = 3.5 msec

4

τm = 2.0 msec

3 2 1 0 0

1

2

3

4

5

6

7

8

9

10

Waveform time constant (msec) Figure 2-5  Waveform durations. Optimal duration of first phase of a biphasic waveform as a function of shock time constant is shown for model responses of 2.0, 3.5, and 4.5 msec. Also shown are the firstphase durations for 50%-tilt and 65%-tilt waveforms.

44

SECTION 1  Basic Principles of Device Therapy

shock can be mapped and related to the electric field that was produced by the shock. For shocks near the defibrillation threshold, the sites of earliest activation after a failed shock occur in the areas of lowest potential gradient. The minimum potential gradient required for defibrillation is lower for biphasic than for monophasic waveforms (4 vs. 6 V/cm). A minimum potential gradient of 6 V/cm was required for successful defibrillation using a 10-msec truncated exponential monophasic waveform in the open-chest dog model.16 Similar findings were observed using a 14-msec truncated exponential monophasic waveform and multiple electrode configurations.15 In contrast, a minimum potential gradient of 4 V/cm was required for successful defibrillation using a truncated exponential biphasic waveform. Because higher shock strengths are required to induce a higher potential gradient, biphasic shocks successfully defibrillate with lower energy than monophasic shocks (i.e., a lower-voltage gradient is required). The requirement for a minimum potential gradient may reflect the need for a shock to prevent the generation of new activation fronts that can result in reinitiation of fibrillation.69 Examination of activation patterns after failed defibrillation for progressively larger shock strengths indicate that postshock activation occurs at numerous sites throughout the ventricle, and that reentry is common when the shock strength is much lower than that needed for defibrillation70 (Fig. 2-6). At shock strengths just lower than those required for defibrillation, postshock activation arises in a limited number of myocardial regions. The activation fronts then propagate to activate other regions of the myocardium for a few cycles before reentry occurs; activation becomes disorganized; and fibrillation is reinitiated. Although postshock activation sites can still arise in regions of lowest potential gradient after a shock slightly greater than that required for defibrillation, the cycles of activation that originate from these sites are slower. These activations terminate after a few cycles without reinitiating fibrillation.69-71 At least two inferences can be drawn from the model that the lowest potential gradient region determines whether or not a shock will halt fibrillation. First, different shock electrode configurations with the same defibrillation threshold (DFT) have the same lowest potential gradient value, but in different regions of the heart. Single-coil versus dual-coil defibrillator systems have similar DFTs. Mapping of postshock activations shows that the earliest recorded activity after the shock is the anterior left ventricle for dual-coil shocks but the posterior area for single-coil shocks.72 Thus the low gradient region presumably is anterior for dual-coil shocks and posterior for single-coil shocks, although this inference needs to be confirmed experimentally. Crossley et al.73 measured DFTs for shocks from either an electrode in the right ventricular (RV) apex or RV outflow tract to the pulse generator can and showed that DFTs were not significantly different for the two configurations. We can infer that the lowest potential gradient level was the same for each configuration, but likely in a different location. Second, high DFTs occur in some patients because either (1) the geometry of their heart is such that the low potential gradient region has a lower potential gradient than in most patients, or (2) these patients require a higher gradient level in the low gradient region to defibrillate. In either case, unusual lead configurations may help in these patients. A subcutaneous array can lower high DFTs,74 most likely by directing current to the left ventricular free wall. Likewise, an azygos vein electrode can be useful in lowering high thresholds,75 likely by directing current to the posterior portion of the heart. The previous discussion shows how defibrillation can fail because a shock is of insufficient strength. Another issue involves the defibrillation shock that becomes extremely large. At high shock strengths, the probability of defibrillation success again begins to decrease. It is believed that, at large strengths, defibrillation shocks can have detrimental effects on the heart. Increasing the shock strength to very high levels (>1000 V with transvenous electrodes) can result in activation fronts arising from regions of high potential gradient that reinduce VF.76 Cates et al.77 showed that, for both monophasic and biphasic shocks, increasing shock strength does not always improve the probability of successful defibrillation and may even increase the incidence

Preshock 100V

+ +

+ -+

++-

Postshock

A

+ +

+ + + - + -+

+

+ + +- - + +

+ -+ -

-

- +-++ + +

+

+-

+-

+

-

-

-

+ +-

+

- +

-

+

+

-

-

+-

- +

B

200V

++

-+

+ +-

C

600V

+ +

+ +

D 800V

- +-

+- - +

Figure 2-6  Phase maps of single rabbit heart. Maps show the last cycle before a shock (left side) and the first cycle after a shock (right side) of 100 V (A), 200 V (B), 600 V (C), and 800 V (D) that failed to defibrillate. The defibrillation threshold was 800 ± 200 V in this series. Colors represent phase, and the symbols + and − indicate phase singularities or centers of reentrant circuits of opposite direction. Phase singularities as a marker of reentry were observed during ventricular fibrillation just before the shock in all cases. A and B, Postshock phase singularities were observed after failed 100-V and 200-V shocks. Visual analysis of animations of the optical recordings indicated that many of the phase singularities represented reentrant activations occurring immediately after the shock, so that the postshock interval was 0 msec. C and D, No phase singularities were observed after the 600-V and 800-V shocks. For the 600-V shock, activation propagated away in all directions from two early sites, at the apex and at the lateral base of the left ventricle, both of which appeared after a postshock interval of 42 msec. For the 800-V shock, a single wavefront of activation appeared at the apex and propagated away in all directions in a focal pattern after a postshock interval of 72 msec. (From Chattipakorn N, Banville I, Gray RA, Ideker RE: Effects of shock strengths on ventricular defibrillation failure. Cardiovasc Res 61:39-44, 2004.)

of postshock arrhythmias. Chapman et al.78 showed in dogs that the time required for the heart to recover hemodynamically after a defibrillation episode was shorter for biphasic than for monophasic shocks. Further, they showed that hemodynamic recovery took longer after high-energy shocks than after low-energy shocks. Reddy et al.79 showed that transthoracic defibrillation with biphasic shocks resulted in less postshock electrocardiographic evidence of myocardial dysfunction (injury or ischemia) than standard monophasic damped sinusoidal waveforms, and without compromise of defibrillation efficacy. One mechanism implicated in the means by which shocks cause damage to the myocardium is electroporation, the formation of holes or pores in the cell membrane. Electroporation may occur in regions where the shock potential gradient is high (>50 to 70 V/cm) and may even occur in regions where the potential gradient is much less than 50 V/cm.80 The very high voltage can result in disruption of the phospholipid membrane bilayer and in the formation of pores that permit



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

the free influx and efflux of ions and micromolecules. Electroporation can cause the transmembrane potential to change temporarily to a value almost equal that of the plateau of the action potential. At this transmembrane potential, the cell is paralyzed electrically, being both unresponsive and unable to conduct an action potential. Exposure of the myocardium to yet higher potential gradients, probably greater than 150 V/cm, results in arrhythmic beating, and at extremely high potential gradients, necrosis may occur.81 The shape of the waveform alters the strength of the shock at which these detrimental effects occur. Use of a 10-msec, truncated exponential monophasic waveform for VF in dogs resulted in conduction block in regions where the potential gradient was greater than 64 ± 4 V/cm.82 Shocks that created even higher potential gradients in the myocardium (71 ± 6 V/cm) were required for conduction block when a 5-msec/5msec, truncated exponential biphasic shock was used. Adding a second phase to a monophasic waveform, thereby making it a biphasic waveform, reduced the damage sustained by cultured chick myocytes compared with that induced by the monophasic waveform alone.83 Therefore, biphasic waveforms are less likely to cause damage or dysfunction in high-gradient regions than monophasic waveforms. MODELS PROPOSED TO EXPLAIN INDUCTION OF CHANGES IN TRANSMEMBRANE POTENTIAL THROUGHOUT HEART DURING DEFIBRILLATION SHOCK A shock in the form of a square wave given across the defibrillation electrodes appears almost immediately as a square wave in the extracellular space of the heart. There is no significant distortion, because the extracellular space throughout the body is primarily resistive, with little reactive component. Phase delays and alterations of the appearance of the shock wave occur in the transmembrane potential, however, because of the capacitance and ion channels of the myocyte membrane.84 Consequently, a square-wave shock can elicit an exponential change with time in the transmembrane potential (Fig. 2-7). The nonlinear behavior of the membrane caused by the ion channels also affects the outcome of reversing the polarity of the defibrillation shock. Reversing the polarity may reverse the sign of the change in the transmembrane potential in some regions of the myocardium, and

Extracellular space

10 msec

Transmembrane potential

A Extracellular space

10 msec

Transmembrane potential

B Figure 2-7  Effect of square-wave shock on extracellular potential and transmembrane potential. The square-wave shock appears immediately as a relatively undistorted square wave in the extracellular space. It appears as an exponentially increasing change in the transmembrane potential. When a shock of a given polarity is delivered during the action potential plateau (A), the depolarization obtained is different in magnitude and time course from the hyperpolarization obtained with a shock of the opposite polarity (B). (From Walcott GP, Knisley SB, Zhou X, et al: On the mechanism of ventricular defibrillation. Pacing Clin Electrophysiol 20:422-431, 1997.)

45

the nonlinear behavior of the membrane can alter the magnitude and the time course of this change. As discussed previously, reversing the polarity of the shock may not reverse the sign of the change in the transmembrane potential in all regions of the heart; some areas may be hyperpolarized with both shock polarities.85 This may reflect the nonlinear behavior of the membrane ion channels. Several models have been formulated in an attempt to explain the mechanisms by which the defibrillation shock is distributed throughout the myocardium to restore coordinated, effective action potentials. As yet, none of the models adequately describes all the experimental findings on the action potential changes during defibrillation. It is well established experimentally that changes occur many centimeters from the defibrillating shock electrodes. These changes in transmembrane potential can result in new action potentials or prolongation of the action potential as described previously.23,86 Direct excitation can be observed,23 even far from the electrode (>30 mm),87 as well as across the entire heart.88 Although the one-dimensional cable model described in Chapter 1 adequately describes the generation of self-propagating action potentials close to an electrode as required for pacing, it fails to account for the far-field changes observed during defibrillation. During stimulation or defibrillation, this model predicts that the tissue near the anode should be hyperpolarized, whereas the tissue near the cathode should be depolarized.89 The magnitude of the hyperpolarization or depolarization decreases exponentially with the distance from the electrodes according to the membrane space constant, the distance at which the hyperpolarization or depolarization has decreased by 63%. For cardiac tissue, the space constant is only 0.5 to 1 mm.89,90 Therefore, the onedimensional cable equations predict that tissue more than 10 space constants (~1 cm) distant from the defibrillation electrodes should not directly undergo changes in transmembrane potential because of the shock field. That is, new action potentials should not arise by direct excitation at distances greater than 1 cm from the electrodes. This model fails to describe the experimentally observed global distribution of action potentials during defibrillation. Therefore, several additional mathematical formulations have been proposed, including the sawtooth model,21,91-93 the formation of secondary sources at barriers in the myocardium,20,94 and the bidomain model,95 to explain how a defibrillation shock affects the transmembrane potential a long distance from the shocking electrodes. In the simplest formulation of these models, the extracellular and intracellular spaces are considered to be low-resistance media and the membrane to be a high-resistance medium in parallel with capacitance. The simple case models incorporate only passive myocardial properties. The models have been rendered more realistic by the addition of active components to represent the ion channels in the membrane, gap junctions, and membrane discontinuities.96,97 By convention, the current is defined as the flow of positive ions from the anode to the cathode. Sawtooth Model The one-dimensional cable model positions two low-resistance continuous spaces that conduct current from the shock, the intracellular space and the extracellular space, separated by a high-resistance cell membrane. In the sawtooth model the intracellular space is divided by a series of high-resistance barriers, the gap junctions. Because of these high-resistance barriers, current moving in the intracellular space is forced to exit into the extracellular space and reenter the cell on the other side of the barrier. Exit and reentry of the current from the intracellular domain results in hyperpolarization near the end of the cell closest to the anode and depolarization near the end of the cell closest to the cathode. A tracing of the changes in transmembrane potential along a fiber during the shock should therefore resemble the teeth of a saw, with each tooth corresponding to an individual cell21,91-93 (Fig. 2-8). Increases in the junctional resistances are predicted to increase the magnitude of the potential changes at the ends of the cell.21 Although gap junctions are of low resistivity, they can present significant junctional resistance under certain conditions, such as hypoxia98,99 and calcium depletion.100 As the resistance of the gap junctions

SECTION 1  Basic Principles of Device Therapy

35.0

0.0

35.0

71.0 0.19

0.1

A

0.0

0.1

0.19

Fiber axis (cm) 71.0

Vm0(x) and Vm1(x,y) (mV)

Vm1

Vm0

35.0

0.0

35.0

71.0 0.19

0.1

B

0.0

0.1

0.19

Fiber axis (cm)

Figure 2-8  Sawtooth model of transmembrane potential during a shock. A, Transmembrane potential shown is a summation of the membrane potential profile of the cable model and the periodicity arising from the periodic changes in intracellular resistance. The anode is to the left and the cathode is to the right in this one-dimensional model. The fiber is divided into 31 cells of equal length separated by junctions of high resistance. In the figure, the junctional resistance is shown much greater than is believed to occur in cardiac fibers, to allow the sawtooth pattern to be seen. B, Two parts of the summation in panel A are shown; Vm0, transmembrane potential profile of cable model; Vm1, periodicity arising from periodic changes in intracellular resistance. (Modified from Krassowska W, Pilkington TC, Ideker RE: Periodic conductivity as a mechanism for cardiac stimulation and defibrillation. IEEE Trans Biomed Eng 34:555-560, 1987.)

increases, it is predicted that a greater fraction of current passes preferentially across the cell membrane rather than along the cell. The sawtooth model adequately describes the requirement for a minimum potential gradient, because the magnitudes of the hyperpolarization and polarization at the ends of the cells are directly proportional to the strength of the stimulus. It also adequately describes the generation of action potentials at a distance from the electrodes and the differences in threshold stimuli between cathodal and anodal stimulation. Sawtooth changes in transmembrane potential have been observed in preparations of isolated cardiomyocytes;101,102 however, such a pattern in isolated cells would be consistent with the cable model. This pattern has not been observed in a syncytium of cardiac cells.20,103,104 Secondary Source Model Although the resistivity of the gap junctions at the boundaries between the cells may not adequately explain the physiologic effects of defibrillation, the resistivity of other intracellular discontinuities and

interruptions may well play a role. Most theories concerning the generation of action potentials and their propagation across the ventricle, such as the bidomain theory described later, consider the myocardium to be a uniform electrical continuum. This assumption does not take into account the discontinuities of the intracellular domain, where the myocardium is interrupted by barriers such as connective tissue septa, blood vessels, and scar tissue. As described previously for the sawtooth model, the intracellular current, on encountering such a barrier, must leave the intracellular space, cross the barrier, and reenter the intracellular domain on the other side. Depolarization should occur on one side of the barrier and hyperpolarization on the other side. Therefore, the barrier acts as a set of electrodes during the shock, becoming a secondary source of action potentials (Fig. 2-9). These secondary sources are important causes of depolarization and hyperpolarization throughout the myocardial tissues during a shock.20 The resistive barriers act in a manner similar to that described for the sawtooth model. In this case, however, the resistive barriers represent larger discontinuities, which tend to increase with age and cardiac hypertrophy.105 Computer simulations have shown that the cathodal stimulation delivered to the myocardium near an oval scar results in three distinct activation fronts: the primary activation front and secondary fronts at the distal and proximal edges, which are generated by the exit and reentry of current from the intracellular and extracellular spaces106 (see Fig. 2-8). Optical techniques have directly recorded changes in transmembrane potentials throughout a monolayer of ventricular myocytes.20 Localized regions of depolarization and hyperpolarization coincided with discontinuities in the monolayer, resulting in slow conductance. Microscopic regions of depolarization and hyperpolarization have also been observed in isolated slabs of left ventricle, although their correlation with anatomic structures was not possible using optical mapping techniques because of the light-scattering properties of myocardium.107 The significance of secondary sources was demonstrated in whole hearts by mapping of action potentials and determination of shock thresholds before and after the generation of a transmural lesion in the myocardial walls of dogs.94 Generation of the lesion resulted in the development of a region of direct activation in the area of the lesion, in addition to the region of direct activation resulting from the stimulating electrode observed before the lesion. Furthermore, the strength of the shock required to cause direct

140.3 mV

Cathode Anode

Blood volume

Transmembrane potential

Transmembrane potential (mV)

71.0

Fiber direction

46

–35.1 mV

Endocardium

Figure 2-9  Computer model of secondary sources adjacent to scar elicited by single, large, pacing pulse. Area to the right represents myocardium that contains a rectangular scar (stippled region). On the left is the blood pool with a pacing catheter in it. Note that a pacing pulse depolarizes not only tissue near the cathode but also tissue near the scar. (From Street AM: Effects of connective tissue embedded in viable cardiac tissue on propagation and pacing: implications for arrhythmias. Durham, NC, 1996, Department of Biomedical Engineering, Duke University, p 134.)



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

10

40

Figure 2-10  Isochronal activation maps. Maps obtained after cathodal stimulation before and after creation of a transmural incision that caused secondary sources adjacent to the lesion. Isochrones are drawn at 5-msec intervals, timed from the onset of the S1 or S2 stimulus. Arrows represent direction of activation. Darkened regions represent areas directly activated by the stimulus. Black vertical bars represent the approximate location of the transmural incision. A, S1 stimulus delivered before incision. B, 75-mA S2 stimulus delivered before incision. C, 250-mA S2 stimulus delivered before incision. D, S1 stimulus delivered after incision. E, 75-mA S2 stimulus delivered after incision. F, Orientation of the long axis of myocardial fibers. (From White JB, Walcott GP, Pollard AE, et al: Myocardial discontinuities: a substrate for producing virtual electrodes to increase directly excited areas of the myocardium by shocks. Circulation 97:1738-1745, 1998.)

20 25 30 35

40 45 50

A

15

20 25 30

C

B 20

25 15

50

25 30

20

10

35 40 45 55

15

20

15 20 10

10º

45 15 10

35

40

D

10

E

activation in the area of the lesion was less than one half of that required before generation of the lesion (Fig. 2-10). The effects of secondary sources have major implications for the probability of successful defibrillation at different shock strengths in individual patients, particularly elderly patients, as well as the potential for reentry. Furthermore, the size and placement of operative lesions may play significant roles in the success of subsequent defibrillation. Bidomain Model The bidomain model is an extension of the one-dimensional cable model into two or three dimensions. That is, the extracellular and intracellular spaces are represented as single, continuous domains that extend in two or three dimensions and are separated by the highly resistive cell membrane95 (Fig. 2-11). If the conductivities of the intracellular and extracellular spaces are constant in all directions, the

rey rex

riy rix

35

55 60

47

y x

Figure 2-11  Circuit diagram of two-dimensional bidomain model. Top of the resistor network represents the extracellular space; bottom of network represents the intracellular space. The symbol reΔx represents the extracellular resistivity in the x direction; reΔy represents the extracellular resistivity in the y direction; riΔx and riΔy represent the intracellular resistivities in the x and y directions. The rectangles represent the cell membrane. For a passive model, the rectangle would be replaced by a parallel resistor-capacitor network. For an active model, the rectangle would be replaced by a membrane ion model.

F

model collapses to the one-dimensional cable model. Anisotropy refers to the manner in which conductivities change with the direction of myocardial fiber orientation. Clerc108 showed that conductivity is higher in the direction parallel to the long axis of myocardial fibers (longitudinal) than in the direction perpendicular to the fibers (transverse) for both the intracellular and extracellular spaces. If conductivities change with direction but change the same for the intracellular and extracellular spaces, the bidomain model collapses to the onedimensional cable model. Studies have shown that the anisotropy ratio in ventricle is about 3 : 1 in the extracellular space and 10 : 1 in the intracellular space. When anisotropy ratios are used, the bidomain model begins to give new insights into how shocks change the transmembrane potential. Similar to the one-dimensional cable model, the bidomain model predicts that hyperpolarization occurs in tissue that lies under the extracellular anodal electrode. Likewise, depolarization occurs in tissue under the extracellular cathodal electrode. Unlike the one-dimensional cable model, the bidomain model also predicts that depolarization occurs along the long axis of the myocardial fibers at distances just a few millimeters from the anode. A similar effect is predicted to occur at the cathode, with hyperpolarization at distances of a few millimeters.109 Therefore, the effect on the transmembrane potential near the shocking electrode is predicted to be much more complicated by the bidomain model than by the one-dimensional cable model. The power of the bidomain model, however, is that it hypothesizes that there should be changes in the transmembrane potential, either hyperpolarization or depolarization, across the entire heart. In this model, the change in transmembrane potential elicited by the shock depends on the distribution of intracellular and extracellular current, which is affected by the change in potential gradient with distance, the distance from the electrode, and the orientation of the myocardial fibers. Experimental studies show a complex pattern of transmembrane potential changes during the delivery of a defibrillation shock, similar to those predicted by the bidomain model.85,110,111 The transmembrane potential changes that occur during the delivery of a defibrillation shock can lead to the initiation of reentry and subsequent reinitiation of fibrillation after the shock. Reentrant circuits can be described by the mathematical concept of a phase singularity.112 Phase can be used to describe the cardiac action potential, with 0 phase assigned to the upstroke of the action potential and 2Π phase assigned to the end of the action potential. A reentrant circuit can be thought of as a circle of phase starting at 0 (excitation) and continuing

48

SECTION 1  Basic Principles of Device Therapy

Postshock transmembrane voltage (mV´)

Postshock activation isochronal maps (5 ms) 1st beat 2nd beat 125 11.5  11.5 mm

100

135 75

5

125 30

75

0

75 mV´

5  115 ms 105  145 ms Time after the shock phase reversal

Shock Figure 2-12  Creation of shock-induced phase singularity. Left upper panel shows the change in transmembrane potential at the end of a +100/−200 V biphasic shock (i.e., at 15th msec of 16-msec shock), which resulted in a single extra beat. Scale is shown in millivolts, calibrated to a control 100-mV action potential. Point of phase singularity is indicated by the black circle. Middle upper panel shows a 5-msec isochronal map that depicts the initiation of the postshock spread of activation. The map starts at the onset of the 8-msec phase 2 of the shock (polarity reversal). Lower panels show optical recordings from several recording sites used to reconstruct the activation maps. Right upper panel shows a continuation of the reentrant activation shown in the middle panel. Reentrant activity self-terminates after encountering refractory tissue in the lower right corner of the field of view (see traces in right lower panel). (From Efimov IR, Cheng Y, Van Wagoner DR, et al: Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure. Circ Res 82:918-925, 1998.)

to 2Π (recovery). The reentrant circuit moves around a central point, called a phase singularity. Efimov et al.110 showed that a defibrillation shock can impose changes on the transmembrane potential extending from 0 phase through 2Π phase (Fig. 2-12). Thus, a reentrant circuit is generated and fibrillation induced. The authors suggest that induced reentrant circuits may be one way that defibrillation shocks can fail. The secondary source and bidomain models may not be mutually exclusive; rather, both may contribute to the changes in transmembrane potential. The exact mechanism by which an electrical pulse results in defibrillation remains incompletely understood at the level of the cell membrane and the ion channels. As the transmembrane potential attains values closer to the typical resting transmembrane potential than the usual minimum of −65 mV observed in fibrillating myocytes, this may allow the voltage-gated Na+ channels to recover sufficiently and the myocytes to regain full excitability. EFFECT OF DEFIBRILLATING SHOCK FIELD ON CELLULAR ACTION POTENTIAL The final common pathway of changes in the transmembrane potential caused by a defibrillation shock involves effects on the shape and duration of the cellular action potential. The shock can have one of three effects on the myocardium, depending on the local strength of the shock and its timing with respect to the local action potential. If the shock is delivered during the early plateau, there will be little or no prolongation of the action potential. If the shock is strong enough and is delivered relatively late during the action potential, it will initiate a new action potential. A shock that is strong enough but is delivered during early phase 3 of the action potential will modify and prolong an ongoing action potential without initiating an entirely new action potential (Fig. 2-13).

To defibrillate the heart successfully, a defibrillating shock (1) must stop most or all activation wavefronts on the heart and (2) must not reinitiate fibrillation. The extension of refractoriness hypothesis helps to explain how a shock can stop fibrillation. A shock can prolong the refractory period of an action potential without triggering a new potential if it is of sufficient strength and is delivered at an appropriate interval with respect to the upstroke.23,113 If the first activation front that forms after a defibrillation shock encounters tissue with an extended refractory period, the front will be stopped because it cannot propagate into the region of refractory tissue. Also, a defibrillation shock must not restart fibrillation. If only part of the front encounters tissue with an extended refractory period, only part of the front will be halted. The rest of the activation front will propagate forward and will eventually move into the area that could not be stimulated or that would not allow propagation (unidirectional block). This process of stimulating some tissue and creating unidirectional block in adjacent regions creates a reentrant circuit that eventually breaks down into fibrillation. The critical point is that point at which a critical shock strength intersects a critical level of refractoriness, leading to the formation of a reentrant circuit.114-116 Optical mapping has revealed another type of critical point about which reentry can occur in response to the shock electric field.110 This type of critical point is formed when the shock electric field causes a large region of hyperpolarization immediately adjacent to a large region of depolarization. According to Efimov et al.,117 a biphasic shock waveform is more efficacious because the second phase of the shock obliterates the regions of hyperpolarization and depolarization so that the critical-point reentrant wavefront does not arise. Both types of critical points share two attributes; first, they produce a wavefront that appears immediately after the shock, and second, the wavefront forms a reentrant circuit.



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms 1.6 V/cm, 2 msec

S1-S2 (ms)

0 (mV)

222 225

80

A

100 msec 8.4 V/cm, 2 msec S1-S2 (ms) 90 110 130, 150, 170 180 200 210 220 230

(mV)

0

80

B

230 90 S1-S2 (msec) 100 msec

Figure 2-13  Transmembrane recordings from guinea pig papillary muscle. Recordings show an all-or-none response to a weak field stimulus and action potential prolongation in response to a larger stimulus. A, Recordings that illustrate the response to an S2 stimulus of 1.6 V/cm oriented along the fibers. The S1-S2 stimulus interval for each response (milliseconds) is indicated to the right of the recordings. The responses are much different, even though the change in S2 timing was only 3 msec. An S1-S2 interval of 222 msec caused almost no response, whereas an interval of 225 msec produced a new action potential.  B, Range of action potential extensions produced by an S2 stimulus generating a potential gradient of 8.4 V/cm oriented along long axis of myofibers; recordings from same cell as in A. The action potential recordings, obtained from one cellular impairment, are aligned with the S2 time. An S1 stimulus was applied 3 msec before phase 0 of each recording. The longest (230 msec) and shortest (90 msec) S1-S2 intervals tested are indicated beneath their respective phase 0 depolarizations. The S1-S2 interval for each response is indicated to the right. (From Knisley SB, Smith WM, Ideker RE: Effect of field stimulation on cellular repolarization in rabbit myocardium: Implications for reentry induction. Circ Res 70:707-715, 1992.)

REFIBRILLATION CAUSED BY DEFIBRILLATION SHOCK Although activation wavefronts consistent with the two types of critical points are observed following shocks given during the vulnerable period of paced rhythm and after shocks much weaker than the DFT during VF, these wavefronts are usually not observed after shocks near DFT strength during VF.118-123 Instead, earliest activation is not recorded until 50 to 60 msec after the shock, an interval called the isoelectric window, and wavefronts spread centrifugally away from this early site in a focal activation pattern. This pattern is present not only in electrical epicardial recordings (Fig. 2-14) but also in optical epicardial recordings (Fig. 2-15), which are not subject to saturation of the amplifiers by the shock as are electrical recordings. This activation pattern may represent epicardial breakthrough of an intramural reentrant circuit caused by a critical point. However, the same focal activation pattern has been observed in three-dimensional transmural electrical

49

recordings with plunge needles, during which an isoelectric window was also observed intramurally.122 This window has also been observed in optical recordings of a thin layer of spared epicardial tissue in which the intramural myocardium was frozen.123 Following a failed shock slightly weaker than the DFT, the focal activation pattern is seen for several cycles before the less organized pattern of VF reappears (see Fig. 2-14). However, this same focal activation pattern can be observed for one or more cycles after a successful defibrillation shock (see Fig. 2-15, B). These findings suggest that the failed shock reinitiates VF by causing a trigger (the focus) that interacts with the substrate (the ventricular tissue). If the trigger focus lasts long enough for reentry to develop in the ventricular myocardium substrate, the shock fails. If the trigger focus halts before reentry is induced in the myocardial substrate, the shock succeeds. This concept raises the possibility that cardiac disease or drugs can alter DFT by altering the trigger, the substrate, or both. For example, conditions that increase the number of cycles of the focal trigger or that decrease the cycle length of the trigger might increase DFT. Similarly, conditions that allow more easily induced reentry in the substrate, such as an increased dispersion of refractoriness, could also increase DFT. Although several mechanisms have been hypothesized, the cause of the focal activations after the shock is not definitively known, nor is it known why increasing the shock electric field decreases the number of focal postshock activations. One hypothesis is that the focus is not a true focus but arises from “tunnel propagation.”124 According to this hypothesis, a small part of a VF activation wavefront is not extinguished but propagates intramurally during the postshock isoelectric window, where it is undetected by three-dimensional mapping because it is so small. When sufficient tissue recovers, it is able to break out as a large wavefront. This wavefront appears to arise focally because the small, slowly propagating tunnel of activation is not detected by mapping. According to this hypothesis, a biphasic waveform has a lower DFT than a monophasic waveform because it decreases the number and size of the tunnels for the same-strength shock. However, the finding at multiple focal cycles is difficult to explain with the tunnel propagation hypothesis; multiple focal cycles, not just one, are present after the shock (see Fig. 2-14). Another hypothesis is that the focal activation arises where an intracellular calcium (Cai) “sinkhole” is present after the shock.123 This hypothesis is based on optical recordings demonstrating that Cai decreases during the isoelectric period in the region where the focus will later appear (Fig. 2-16). After the formation of the sinkhole, the action potential in this region is immediately preceded by an increase in Cai, suggesting the potential arises from triggered activity. According to this hypothesis, a biphasic waveform has a lower DFT than a monophasic waveform because it causes less postshock heterogeneity in Cai.125 In one study the DFT after VF of 10 seconds was significantly decreased by flunarizine, a drug that prevents activity triggered by delayed afterdepolarization (DAD).126 However, another study did not find that DFT after 10 seconds of VF was altered either by flunarizine or by pinacidil, a drug that prevents activity triggered by early afterdepolarization (EAD).127 A third study found that DFT after 20 seconds of VF was not altered by flunarizine, but that DFT was reduced by flunarizine after 7 minutes of VF by 82%.128 This suggests that after long-duration VF, but not short-duration VF, the focal postshock activation may arise from a DAD. Another finding indicates that the mechanism of defibrillation may differ depending on the duration of VF. The earliest postshock activation after the isoelectric period arises primarily in the working myocardium following VF of about 30 seconds, but arises primarily in Purkinje fibers after VF of 180 seconds.129 These differences in defibrillation after short- versus long-duration VF are probably related to the different characteristics of the activation wavefronts maintaining these short or long VFs.130-132 It has even been reported recently that endocardial ventricular activation is not reentrant but arises focally from Purkinje fibers in up to 30% of cases during long-duration VF133 (Fig. 2-17). This finding raises the startling possibility that to defibrillate

50

SECTION 1  Basic Principles of Device Therapy

64

74

84

94

104

114

124

134

144

154

164

174

184

194

204

214

224

234

244

254

264

274

284

294

304

314

324

334

344

354

Figure 2-14  Example of postshock cycles after failed shock in pig. Defibrillation shock was of a strength near the defibrillation threshold (DFT), delivered from electrodes in the right ventricular apex and the superior vena cava. Recordings were made simultaneously from 504 electrodes distributed globally over the porcine ventricular epicardium. Electrode sites are indicated in gray on a polar projection, with the atrioventricular groove at the periphery and the left ventricular apex in the center. Anterior is at the bottom of the projection, and the left ventricle is to the right. Each panel shows in black the electrode sites at which an activation occurred at any time during each 10-msec interval. Numbers above the panels indicate the start of each 10-msec interval relative to the shock onset. Red arrows indicate the site of earliest recorded activation for each cycle. The first cycle appeared on the epicardium 64 msec after the shock at the anteroapical left ventricle. The second cycle (154 msec) arose on the epicardium in the same region as the first cycle and also propagated away in a focal pattern. The third (235 msec) and fourth (315 msec) cycles arose before the activation front from the previous cycle disappeared. (From Chattipakorn N, Fotuhi PC, Ideker RE: Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold. J Cardiovasc Electrophysiol 11:1014-1021, 2000.)



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

51

RV Posterior coronary vein

LAD

LV

LV

Anterior

RV

2 cm

Posterior

84

92

100

108

116

124

132

140

148

156

164

172

180

188

196

72

80

88

96

108

116

124

132

140

148

156

164

172

180

188

A

B Figure 2-15  Similar activation patterns of postshock cycle 1 after failed (A) and successful (B) shocks. Maps from a pig heart are oriented as shown at top of figure; RV, right ventricle; LV, left ventricle; LAD, left anterior descending (coronary artery). Numbers above maps are times in milliseconds relative to defibrillation shock onset. Recording sites where action potential upstroke reached 50% of the action potential amplitude at any time during each 8-msec interval are black. Activation arose focally at the left ventricular apex where the shock electric field is weak and appeared 84 msec after the shock in A and 72 msec after the shock in B. Activation wavefronts propagated focally away from the apex toward the base in an organized pattern for both the failed and the successful shock episodes. (From Chattipakorn N, Banville I, Gray RA, Ideker RE: Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine. Circulation 104:1313-1319, 2001.)

52

SECTION 1  Basic Principles of Device Therapy

Cai

A

100 msec

Vm Vm

Activation isochrone

Cai

C

–8 –4

0 msec

0

*

4 8 (F–F)/F (%)

25 msec

*

0 msec

* 25 msec

*

Act 0 15 20 30 40 50 msec

Rep 50

60 msec

143 msec

Repolarization isochrone

8 msec

90 msec

Cai

50 msec

140 msec

28 15

50 msec

*

50 msec

*

0 msec

198 msec

73 msec

73 msec

Vm

D

185 msec

Cai

Cai

B

163 msec

100 msec

Vm

Figure 2-16  Intracellular calcium (Cai) “sinkhole” and earliest postshock activation during unsuccessful shock in isolated rabbit heart. A, Optical signals from the site marked by an asterisk in B. The isoelectric window is the time between the time of the defibrillation shock (red line) and the time when the postshock Vm tracing crosses F (fluorescence strength, black line). B, Optical maps after failed shock (200 V), with time of the shock as time 0. C, Consecutive isochronal activation maps (left), isochronal repolarization map (middle), and Cai maps (right). Cai sinkholes (white arrows) are seen at the same site before the onset of the repetitive activations; Act, activation; Rep, repolarization. D, Optical tracings from the center (top two tracings) and edge (bottom two tracings) of the Cai sinkhole. Horizontal line segments on the tracings represent the levels of F. (From Hwang GS, Hayashi H, Tang L, et al: Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorff-perfused rabbit ventricles. Circulation 114:2595-2603, 2006.)



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

2

3

4

5 6

7 8 9 10 11 12 13 14 15

Recordings

1

53

RV apex

Activation times

aVR

A

B

550 msec

Figure 2-17  Recordings and activation times for 15 cycles after ventricular fibrillation in dog. A, Soon after onset of VF; B, after 5 minutes of VF. Left ventricular endocardial basket recordings from 64 unipolar electrodes are shown at the top of each panel, with a right ventricular (RV) unipolar recording and ECG lead (aVR) below them. Below the ECG are the ventricular activation times recorded at the 64 basket electrodes during the same period, with each short vertical line representing an activation. At the bottom of each panel, the activations for all 64 electrodes are shown on a single line. The 15 cycles are numbered at the top of B. In A, endocardial activations are present throughout the cardiac cycles, consistent with reentry. In B, however, activation is highly synchronized with activation present during only a small part of the cardiac cycle, so that 14 large temporal gaps are present between the 15 cycles of activation in which no activations are present. This finding is inconsistent with reentry near the left ventricular endocardium. In both A and B, RV activation and ECG appear disorganized, as expected for VF. (From Robichaux RP et al: Periods of highly synchronous, non-reentrant endocardial activation cycles occur during long-duration ventricular fibrillation. J Cardiovasc Electrophysiol 21:1266-1273, 2010.)

long-duration VF, a shock must not only halt reentrant activation wavefronts, but also halt focal, possibly triggered, activity. Thus, although significant advances have been made in our understanding of the mechanisms of defibrillation, it is clear that there is still much more to be learned.

Acknowledgment This work was supported in part by National Institutes of Health grant HL-42760.

REFERENCES 1. Beck CS, Pritchard WH, Feil HS: Ventricular fibrillation of long duration abolished by electric shock. JAMA 135:985-986, 1947. 2. Prevost JL, Battelli F: Sur quelques effets des décharges électriques sur le coeur des Mammifères. CRSAS 129:1267-1268, 1899. 3. Zoll PM, Linethal AJ, Gibson W, et al: Termination of ventricular fibrillation in man by externally applied electric countershock. N Engl J Med 254:727-732, 1956. 4. Akiyama T: Intracellular recording of in situ ventricular cells during ventricular fibrillation. Am J Physiol 240:465-471, 1981. 5. Gray RAJalife J, Panfilov AV, et al: Mechanisms of cardiac fibrillation. Science 270:1222-1223, 1995. 6. Swartz JF, Jones JL, Fletcher RD: Characterization of ventricular fibrillation based on monophasic action potential morphology in the human heart. Circulation 87:1907-1914, 1993. 7. Witkowski FX, Penkoske PS, Kavanagh KM: Activation patterns during ventricular fibrillation. In Zipes DP, Jalife J, editors: Cardiac electrophysiology: from cell to bedside, Philadelphia, 1995, Saunders, pp 539-544. 8. Zhou X, Guse P, Wolf PD, et al: Existence of both fast and slow channel activity during the early stages of ventricular fibrillation. Circ Res 70:773-786, 1992. 9. Chen PS, Shibata N, Wolf PD, et al: Epicardial activation during successful and unsuccessful ventricular defibrillation in open chest dogs. Cardiovasc Rev Rep 7:625-648, 1986. 10. Gray RA, Ayers G, Jalife J: Video imaging of atrial defibrillation in the sheep heart. Circulation 95:1038-1047, 1997.

11. Mower MM, Mirowshi M, Spears JF, Moore EN: Patterns of ventricular activity during catheter defibrillation. Circulation 49:858-861, 1974. 12. Wiggers CJ: The physiologic basis for cardiac resuscitation from ventricular fibrillation: method for serial defibrillation. Am Heart J 20:413-422, 1940. 13. Zipes DP, Fischer J, King RM, et al: Termination of ventricular fibrillation in dogs by depolarizing a critical amount of myocardium. Am J Cardiol 36:37-44, 1975. 14. Chen PS, Wolf PD, Claydon FJ III, et al: The potential gradient field created by epicardial defibrillation electrodes in dogs. Circulation 74:626-636, 1986. 15. Wharton JM, Wolf PD, Smith WM, et al: Cardiac potential and potential gradient fields generated by single, combined, and sequential shocks during ventricular defibrillation. Circulation 85:1510-1523, 1992. 16. Zhou X, Daubert JP, Wolf PD, et al: Epicardial mapping of ventricular defibrillation with monophasic and biphasic shocks in dogs. Circ Res 72:145-160, 1993. 17. Fishler MG, Sobie EA, Thakor NV, Tung L: Mechanisms of cardiac cell excitation with premature monophasic and biphasic field stimuli: a model study. Biophys J 70:1347-1362, 1996. 18. Henriquez CS: Simulating the electrical behavior of cardiac tissue using the bidomain model. Crit Rev Biomed Eng 21:1-77, 1993. 19. Fast VG, Rohr S, Gillis AM, Kléber AG: Activation of cardiac tissue by extracellular electrical shocks: formation of “secondary

sources” at intercellular clefts in monolayers of cultured myocytes. Circ Res 82:375-385, 1998. 20. Gillis AM, Fast VG, Rohr S, Kléber AG: Spatial changes in transmembrane potential during extracellular electrical shocks in cultured monolayers of neonatal rat ventricular myocytes. Circ Res 79:676-690, 1996. 21. Plonsey R, Barr RC: Inclusion of junction elements in a linear cardiac model through secondary sources: application to defibrillation. Med Biol Eng Comput 24:137-144, 1986. 22. Moe GK, Abildskov JA, Han J: Factors responsible for the initiation and maintenance of ventricular fibrillation. In Surawicz B, Pellegrino ED, editors: Sudden cardiac death, New York, 1964, Grune & Stratton. 23. Dillon SM, Mehra R: Prolongation of ventricular refractoriness by defibrillation shocks may be due to additional depolarization of the action potential. J Cardiovasc Electrophysiol 3:442-456, 1992. 24. Wiggers CJ: Studies of ventricular fibrillation caused by electric shock: cinematographic and electrocardiographic observations of the natural process in the dog’s heart—its inhibition by potassium and the revival of coordinated beats by calcium. Am Heart J 5:351-365, 1930. 25. Opthof T, Misier AR, Coronel R, et al: Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. Circ Res 68:1204-1215, 1991. 26. Worley SJ, Swain JL, Colavita PG, et al: Development of an endocardial-epicardial gradient of activation rate during

54

SECTION 1  Basic Principles of Device Therapy

electrically induced, sustained ventricular fibrillation in dogs. Am J Cardiol 55:813-820, 1985. 27. Ideker RE, Klein GJ, Harrison L, et al: Epicardial mapping of the initiation of ventricular fibrillation induced by reperfusion following acute ischemia. Circulation 58:II-64, 1978. 28. Rogers, J.M., Usui M, KenKnight B,et al: Recurrent wavefront morphologies: a method for quantifying the complexity of epicardial activation patterns. Ann Biomed Eng 25:761-768, 1997. 29. Samie FH, Berenfeld O, Anumonwo J, et al: Rectification of the background potassium current: a determinant of rotor dynamics in ventricular fibrillation. Circ Res 89:1216-1223, 2001. 30. Lewis T: The mechanism and graphic registration of the heart beat, ed 3, London, 1925, Shaw & Sons. 31. Gray RA, Jalife J: Self-organizing drifting spiral waves as a mechanism for atrial fibrillation. Circulation 94:I-94, 1996. 32. Newton JC, Evans FG, Chattipakorn N, et al: Peak frequency distribution across the whole fibrillating heart. Pacing Clin Electrophysiol 23:617, 2000. 33. Newton JC, Ideker RE: Estimated global transmural distribution of activation rate and conduction block during porcine and canine ventricular fibrillation. Circ Res 94:836-842, 2004. 34. Allessie M, Kirchhof C,Scheffer GJ, et al: Regional control of atrial fibrillation by rapid pacing in conscious dogs. Circulation 84:1689-1697, 1991. 35. KenKnight BH, Bayly PV, Gerstle RJ, et al: Regional capture of fibrillating ventricular myocardium. Evidence of an excitable gap. Circ Res 77:849-855, 1995. 36. Witkowski FX, Penkoske PA, Plonsey R: Mechanism of cardiac defibrillation in open-chest dogs with unipolar DC-coupled simultaneous activation and shock potential recordings. Circulation 82:244-260, 1990. 37. Bardy GH, Ivey TD, Allen MD, et al: A prospective randomized evaluation of biphasic versus monophasic waveform pulses on defibrillation efficacy in humans. J Am Coll Cardiol 14:728-733, 1989. 38. Block M, Hammel D, Böcker D, et al: A prospective randomized cross-over comparison of mono- and biphasic defibrillation using nonthoracotomy lead configurations in humans. J Cardiovasc Electrophysiol 5:581-590, 1994. 39. Chapman PD, Vetter JW, Souza JJ, et al: Comparison of monophasic with single and dual capacitor biphasic waveforms for nonthoracotomy canine internal defibrillation. J Am Coll Cardiol 14:242-245, 1989. 40. Dixon EG, Tang ASL, Wolf PD, et al: Improved defibrillation thresholds with large contoured epicardial electrodes and biphasic waveforms. Circulation 76:1176-1184, 1987. 41. Gurvich NL, Markarychev VA: Defibrillation of the heart with biphasic electrical impulses. Kardiologiia 7:109-112, 1967. 42. Walcott GP, Melnick SB, Chapman FW, et al: Comparison of monophasic and biphasic waveforms for external defibrillation in an animal model of cardiac arrest and resuscitation. J Am Coll Cardiol 25:405A, 1995. 43. Feeser SA, Tang ASL, Kavanagh KM, et al: Strength-duration and probability of success curves for defibrillation with biphasic waveforms. Circulation 82:2128-2141, 1990. 44. Tang AS, Yabe S, Wharton JM, et al: Ventricular defibrillation using biphasic waveforms: the importance of phasic duration. J Am Coll Cardiol 13:207-214, 1989. 45. Kroll MW: A minimal model of the monophasic defibrillation pulse. Pacing Clin Electrophysiol 16:769-777, 1993. 46. Kroll MW: A minimal model of the single capacitor biphasic defibrillation waveform. Pacing Clin Electrophysiol 17:17821792, 1994. 47. Swerdlow CD, Fan W, Brewer JE: Charge-burping theory correctly predicts optimal ratios of phase duration for biphasic defibrillation waveforms. Circulation 94:2278-2284, 1996. 48. Walcott GP, Walker RG, Krassowska W, et al: Choosing the optimum monophasic and biphasic waveforms for defibrillation. Pacing Clin Electrophysiol 17:789, 1994. 49. Blair HA: On the intensity-time relations for stimulation by electric currents. II. J Gen Physiol 15:731-755, 1932. 50. Lapicque L: L’Excitabilite en fonction du temps. Paris, 1926, Libraire J Gilbert, p 371. 51. Irnich W: The fundamental law of electrostimulation and its application to defibrillation. Pacing Clin Electrophysiol 13:14331447, 1990. 52. Sweeney RJ, Gill GM, Jones JL, Reid PR: Defibrillation using a high-frequency series of monophasic rectangular pulses: observations and model predictions. J Cardiovasc Electrophysiol 7:134143, 1996. 53. Walcott GP, Walker RG, Cates AW, et al: Choosing the optimal monophasic and biphasic waveforms for ventricular defibrillation. J Cardiovasc Electrophysiol 6:737-750, 1995. 54. Gold MR, Shorofsky SR: Strength-duration relationship for human transvenous defibrillation. Circulation 96:3517-3520, 1997. 55. Schuder JC, Stoeckle H, West JA,Kesar PY: Transthoracic ventricular defibrillation in the dog with truncated and untruncated exponential stimuli. IEEE Trans Biomed Eng 18:410-415, 1971. 56. Walcott GP, Melnick SB, Chapman FW, et al: Comparison of damped sinusoidal and truncated exponential waveforms for external defibrillation. J Am Coll Cardiol 27:237A, 1996. 57. Harbinson MT, Allen JD, Imam Z, et al: Rounded biphasic waveform reduces energy requirements for transvenous catheter cardioversion of atrial fibrillation and flutter. Pacing Clin Electrophysiol 20:226-229, 1997.

58. Hillsley RE, Walker RG, Swanson DK, et al: Is the second phase of a biphasic defibrillation waveform the defibrillating phase? Pacing Clin Electrophysiol 16:1401-1411, 1993. 59. Schuder JC, Rahmoeller GA, Stoeckle H: Transthoracic ventricular defibrillation with triangular and trapezoidal waveforms. Circ Res 19:689-694, 1966. 60. Denman RA, Umesan C, Martin PT, et al: Benefit of millisecond waveform durations for patients with high defibrillation thresholds. Heart Rhythm 3:536-541, 2006. 61. Keane D, Aweh N, Hynes B, et al: Achieving sufficient safety margins with fixed duration waveforms and the use of multiple time constants. Pacing Clin Electrophysiol 30:596-602, 2007. 62. Bardy GH, Marchlinski FE, Sharma AD, et al: Multicenter comparison of truncated biphasic shocks and standard damped sine wave monophasic shocks for transthoracic ventricular defibrillation. Transthoracic Investigators. Circulation 94:2507-2514, 1996. 63. Camacho MA, Lehr JL, Eisenberg SR: A three-dimensional finite element model of human transthoracic defibrillation: paddle placement and size. IEEE Trans Biomed Eng 42:572-578, 1995. 64. Lerman BB, Deale OC: Relation between transcardiac and transthoracic current during defibrillation in humans. Circ Res 67:1420-1426, 1990. 65. Karlon WJ, Eisenberg SR, Lehr JL: Effects of paddle placement and size on defibrillation current distribution: a threedimensional finite element model. IEEE Trans Biomed Eng 40:246-255, 1993. 66. Block M, Hammel D, Isburch F, et al: Results and realistic expectations with transvenous lead systems. Pacing Clin Electrophysiol 15:665-670, 1992. 67. Tang ASL, Wolf PD, Afework Y, et al: Three-dimensional potential gradient fields generated by intracardiac catheter and cutaneous patch electrodes. Circulation 85:1857-1864, 1992. 68. Tang ASL, Wolf PD, Claydown FJ III, et al: Measurement of defibrillation shock potential distributions and activation sequences of the heart in three-dimensions. Proc IEEE 76:11761186, 1988. 69. Chen PS, Wolf PD, Melnick SD, et al: Comparison of activation during ventricular fibrillation and following unsuccessful defibrillation shocks in open-chest dogs. Circ Res 66:1544-1560, 1990. 70. Chattipakorn N, Banville I, Gray RA, Ideker RE: Effects of shock strengths on ventricular defibrillation failure. Cardiovasc Res 61:39-44, 2004. 71. Shibata N, Chen PS, Dixon EG, et al: Epicardial activation after unsuccessful defibrillation shocks in dogs. Am J Physiol 255: 902-909, 1988. 72. Walcott GP, Chau WC, Ideker RE, et al: Early activation following shocks delivered in humans: the difference between transvenous and “active can” ICD systems. J Am Coll Cardiol 29:427A, 1997. 73. Crossley GH, Boyce K, Roelke M, et al: A prospective randomized trial of defibrillation thresholds from the right ventricular outflow tract and the right ventricular apex. Pacing Clin Electrophysiol 32:166-171, 2009. 74. Verma A, Kaplan AJ, Sarak B, et al: Incidence of very high defibrillation thresholds (DFT) and efficacy of subcutaneous (SQ) array insertion during implantable cardioverter defibrillator (ICD) implantation. J Interv Card Electrophysiol 29:127-133, 2010. 75. Kommuri NV, Kollepara SL, Saulitis E, et al: Azygos vein lead implantation for high defibrillation thresholds in implantable cardioverter defibrillator placement. Indian Pacing Electrophysiol J 10:49-54, 2010. 76. Walker RG, Walcott GP, Smith WM, Ideker IE: Sites of earliest activation following transvenous defibrillation. Circulation 90(pt 2):I-447, 1994. 77. Cates AW, Wolf PD, Hillsley RE, et al: The probability of defibrillation success and the incidence of postshock arrhythmia as a function of shock strength. Pacing Clin Electrophysiol 17:12081217, 1994. 78. Chapman FW, El-Abbaday TZ, Walcott GP, et al: Dysfunction following transthoracic defibrillation shocks in dogs. Pacing Clin Electrophysiol 20:1128, 1997. 79. Reddy RK, Gleva MJ, Gliner BE, et al: Biphasic transthoracic defibrillation causes fewer ECG ST-segment changes after shock. Ann Emerg Med 30:127-134, 1997. 80. DeBruin KA, Krassowska W: Electroporation and shockinduced transmembrane potential in a cardiac fiber during defibrillation strength shocks. Ann Biomed Eng 26:584-596, 1998. 81. Schuder JC, Gold JH, Stoeckle H, et al: Transthoracic ventricular defibrillation in the 100 kg calf with symmetrical one-cycle bidirectional rectangular wave stimuli. IEEE Trans Biomed Eng 30:415-422, 1983. 82. Yabe S, Smith DM, Duabert JP, et al: Conduction disturbances caused by high current density electric fields. Circ Res 66:11901203, 1990. 83. Jones JL, Jones RE: Decreased defibrillator-induced dysfunction with biphasic rectangular waveforms. Am J Physiol 247: H792H796, 1984. 84. Walcott GP, Knisley SB, Zhou X, et al: On the mechanism of ventricular defibrillation. Pacing Clin Electrophysiol 20:422-431, 1997. 85. Clark DM, Rogers JM, Ideker RE, Knisley SB: Intracardiac defibrillation-strength shocks produce large regions of hyperpolarization and depolarization. J Am Coll Cardiol 27:147A, 1996.

86. Zhou X, Wolf PD, Rollins DL, et al: Effects of monophasic and biphasic shocks on action potentials during ventricular fibrillation in dogs. Circ Res 73:325-334, 1993. 87. Daubert JP, Frazier DW, Wolf PD, et al: Response of relatively refractory canine myocardium to monophasic and biphasic shocks. Circulation 84:2522-2538, 1991. 88. Colavita PG, Wolf PD, Smith WM, et al: Determination of effects of internal countershock by direct cardiac recordings during normal rhythm. Am J Physiol 250: H736-H740, 1986. 89. Weidmann S: Electrical constants of trabecular muscle from mammalian heart. J Physiol 210:1041-1054, 1970. 90. Kléber AG, Riegger CB: Electrical constants of arterially perfused rabbit papillary muscle. J Physiol 385:307-324, 1987. 91. Krassowska W, Frazier DW, Pilkington TC, Ideker RE: Potential distribution in three-dimensional periodic myocardium. Part II. Application to extracellular stimulation. IEEE Trans Biomed Eng 37:267-284, 1990. 92. Krassowska W, Pilkington TC, Ideker RE: Potential distribution in three-dimensional periodic myocardium. Part I. Solution with two-scale asymptotic analysis. IEEE Trans Biomed Eng 37:252-266, 1990. 93. Plonsey R, Barr RC: Effect of microscopic and macroscopic discontinuities on the response of cardiac tissue to defibrillating (stimulating) currents. Med Biol Eng Comput 24:130-136, 1986. 94. White JB, Walcott GP, Pollard AE, Ideker RE: Myocardial discontinuities: a substrate for producing virtual electrodes that directly excite the myocardium by shocks. Circulation 97:17381745, 1998. 95. Tung L: A bidomain model for describing ischemic myocardial DC potentials, Cambridge, 1978, Massachusetts Institute of Technology. 96. Trayanova N: Discrete versus syncytial tissue behavior in a model of cardiac stimulation. II. Results of simulation. IEEE Trans Biomed Eng 43:1141-1150, 1996. 97. Trayanova N: Discrete versus syncytial tissue behavior in a model of cardiac stimulation. I. Mathematical formulation. IEEE Trans Biomed Eng 43:1129-1140, 1996. 98. Kieval RS, Spear JF, Moore EN: Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium. Circ Res 71:127-136, 1992. 99. Shaw RM, Rudy Y: Electrophysiologic effects of acute myocardial ischemia: a mechanistic investigation of action potential conduction and conduction failure. Circ Res 80:124-138, 1997. 100. Shaw RM, Rudy Y: Ionic mechanisms of propagation in cardiac tissue: roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling. Circ Res 81:727-741, 1997. 101. Knisley SB, Blitchington TF, Hill BC, et al: Optical measurements of transmembrane potential changes during electric field stimulation of ventricular cells. Circ Res 72:255-270, 1993. 102. Windisch H, Ahammer H, Schaffer P, et al: Optical multisite monitoring of cell excitation phenomena in isolated cardiomyocytes. Pflugers Arch 430:508-518, 1995. 103. Wikswo JP, Lin SF, Abbas RA: Virtual electrodes in cardiac tissue: a common mechanism for anodal and cathodal stimulation. Biophys J 69:2195-2210, 1995. 104. Zhou, X., Ideker RE, Blitchington TF, et al: Optical transmembrane potential measurements during defibrillation-strength shocks in perfused rabbit hearts. Circ Res 77:593-602, 1995. 105. Sommer JR, Scherer B: Geometry of cell and bundle appositions in cardiac muscle: light microscopy. Am J Physiol 248:H792H803, 1985. 106. Street AM, Plonsey R: Activation fronts elicited remote to the pacing site due to the presence of scar tissue. In Proc 18th Annu Int Conf IEEE Eng Med Biol Soc, Amsterdam, 1996, Piscataway, NJ, Institute of Electrical and Electronics Engineers. 107. Sharifov OF, Ideker RE, Fast VG: High-resolution optical mapping of intramural virtual electrodes in porcine left ventricular wall. Cardiovasc Res 64:448-456, 2004. 108. Clerc L: Directional differences of impulse spread in trabecular muscle from mammalian heart. J Physiol 255:335-346, 1976. 109. Knisley SB: Transmembrane voltage changes during unipolar stimulation of rabbit ventricle. Circ Res 77:1229-1239, 1995. 110. Efimov IR, Cheng YN, Van Wagoner DR, et al: Virtual electrodeinduced phase singularity: a basic mechanism of defibrillation failure. Circ Res 82:918-925, 1998. 111. Efimov IR, Cheng YN, Bierman M, et al: Transmembrane voltage changes produced by real and virtual electrodes during monophasic defibrillation shock delivered by an implantable electrode. J Cardiovasc Electrophysiol 8:1031-1045, 1997. 112. Iyer AN, Gray RA: An experimentalist’s approach to accurate localization of phase singularities during reentry. Ann Biomed Eng 29:47-59, 2001. 113. Knisley SB, Smith WM, Ideker RE: Effect of field stimulation on cellular repolarization in rabbit myocardium. Implications for reentry induction. Circ Res 70:707-715, 1992. 114. Chen PS, Wolf PD, Dixon EG, et al: Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogs. Circ Res 62:1191-1209, 1988. 115. Frazier DW, Wolf PD, Wharton JM, et al: Stimulus-induced critical point: mechanism for electrical initiation of reentry in normal canine myocardium. J Clin Invest 83:1039-1052, 1989. 116. Winfree AT: When time breaks down: the three-dimensional dynamics of electrochemical waves and cardiac arrhythmias, Princeton, NJ, 1987, Princeton University Press. 117. Efimov IR, Cheng Y, Yamanouchi Y, et al: Direct evidence of the role of virtual electrode-induced phase singularity in success and



2  Principles of Defibrillation: From Cellular Physiology to Fields and Waveforms

failure of defibrillation. J Cardiovasc Electrophysiol 11:861-868, 2000. 118. Chen PS, Shibata N, Dixon EG, et al: Activation during ventricular defibrillation in open-chest dogs: evidence of complete cessation and regeneration of ventricular fibrillation after unsuccessful shocks. J Clin Invest 77:810-823, 1986. 119. Chattipakorn N, Fotuhi PC, Ideker RE: Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold. J Cardiovasc Electrophysiol 11:1014-1021, 2000. 120. Chattipakorn N, Banville I, Gray RA, Ideker RE: Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine. Circulation 104:1313-1319, 2001. 121. Wang NC, Lee MH, Ohara T, et al: Optical mapping of ventricular defibrillation in isolated swine right ventricles: demonstration of a postshock isoelectric window after near-threshold defibrillation shocks. Circulation 104:227-233, 2001. 122. Chattipakorn N, Fotuhi PC, Chattipakorn SC, et al: Threedimensional mapping of earliest activation after near-threshold

ventricular defibrillation shocks. J Cardiovasc Electrophysiol 14:65-69, 2003. 123. Hwang GS, Hayashi H, Tang L, et al: Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorffperfused rabbit ventricles. Circulation 114:2595-2603, 2006. 124. Constantino J, Long Y, Ashihara T, Trayanova NA: Tunnel propagation following defibrillation with ICD shocks: hidden postshock activations in the left ventricular wall underlie isoelectric window. Heart Rhythm 7:953-961, 2010. 125. Hwang GS, Tang L, Joung B, et al: Superiority of biphasic over monophasic defibrillation shocks is attributable to less intracellular calcium transient heterogeneity. J Am Coll Cardiol 52:828835, 2008. 126. Chattipakorn N, Ideker RE: Delayed afterdepolarization inhibitor: a potential pharmacologic intervention to improve defibrillation efficacy. J Cardiovasc Electrophysiol 14:72-75, 2003. 127. Zheng X, Walcott GP, Smith WM, et al: Evidence that activation following failed defibrillation is not caused by triggered activity. J Cardiovasc Electrophysiol 16:1200-1205, 2005.

55

128. Zheng X, Li L, Dosdall DJ, et al: Following long duration ventricular fibrillation, flunarizine greatly reduces the defibrillation threshold and the incidence of refibrillation. Circulation 120(Suppl 2):1481, 2009. 129. Dosdall DJ, Osorio J, Robichaux RP, et al: Purkinje activation precedes myocardial activation following defibrillation after long-duration ventricular fibrillation. Heart Rhythm 7:405-412, 2010. 130. Wiggers CJ: The mechanism and nature of ventricular fibrillation. Am Heart J 20:399-412, 1940. 131. Huang J, Rogers JM, Killingsworth CR, et al: Evolution of activation patterns during long-duration ventricular fibrillation in dogs. Am J Physiol Heart Circ Physiol 286:H1193-H1200, 2004. 132. Huizar JF, Warren MD, Shvedko AG, et al: Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart. Am J Physiol Heart Circ Physiol 293:H1617-H1628, 2007. 133. Robichaux RP, Dosdall DJ, Osorio J, et al: Periods of highly synchronous, non-reentrant endocardial activation cycles occur during long-duration ventricular fibrillation. J Cardiovasc Electrophysiol 21:1266-1273, 2010.

56

3 

SECTION 1  Basic Principles of Device Therapy

Sensing and Detection CHARLES D. SWERDLOW  |  JEFFREY M. GILLBERG  |  PAUL KHAIRY

Sensing of cardiac depolarizations and detection of arrhythmias

control the electrical therapies of pacemakers and implantable cardioverter-defibrillators (ICDs). When a wavefront of depolarization passes the tip electrode of an intracardiac lead, a deflection in the continuous electrogram signal travels instantaneously up the lead wire to the pacemaker or ICD, where sensing electronics amplifies, filters, digitizes, and processes the signal. A sensed event occurs at the instant when the sensing system determines that an atrial or ventricular depolarization has occurred. Dual-chamber pacemakers and ICDs have separate sensing systems for the atrium and ventricle. Appropriate sensing results in one sensed event for each activation wavefront in the corresponding chamber. Failure to sense activation wavefronts results in undersensing, which can cause inappropriate pacing, failure to switch modes, or failure to detect a tachyarrhythmia. Undersensing occurs if the depolarization signal has insufficient amplitude or frequency content to be recognized as a sensed event, or if a blanking period disables the sensing amplifier at the time of the event. Oversensing occurs when nonphysiologic signals or physiologic signals that do not reflect local myocardial depolarization are sensed. Oversensing can cause inappropriate pacing inhibition, pacemaker tracking, or ICD therapy. Detection algorithms process sensed events to classify the atrial or ventricular rhythm. This classification is used to control beat-by-beat paced events, to change the pacing mode, to store data regarding tachyarrhythmias, and to terminate sustained tachyarrhythmias with antitachycardia pacing or shocks.

Electrograms SURFACE ELECTROCARDIOGRAM VS. INTRACARDIAC ELECTROGRAM An electrogram (EGM) is a graphic display of the potential difference between two points in space over time. During the upstroke of a myocardial action potential, the inside of the cell abruptly changes from its resting negative potential (with respect to the outside of the cell) to a neutral or slightly positive potential. After about 250 to 400 milliseconds (msec), the cell membrane is then repolarized, with the inside of the cell returning to its resting, negatively charged state. Figure 3-1 illustrates how an EGM is recorded between two electrodes in contact with the myocardium. The electrocardiogram (ECG) is recorded from two electrodes on the surface of the body at some distance from the heart. The typical amplitude of its QRS complex is about 1 millivolt (mV). The locations of the two electrodes determine the vectorial “viewpoint” from which the electrical activity of the entire heart is observed from the body surface. In contrast, the ventricular endocardial unipolar EGM typically is 5 to 20 mV in amplitude when recorded from a small electrode on the tip of a lead placed in direct contact with the apex of the right ventricle (Fig. 3-2). The second electrode needed to record this unipolar EGM is the pacemaker or ICD metal “can,” which is located some distance from the heart. The location of this distant second electrode, sometimes called the “indifferent electrode,” has a much smaller effect on the signal’s properties, although it may record noncardiac electric potentials (e.g., from pectoral muscle). The ECG records electrical activity from the entire heart, whereas the EGM records only local wavefronts of depolarization and repolarization. The EGM depends on

56

the viability of approximately 1 or 2 cm3 of myocardium immediately under the tip electrode,1,2 as depicted in Figure 3-2. ELECTRODE SYSTEMS Figure 3-3 contrasts endocardial unipolar (tip-to-can), bipolar (tip-toring), and integrated bipolar (tip-to-coil) electrode systems, and Figure 3-4 shows representative examples. Epicardial electrode systems may be either unipolar (tip-to-can) or bipolar (tip-to-tip). These different electrode configurations have EGMs with similar R-wave amplitudes and slew rates, provided that the interelectrode spacing is at least 10 mm, as is true of almost all commercial pacemaker and defibrillator leads. Because they are more likely to oversense than bipolar EGMs, unipolar electrode systems are contraindicated for ICDs and are used infrequently for modern pacemakers. ICD integrated bipolar electrodes sense between the right ventricular tip electrode and right ventricular high-voltage coil, with sensing characteristics closer to the bipolar than the unipolar configuration. Compared with true bipolar electrodes, integrated ICD bipolar electrodes are more likely to oversense myopotentials and electromagnetic interference (EMI).3,4 In one study, oversensing occurred in 40% of patients with integrated bipolar sensing, compared with 8% of patients with true bipolar systems.4 AMPLITUDE, SLEW RATE, AND WAVESHAPE The largest and steepest deflection on the local EGM, called the intrinsic deflection, occurs when the wavefront of depolarization passes the small-tip electrode. The EGM amplitude traditionally is defined as the peak-to-peak amplitude of the intrinsic deflection (measured in mV), as shown in Figure 3-5. The duration of a ventricular EGM usually is less than that of the QRS of the surface ECG, because the EGM is a local signal. The amplitude of an atrial electrogram (AEGM) or ventricular electrogram (VEGM) is determined primarily by the excitable tissue near the tip electrode and therefore is usually similar for unipolar and bipolar signals. Typical amplitudes are 5 to 30 mV for VEGMs and 1.5 to 6 mV for AEGMs.1,2,5 The maximum slope of the intrinsic deflection is the slew rate, measured in volts per second, which represents the maximum rate of change of EGM voltage. Mathematically, it is the first derivative of the voltage, dV/dt, so it depends on both the amplitude and the duration of the EGM, and it provides a crude representation of the frequency content. The frequency content of ventricular and atrial EGMs is similar and in the range of 5 to 50 Hz. T waves and far-field R waves have lower frequency content, whereas most myopotentials and EMI have higher frequency content (Fig. 3-6). Typical values for slew rates are 2 to 3 V/sec for VEGMs and 1 to 2 V/sec for AEGMs.3,4 Usually, an EGM with acceptable amplitude also has an acceptable minimum slew rate (>1 V/sec for VEGMs, >0.3 V/sec for AEGMs). EGMs with very low amplitude will not be sensed, regardless of the slew rate. Increasing the size of the tip electrode in the range of 2 to 10 millimeters (mm) has minimal effect on atrial EGM amplitude but increases EGM duration (Fig. 3-7). For short ventricular bipolar interelectrode spacing of 5 mm or less, the R-wave amplitude decreases, because the difference between the two unipolar EGMs from each electrode causes cancellation in the net bipolar signal. The slew rate increases, because the time between arrival of the wavefront at the two electrodes decreases more than the EGM amplitude. When two electrodes are widely separated, as in early Y-adapted cardiac



3  Sensing and Detection

1

2

     

     

     

     

A

1

2   

    

     

57

resynchronization electrode systems, two distinct intrinsic deflections may be recorded on the EGM—one representing right ventricular (RV) activation and the other left ventricular (LV) activation. The interval between these deflections is determined by the conduction delay between the ventricles near the two electrodes. The waveshapes of EGMs are quite variable (Fig. 3-8), probably because geometry of the trabecular endocardium adjacent to the tip electrode is complex. In one study at pacemaker lead implantation, 58% of unipolar EGMs were biphasic, with an initial upstroke followed by a roughly equal downstroke; 30% were predominantly monophasic negative, and 12% were predominantly monophasic positive.1 The ventricular depolarization recorded on the atrial electrode is referred to as the far-field R wave (FFRW). Oversensing of the FFRW confounds interpretation of the atrial rhythm. The amplitude of the FFRW depends on the location of the atrial electrode. It is greatest near the septum, intermediate in the right atrial appendage, and least on

     

B

1

2   

    

     

C

Tip electrode

1

1

2

3 2

    

     

1

Voltage

D

3

2

         

1

2      

E Figure 3-1  An electrogram (EGM) is recorded between two electrodes in contact with the myocardium. A, At rest, both electrodes record a similar charge, with no potential difference between them.  B and C, As a wavefront of depolarization moves under electrode 1, a difference in electrical charge is generated such that electrode  1 becomes electrically negative with respect to electrode 2. D, As the wavefront propagates under electrode 2, no potential difference between the two electrodes is recorded. E, The depolarization wavefront is followed by a wavefront of repolarization, during which a potential difference of opposite polarity is recorded. Because the EGM is determined by the instantaneous potential difference between the electrodes, the amplitude and shape of the recorded signal are determined by the direction from which the wavefront approaches the electrodes. For example, if a wavefront of depolarization reached both electrodes at the same time, there would be no potential difference between the electrodes, and an EGM would not be inscribed.

Time Figure 3-2  Concept drawing of spatial and temporal relationships for unipolar endocardial EGM. Upper panel, Anatomic drawing. Lower panel, EGM recorded from a small-surface-area electrode at the tip of a pacemaker or defibrillator lead that makes direct contact with the endocardium in the right ventricular (RV) apex. The second electrode required to record an EGM is not shown, because it is a distant and “indifferent” electrode, usually the metal can of the pulse generator, and its location is not important provided that it is a substantial distance from the tip electrode. During a ventricular depolarization, the depolarization wavefront propagates from the septum, around the RV apex, and up the RV free wall (arrows). When the wavefront of depolarization arrives at location 1, just as it approaches the electrode, the initial positive deflection of the EGM occurs, at time 1. When the wavefront passes closest to the tip electrode at location 2, the major negative deflection on the EGM occurs, labeled as time 2. As the wavefront recedes from the electrode at location 3, the final portion of the EGM is inscribed at time 3. This local EGM is not affected by the depolarization wavefront as it travels farther from the electrode. Therefore, the local EGM is shorter in duration than the surface electrocardiographic QRS complex.

58

SECTION 1  Basic Principles of Device Therapy

pulse generator. Greater sensing safety margins are preferred for activefixation leads. The method of lead tip stabilization, active screw-in or passive tines, has had no significant effect on sensing characteristics in most studies.8,9 Steroid-eluting electrodes reduce chronic pacing thresholds substantially, but also have no significant effects on sensing.10-13 Metabolic, Ischemic, Aging, and Drug Effects RV-Coil

Ring Tip

Figure 3-3  The three practical endocardial electrode configurations used by most pacemakers and ICDs. The distant and indifferent or “can” electrode is not shown because it is out of the field of view. The unipolar configuration used in Figure 3-1 to explain EGM formation simply records the signal between the tip electrode and the can. The tip electrode can be an active-fixation screw or a small-surface-area tip electrode with various geometries. This unipolar configuration is subject to considerable noise and interference signals and is not suitable for ICDs. The bipolar configuration uses the Tip and Ring electrodes shown in this figure. The interelectrode spacing is typically 12 to 15 mm, and the ring electrode may or may not make contact with the endocardium. The integrated bipolar configuration uses the Tip and RV-Coil electrodes shown in the figure. EGMs recorded from bipolar and integrated bipolar configurations are very similar, and one less conductor is needed for the integrated bipolar configuration. The main disadvantages of the integrated bipolar configuration are susceptibility to diaphragmatic myopotentials, undesired atrial EGMs in small hearts, and slower postshock recovery times caused by electrode polarization. RV, Right ventricular.

the right atrial free wall. Even if the FFRW has comparable amplitude to the P wave, its slew rate usually is much lower. In one series, the mean slew rate was 1.2 V/sec for AEGMs and 0.13 V/sec for FFRWs.1 If an active-fixation, screw-in tip electrode is successfully attached to the myocardium, the acute VEGM has a current of injury, with an elevated ST segment (Fig. 3-9) that is usually greatly reduced within 10 minutes after electrode fixation. During this 10-minute period, the EGM amplitude and slew rate usually do not change despite changes in waveshape, but the pacing threshold decreases by an average of 40%.2 Acute to Chronic Changes and Fixation The amplitude and slew rate of intracardiac EGMs typically decline during the first several days to weeks after lead implantation and then increase to chronic values that are slightly lower than those measured at implantation.6 The initial decrease in EGM amplitude is caused by the inflammatory response and edema at the electrode-tissue interface. This gradually resolves and is followed by development of a small, inexcitable fibrotic zone surrounding the electrode tip (Fig. 3-10). This inflammation and fibrotic tissue effectively increases the distance between the surface of the electrode and excitable myocardium that generates the EGM signal. Although chronic EGM amplitudes usually are reduced by less than 10% compared with acute amplitudes, chronic slew rates are reduced by 30% to 40%.7 The acute reduction in EGM amplitude is often greater with activefixation leads than with passive fixation leads. Atrial undersensing can occur during the acute phase despite adequate EGM amplitudes at implantation. To account for these time-related changes in EGM amplitude, the filtered EGM recorded at lead implantation should be at least twice the sensitivity threshold that will be programmed in the

The effects of metabolic abnormalities and drugs on pacing thresholds are well described. Much less information is available concerning their effects on EGMs and sensing. Factors that reduce EGM amplitude, slow conduction velocity, or diminish slew rate may produce either oversensing or undersensing. By prolonging the intracardiac EGM duration beyond blanking periods, ischemia or antiarrhythmic drugs can produce double-counting of the QRS complex.14 Similarly, drugs that prolong the PR or QT interval beyond the refractory period may result in oversensing.15,16 Undersensing may result from reduction in EGM amplitude or slew rate after myocardial infarction at the electrode-tissue interface, from drug and electrolyte effects,15,16 or from progression of conduction system disease. Acute ischemia causes ST-segment changes that can be detected on VEGMs. Monitoring of EGM ST-segment shifts has been proposed as a method for monitoring ischemia for pacemakers and ICDs.17 The likelihood of recording abnormal AEGMs (defined as ≥100 msec in duration or having ≥8 fragmented deflections) correlates with age of the patient (r = 0.34; P < .0005).18 Exercise, Respiratory, and Postural Effects The effect of exercise on the AEGM amplitude and slew rate is variable. Some studies have reported statistically significant decreases in amplitude that average 10% to 20% but may reach 40% in some patients.19,20 Other studies did not find significant changes between rest and exercise.21,22 Decreases in AEGM amplitude were not caused by atrial rate alone or by beta blockade.23 VDD/R lead studies with “floating” atrial electrodes showed particularly large decreases with exercise.24,25 Decreases in AEGM amplitude with lead maturation support the programming of a large safety margin for sensing at implantation to offset effects of lead maturation. P-wave amplitude increases significantly during full inspiration, during full expiration, and with erect posture.22 Respiratory variation averaged 9.7% for unipolar AEGMs and 11.5% for bipolar AEGMs.25,26 The effect of respiration on VEGMs was less, especially with the unipolar configuration.26 Ventricular Electrograms during Premature Ventricular Complexes, Ventricular Tachycardia, and Ventricular Fibrillation Premature ventricular complexes (PVCs) may have lower-amplitude R waves than sinus-rhythm R waves, as shown in Figure 3-11, but the reverse may also be true. For monomorphic ventricular tachycardia (VT), mean amplitude decreased only slightly from values in sinus rhythm—14% for epicardial EGMs and 5% for endocardial EGMs.27 In contrast, EGM amplitudes during ventricular fibrillation (VF) decreased by 25% for epicardial and 41% for endocardial EGMs. More importantly, EGMs in VF often have low, highly variable, and rapidly changing amplitudes and slew rates. Figure 3-12 shows endocardial spontaneous VF EGMs from different patients, illustrating variability in intrinsic deflections, amplitudes, slew rates, and morphologies. In a study of induced VF reproducibility, 50% of the variability was caused by interpatient differences and the other 50% occurred among repeated episodes in the same patient.28 In another study, the VEGM amplitude in VF was 1 mV or less in at least one VF episode in 29% of patients.27 If VF lasts for minutes, the amplitude and slew rate of the EGMs decrease. Atrial Electrograms during Rhythms Other Than Sinus Atrial activation from ectopic sites or atrial arrhythmias can alter the amplitude, frequency content, slew rate, and morphology of the



3  Sensing and Detection

59

Figure 3-4  Ventricular electrocardiograms (ECGs) recorded from different electrode configurations in the same patient. The central panel shows a left anterior oblique radiograph of a cardiac resynchronization ICD system. Each of the four tracings shows surface ECG lead II, EGM markers, and one ventricular EGM during atrial pacing at a rate of 75 bpm. Top left, Far-field EGM recorded between the right ventricular (RV) coil electrode and the electrically active ICD housing (CAN). Lower left, Integrated bipolar EGM recorded between RV tip and RV coil electrodes. Lower right, True bipolar EGM recorded between the RV tip and ring electrodes. Top right, Left ventricular (LV) unipolar EGM recorded between the LV tip electrode and can. EGM scale is 0.5 mV/mm, except for the LV unipolar EGM, which has a scale of 2 mV/mm. The downward EGM ventricular sense (VS) markers correspond to the time at which the true bipolar RV tip-ring EGM crosses the sensing threshold. Because the “field of view” of this EGM is local, its duration is short. It occurs early in the QRS complex of this patient with left bundle branch block. The integrated bipolar tipcoil EGM has a peak-to-peak amplitude and slew rate similar to those of the true bipolar EGM. However, its field of view is larger due to the size of the RV coil, and therefore the T wave is larger. Low-amplitude atrial EGMs are visible because of the proximity of the coil to the tricuspid anulus. Both the RV coil-CAN and the LV unipolar EGM are widely spaced, between an intracardiac electrode and the extracardiac can. Their duration is closer to that of the QRS complex. The intrinsic deflection of the LV unipolar electrode is late in the QRS complex, corresponding to late activation of the lateral left ventricle. The greater amplitude of the LV unipolar EGM reflects the greater muscle mass of the left ventricle. EGMs recorded from the superior vena cava (SVC) coil and from the atrial bipole (right atrium, RA) are not shown. Radiograph and EGMs are from different patients. Radiograph is for illustrative purposes only.

AEGM. Retrograde atrial activation during ventricular pacing reduces AEGM amplitude and slew rate by up to 50%.29 These EGM changes are more pronounced in the high right atrium than in the right atrial appendage or low right atrium.30 The frequency content of the AEGM is not significantly altered by retrograde atrial activation.31 Analysis of EGM turning-point morphology or the first-differential coefficient of slew rate has been used to discriminate sinus EGMs from those recorded during retrograde and ectopic atrial activation in small groups of patients.32 Atrial EGMs during atrial fibrillation (AF) are characterized by extreme temporal and spatial variability. EGMs tend to be most organized in the trabeculated right atrial appendage and more disorganized in the smooth right atrium or coronary sinus.33-35 Thus electrode spacing and positioning of atrial leads influence EGM characteristics during AF36-38 and may cause inconsistent diagnosis of AF based on rate criteria. The amplitude of chronic, unipolar pacemaker EGMs was 40% less in AF than in sinus rhythm.39 A comparison of acute AEGM amplitudes recorded with temporary pacing catheters showed that the mean sinus-rhythm EGM amplitude decreased only slightly in atrial flutter but decreased by about 50% in AF.35 Antiarrhythmic drugs may also

interfere with sensing during AF by reducing atrial rate, median frequency, and EGM amplitude.40 SUBCUTANEOUS ELECTROCARDIOGRAPHY The subcutaneous ECG is similar to the surface ECG because the two subcutaneous electrodes are sufficiently distant from the heart that they record electrical activity from the entire heart. As with the surface ECG, the amplitude of subcutaneous ECG signals usually is 1 mV or less. Simultaneous recordings of subcutaneous ECG signals and surface ECG signals from electrodes placed directly over the subcutaneous locations have similar amplitude and signal-to-noise ratio.41 Practical implantation considerations usually limit the subcutaneous electrode separation distance to 4 to 8 cm, compared with the typical surface ECG limb lead electrode separation of 40 to 60 cm. The orientation of the two subcutaneous electrodes relative to the heart can affect the amplitude of the signal recorded.42 Mapping studies on the chest skin with 4-cm electrode spacing in the range used by implantable loop recorders (ILRs) show larger intrinsic QRS amplitudes of 0.5 ± 0.1 mV for vertical orientation in the left parasternal zone and for horizontal orientation near the apex of the heart.

60

SECTION 1  Basic Principles of Device Therapy

Time (∆T)

chamber is turned off or “blanked” for a short blanking period (20-250 msec) after each spontaneous depolarization or pacing stimulus, to prevent a single depolarization resulting in multiple sensed events. In the refractory period that follows the blanking period, the sense amplifier remains enabled. Sensed events occurring in refractory periods do not alter pacemaker timing cycles but may be sensed for tachyarrhythmia detection algorithms. BLANKING AND REFRACTORY PERIODS

Amplitude Slew rate =

Voltage (mV) (∆V) in volts/sec (∆T)

SENSING

ATRIUM

VENTRICLE

Electrogram

>1.5-2.0 mV

>5-6 mV

Slew rate (V/sec)

>0.3

>1.0

Figure 3-5  Major clinical descriptors of electrogram. The peak-topeak amplitude of the EGM is the difference in voltage recorded between two electrodes and is measured in millivolts (mV). The slew rate is equal to the first derivative of the EGM (dV/dt) and is a measure of the sharpness of the EGM and therefore its frequency content. Slew rate is measured in volts per second (V/sec). Usually, the amplitude of the EGM should be greater than 1.5 to 2.0 mV in the atrium and at least 5 to 6 mV in the ventricle at the time of lead implantation, to ensure adequate sensing. The slew rate should be at least 0.3 V/sec in the atrium and at least 1 V/sec in the ventricle.

Subcutaneous ECGs are used to detect arrhythmias in ILRs, to obviate the need for surface ECG electrodes during follow-up of pacemakers and ICDs, and to detect VT/VF in an ICD without intravascular electrodes.

Sensing The methods and technology of sensing and detection in ICDs and pacemakers share many features, but there are two major differences. First, ICDs need reliable sensing and detection during VF, but pacemakers do not. Second, pacemakers may use unipolar or bipolar sensing, whereas ICDs always use bipolar sensing. GENERAL CONCEPTS Figure 3-13 shows the primary functional operations of sensing systems used by pacemakers and ICDs. The raw signal passes from the leads to the connector, through hermetic feedthroughs with highfrequency filters and high-voltage protection circuitry, before reaching the sensing amplifier. After the signal is amplified, a band-pass filter processes it to reduce T waves, myopotentials, and EMI (filtering). Then, it is rectified to nullify effects of signal polarity (rectification). Finally, it is compared with the sensing-threshold voltage. At the instant the processed signal exceeds the sensing-threshold voltage, a sensed event is declared to the timing circuits and indicated by a marker pulse on the programmer marker channel. The sense amplifier in the same

Signal amplitude (mV)

Voltage (∆V)

Blanking periods and refractory periods are used to prevent undesirable behavior caused by oversensing or double-counting of cardiac activity (Figs. 3-14 and 3-15). The specifications of blanking/refractory periods have substantial impact on ICD sensing and pacing functions (Fig. 3-16). Same-chamber blanking/refractory periods after sensed events reduce double-counting of intrinsic cardiac depolarizations that may result in escape pacing at a rate slower than the programmed lower rate in pacemakers or inappropriate detection of VF in ICDs. After paced events, the same-chamber blanking/refractory periods are typically longer and prevent oversensing of the pacing artifact and evoked response. The blanking/refractory periods in the ventricle after atrial sensed or paced events and in the atrium after ventricular sensed or paced events are called cross-chamber blanking/refractory periods. Cross-chamber blanking periods help to prevent oversensing of the pacing artifact after a paced event in the opposite chamber. The atrial blanking period after ventricular events, postventricular atrial blanking (PVAB), is designed to avoid oversensing of ventricular pacing stimuli and FFRWs. Longer postventricular atrial refractory periods (PVARPs) prevent retrogradely conducted atrial activation from resetting atrial timing cycles for dual-chamber pacing. Crosschamber blanking in the atrium after a ventricular event must be minimized in ICDs with tachyarrhythmia detection (ICDs or atrial therapy ICDs) to avoid undersensing the atrial rhythm, particularly during high ventricular rates. Long PVAB periods prevent reliable sensing of AF and atrial flutter/atrial tachycardia (AT). However, short PVAB periods may result in atrial sensing of FFRWs. NOT SENSED

SENSED

70 50 40 30 20 10

Amplifier threshold R Waves

5 P Waves

4

EMI

T Waves Far-field R wave

3 2

Muscle potentials

1 0.7 1

2

5

10

20

50

100

200

Frequency (Hz) Figure 3-6  Signal amplitude versus frequency. This plot shows the approximate characteristics of the P and R waves that pacemakers and ICDs are intended to sense and the approximate characteristics of  the electromagnetic interference (EMI, muscle potentials), T waves, and far-field R waves that they are intended not to sense. The sense amplifier’s filters are designed to sense signals that are above the U-shaped amplifier threshold curve and to reject signals that are below the curve. P waves and R waves have similar frequency characteristics, but usually R waves have higher dominant frequency than P waves. Muscle potentials usually have higher-frequency components than intracardiac signals. T waves and far-field R waves have lower frequencies. As shown, there are some overlaps in these amplitude-frequency characteristics that cause oversensing or undersensing in particular situations. The ellipses representing the amplitude-frequency characteristics in  this figure are conceptual and are not based on quantitative measurements.

61

3  Sensing and Detection

Unipolar (mV)



200 ms

1.7 mV

2 mm Bipolar contact

32 msec 1.6 mV

10 mm Bipolar contact

Bipolar (mV)

1 mV

5 0 5

1

5

1.3 mV

Orthogonal contact

20 msec 0.8 mV

Orthogonal floating

20 msec Figure 3-7  Effects of electrode configurations on atrial endocardial electrogram. The EGMs were obtained from a single patient with two catheters placed simultaneously in the right atrial appendage. One catheter had 2-mm ring electrodes (top three tracings), and the other catheter had 1-mm orthogonal electrodes. The surface electrocardiogram tracing is shown at the top of the figure. Time and voltage amplitude scales are shown. For each electrode configuration (right), the corresponding EGM is shown (left), with the peak-to-peak amplitude and EGM duration labeled. “Contact” refers to electrodes in contact with the atrial tissue. “Floating” refers to noncontact electrodes in the atrial chamber. Note that greater ring electrode spacing, from 2 to 10 mm, prolongs EGM duration without altering the amplitude. The unipolar EGM shows a wider and diminished atrial EGM and a prominent far-field ventricular EGM as well. The orthogonal electrode configurations provide EGMs of lesser amplitude and shorter duration, compared with the ring electrodes.

Implantable cardioverter-defibrillators that require tachyarrhythmia detection typically have shorter blanking and refractory periods than standard pacemakers, so that short cardiac cycles can be sensed reliably. As shown in the bottom marker diagrams of Figure 3-16, blanking periods may be adaptively extended based on noise-sampling windows (30-60 msec) if suprathreshold activity (due to cardiac or extracardiac sources such as EMI) is identified on the EGM immediately after a sensed event. If noise is seen in consecutive windows after a sensed event, the blanking period is “retriggered” for that beat to avoid double-counting or continuous oversensing. This operation may result in paradoxical undersensing of the cardiac rhythm when more sensitive sensing levels are programmed if noise is oversensed.43,44 The duration of the total atrial refractory period (TARP), equal to the atrioventricular (AV) delay plus the PVARP, in DDD pacing modes limits atrial tracking of the atrium at high sinus rates without affecting atrial sensing, as shown in Figure 3-17. Because the AV delay of most dual-chamber pacemakers shortens in response to increasing atrial rates or sensor input, the TARP also shortens. Several manufacturers now offer dual-chamber pacemakers that shorten the PVARP with increasing atrial or sensor-indicated rates, further reducing the TARP during exercise. The result of these newer algorithms is that the programmed upper tracking rate can be safely increased while providing protection at lower heart rates from initiation of pacemaker-mediated tachycardia caused by retrograde conduction.

Unipolar (mV)

55 msec

Bipolar (mV)

1.0 mV

3

4

7

8

9

5

0 5

0

50 msec Unipolar contact

2

100 (ms)

5 0 5

6

5

10

0 5

0

100 (ms)

Figure 3-8  Similarities of unipolar and bipolar electrograms. Examples recorded from a lead placed in the right atrial appendage in 10 patients. Note that the amplitudes of unipolar and bipolar EGMs are similar for each patient. The waveshapes of unipolar and bipolar EGMs for a given patient may be quite similar (patient 3) or quite different (patient 8), although these differences can be attributed to the relative size of the major inflections. Some of these differences may depend on whether the ring electrode for the bipolar recording makes contact with the myocardium. On the whole, intrapatient differences between unipolar and bipolar recordings appear to be less than interpatient differences.

120 mV 110 mV

Acute

18.4 mV

10 minutes

14.4 mV

1 hour

13.1 mV

210 mV 220 mV 120 mV 110 mV

210 mV 220 mV 120 mV 110 mV

10 mV 20 mV Figure 3-9  Acute current of injury at implantation. Top panel, Highresolution recording shows marked ST-segment elevation, indicating the current of injury when an active fixation screw-in tip electrode is extended into the endocardium. Middle panel, After only 10 minutes, most of the ST-segment elevation in the signal has disappeared. Bottom panel, The EGM is not appreciably different at 1 hour after implantation.

62

SECTION 1  Basic Principles of Device Therapy

SENSING THRESHOLDS IN PACEMAKERS

Approximate outline of lead body and helix Figure 3-10  Gross microscopic slide specimen shows myocardium remaining after removal of endocardial active-fixation screw lead. The large dotted line shows where the lead body was located, and the colored staining shows a thin, fibrotic sheath around the lead body. The approximate location of the helical screw-tip electrode is shown by  the solid coiled line. The oval shape (dotted line) shows the size of the fibrotic capsule that formed around the helical extended-tip electrode. Most of the tissue outside the dotted lines stained red, indicating that it was active myocardium capable of conducting depolarizations. The tip region of this electrode is similar to that of the tip electrode in Figure 3-1, so propagation of depolarization wavefronts must travel around the tip electrode, in tissue largely out of the field of view on the right side of this figure.

Sensing thresholds in most pacemakers are programmable to a constant value. Ventricular sensing channels in conventional pacemakers typically operate at sensing thresholds of 2.5 to 3.5 mV, about 10 times less sensitive than those in ICDs. Therefore, pacemakers may undersense VF. Atrial sensitivity thresholds are typically 0.3 to 0.6 mV, to allow sensing of small-amplitude atrial EGMs during AF and to improve the accuracy of AF diagnostics. Unipolar sensing thresholds typically are set higher (less sensitive) than bipolar sensing thresholds to reduce oversensing of far-field cardiac and extracardiac signals that can lead to inappropriate pacemaker inhibition or tracking. Newer pacemakers automatically adjust the sensitivity setting to adapt to changes in EGM amplitude over time. Typically, these functions operate to modify sensing thresholds based on a series of 10 to 20 ventricular beats. One such algorithm employs two simultaneous sensing levels: the programmed sensitivity (inner target) and a value twice the programmed value (outer target) (Fig. 3-18).45 Sensed EGMs exceeding both target values decrease the sensitivity. Signals exceeding only the inner target increase the sensitivity. In this manner, a 2 : 1 sensing margin is maintained. Rapid, automated sensitivity adjustments may be desired when EGM amplitudes can be expected to change over a brief period, such as beat-to-beat variations from respiration, body position changes, or fluctuating EGM morphologies during AF.46 Far-field R-wave oversensing can be minimized by (1) selecting an atrial lead with a closely spaced bipolar electrode pair (≤10 mm), (2) choosing an implantation location that yields an FFRW/P-wave ratio of less than 0.5,47 (3) titrating programmed sensitivity to reject FFRWs without undersensing P waves and low-amplitude AF, and (4) using PVAB.

CHART SPEED 25.0 mm/s ECG

0.2 mV/mm LEAD II

V EGM

1.0 mV/mm

Slew rate=dV/dt ∆V

P-P Amplitude

∆t

Marker channel

V S

V S

V S

V S

V S

V S

V S

V S

Figure 3-11  Surface electrocardiogram (ECG) lead II, bipolar right ventricular electrogram, and event markers with downward pulses that show when sensing occurred. The QRS amplitude on the ECG is about 1 mV, which is typical. The peak-to-peak amplitude of the sinus R waves is about 10 to 12 mV, which is also typical. The slew rate is the maximum slope (dV/dt) of the EGM intrinsic deflection; it is difficult to measure with a paper speed this slow. The two premature ventricular complexes (PVCs) (fourth and sixth) have different amplitudes and shapes on both the ECG and the EGM. The sinus beat in the center, between the two PVCs, has its main intrinsic deflection during the last part of the ECG QRS complex. The left edge of the sense marker indicates the instant that sensing by the ICD occurred. Therefore, EGM morphology and timing of the sense marker may not correspond to the start of the QRS on the ECG as electrocardiographers expect. Each R wave was sensed only once because sensing is blanked by the ICD for 120 msec after each ventricular sense (VS).



3  Sensing and Detection

63

1 mV

1 mV

1 mV

1 mV

1 mV

1 mV

1 mV

1 mV

1 sec

1 mV Figure 3-12  Variability in electrograms during spontaneous ventricular fibrillation (VF). Bipolar EGMs recorded during VF detection and charging by Medtronic Gem ICDs are shown for nine patients. The 1-mV calibration markers are the same except for the bottom tracing, where the calibration pulse is about three times larger, meaning that the ventricular EGM for this patient was three times smaller than for the other eight patients. Also note that rapid intrinsic deflections are visible on all tracings, although some substantial beat-to-beat variations in amplitude occurred. The abbreviated sense markers are shown at the bottom edge of each stored EGM strip. The sense amplifier blanking period was 120 msec, and the programmed sensitivity in each case was 0.3 mV, except in the sixth tracing from the top, which had 0.6 mV sensitivity. Note that there was slight VF undersensing on the bottom tracing when large EGMs were followed by smaller EGMs.

64

SECTION 1  Basic Principles of Device Therapy

Time of sensed event Electrograms

Filter

Output

Voltage

100

0

Input

1

Rectifier

0

Frequency

To timing circuits

Threshold Voltage

Amplifier

Output

Electrodes and lead

Blanking period

Threshold

0

Input

Variable for Auto-gain control

Time

Variable for Auto-gain threshold

Figure 3-13  Functional block diagram for pacemaker or implantable cardioverter-defibrillator (ICD) sense amplifier. The EGM signal from the two implanted electrodes is first amplified for subsequent processing. Band-pass filtering reduces the amplitude of lower-frequency signals such as T waves and far-field R waves and higher-frequency signals such as myopotentials and electromagnetic interference. After band-pass filtering, the signal is rectified to make polarity unimportant. The thresholding operation compares the amplified, filtered, and rectified signals with the sensing threshold voltage. At the instant the processed signal exceeds the sensing threshold voltage, the sense amplifier is blanked (turned off) for 20 to 120 msec, so each depolarization is sensed only once, and a sensed event is declared to pacemaker or ICD timing circuits. For pacemakers, the programmed sensitivity controls the constant sensing threshold voltage. For ICDs, the amplifier gain may be controlled by the input EGM amplitude. The programmable sensing threshold for ICDs controls the high and low limits on the sensing threshold, which automatically adjusts on a beat-by-beat basis (see text discussion). In actual circuits, some functions (e.g., amplification, filtering) may be integrated.

VENTRICULAR SENSING IN VENTRICULAR ICDS The guiding design principle is that sensing of VF and polymorphic VT should be sufficiently reliable that clinically significant delays in detection do not occur. Although high sensitivity is required to ensure reliable sensing during VF, continuous high sensitivity results in oversensing of cardiac or extracardiac signals during regular rhythm, which may cause inappropriate detection of VT or VF. To minimize both undersensing during VF and oversensing during regular rhythms, ICDs use feedback mechanisms based on R-wave amplitude that adjust the sensing threshold dynamically. To maximize the likelihood of detecting VF, blanking periods are kept short. Automatic Adjustment of Sensitivity Adjustment of Sensitivity in Normal Rhythm.  All ICDs automatically adjust sensitivity in relation to the amplitude of each sensed R wave (Fig. 3-19). At the end of the blanking period after each sensed ventricular event, the sensing threshold is set to a high value. It then decreases with time until a minimum value is reached. Compared with a fixed sensing threshold, automatic adjustment of sensitivity increases the likelihood of sensing low-amplitude and varying EGMs, while minimizing the likelihood of T-wave oversensing. The methods of the different manufacturers for automatic adjustment of sensitivity perform similarly after small R waves but differently

after large R waves. Figure 3-20 shows that after large R waves, the Boston Scientific ICDs increase the sensing floor. In the Cognis/Teligen family, the sensing floor is set to one-eighth the amplitude of the measured R wave if that value is greater than the programmed sensitivity. This prevents T-wave oversensing in the setting of large R waves and reduces oversensing of low-amplitude noncardiac signals (e.g., diaphragmatic myopotentials, EMI). However, it may increase the risk of undersensing during rare episodes of VF with highly variable EGM amplitude.48 Postpacing Automatic Adjustment of Sensitivity.  After ventricular pacing, all ICDs set ventricular sensitivity to a highly sensitive value to prevent pacing during VF. The sensitivity threshold then decays to the programmed sensitivity level (Fig. 3-21). Thus ICDs are especially vulnerable to oversensing of low-amplitude signals late in diastole during pacing, when the amplifier sensitivity or gain is maximal. Clinically, the most important manifestation is the oversensing of diaphragmatic myopotentials.3

V P Figure 3-14  Loss of atrial sensing with apparent ventricular undersensing and ventricular pacing. In the second complex, an atrial pacing stimulus follows the P wave because of undersensing in the atrium. The atrial pacing stimulus occurs at the start of the ventricular QRS complex. The ventricular EGM is not sensed because of blanking in the ventricular sensing amplifier immediately after the atrial pacing stimulus. This sequence is repeated in the fourth, sixth, and eighth complexes. Atrial undersensing may lead to apparent ventricular undersensing because the ventricular blanking period does not permit sensing of electrical signals for 10 to 40 msec after an atrial output pulse.

V P

V P

V S

V P

V S

V P

Figure 3-15  Oversensing of T waves causing interruptions in VVI pacemaker timing. The surface electrocardiogram (top tracing) and pacemaker marker channel (bottom tracing) show ventricular oversensing of T waves. The first three complexes show ventricular pacing (VP) with capture. The pauses after the third and fourth complexes result from T-wave oversensing (VS), demonstrated by the marker channel.



3  Sensing and Detection

65

ECG AEGM VEGM

ICD

Marker channel AS 0 100

AS 30 100

120 VS AS

30 AP 200

200 VP

30

Adaptive (retriggerable) blanking periods

AS

AS 30 100

0 AP 200

200 VP

30 120 VS

200 VP

AP

AS

AP

Pacemaker VS

VP

VP

ICD same chamber: 200 ms postpace 120 ms post V sense 100 ms post A sense Cross-chamber: 30 ms postpace blank 0 ms postsense blank 310 ms postventricular refractory

VP

VS

Pacemaker same chamber: 63 ms postpace or postsense (retriggerable) 230 ms ventricular refractory period Cross-chamber: 180 ms postventricular atrial blanking 250-400 ms postventricular atrial refractory (auto) 20-45 ms postatrial pace ventricular blanking

Figure 3-16  Basic blanking and refractory periods for DDDR mode (Medtronic Marquis DR ICD and EnPulse DR pacemakers). The top tracings show the surface electrocardiogram (ECG), atrial electrogram (AEGM), and ventricular electrogram (VEGM) signals. The bottom two marker diagrams illustrate atrial or ventricular pacing (AP, VP), atrial or ventricular sensing (AS, VS), blanking periods (purple), and refractory periods (blue). Blanking periods in ICDs are usually of fixed duration, whereas same-chamber blanking in pacemakers is generally adaptive, with short (30-50 msec) blanking periods that “retrigger” when suprathreshold signals are present during the blanking period. Adaptive blanking periods can extend indefinitely, resulting in activation of noise-reversion asynchronous pacing. Note the considerably shorter blanking periods on the atrial channel in the ICD; this allows more accurate sensing of atrial depolarizations during high ventricular rates, which is critical for tachyarrhythmia detection and discrimination algorithms. Also note the lack of ventricular refractory periods in ICDs; this allows inhibition of pacing when high rates are sensed. Ventricular blanking periods in pacemakers may be shorter than in ICDs because of the approximately 10-fold less sensitive sensing threshold in pacemakers compared with ICDs.

Automatic Gain Control.  Early Ventritex ICDs (St. Jude Medical) used automatic step adjustments of gain as a primary means for avoiding T-wave oversensing and ensuring detection of low-amplitude VF EGMs. This resulted in sensing errors when EGM amplitude changed abruptly.49-51 In Boston Scientific ICDs before the Cognis/Teligen models, “slow” Automatic Gain Control adjusts the dynamic gain of the sensing amplifier slowly in response to temporal changes in R-wave amplitude. This ensures that the peak of the sensed R wave reaches about 75% of the amplifier gain, and that the sensing EGM is not truncated or “clipped.”

The minimum value of amplifier range is one eighth of the maximum value, so the minimum sensitivity decreases as R-wave amplitude increases. In Cognis/Teligen models, the range sense amplifier is sufficient (0 to 32 mV) that “slow” Automatic Gain Control is not used. In these Boston Scientific ICDs, “Automatic Gain Control” refers to automatic adjustment of sensitivity. In older Boston Scientific ICDs, “fast” Automatic Gain Control refers to automatic adjustment of sensitivity. Thus, whatever the name applied, automatic control of sensitivity, rather than gain, has become the primary method of beat-to-beat sensing adjustment in all ICDs. 2 seconds

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS AS

VP

AS

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS

VP

AS

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS AS

VP

AS

AS

VP

AS

AS

VP

AS

AS AS

VP

AS

AS AS

VP

AS

AS

VP

Figure 3-17  Intracardiac marker channels. In a patient with a DDD pacemaker, channels identify atrial events within postventricular atrial refractory periods (PVARPs) that are sensed but not tracked. The surface electrocardiogram (top tracing) demonstrates ventricular pacing at the upper rate limit during atrial flutter. The atrial marker channel demonstrates atrial events that were sensed within PVARP (AS) and atrial events sensed outside PVARP (AS). After a ventricular pacing stimulus (VP), some atrial EGMs are not sensed, resulting in apparent EGM dropout because the atrium is blanked for a period after delivery of a VP. Only atrial signals recorded outside PVARP (AS) are tracked.

66

SECTION 1  Basic Principles of Device Therapy

mV

mV

10 8 6 4 2 0 2 4 6 8 10 Increase Increase Increase Increase Increase Decrease Increase Decrease sensitivity sensitivity sensitivity sensitivity sensitivity sensitivity sensitivity sensitivity 2:1 safety Barely Converging on 2:1 safety Optimal sensing margin sensing margin for sensing (equilibrium around a achieved 2:1 safety margin) Outer target (1/2 sensitivity level) Inner target (programmed sensitivity level)

Figure 3-18  Autosensing algorithm to maintain a 2 : 1 sensing safety margin. See text for details. (From Castro A, Liebold A, Vincente J, et al: Evaluation of autosensing as an automatic means of maintaining a 2:1 sensing safety margin in an implanted pacemaker. Autosensing Investigation Team. Pacing Clin Electrophysiol 19:1708-1713, 1996.)

Ventricular Blanking Periods Ventricular blanking periods prevent ventricular oversensing of samechamber signals (R-wave double-counting) and cross-chamber signals (atrial pacing pulses and P waves) in regular rhythms. Because reliable sensing in VF requires minimizing blanking periods, blanking periods in ICDs are short and may occasionally be insufficient to prevent oversensing. Short Same-Chamber Blanking Periods and R-wave DoubleCounting.  In adults who are not taking antiarrhythmic drugs, interEGM intervals for filtered EGMs in VF vary from about 130 to 300 msec, with a peak near 200 msec (Fig. 3-22). Therefore, fixed or nominal blanking ICD periods after ventricular sensed events range from 120 to 135 msec. R-wave double-counting occurs if the duration of the sensing EGM exceeds the ventricular blanking period. Cross-Chamber Blanking Periods and Undersensing of VT/VF.  Under most conditions, ICDs apply only the minimum cross-chamber ventricular blanking required to prevent “crosstalk” resulting from an

Unfiltered R ventricular EGM

T

atrial pacing stimulus. During high-rate atrial or dual-chamber pacing, ventricular sensing may be restricted to short periods of the cardiac cycle because of the combined effects of ventricular blanking after ventricular events and cross-chamber ventricular blanking after atrial pacing. If a sufficient fraction of the cardiac cycle is blanked, systematic undersensing of VT or VF may occur. When pacing and blanking events occur at intervals that are multiples of a VT cycle length, ventricular complexes may be repeatedly undersensed, delaying or preventing detection.52-54 This occurs most often with rate-smoothing algorithms. “Sensing” Other Ventricular Electrograms Implantable cardioverter-defibrillator may use information derived from other VEGMs (shock-channel EGM, LV EGM in resynchronization systems) to enhance their functionality. The EGM from the shock channel (far-field EGM) is not used by transvenous ICDs for rate counting because bipolar or integrated bipolar EGMs are less susceptible to extracardiac signals. However, some manufacturers (Boston Scientific, Medtronic) use morphologic characteristics of far-field EGMs for discrimination of supraventricular tachycardia (SVT) from VT. Ventricular fibrillation

1 sec

Automatically adjusting sensing threshold

Filtered and rectified EGM 0.3 mV

Programmed sensitivity

Figure 3-19  Automatic adjustment of sensitivity. ICDs adjust sensitivity in relation to the amplitude of each sensed R wave. The goal of this feature is to permit sensing of low-amplitude and varying-amplitude EGMs while minimizing T-wave oversensing. The figure shows two sinus beats followed by the onset of ventricular fibrillation (VF). The upper panel shows the unfiltered ventricular EGM. The lower panel shows the corresponding filtered and rectified EGM. After each sensed ventricular event, the sensing threshold is set to a predetermined fraction of the R-wave amplitude. For large R waves, the initial sensing threshold may have a maximum value. The threshold then decreases with time until it reaches a minimum value equal to the programmed sensitivity, which is nominally about 0.3 mV. For sinus beats, the threshold is larger than the T waves, preventing oversensing. When VF begins, the smaller R waves keep the threshold at a lower value, which allows sensing of R waves that are even smaller than the T waves in sinus rhythm.



3  Sensing and Detection

Automatically adjusted sensitivity (mV)

10.0 Boston Scientific Medtronic St. Jude Threshold

9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 0

200

400

600

800

1000

Time (msec) Figure 3-20  Comparison of automatically adjusted sensitivity after sensed ventricular events for three manufacturers of ICDs after large (10 mV) R wave. The programmed sensing threshold is approximately 0.3 mV. After sensed ventricular events, Medtronic ICDs reset the sensing threshold to 8 to 10 times the programmed sensitivity, up to a maximum of 75% of the sensed R wave. The value of Auto-Adjusting Sensitivity then decays exponentially from the end of the (sense) blanking period, with a time constant of 450 msec, until it reaches the programmed (maximum) sensitivity. At the nominal sensitivity of 0.3 mV, there is little difference between the sensitivity curves of Medtronic ICDs after large and small spontaneous R waves. If the R wave is large, the entire Auto-Adjusting Sensitivity curve can be altered substantially by changing the programmed value of maximum sensitivity (see Fig. 3-19). At nominal settings, the St. Jude Threshold Start begins at 62.5% of the measured R wave for values between 3 and 6 mV. If the R-wave amplitude is greater than 6 mV or less than 3 mV, the Threshold Start is set to 62.5% of these values (3.75 mV and 1.875 mV, respectively). The sensing threshold remains constant for a Decay Delay period of 60 msec and then decays linearly with a slope of 3 mV/sec. Both the Threshold Start percent and the Decay Delay are programmable, over the range of 50% to 75% and 0 to 220 msec, respectively (see Fig. 3-21). Boston Scientific Cognis-Telegin ICDs set the starting threshold to 75% of sensed R waves with a maximum limit of 3/2 · Peak Running Average. Sensitivity then decays using digital steps, each seven-eighths the amplitude of the previous step. For sensed events, the duration of the first step is 65 msec, and the duration of subsequent steps is 35 msec. This results in a sensitivity of one-half the peak R wave in about 170 msec. (See text for further details.) After a paced ventricular event, all ICDs also adjust sensitivity dynamically, starting at the end of the (pace) blanking period, but the threshold starts at a more sensitive setting. (Modified from Swerdlow C, Friedman P: Advanced ICD troubleshooting. Part I. Pacing Clin Electrophysiol 28:1322-1346, 2005.)

Automatic analysis of the far-field EGM has also been proposed as a method to identify oversensing in ICDs resulting from lead fracture or sensing-lead connection problem. In one approach, the peak-peak far-field EGM amplitude is measured in a small window centered around each sensed event (on near-field channel) to discriminate rapid oversensing from true VT/VF. Oversensing is identified when sensed events on the near-field channel correspond to isoelectric periods on the far-field channel.55,56 In true VF, isoelectric periods are rare on the far-field channel (Fig. 3-23). Evaluating Sensing of Ventricular Fibrillation at Implantation Increasing interest in implanting ICDs without assessing defibrillation efficacy has focused attention on the extent to which adequacy of VF sensing can be determined from EGMs recorded in baseline rhythm.

67

Although the statistical correlation between R-wave amplitude in VF and baseline rhythm is weak,57,58 two studies reported that sensing of VF is adequate with nominal sensitivities near 0.3 mV if the baseline R wave is sufficiently large (≥5 mV or ≥7 mV).59 Rarely, clinically significant undersensing of VF or polymorphic VT may occur despite adequate sinus-rhythm R waves.48,60 In these cases, undersensing occurs because auto-adjusting sensitivity criteria respond inadequately to variations in R-wave amplitude, rather than consistently low-amplitude R waves. The reproducibility of this phenomenon is unknown, as is its predicted extent at implantation. Therefore, it is uncertain whether clinically appropriate testing at implantation can detect this infrequent cause of undersensing. During ICD implant with true bipolar sensing and current digital sensing amplifiers, clinically significant undersensing of VF is rare and unrelated to sinus-rhythm R-wave amplitude.61 Undersensing of spontaneous VT/VF in the VF zone is similarly rare. Reliable sensing of VF cannot be predicted from baseline EGMs if the baseline ventricular rhythm is paced. Sensitivity is programmed to a less sensitive value than nominal (e.g., to avoid T-wave oversensing), or patients have other implanted electronic ICDs, such as pacemakers, cardiac contractility modulation devices, or transcutaneous electrical nerve stimulation (TENS) units, that could cause device-device interactions. Postshock Sensing Postshock sensing is critical for redetection of VF after unsuccessful shocks and for accurate detection of episode termination. Electroporation, the process by which strong electric fields create microscopic holes in the cardiac cell membranes, has been proposed as the mechanism for postshock distortion of EGMs recorded from high-voltage electrodes.62 Because EGMs of dedicated bipolar sensing electrodes are minimally affected by shocks,63 they became standard for early epicardial ICDs. For transvenous ICDs, postshock sensing recovers more rapidly with true bipolar sensing configurations than with integrated bipolar sensing.64,65 This is a minor issue for current integrated bipolar leads with a pacing tip electrode–to–distal coil spacing of approximately 12 mm.66 ATRIAL SENSING IN DUAL-CHAMBER ICDS AND ATRIAL ICDS Accurate sensing of atrial EGMs is essential for accurate discrimination between VT/VF and rapidly conducted SVTs that satisfy ventricular rate criteria in dual- or triple-chamber ICDs. Rapid discrimination is essential to ensure prompt delivery of ventricular therapy while minimizing inappropriate shocks. Historically, some inappropriate detection of AT/AF has been considered an acceptable consequence of maintaining high sensitivity for detecting VT/VF. The atrial lead should be positioned at implantation to minimize FFRWs. Leads with an interelectrode spacing of 10 mm or less reduce oversensing of FFRWs. Atrial lead dislodgement, oversensing of FFRWs, or undersensing from low-amplitude AEGMs or atrial blanking periods can cause inaccurate identification of AEGMs. These errors in sensing may result in misclassification of VT as SVT, or vice versa. Postventricular Atrial Blanking and Rejection of Far-Field R Waves To prevent oversensing of FFRWs, older dual-chamber ICDs had fixed PVAB periods, similar to those in pacemakers (Fig. 3-24). With a fixed blanking period, the blanked proportion of the cardiac cycle increases with the ventricular rate. Atrial undersensing caused by PVAB causes underestimation of the atrial rate during rapidly conducted atrial flutter or AF, resulting in inappropriate detection of VT67 (Fig. 3-24, lower panel). Without PVAB, however, atrial oversensing of FFRWs could cause overestimation of the atrial rate during tachycardias with a 1 : 1 AV relationship.68 This may result in either inappropriate rejection of VT as SVT, if FFRWs are counted consistently as atrial EGMs, or inappropriate detection of SVT as VT, if FFRWs are counted inconsistently.69

68

SECTION 1  Basic Principles of Device Therapy

Postpace

Postsense

Filtered and rectified EGM Postsensed maximum

8x

Postpaced maximum

4.5x

Programmed sensitivity

0.3mV

Postpace blanking Marker channel V Pace

V Pace

V Sense

V Pace

V Sense

Figure 3-21  Comparison of automatic adjustment of sensitivity after paced and sensed ventricular events. The filtered and rectified ventricular EGM, the corresponding sensing threshold, and ventricular (V) event markers are shown. Horizontal bars denote postpacing blanking periods. The blanking periods after paced events are longer than those after sensed events (250-350 vs. 120-140 msec), and the initial values of sensitivity are less. In this Medtronic ICD example, the initial sensing threshold after sensed events is 8 times the minimum programmed sensitivity of 0.3 mV, whereas the initial threshold after paced events is 4.5 times that value. The goal of a lower initial postpacing threshold is to prevent pacing into ventricular fibrillation. It compensates in part for the longer postpacing blanking period.

Medtronic ICDs also reject FFRWs algorithmically by identifying a specific pattern of atrial and ventricular events that fulfill specific criteria (Fig. 3-25). Intermittent sensing of FFRWs or frequent premature atrial events may disrupt this pattern, resulting in misclassification of a tachycardia. Therefore, it is preferable to reject FFRWs after sensed ventricular events by decreasing atrial sensitivity, if this can be done without undersensing of AF. Atrial sensitivity can be reduced to 0.45 mV with a low risk of undersensing AF. Less sensitive values should be programmed only if the likelihood of rapidly conducted AF is low. FFRW oversensing that occurs only after paced ventricular events (when auto-adjusting atrial sensitivity is maximal) does not cause inappropriate detection of SVT as VT, but it may cause inappropriate 100

Number of intervals

SENSING IN CARDIAC RESYNCHRONIZATION ICDS

Sensitivity = 0.3 mV n=772 Measured VF intervals n=786

80

60

40

20

0 0

100

200

300

400

500

mode switching and can contribute to inappropriate detection of AF or atrial flutter. Medtronic ICDs (starting with Entrust) and Boston Scientific ICDs (starting with Vitality) may use brief atrial blanking or a period of reduced, automatically-adjusting sensitivity (or both) to reject FFRWs without preventing detection of AF (Fig. 3-26). St. Jude ICDs and Medtronic ICDs starting with Entrust provide programmable atrial blanking after sensed ventricular events to individualize the trade-off between oversensing of FFRWs and undersensing of AEGMs in AF. St. Jude ICDs also provide programmable atrial sensing Threshold Start and Decay Delay, corresponding to the same features in the ventricular channel.

600

Cycle length (msec) Figure 3-22  Sensed cycle lengths of human ventricular fibrillation (VF) EGMs by ICD sensing system compared with manual cyclelength measurements of same signals from many patients. Two histograms are superimposed. The red and orange vertical bars show the manually measured cycle lengths during VF (786 intervals); the blue bars show the intervals sensed by the ICD (772 intervals). Intervals of less than 120 msec, the blanking period, were not permitted. Note that there was some oversensing for intervals shorter than 180 msec, a slight amount of undersensing for intervals between 180 and 280 msec, and a small number of long intervals greater than 280 msec, which represent undersensing during VF. The peak in the histograms occurs at about 220 msec.

Left ventricular PVCs may activate the left ventricle but may not be sensed in the right ventricle before pacing is delivered. In this case, LV pacing could be delivered during the vulnerable period of the PVC. Boston Scientific cardiac resynchronization ICDs also sense in the left ventricle to reduce ventricular proarrhythmia by preventing pacing into the LV vulnerable period. The left ventricular protection period (LVPP) is a programmable interval (300-500 msec) following an LV event when the ICD will not pace in the left ventricle (Fig. 3-27). This prevents inadvertent delivery of an LV pacing pulse during the LV vulnerable period. The LVPP differs from other pacing refractory periods, which are designed to prevent inappropriate inhibition of pacing. In contrast, the left ventricular refractory period (LVRP), after a sensed or paced event on the LV lead, is a conventional refractory period. It prevents sensed events from causing inappropriate loss of cardiac resynchronization pacing following sensed events such as T-wave oversensing on the LV lead. The LVRP provides an interval following either an LV sense or an LV pace event (or leading ventricular pace event when LV offset is not programmed to zero), during which LV sensed events do not inhibit pacing. Use of a long LVRP shortens the LV sensing window. LVRP is available whenever LV sensing is enabled. Thus, LVRP minimizes unnecessary inhibition of resynchronization pacing while the LVPP minimizes the risk of LV pacing during the LV vulnerable periods.

Ventricular Oversensing: Recognition and Troubleshooting Oversensing is defined as sensing of unintended nonphysiologic signals or of physiologic signals that do not accurately reflect local depolarization. Nonphysiologic signals usually arise from extracardiac EMI (e.g.,



3  Sensing and Detection Lead noise

69

Ventricular fibrillation

Near-field EGM

Near-field EGM

Far-field EGM

Far-field EGM

Marker

Marker F 2 S2 1 7 0 0

F F S1 S 3 4 3 0 0

F S 3 7 0

F F F S1 S 1 S 3 3 5 1 0 0 0

F F F S 1 S1 S 3 4 0 0

4 5 0

V F F S1 S 2 S 3 2 0 0

5 5 0

V S 2 5 0

2 0 0

V F S2 S 7 0

4 0 0

V F F F S1 S1 S 2 S 2 3 4 4 7 0 0 0 0

V S 2 3 0

V S 2 2 0

V F F F F S 1 S1 S1 S 2 S 2 0 7 5 5 0 0 0 0 0 0

V F F S 2 S1 S 3 2 0 0

4 7 0

VF Rx: Defib

Figure 3-23  Algorithm to discriminate pace-sense conductor failure of true bipolar ICD leads from ventricular fibrillation using far-field EGM (Medtronic Protecta ICDs, currently investigational). In pace-sense conductor failures, the far-field EGM has long isoelectric segments, which are not present in true VF. Stored EGM tracings during lead noise oversensing (left) and spontaneous VF (right) are shown; top tracings are the near-field (RVtip-RVring) EGM, middle tracings are the far-field EGM (RV coil-can), and the sensing markers are the lower tracing. Oversensing is identified by analyzing the peak-peak amplitudes of the far-field EGM in a 200-msec window centered at each of 12 sense markers (sensing derived from near-field EGM), as shown by the red arrows and boxes. Oversensing is identified when there are at least two far-field EGM analysis windows with isoelectric (<1 mV) amplitudes and at least one analysis window with peak-peak amplitude at least six times greater than the average of the two smallest amplitudes. Lead noise oversensing would have been properly discriminated from VF in these two examples.

ungrounded electrical equipment, antitheft detectors, surgical electrocautery) or mechanical problems in the sensing circuit, which may occur in the lead (insulation failure or fracture), connection between lead and header, or feedthrough wires from the header to the inside of the pulse generator. Rarely, electrical artifacts arise from retained fragments of abandoned intracardiac leads. Physiologic signals may be intracardiac (P, R, or T waves) or extracardiac myopotentials. Oversensing often results in characteristic patterns of stored EGMs and associated markers70,71 (Fig. 3-28). In pacemakers, oversensing may manifest as either failure to deliver an expected pacing stimulus or inappropriate tracking of nonphysiologic signals in the atrial channel of a dual-chamber ICD. In ICDs, oversensing usually manifests as inappropriate detection of VT or VF. This section focuses on oversensing in ICDs.

Figure 3-24  Effect of postventricular atrial blanking (PVAB) on atrial sensing. Upper panel shows the surface electrocardiogram (ECG), atrial electrogram (AEGM), and event markers during atrial sensed (As)–ventricular paced (Vp) rhythm. The first segment of each upper horizontal bar denotes the period of PVAB; the second segment denotes the postventricular atrial refractory period (PVARP); FFRW, far-field R wave on the atrial channel. The lower horizontal bars denote the postpacing ventricular blanking periods. With a short PVAB (left), the FFRWs are oversensed. A longer PVABP (right) prevents oversensing of FFRWs. Lower panel shows the ECG, AEGM, and ventricular electrogram (VEGM) tracings from a patient with atrial flutter with 2 : 1 atrioventricular (AV) conduction. The thin horizontal bars on the ventricular channel denote the periods of PVAB, which resulted in atrial undersensing of alternate atrial flutter EGMs (in boxes). The resultant incorrect calculation of atrial rate resulted in inappropriate ventricular therapy for atrial flutter (not shown), because the ICD did not classify the ventricular rate as less than the atrial rate.

PVAB

INTRACARDIAC SIGNALS Ventricular oversensing of physiologic intracardiac signals results in exactly two ventricular events for each cardiac cycle. This may result in inappropriate detection of VT or VF. T-wave Oversensing T-wave oversensing is the most common clinically-significant cause of intracardiac oversensing. Oversensing of spontaneous T waves may cause inappropriate detection of either VT or VF, depending on the sensed R wave–to–T wave interval and the programmed VF detection interval. T-wave oversensing is typically identified by alternating EGM morphologies.70 Device-measured intervals during T-wave oversensing may also alternate, but the degree of alternation often is small and

PVAB

PVARP

1000

AEGM FFRW As As VP

AEGM

VEGM

As As VP

As As VP

FFRW As As VP

As VP

As VP

As VP

As VP

70

SECTION 1  Basic Principles of Device Therapy

P

Figure 3-25  Algorithmic rejection of far-field R waves (FFRW) by pattern analysis. ICDs with minimum cross-chamber blanking (Medtronic) reject FFRWs by the timing pattern of atrial and ventricular intervals. Atrial events are classified as FFRWs if all the following criteria are met: (1) there are exactly two atrial events for each V-V interval; (2) timing of one P wave is consistent with a FFRW (R-P interval <160 msec); (3) there is a stable interval between the FFRW and the ventricular electrogram (VEGM); (4) there is a short-long pattern of P-P intervals (to distinguish FFRW oversensing from atrial flutter); and (5) the pattern occurs frequently (4 of 12 intervals). A, Atrial electrogram (AEGM), VEGM, and dual-chamber event markers are shown. All five criteria for FFRWs are fulfilled. Horizontal double-ended arrows below event markers denote alternation of long (L) and short (S) atrial intervals. AR, Atrial refractory event; P, P wave; TS, ventricular event in ventricular tachycardia zone. B, Interval plot (left) and stored EGM (right) from episode of sinus tachycardia with consistent FFRW oversensing that is classified correctly. On the interval plot, open squares denote A-A interval and closed circles denote V-V interval. Horizontal lines denote ventricular tachycardia (VT) and ventricular fibrillation (VF) detection intervals of 400 and 320 msec, respectively. Alternating A-A intervals whose sum equals that of the VV intervals produce a characteristic “railroad track” appearance (arrow). The algorithm rejects FFRWs despite that FFRW oversensing does not occur for one V-V interval between seconds 9 and 10.  C, Interval plot (left) and stored EGM (right) from episode of sinus tachycardia with consistent FFRW oversensing that was detected inappropriately as VT. Intermittent oversensing of FFRWs occurs as sinus tachycardia accelerates gradually across the VT detection interval of 480 msec (arrow), resulting in inappropriate therapy (“Burst” antitachycardia pacing marker on interval plot, VT marker on EGM event markers).

FFRW

AEGM

VEGM

1 4 0

2 1 0

A R

1 3 A 0 R

L

T S

A R

S 3 5 0

2 1 0

1 3 A 0 R

L

T S

A R

S

2 1 0

T S

3 5 0

A Interval (ms) 1800 1500 1200 900 600

V-V

A-A

VF=320 ms VT=360 ms

P

AEGM

FFRW

VEGM

400 1 4 0

200

A R S

6

7

8

9

10

11

12

13

14

2 0 0

A R

1 4 0

A R S

3 4 0

ST

2 0 0

A R

1 4 0

A R S

3 4 0

ST

2 0 0

A R

1 4 0

3 5 0

ST

A R S

2 0 0

A R

1 4 0

A R

2 0 0

S

3 5 0

ST

A R

3 4 0

ST

3 4 0

S

A R

1 4 0

A R

2 0 0

S

3 4 0

ST

ST

A R

1 4 0

A R

2 1 0

S

3 4 0

ST

A R

1 4 0

3 5 0

A R

2 0 0

S

ST

A R

1 4 0

A R

2 1 0

S

3 5 0

ST

A R

1 4 0

2 0 0

A R S

3 5 0

ST

A R

1 4 0

A R

2 1 0

A R

S

3 5 0

1 4 0

ST

Time (sec) [0 = Collection start]

B V-V A-A Interval (ms) Burst 1800 1500 Intermittent FFRW 1200 oversensing 900 600

VF

FFRW

P

AEGM

VEGM

400 200

220

C

A R

215

210

25 Time

0

5

4 7 0

4 7 0

S

1 2 9 6 A 0 A 0 R R

4 7 0

S

2 0 A0 R

4 6 0

2 6 A 0 R

S

A R

4 6 0

4 6 0

S

A R

4 6 0

4 6 0

S

1 2 8 7 A0 A 0 R R

4 6 0

S

1 2 9 6 A0 A 0 R R

4 5 0

S

A R

4 5 0

4 4 0

S

A R

4 5 0

4 5 0

S

2 2 0 5 A0 A 0 R R

4 5 0

S

A R

4 5 0

4 6 0

S

A R

4 5 0

4 5 0

S

A R

4 4 0

4 4 0

S

2 1 0

S

3 5 0

ST

A R

4 7 0

A R

3 5 0

1 3 0

A R S

ST



71

3  Sensing and Detection

Sensitivity threshold

1

2

3

Desensitization period (40-100 mS)

Rectified and filtered AEGM A P

A S

Marker channel V S

A As 75% of AS

B

75% of 3/8 of AS As Blanking 15 ms

Vs

Far-field V

Figure 3-26  Atrial sensing features intended to prevent far-field R-wave (FFRW) oversensing while still permitting detection of atrial fibrillation. These features, which combine limited atrial blanking with automatic adjustment of atrial sensitivity, are less strict than conventional blanking periods. A, Medtronic ICDs, starting with Entrust, have an optional “Partial+” postventricular atrial blanking period (PVAB) setting that increases the sensing threshold for a programmable duration (40-100 msec) after a ventricular event (2). Entrust operation after ventricular sensed events nominally has no absolute blanking or sensitivity changes. With Partial + PVAB enabled, the sensing threshold is raised to 75% of the prior sensed atrial electrogram (AEGM) amplitude to reduce the likelihood of sensing FFRWs. “Absolute” PVAB, another selectable option, blanks all atrial sensed events within the programmable PVAB interval. Because significant atrial undersensing can occur, this method is recommended only for addressing complications not addressed by the Partial + PVAB method. Partial + or Absolute PVAB does not affect atrial sensing operation after sensed events (1) or after atrial paced events (3). AP, Atrial paced event; AS, Atrial sensed event; mS, microseconds; VS, ventricular sensed event. B, Boston Scientific ICDs, starting with Vitality, introduce a brief (15 msec) blanking period after each sensed ventricular event, followed by a decrease in atrial sensitivity to three-eighths the mean P-wave amplitude. This is sufficient to prevent oversensing of FFRWs, provided that the amplitude of the AEGM is at least eight-thirds that of the FFRW.

2. St. Jude ICDs provide programmable Threshold Start and Decay Delay to reduce oversensing of spontaneous T waves. These features may be helpful even if the R wave is small (Fig. 3-30). 3. The apparent alternation of ventricular EGM morphologies caused by T-wave oversensing may be exploited to prevent inappropriate detection of VT. The SVT-VT morphology discriminator may be programmed “on” to classify alternate EGMs as “sinus” and thereby withhold inappropriate detection. The long-term reliability of this approach is not established. 4. As a temporary measure, some T-wave oversensing may be eliminated by forcing short-term ventricular pacing. This alters the sequence of repolarization and may reduce T-wave amplitude. However, unnecessary ventricular pacing may result in adverse, desynchronizing hemodynamic effects. 5. Medtronic ICD models (Secura VR/DR, Consulta) permit sensing from either the true bipolar EGM or the integrated bipolar EGM when a true bipolar lead is connected. Integrated-bipolar sensing may prevent T-wave oversensing, especially when true bipolar R-waves are small compared to the integrated bipolar R waves (Fig. 3-31).

1

AS

AS

RV+LVp

2

AS

RVp LVp

3

LVp RVp

A V-V interval

V-V interval

V-V interval

AS

AS

AS

AS RV RVP AS BiV

RVS AS

LVPP

LVP RVP

RVP AS

LVPP

LVS RVS

RVP AS

LVPP

LVS RVP

LVPP

LVP RVP

B difficult to recognize, especially during sinus tachycardia or if the QT interval is prolonged. T-wave oversensing may be divided into three classes: postpacing, large R wave (>3 mV) in spontaneous rhythm, and small R wave (<3 mV) in spontaneous rhythm (Fig. 3-29). Postpacing T-wave oversensing can inhibit bradycardia pacing49,72 or cause antitachycardia pacing to be delivered at the wrong cycle length.49 It does not typically cause inappropriate detection of VT but may increment VT or VF counters, making detection of nonsustained VT more likely. It is corrected by increasing the postpacing ventricular blanking period. Oversensing of spontaneous T waves often occurs in the setting of low-amplitude R waves because the sensing threshold decays from a fraction of the preceding low-amplitude R wave.73 To compound the problem, patients with low-amplitude R waves may require lower minimum sensing thresholds to ensure reliable sensing of VF. T-wave oversensing in these patients is a warning that detection of VF may be unreliable. The ventricular lead should be revised or a separate pace/ sense lead added if the safety margin for sensing VF is insufficient. Specific programming features may be used to reduce T-wave oversensing, provided that detection of VF is reliable, as follows: 1. The simplest approach is to reduce ventricular sensitivity to a less sensitive (higher) value. This may result in undersensing during VF if the R wave amplitude is low.

Figure 3-27  Event markers illustrate blanking periods in cardiac resynchronization ICDs. A, Blanking periods in Medtronic Marquis Insync III ICD. In condition 1, there is simultaneous right ventricular and left ventricular pacing (RV+LVp). There is a single cross-chamber blanking period (~30 msec in duration) on the atrial channel. In condition 2, RVp first with LVp delayed (up to 80 msec), and in condition 3, LVp first with RVp delayed, there are two cross-chamber blanking periods on the atrial channel, one for each ventricular paced event. In both cases, ventricular blanking is timed from the RVp event, resulting in a postpace ventricular blanking period that is longer by the V-V pacing delay (up to 80 msec). These additional blanking periods increase the risk of undersensing in both chambers. To date, there are no reports of undetected ventricular tachycardia (VT) caused by offsets in timing of V-V pacing. B, Left ventricular protection period (LVPP) of the Boston Scientific Renewal ICD. This ICD has RV timing and independent RV and LV stimulation channels without a programmable RV-LV delay. The LVPP allows LV sensing to occur with inhibition of the LV stimulus for a period that is programmable to prevent pacing into the vulnerable period of the left ventricle. Therefore, this feature allows biventricular sensing but RV-based timing. AS, Atrial sensed event; BiV, biventricular; LVP, left ventricular paced; LVS, left ventricular sensed; RVP, right ventricular sensed. (Courtesy Boston Scientific, Indianapolis; B from Kay G: Troubleshooting and programming of cardiac resynchronization therapy. In Ellenbogen K, Kay G, Wilkoff B, editors: ICD therapy for congestive heart failure. Philadelphia, 2004, Elsevier.)

72

SECTION 1  Basic Principles of Device Therapy

RA

RA

RA

RV

X X

X X F

0 0

0 0

484 6 4 0

A R T S

A

1 7 0

F S

5 4 0

A R

3 7 0

T S

1 7 0

RV

RV 1 mV 200 ms

605

R R

F S

HV

6 8 0

R R

A R

A R T S

RV

RA

RV

RV

8 3 0

HV

E

F S

F

1 6 0

8 3 0

A R F S

1 9 0

F F F F F S S S S S 1 1 1 1 2 4 2 4 0 0 0 0

V F S S 1 2 0

5 1 0

3 5 0

T S 3 3 0

8 4 0

A S

A R

T S

3 3 0

C

B

RA

6 8 0

V S

F S

T S

3 5 0

3 2 0

F S

1 4 0

D

8 4 0

A S

7 5 0

T S

F D

3 0 0

V S

V S

1 1 3 2 0 0

4 7 0

VF Rx 1 Defib

8 4 0

A S V S

9 1 0

F S

1 2 0

8 2 0

A S V F S S 1 3 0

7 0 0

A R V S

5 4 0

1 6 0

F F S S 1 2 4 9 0 0

8 3 0

F S

1 8 0

F S

3 5 0

Figure 3-28  Types of oversensing resulting in inappropriate detection of ventricular tachycardia/fibrillation (VT/VF). A, B, and C, Oversensing of physiologic intracardiac signals. D, E, and F, Oversensing of extracardiac signals. A, P-wave oversensing in sinus rhythm from an integrated bipolar lead with distal coil near the tricuspid valve. B, R-wave double-counting during conducted atrial fibrillation (AF) in a biventricular sensing ICD. C, T-wave oversensing in a patient with low-amplitude R wave (note millivolt calibration marker). D, Electromagnetic interference from a power drill has higher amplitude on widely spaced, high-voltage EGM than on closely spaced, true bipolar sensing EGM. E, Diaphragmatic myopotential oversensing in a patient with an integrated bipolar lead at the right ventricular apex. Note that the noise level is constant, but oversensing does not occur until automatic gain control increases the gain sufficiently, about 600 msec after the sensed R waves. F, Lead fracture noise results in intermittent saturation of amplifier range, denoted by arrows. RA, Right atrium; RV, right ventricular sensing EGM; HV, high-voltage EGM. (From Swerdlow C, Shivkumar K: Implantable cardioverter defibrillators: clinical aspects. In Zipes DP, Jalife J, editors: Cardiac electrophysiology: from cell to bedside, ed 4, Philadelphia, 2004, Saunders.)

Spontaneous rhythm: Inappropriate therapy

Postpacing: Pauses in paced rhythm or ATP ECG

Small R waves Normal-sized T waves

RA

RA

RV Tip-Coil

RV

Large R waves Large T ratio

(1 mV)

5 1 0 AS 871 VP 597

AS 439 VP 426

AN PVC * 288

AS 875 VP 602

AN AS 438 VP 423

PVC * 266

T F2 3 0

EGM2: Vtip to Vring

A R F S 2 7 0

5 1 0 T F2 3 0

A R F S 2 7 0

5 1 0 T F 2 3 0

A R F S2 8 0

5 1 0 T F2 4 0

A R F S 2 7 0

5 1 0 T F2 4 0

V S F S

2 9 0

F S

2 9 0

F S

2 9 0

(1 mV)

F S

2 7 0

F S

5 9 0

V S

2 9 0

F S

2 9 0

Figure 3-29  Classification of T-wave oversensing. Left panel, Postpacing oversensing results in inhibition of pacing. Inhibition of antitachycardia pacing may also occur. Middle and right panels, T-wave oversensing in spontaneous rhythm can result in inappropriate detection of ventricular tachycardia or ventricular fibrillation. Management often depends on whether the R waves are small (middle) or large (right panel).



3  Sensing and Detection 8

9

10

11

12

13

14

15

73

16

VVI

*

* R

*

* R

*

* S

320 289 328 285 336 617 R R R R R R

S

R

R

R

R

H V

R

297 324 285 332 297 320 293 324 285 332 293 320 297 R R R R R R R R R R R R R 20 21 22 S

After Reprogramming

S

830V

S

1053 R

395 R

609 R 24

23 S

1087 R

1087 R

R

Threshold start Decay delay 60 msec R wave is sensed

Decay delay 0 msec

125 msec Figure 3-30  Specific programmable features to correct T-wave oversensing. Upper panel, Stored EGM from St. Jude ICD showing inappropriate shock for sinus tachycardia with T-wave oversensing. The lower strip was recorded from the programmer after reprogramming of the Decay Delay from 0 to 220 msec. Lower panel, Diagram of programmable features to avoid and correct T-wave oversensing in St. Jude ICDs. Automatic Sensitivity Control begins to adjust sensing at the end of the 125-msec ventricular blanking period. Both the initial sensitivity (Threshold Start as percentage of R-wave amplitude) and the time delay before onset of linear decrease in sensing threshold (increase in sensitivity) are programmable parameters. (From Swerdlow CD, Friedman PA: Advanced ICD troubleshooting. Part I. Pacing Clin Electrophysiol 28:1322-1346, 2005.)

EGM1: RVtip to RVring (1 mV)

EGM2: RVtip to RVcoil (1 mV)

Oversensed T wave Markers

↑ V S 5 4 0

↑ V S

↑ V S 5 4 0

↑ V S 5 4 0

↑ V S 5 4 0

↑ V S 5 5 0

↑ F S 2 8 0

↑ F S 2 3 0

↑ V S 5 3 0

Figure 3-31  True bipolar (RVtip to RVring) signal, integrated bipolar (RVtip to RVcoil) signal, and ventricular marker channel during true bipolar sensing shows intermittent T-wave oversensing (arrow) caused by low-amplitude true bipolar signal, despite raising sensing threshold from nominal 0.30 mV to 0.45mV. Programming sensing to the integrated bipolar signal, if available, would prevent T-wave oversensing.

74

SECTION 1  Basic Principles of Device Therapy

Vtip-Vring EGM

Filtered and rectified Vtip-Vring EGM

First differential R filtered and rectified Vtip-Vring EGM Vs

R T Vs

R T

Vs

Vs

R T

Vs

Vs

Vs

Figure 3-32  Algorithm to reject T-wave oversensing. Upper tracing, Vtip-Vring EGM with large T waves and T-wave oversensing. Middle tracing, Signal after standard sense amplifier filtering and rectification (purple line), automatic adjusting sensing threshold (red), and peak amplitude at each sensed event (blue; the peak amplitude for each sensed event is held until the next sensed event). Bottom tracing, First derivative of the filtered and rectified EGM (purple line) its peak amplitude at each sensed event (blue), and adaptive threshold used to separate possible R waves and T waves (red horizontal line). The algorithm recognizes oversensed T waves with lower frequency content than the preceding sensed R waves by automatically comparing signal amplitudes in the filtered/rectified sensing EGM and its first derivative (which further attenuates low-frequency signals) to identify patterns of alternating signal frequency content. Using an analysis window of six sensed events, the algorithm first automatically identifies possible R waves and T waves based on comparing peak amplitudes and patterns of the first derivative of the filtered/rectified sensing EGM. For each analysis window, the adaptive threshold is set to a fraction of the three largest first differential EGM peak amplitudes. The algorithm assumes that possible R waves are above threshold and possible T waves are below threshold. An alternating RT pattern with 3Rs and 3Ts or 4Rs and 2Ts in the six sensed events analysis window is required. RT pairs are confirmed when the R-wave/T-wave (R/T) ratio in the filtered/rectified sensing EGM is less than the R/T ratio measured in the first differential filtered/rectified EGM. This approach does not increase the risk of undersensing because the operation of the standard ICD sensing channel is not modified. It does not prevent oversensing of T waves, but rather allows the ICD to withhold therapy when T-wave oversensing pattern is recognized. Testing on more than 1000 VT/VF episodes showed no loss in sensitivity to true VT/VF. Vs, Ventricular sensed event.

6. An investigational ICD (Medtronic Protecta) has an algorithm that withholds ICD therapy when T-wave oversensing is identified as the source of device-detected tachycardia based on lower frequency content of the oversensed T waves (Fig. 3-32).74

between RV and LV electrodes.75 The composite ventricular EGM included deflections from the right ventricle and the left ventricle, both of which could be counted as separate R waves. Occasional R-wave double-counting may occur during PVCs and is more common with integrated bipolar than true bipolar leads.76 R-wave double-counting results in alternation of ventricular cycle lengths that produces a characteristic “railroad track” pattern on a plot of stored ventricular intervals. Because the second component of the R wave is sensed as soon as the blanking period terminates, the doublecounted RV-RV or RV-LV interval measures within 20 msec of the ventricular blanking period and is always classified in the VF zone (Fig. 3-33). Inappropriate detection of VF may occur despite a true ventricular rate below the VT detection interval. Most consistent R-wave double-counting now results from transient or reversible events such as hyperkalemia, drug effects, or lead failure in cardiac resynchronization ICDs; and most intermittent R-wave double-counting is not clinically significant. Some ICDs permit programming to increase the ventricular blanking period from the nominal value (120-125 msec) to higher values, up to 170 msec. Occasionally, reducing ventricular sensitivity can avoid R-wave doublecounting; but ventricular sensitivity should not be reduced unless reliable sensing of VF is confirmed at the reduced level of sensitivity. Rarely, lead revision is required. P-wave Oversensing P-wave oversensing may occur if the distal coil of an integrated bipolar lead is close to the tricuspid valve and if the sensed P-R interval exceeds the cross-chamber ventricular blanking period4 (Fig. 3-34). It is rare in adults with ventricular sensing electrodes near the RV apex, but it may occur in children or in adults if the RV electrode dislodges or is positioned in the proximal septum or inflow portion of the right ventricle. If P-wave oversensing occurs during a 1 : 1 rhythm, the sensed “R-R” pattern is similar to that of R-wave double-counting, provided that the sensed P-R or R-P interval is less than the VF detection interval. However, oversensing of P waves as R waves can cause inappropriate detection of VF during AF or atrial flutter, independent of the ventricular rate. Consistent oversensing of spontaneous P waves often requires lead revision. One amelioration strategy is to force atrial pacing using DDDR or Dynamic Overdrive modes. This shortens the ventricular cycle length (preventing ventricular sensitivity from reaching its minimum value) and introduces cross-chamber ventricular blanking after each atrial event (reducing the likelihood of oversensing P waves). Far-Field R-wave Oversensing The FFRW oversensing on the atrial channel, the inverse of P-wave oversensing on the ventricular channel, shows a pattern of alternating atrial cycle lengths with one sense marker timed close to the ventricular EGM. If rate and duration criteria for VT are fulfilled, FFRW oversensing may confound dual-chamber SVT-VT discrimination. FFRW oversensing does not cause inappropriate detection of VT if the ventricular rate is in the sinus zone, but it may cause inappropriate mode switching.

R-wave Double-Counting

EXTRACARDIAC SIGNALS

R-wave double-counting occurs if the duration of the sensed EGM exceeds the short ventricular blanking period in ICDs; currently, this is a rare clinical problem. Consistent R-wave double-counting may result from local ventricular delays in the baseline state in native rhythm or those resulting from use-dependent effects of sodium channel–blocking antiarrhythmic drugs or of hyperkalemia. Doublecounting may also occur with loss of RV capture in cardiac resynchronization ICDs: The ICD counts both the paced ventricular event and the conducted wavefront arriving at the RV bipole as a result of LV capture, if the interventricular conduction delay exceeded the ventricular blanking period. R-wave double-counting was a common problem in early ICDs that used Y-adapted or extended bipolar sensing

The distinctive feature of oversensing of extracardiac signals is replacement of the isoelectric baseline with high-frequency noise that does not have a constant relationship to the cardiac cycle.70,71,75,77 External Electromagnetic Interference With oversensing of external electromagnetic interference, signal amplitude is greater on the high-voltage EGM recorded from widely spaced electrodes than on the sensing EGM recorded from closely spaced electrodes. Although the interference signal may be continuous, oversensing is often intermittent because of auto-adjusting sensitivity. Clinical data may suggest a specific identifiable cause (Fig. 3-35). Some manufacturers (St. Jude, Sorin, Boston Scientific) have specific ICD



3  Sensing and Detection

75

ECG

A P

Marker

RVtip

LV-RV delay

RVringt

V blank A P

F S

RV Sensed event

VT interval = 400 msec FVT interval = 270 msec VF interval = 320 msec Placed event LV capture No RV capture Figure 3-33  Intermittent R-wave double-counting as a result of loss of RV capture in a cardiac resynchronization ICD patient with left bundle branch block. Left main panel shows surface ECG, atrial and ventricular marker channels, and true bipolar right ventricular (RV) EGM. The third, fifth, and sixth R waves are double-counted, as shown in insert on right. Simultaneous biventricular pacing activates the left ventricle (LV). After the LV-RV conduction delay, the wavefront arrives at the RV sensing bipole, corresponding to a sensed interval in the ventricular fibrillation (VF) zone (VS) and incrementing the VF counter. This condition alone will not result in VF being detected even if all beats are oversensed, but transient nonsustained ventricular tachycardia (VT) in the VF zone could result in inappropriate detection of VF, since the baseline VF counter may be as high as 50% of its maximum value.

algorithms to prevent inappropriate detection of VF in the presence of EMI (Fig. 3-36). Lead/Connector Problems Oversensing caused by lead insulation failure or conductor fracture, lead-lead mechanical interactions (“chatter”),76 or connector (header, adapter, set-screw) problems is intermittent and may occur only during a small fraction of the cardiac cycle. In ICDs, it is limited to the sensing EGM unless the problem relates to the RV coil in an integrated bipolar lead or to both sensing and high-voltage conductors/connectors. The rate of oversensed signals is always in the VF zone. Intervals below 200 msec are typical. Signals almost always display substantial variability in amplitude or frequency. High-frequency components are

common, and high-amplitude signals often saturate the amplifier (Figs. 3-37 to 3-39). In ICDs, extremely short R-R intervals near the ventricular blanking period (120-150 msec) do not represent successive cardiac depolarizations, except occasionally during VF. Medtronic ICDs count these very short intervals as a measure of nonphysiologic oversensing to provide early warning of lead fracture; they store this count as the sensing integrity counter (SIC). A high or rapidly accumulating Sensing Integrity Count (total >300 or 10/day for 3 consecutive days) is a sensitive indicator of pace-sense lead fracture,3,21,22 but in isolation is nonspecific. The most common cause of isolated, extremely short “R-R” intervals is a combination of an oversensed physiologic event and appropriately sensed R wave.

ECG

RV Tip-coil

Shock

Marker VT-1 VS 368 630

VS 695

VS 535

VS 538

VS 483

VS 560

VS 540

VS 520

VS 525

VS 435

VS 613

VS 535

VS 520

VS VS 425 510

VS 598

VS 508

VS 508

Figure 3-34  P-wave oversensing. The surface electrocardiographic (ECG) lead, integrated bipolar right ventricular electrogram (RV Tip-coil), and ventricular event markers are shown. P-wave oversensing caused by the proximity of the RV coil to the right atrium results in ICD sensing of alternating sinus (ventricular sensed, VS) and ventricular fibrillation (VF) intervals, the latter corresponding to the P-R interval. The sum of the VS and VF intervals equals the true R-R interval.

76

SECTION 1  Basic Principles of Device Therapy

Atrial

RV tip-coil Shock

--735

--

-783

-803

-783

-785

-803

-785

-705

-521 -193

-289 -501

-AS AS 129 143 205 -AS AS 455 473 121 -VF 201 209 --VP 403 160 501

AS 215 VS 380

AS 168

AS AS AS AS AS AS 117 127 137 88 156 246 AS AS AS AS AS AS AS 174 127 102 314 125 176 111 VS VF VF VF VF 429 137 234 176 180 VF VF VF VF VP 152 143 207 137 507

Figure 3-35  External electromagnetic interference caused by electric drill. Atrial EGM, integrated bipolar (RV tip-coil) EGM, and high-voltage (Shock) EGM are shown, together with a dual-chamber channel showing event markers. Electromagnetic interference (EMI) is continuous. Oversensing occurs first on the atrial channel, which has a higher sensitivity setting (and gain) than the ventricular sensing channel. Although the amplitude of external EMI is typically less on true bipolar sensing electrodes than on shocking electrodes, it may be similar on integrated bipolar and shocking electrodes.

In P-wave oversensing, the nonphysiologic short interval is the P-R interval. In R-wave double-counting, it is the interval between initial and terminal deflections of a true ventricular EGM. In T-wave oversensing, the interval is bounded by an oversensed T-wave and a PVC.76 However, these nonphysiologic combinations of physiologic signals rarely result in repetitive oversensing, which is common in lead or connector problems. Repetitive, transient oversensing may be identified by stored “nonsustained tachycardias.” The combination of isolated, extremely short RR intervals and repetitive rapid oversensing (defined as at least two nonsustained tachycardias with duration ≥5 intervals and mean cycle length ≤220 msec) has a positive predictive value for lead or connector problems of about 80%,76,78 even with a normal pace-sense impedance. Unusual cases of true VF76 and other unusual conditions, such as device-device interactions or header sealplug problems shortly after implant,79 can produce both isolated, very short intervals and rapid, repetitive oversensing. Role of lead impedance.  Modern pacemakers and ICDs perform daily, automated measurements of impedance in lead conductors. A large, abrupt change in impedance associated with rapid oversensing

VT-1 VS 368 630

VS 695

VS 535

VS 538

VS 483

VS 568

VS 540

VS 520

is, for practical purposes, diagnostic of a lead or header-connector problem. However, pace-sense conductor fractures typically present as rapid, repetitive oversensing without abnormal impedance.78 A fracture may generate sufficient oversensing to cause inappropriate shocks without an impedance increase or with an impedance increase in the interval between daily impedance measurements.78,80-82 Rarely, pacing precipitates lead-related oversensing.81 Lead fractures or headerconnector problems also present frequently as abrupt increases in impedance without oversensing. The Medtronic Lead Integrity Alert (LIA) is triggered by either abnormally high impedance relative to the patient’s baseline impedance or rapid oversensing unlikely to represent a physiologic event55,78 (Figs. 3-40 and 3-41). Once an alert is triggered, an audible tone sounds immediately and every 4 hours thereafter. LIA alerts also reprogram the number of intervals to detect VF (NID) from the value programmed at the physician’s discretion (nominally 18/24) to 30/40; EGMs are stored for any interval shorter than 200 msec. The purpose of the high NID is to reduce inappropriate shocks caused by transient, fracture-induced oversensing.78 The stored EGMs provide a diagnostic clue to determine the cause of rapid oversensing based on EGM

VS 525

VS 435

VS 613

VS 535

VS 520

VS VS 425 510

VS 598

VS 508

VS 508

Figure 3-36  Noise rejection algorithm prevents oversensing of external electromagnetic interference caused by electroconvulsive therapy, despite noise amplitude exceeding programmed sensitivity. Surface ECG, integrated bipolar sensing EGM, shock EGM, and ventricular marker channel are shown. The Dynamic Noise Algorithm in Boston Scientific Cognis-Telegin ICDs measures the energy in the upper half of the sensing bandwidth (20-85 Hz) and sets a noise-energy–based sensing level (“noise floor”), which is usually lower than the programmed maximum sensitivity. A higher-than-expected fraction of energy in the upper half of the bandwidth suggests the presence of noise, and the ICD responds by increasing the noise floor above the minimum programmed level of sensitivity while noise is present. (Courtesy Dr. Andrei Catanchin.)



77

3  Sensing and Detection

Atip-Aring

0.5mV

8mV

Vtip-Vring

5

5

5

0

0 A

0

0

S V S

5

0 A

5

0 A

0

R

0

R F

0

R F

F

4

0 A

0

R

F

F

S 2

S2

S1 S 2

F

0

1

4

6

3

5

6

7

0

6

3

6

0

0

0

0

0

0

0

0

0

0

0

0

S

A-A

Interval (ms) 1800

V 4

F

F

S1 S1 S

0

F

0

4

1 A

0

R

5

9 A

0

R

V F

V

F

F F

S1 S 3

S 2

S 2

S1 S1 S 2

F

6

3

3

0

9

7

2

5

0

0

0

0

0

0

0

0

5

1 A

0

R

3

S1 S

1 A

0

R F

0

R

V

F

F

4

S 2

S 2

D1

2

3

9

9

8

0

0

0

0

0 VF

S

VF = 300 ms 29.6 J

11.9 J

1500 1200

5

0 A

R V

3

5

0 A

R

V

S1 S1 S 2

5

9 A

5

V-V

F

5

0 A

30.1 J 30.1 J

20.2 J

900 600 400 200

−20

−10

0

10

20

30

40

50

60

70

80

Time (sec) [0=Detection] Figure 3-37  Oversensing caused by lead insulation failure. Top panel shows the atrial (Atip-Aring) EGM, the ventricular true bipolar (Vtip-Vring) EGM, and event markers. Bottom panel shows the interval plot. In the ventricular channel, there are intermittent, erratic signals that saturate the sensing amplifier. The interval plot highlights the wide range of sensed intervals, including many “short” intervals close to the ventricular blanking period of 120 msec. Arrows denote five inappropriate shocks.

characteristics.76 In newer ICDs with wireless telemetry, alerts in both groups may also initiate Internet notifications. Myopotential Oversensing Myopotential oversensing may persist for variable fractions of the cardiac cycle. Diaphragmatic myopotentials are most prominent on the sensing EGM. Oversensing usually occurs after long diastolic intervals or after ventricular paced events when amplifier sensitivity or gain is maximal. It often ends with a sensed R wave, which abruptly reduces sensitivity. In pacemaker-dependent patients, diaphragmatic oversensing causes inhibition of pacing, resulting in persistent oversensing and inappropriate detection of VF (Fig. 3-42). Clinically, this may manifest as syncope from inhibition of pacing followed by an inappropriate shock. This is an exception to the clinical rule that antecedent syncope usually indicates an appropriate shock. A short time constant for automatic adjustment of sensitivity increases the probability of this type of oversensing. It is most common in male patients who have integrated bipolar leads in the RV apex.3,4 Oversensing of diaphragmatic myopotentials may be corrected by reducing ventricular sensitivity, provided that VF sensing and detection are reliable at the reduced level of sensitivity. In pacemaker-dependent patients, oversensing may also be reduced by pacing at a faster rate. Occasionally, correction requires insertion of a new rate-sensing lead away from the diaphragm.

Pectoral myopotentials are more prominent on a far-field EGM that includes the ICD can rather than the near-field EGM. Because ICDs do not use this EGM for rate counting, oversensing of pectoral myopotentials does not cause inappropriate detection, but they may reduce the effectiveness of SVT-VT discrimination by EGM morphology algorithms during exercise-induced sinus tachycardia. Pectoral myopotentials are a major cause of oversensing in unipolar pacemakers and may result in either inhibition of ventricular pacing (if sensed by ventricular channel) or rapid ventricular pacing (if sensed and tracked by atrial channel). Myopotential oversensing may be suspected if symptoms occur during arm motion and can often be demonstrated in the clinic by having the patient forcefully press the hands together while the EGM is monitored. DETECTION ALGORITHMS FOR AUTOMATIC OPTIMIZATION OF PACEMAKER FUNCTION Pacemakers and ICDs incorporate special algorithms to prevent serious errors in pacemaker function such as inhibition during oversensing, inappropriately high pacing rates caused by tracking of atrial tachyarrhythmias, unnecessary ventricular pacing in patients with intact AV conduction, and loss of pacemaker capture. Ventricular safety pacing prevents inappropriate pacemaker inhibition caused by ventricular

78

SECTION 1  Basic Principles of Device Therapy

MR 81 PVC 0 [AG008VD] M

M

?

ECG Tip-RV Coil Tip-Ring AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS

1600 1400 1200 1000 800 600 400 200 0

VP

VP 750

VP 750

VP 750

VP 750

TS 360

VP 750

VP 750

VP 750

VP 750

ECG

LV pace RV pace

Ring-Can Tip-Ring AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS

4/ 13 4/ 14 4/ 15 4/ 16 4/ 17 4/ 18 4/ 19 4/ 20 4/ 21 4/ 22 4/ 23 4/ 24 4/ 25 4/ 26

Impedance

VP V-RRint

VP V-RRint

VP

VP TF 750 260

VP 750

VP 750

VS 740.30

VP 750

VP 750

VP 750

VP 750

Figure 3-38  Ventricular oversensing leads to inhibition of pacing in a pacemaker-dependent patient 2 weeks after replacement of an ICD pulse generator. Top left, In-hospital electrocardiogram (ECG) monitoring strip with 4.46-second pause in paced ventricular rhythm. The atrial rhythm is atrial fibrillation. Bottom left, Marked variability in right ventricular (RV) pacing impedance with constant impedance in left ventricular (LV) lead. The two right panels show telemetry Holter recordings, including one ECG channel, two ventricular EGMs, and event markers. Top right, Oversensing on tip-ring EGM (arrow, box) but not on tip-RV coil EGM. Oversensing is intermittent and saturates the amplifier. Bottom right, Oversensing on both tip-ring and ring-can EGMs, localizing the oversensing problem to connections related to the ring EGM (box). AS, Atrial sensed event; TS, ventricular interval in ventricular tachycardia (VT) zone; VP, ventricular paced event.

oversensing of atrial pacing stimuli (crosstalk). Noise reversion to fixedrate pacing prevents pacemaker inhibition during continuous ventricular oversensing. Automatic mode switching in dual-chamber pacing systems helps avoid inappropriate tracking of high atrial rates during atrial tachyarrhythmias. Ventricular Safety Pacing and Noise Reversion Ventricular safety pacing prevents inappropriate inhibition of ventricular pacing after atrial paced events. This feature augments the protection provided by cross-chamber blanking after atrial pacing stimuli. If a ventricular event is sensed after the delivery of an atrial pacing stimulus in a “nonphysiologic” period (10-100 msec) during the AV delay, a ventricular pacing stimulus is delivered at the end of the nonphysiologic interval (110-120 msec). This prevents pacemaker crosstalk from causing inhibition of ventricular pacing output, but it may also result in (noncaptured) ventricular pacing immediately after Before revision

After revision

Figure 3-39  Intraoperative fluoroscopic images corresponding to the data presented in Figure 3-38. The ICD has been removed from the pocket to enhance image quality. Before revision, the lead connector pin was not advanced completely into the header (arrow). The proximal connection between the ring electrode and the header was intermittent, accounting for the high impedance and oversensing illustrated in Figure 3-38. After revision, the ventricular electrode is advanced completely into the header.

true ventricular events that occur during the AV delay. Ventricular safety pacing is especially likely to occur during atrial undersensing, during AF, or during a junctional rhythm. Pacemakers also contain algorithms to protect against prolonged inhibition of ventricular pacing caused by oversensing. Noise-sampling windows (30-60 msec in duration) are used during the blanking periods to identify spurious signals and cause the ICD to change to an asynchronous “reversion” pacing mode, to ensure ventricular backup pacing.83 Noise-reversion operation is particularly important for unipolar sensing, which is more likely than bipolar sensing to exhibit oversensing of extracardiac signals84 (Fig. 3-43). Automatic Mode Switching to Avoid Ventricular Tracking of Atrial Tachyarrhythmias Pacemakers programmed to dual-chamber synchronous pacing modes may use automatic “mode switching” algorithms to initiate a temporary change to a nontracking pacing mode during paroxysmal atrial tachyarrhythmias, to avoid inappropriately high ventricular pacing rates. Methods of mode switching differ among pacemakers and ICDs and can be classified into five different categories85,86 (Fig. 3-44). Accurate atrial sensing is critical to appropriate mode switching, because all methods depend on measurement of atrial rate, A-V patterns, or both. The atrial sensing configuration (unipolar vs. bipolar), programmed atrial sensitivity, and atrial blanking periods influence the methods used by the various manufacturers and their performance for detection of atrial tachyarrhythmias. Algorithms to recognize repetitive blanking of atrial events during atrial flutter allow mode switching to occur more rapidly when this condition is confirmed (Fig. 3-45). Whatever method is employed, unreliable atrial sensing, whether from lowamplitude P waves or insensitive programming to avoid FFRW oversensing, will degrade performance of these algorithms.85-88 ICDs with long PVAB periods or low atrial sensitivity may fail to switch modes if a substantial fraction of atrial events are undersensed. Algorithms to Reduce Ventricular Pacing Unnecessary ventricular pacing contributes to adverse clinical outcomes (e.g., heart failure hospitalizations) and increased risk of AF.89,90 Algorithms that lengthen AV intervals adaptively to promote intrinsic conduction reduce ventricular pacing.91-94 Medtronic and Sorin



3  Sensing and Detection

79

Vtip−Vring

RVcoil−can

↑ F S

Marker

↑ ↑ ↑ V F F S 1 S1 S 7 6 0 0

8 2 0

↑ V S

5 7 0

↑ ↑ ↑ ↑ T F F F 3 S 1 S 1 S 1D 4 6 2 3 0 0 0 0

↑ ↑ V F S1S 2 0

7 3 0

↑ ↑ V F S 2S 0 0

↑ V S

7 7 0

5 1 0

↑ V S

↑ ↑ ↑ V F F S 1S 1S 3 3 0 0

6 8 0

Detected NID 18/24

↑ V S

7 5 0

↑ V S

7 6 0

4 4 0

↑ V S

↑ V S

7 6 0

↑ ↑ ↑ ↑ T T F F 3 S 3 S 2S 1S 0 0 3 2 0 0 0 0

↑ V S

4 1 0

3 3 0

↑ ↑ F V S 2 S 6 0

↑ ↑ ↑ T T F S 2 S 1S 4 3 0 0

7 1 0

↑ V S 1 8 0

5 6 0

↑ V S

6 2 0

Not detected NID 30/40

Figure 3-40  Stored electrogram shows intermittent oversensing caused by lead fracture. Pace-sense (Vtip-Vring), high-voltage (RVcoil-can), and marker channels are shown; VS, TS, and FS, intervals in sinus, ventricular tachycardia (VT), and ventricular fibrillation (VF) zones, respectively; FD, detection of VF. Upper and lower panels are continuous. Pace-sense channel shows intermittent, high-frequency, oversensing of nonphysiologic noise characteristic of lead fracture or header-connector problem. At the programmed number of intervals to detect VF (NID) 18/24, inappropriate detection of VF occurs near left of the bottom panel, resulting in an inappropriate shock (not shown). Coincident with detection of VF, oversensing decreases greatly. VF would not have been detected at higher values of NID. FS, Ventricular interval in VF zone; VS, ventricular sensed event; VP, ventricular paced event. (From Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008.)

developed new pacing modes (MVP and SafeR) that operate in AAI(R) mode, with mode switching to DDD(R) to prevent excessive ventricular pauses or asystole.19,95,96 Single beats of AV conduction failure are allowed by both algorithms, with switching to DDD mode occurring only if higher levels of AV conduction block occurs (Medtronic) or if the PR interval is excessive. Once switched to DDD mode, both algorithms test for AV conduction periodically, to avoid unnecessary ventricular pacing for transient AV block. However, these pacing modes may be associated with pacemaker syndrome in patients with marked first-degree AV block, resulting in unnecessary pauses if complete heart block develops.97-99 Automatic Assessment of Pacemaker Capture (“Capture Management”) Automatic sensing of the evoked response (local myocardial depolarization) that results from a pacing stimulus allows for verification of myocardial capture. However, sensing of the evoked response is obscured by the decaying polarization afterpotential that follows the pacing stimulus.100 This polarization artifact can be attenuated by using high-capacitance, low-polarization leads or using multiphasic pacing impulses to neutralize the postpacing polarization. Figure 3-46 shows an example of the evoked response signal combined with polarization artifact after a pacing stimulus.100 To minimize the afterpotential from ventricular pacing stimuli and improve detection of the evoked response, some manufacturers use a smaller-output capacitor. This approach further enhances the accuracy of evoked response detection. Pacemakers use one of two different ventricular capture verification schemes: beat-to-beat approaches that monitor capture almost continuously and periodic approaches that test pacing thresholds intermittently (e.g., once every few hours). Algorithms that perform periodic capture threshold measurements typically set the pacing output at 1.5 to 2.0 times the threshold to avoid transient loss of capture until the next test. Beat-to-beat capture management algorithms adjust pacing

outputs to values that are just above pacing threshold but deliver higher-output backup pulses if loss of capture occurs.101 Ventricular capture verification has been incorporated into some ICDs and resynchronization ICDs. Algorithms for RV capture management use essentially the same methods as pacemakers, except that polarization artifact that challenges evoked response detection in bipolar pacing leads is eliminated or reduced by use of the RV coil-tocan EGM available in ICD systems.102 LV capture management may be achieved by pacing on the LV lead and analyzing the intraventricular conduction time sensed in the right ventricle. This method has been demonstrated to be safe, reliable, and clinically equivalent to operatorperformed LV threshold tests.103 Atrial capture management is more challenging than ventricular management because the atrial evoked response is much smaller than the ventricular response. Thus, reliable detection of the evoked response is difficult, and atrial capture detection using the evoked response method can be performed only using low-polarization electrodes.104 An alternative method relies on critical timing of the atrial and ventricular response to atrial pacing stimuli during normal sinus rhythm (Fig. 3-47). In ambulatory patients, this method has been reported to perform comparably with operator-performed atrial pacing threshold measurements without causing atrial proarrhythmia.105

Basics of Detection of Ventricular Tachycardia/Fibrillation Figure 3-48 provides an overview of the structure of VT/VF detection algorithms. Initial detection of tachycardia is based on rate and duration. The minimum duration of tachycardia required for detection is programmable, either directly (in seconds) or indirectly by setting the number of ventricular intervals required. A tachycardia episode begins when the minimum rate and duration criteria are satisfied. Computationally intensive features of detection algorithms, such

80

SECTION 1  Basic Principles of Device Therapy

Ohms >3000 2000 1500 1000 800 600 400 300 <200

1000 ohms

12/01/ 05

02/09/ 06

04/20/ 06

A

05/29/ 06

09/07/ 06

11/16/ 06

01/25/ 07

Last 80 weeks (min/max per week)

04/03/ 07

04/16/ 07

12 days

Ohms >3000 2000 1500 1000 800 600 400 300 <200

1000 ohms

02/05 06

B

04/17/ 06

06/26 06

09/04/ 06

11/13/ 06

Last 80 weeks (min/max per week)

01/18/ 01/31/ 07 07 Last 14 days

1st shock

LIA Oversensing Met

22:37:53 May 23

18:36:31 May 17

1st shock

LIA Impedance Met

LIA Oversensing Met

2nd shock

01:15:35 Aug 29

03:00:00

03:02:40

08:57:42

6 days Non-sustained tachycardia log

Non-sustained tachycardia log ID#

Date/time

V. cycle

Duration

ID#

Date/time

V. cycle

Duration

5 4

May 17 18:36:31 May 17 10:55:49

200 ms 190 ms

5 beats 5 beats

407 404

Aug 29 03:02:40 Aug 29 01:15:32

120 ms 200 ms

5 beats 5 beats

Ohms >2500 2000 1500 1000 800 600 400 300 <200

Impedance 1000 ohms

03/22/ 06

C

05/31/ 06

08/09/ 06

10/18/ 06

12/27/ 06

03/07/ 07

Last 80 weeks (min/max per week)

05/10/ 05/23/ 07 07 Last 14 days

Ohms

Impedance

At implant 496 ohms last >3000 ohms

1000 ohms

08/31/ 06

D

11/09/ 06

01/18/ 07

03/29/ 07

>3000 2000 1500 1000 800 600 400 300 <200

05/07/ 07

08/16/ 08/29/ 07 07 Last 14 days Last 80 weeks (min/max per week)

Figure 3-41  Individual patient examples of source data used in retrospective simulation of Lead Integrity Alert (LIA, Medtronic) designed to provide warning of lead failure triggered by either high pace-sense impedance or transient rapid oversensing. The goal of this feature is to provide patients and physicians with sufficient warning that patients will receive medical attention prior to delivery of inappropriate shocks.  A, True-positive impedance trigger: abrupt variations in impedance exceeding 1000 Ω, triggering a LIA alert 12 days before an inappropriate shock. B, False-positive impedance trigger shows gradual increase in impedance. New version of algorithm requires abrupt rise in impedance. C, Truepositive oversensing alert triggered 6 days before an inappropriate shock, despite constant impedance. D, LIA was not triggered prior to first inappropriate shock. However, because both impedance and oversensing triggers occurred 1 hour and 45 minutes after that shock, the automatic NID increase would have prevented the subsequent shocks 5 hours later. (From Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008.)



3  Sensing and Detection

81

Atrial

RV Tip-Coil

Shock

AP-Sr -VP-Sr --

AP-Sr 985 VP-Sr 985

VP-Sr 985

AP-Sr 978 VP-Sr 978

AP-Sr 978 VP-Sr 978

AS 870 PVC 760

VP 870

(AS) 1153 VT 325

PVP

(AS) 1025 PVC 723

PVP

VF 160

VF 268

PVP

(AS) 1015 VF VF 153 198 VF VF 183 158 PVP

PVP

VS 550

VF 225 VF 150 Epsd PVP Suddn

Figure 3-42  Oversensing of diaphragmatic myopotentials. Atrial EGM, integrated right ventricular (RV Tip-Coil) bipolar sensing EGM, highvoltage (Shock) EGM, and marker channels from a Boston Scientific Prizm II ICD in a patient with complete heart block are shown. Low-amplitude, high-frequency signals are recorded on the integrated bipolar channel, inhibiting pacing and resulting in inappropriate detection of ventricular fibrillation (VF) at right (labeled Epsd, for episode start/end). Oversensing of diaphragmatic myopotentials usually occurs after long diastolic intervals or after ventricular paced events when amplifier sensitivity or gain is maximal. Repositioning of the lead eliminated the problem. AS, Atrial sensed event; AP, atrial paced event; PVC, premature ventricular complex; PVP→, extension of postventricular atrial refractory period (PVARP); Sr, sensed refractory event; VP, ventricular paced event.

VP

A

B

AB NS

VP

VP

VP

AB NS NS NS NS NS NS NS AB NS NS NS NS NS NS NS AB NS NS

90 bpm

70 bpm

Figure 3-43  A, Extension of refractory period resulting from detection of noise during the noise-sampling (NS) portion of the ventricular refractory period; VP, ventricular paced event. The first portion of the ventricular refractory period is absolute (AB). When suprathreshold signals are seen during the NS portion of the ventricular refractory period, a new NS window is initiated, “retriggering” the ventricular refractory period by a duration equal to the NS window. Continuous extension of the ventricular refractory period invokes noise reversion pacing at the programmed reversion rate. A, Normal VVI pacing at 60 bpm on the left. When electromagnetic interference begins, the ventricular refractory period is continuously retriggered, and noise reversion pacing starts at 90 bpm. B, Combination of ventricular inhibition and noise reversion. The noise reversion rate of this VVI pacemaker is 90 bpm, and the base rate is programmed at 70 bpm. Beats with arrows indicate noise reversion pacing caused by continuous retriggering of the ventricular refractory period, as in A. Some beats are slower than 70 bpm because of intermittent (not continuous) oversensing of noise such that ventricular refractory periods are not continuously retriggered. (B modified from Sweesy MW, Holland JL, Smith KW: Electromagnetic interference in cardiac rhythm management ICDs. AACN Clin Issues 15:391-403, 2004.)

82

SECTION 1  Basic Principles of Device Therapy

as morphology analysis, are activated only after initial detection occurs, to conserve power. Unbiased MAR

VENTRICULAR RATE AND COUNTING METHODS

Specificity

MAR biased to faster rates

The specific methods used to count ventricular intervals vary and influence the sensitivity and specificity of VT detection. Initial detection in the VF zone must be tolerant of undersensing. Detection usually occurs when a certain percentage (typically 70%-80%) of intervals in a sliding window (usually 10-40 intervals) fulfill the programmed rate criterion. Most ICD manufacturers also use this “X out of Y” counting in the slower (VT) zones, although Medtronic requires that all intervals exceed the rate criterion to detect VT. This consecutive-interval method diminishes inappropriate detection of AF without compromising sensitivity for detection of regular, monomorphic VT.106-108 St. Jude ICDs classify intervals based both on the last interval and on the average of the last four intervals (Figs. 3-49 and 3-50). A potential advantage of this method is that averaging minimizes the effects of intermittent undersensing by providing a “smoothing effect.”106 A disadvantage is that averaging exaggerates the effect of extremely short, oversensed intervals or extremely long, undersensed intervals. To satisfy tachycardia criteria, “binned” intervals do not need to be consecutive. As long as sinus rhythm is not redetected, the counter will continue to increment. This may be particularly problematic when the slowest VT zone is used as a monitoring zone: During sinus tachycardia in the monitoring zone, PVCs increment the VT counter, but the counter is not reset until the sinus rate decreases out of the monitoring zone, providing the potential for inappropriate therapy of sinus tachycardia109 (Fig. 3-51). Sorin ICDs first classify the rhythm on the basis of the ventricular cycle length. This algorithm relies on the “majority criterion,” which excludes the initial two, short ventricular cycles from analysis to withdraw cycles that may have unstable R-R intervals at the beginning of an arrhythmia.

RAC with high MS rate and cons counts x out of y with high x/y ratio x out of y with low x/y ratio RAC with low MS rate and non-cons counts Combined algorithms Beat-to-beat Sensitivity

Figure 3-44  Sensitivity and specificity of automatic mode-switching (MS) algorithms for atrial tachyarrhythmia detection. Relative performances of the five different classes of algorithms are shown; performance of the mean atrial rate (MAR), rate and count (RAC), and “x out of y” algorithms are shown twice to emphasize performance variability with specific parameter selections. Algorithms that use MAR calculation favor specificity over sensitivity but are generally slower-acting than algorithms that favor sensitivity (e.g., beat-to-beat). Atrial events with short and long atrial cycle lengths equally affect atrial rate estimation in “unbiased” MAR algorithms; long atrial cycle lengths have less impact on atrial rate estimation in “biased” MAR calculations, to reduce the impact of atrial undersensing. Cons, Consecutive; non-cons, nonconsecutive. (From Israel CW: Analysis of mode switching algorithms in dual chamber pacemakers. Pacing Clin Electrophysiol 25:380-393, 2002.)

A S

A S V P

A S V P

A S

1

V P

A S

V P

A S

V P

A S

V P

A S

V P

A S

V P

2

A S V P

A S

V P

3

6

A S V P

V P

A S

V P

7

A S

V P

1 V P

A S

2 V P

A S

3 V P

A S

4 V P

A S

5 V P

A S

6 V P

A S

7 V P

A S

8 V P

A S

A A A R S S

V P

V P

A A R R

A S

V P

Mode switch

A A A S S R

A S

A R

A R

V P DDI A A A S S R

A S

A R

V P

8

V P

A S

A R

A S

V P

V P

A A A A A A R R S R R S

V P

A R

V P

Mode switch

PVARP extension A S

A R V P

A S

A S

V P

5

A S V P

A S

V P

4

A S

V P

A A R R

V P

A A A A A A S R R S R R

V P

V P

A A S R

V P

Figure 3-45  Algorithm to prevent upper rate limit tracking of alternate atrial EGMs during atrial flutter (Blanked Flutter Search), even if EGMs recorded in postventricular atrial blanking period (PVAB), when sensing cannot occur. Upper panel, Simulated electrocardiogram (ECG) and ladder diagram. Black horizontal bars denote blanking periods, and white bars denote refractory periods for atrium (upper bars) and ventricle (lower bars). Lower panel, Stored ventricular EGM and dual-chamber EGM markers from a clinical event. Upper panel, The intention of this algorithm is to infer that alternate atrial EGMs are “hiding” in the PVAB. To determine whether this is occurring, the algorithm transiently interrupts atrial tracking to assess the atrial rhythm when it is likely that alternate atrial intervals are occurring in the PVAB. The specific criterion is that the measured A-A interval is both less than twice the sum of the sensed AV interval and the PVAB and less than the mode switch interval for 8 beats. When this occurs, the algorithm extends the postventricular atrial refractory period (PVARP extension). The next atrial EGM that would have been tracked is now in the PVARP (AR marker, first arrow) and is not tracked. The next atrial flutter EGM is sensed because it no longer times in the PVAB (AS marker, second arrow). The pacemaker then switches mode rapidly (DDI). Lower panel, In this stored clinical EGM, ventricular intervals are numbered to correspond to those in the simulation in the upper panel. As in the upper panel, the first arrow (AR) corresponds to PVARP extension, and the second arrow (AS) corresponds to a sensed atrial flutter EGM that would have been blanked in tracking mode. Mode switching follows immediately. VP, Ventricular paced event.



3  Sensing and Detection

Monitor-only Zones

Amplitude

Pace polarization artifact

Pacing pulse

−200 msec Time

Programmable monitor-only zones store EGMs of tachycardias based on rate and duration even if they are slower than the slowest zone in which VT therapy is programmed. If therapy is not programmed “on” for slow VT, the slowest rate zone may be programmed as a “monitor only” zone, with detection “on” and therapies “off.” However, interactions between the counters in the VT zone serving as a monitor zone and the next zone may restrict use of SVT-VT discriminators or decrease the number of intervals required for detection in the therapy zone. ICDs with dedicated monitor-only zones may avoid these potential interactions. However, as noted previously, in St. Jude ICDs the combination of counting method and criteria for resetting the VT counter during sinus tachycardia in the monitor-only zone may result in inappropriate therapy.109,110

Time

The SVT-VT discriminators are a programmable subset of an ICD’s detection algorithm for VT/VF. Discriminators withhold ventricular antitachycardia pacing (ATP) or shocks if SVT is diagnosed. These algorithms differ from the SVT detection algorithms used to switch modes during bradycardia pacing or deliver atrial therapy for AF or atrial flutter.

Amplitude

A

B

83

Evoked response

Discriminators

Amplitude

Detected signal (evoked response + pace polarization artifact)

Time

C Figure 3-46  Local myocardial depolarization (evoked response) is obscured by the postpacing polarization artifact. A, Pace polarization artifact is observed as a positive deflection that generally decreases toward the initial cell potential within about 200 msec after the pacing pulse. B, Evoked response is present immediately after the pacing pulse and shows an initial negative deflection. C, The signal sensed by the pacemaker is the summation of the pace polarization artifact and  the evoked response. (From de Voogt WG, Vonk BF, Albers BA, et al: Understanding capture detection. Europace 6:561-569, 2004.)

VENTRICULAR TACHYCARDIA/FIBRILLATION RATE DETECTION ZONES Tiered-therapy ICDs have up to three ventricular rate detection zones that permit programming of zone-specific therapies and SVT-VT discriminators (Fig. 3-52). The duration of a rapid ventricular rate required for detection is programmable independently in at least the slowest and fastest zone (see Zones and Zone Boundaries). The two slower zones are classified as VT zones, and the fastest one as a VF zone. All ICDs use strategies to minimize the risk of prolonged detection if successive VT intervals are classified in different zones. Except for Medtronic ICDs, sensed events in one zone increment counters in all slower zones. To avoid delays in detecting rhythms that straddle zone boundaries, Medtronic ICDs utilize a combined-count (summation) feature, which is satisfied if a sufficient fraction of intervals is in either zone.106

CONFIRMATION, REDETECTION, AND EPISODE TERMINATION If a tachycardia is classified as ventricular, ATP may be delivered immediately; but shocks require capacitor charging, which takes 6 to 15 seconds for maximum-energy shocks. The first shock in a shock sequence is “noncommitted,” meaning that it may be aborted during charging if the detection algorithm identifies termination of the arrhythmia during or immediately after charging of the high-energy capacitors (Fig. 3-53). In contrast, a “committed shock” is always delivered if the capacitor charges. Confirmation or reconfirmation is the brief process that occurs after charging by which ICDs determine whether to deliver or abort the first shock in a sequence. In all ICDs, the confirmation algorithm delivers the stored shock if a few intervals immediately after charge completion are shorter than the programmed VT interval (St. Jude, Boston Scientific, Sorin, Biotronik) or are within 60 msec of the VT interval (Medtronic ICDs before Protecta) (Fig. 3-54). Therefore, the first VF shock is effectively “committed” if the VT interval (or, in some ICDs, the monitor-only interval) is programmed to a long cycle length.111,112 A new shock confirmation algorithm in Medtronic ICDs (investigational, Protecta) aborts a defibrillation shock when ventricular cycle lengths increase by at least 60 msec relative to the detected tachycardia cycle length and exceed the VF detection interval, and the ventricular cycle length at the point of detection is regular. Tachycardias detected in the VF zone that do not have regular cycle length are judged against the VF interval plus 60 msec. Shocks for VT will abort on a 60-msec increase in cycle length relative to the point in detection, regardless of cycle length regularity. Once a shock is aborted, the device continues to apply tachycardia redetection and episode termination criteria. Depending on the manufacturer and programming, each shock after the first shock may be either noncommitted or committed. A shock is also committed if VT or VF is detected after a diverted shock and before episode termination.83 Redetection is the process by which ICDs determine whether VT or VF detection criteria remain satisfied after therapy is delivered. The duration for redetection is programmable independently of the duration for initial detection and typically is shorter than that for initial detection. ICD-defined arrhythmia episodes continue after each tiered therapy until either a tachyarrhythmia is redetected to initiate the next therapy or the rhythm is classified as normal (“sinus”), resulting in episode termination. In most ICDs, episode termination is based on (slow) rate and duration, with 3 to 8 beats classified as sinus. The

84

SECTION 1  Basic Principles of Device Therapy

APt AR

AS Atrial test pace not captured

Atrial backup pace VP

AP

VP

APt

AS Atrial test pace captured, no AV conduction

Capture verification windows VS

VS

VS

VP

VP AS

Atrial backup pace

APt

AP

Atrial test pace captured, AV conduction

A

Atrial overdrive rate

Atrial test pace captured

Atrial overdrive rate AP APt 270 ms Atrial overdrive rate

Atrial test pace not captured VP

VS

B

Atrial overdrive rate

Atrial overdrive rate AP APt 270 ms Atrial overdrive rate

Capture verification windows VS

VS

VS

Figure 3-47  Atrial capture verification method that relies on atrial or ventricular responses to atrial pacing. A high-level control algorithm determines which of two timing assessment methods should be used, based on the recent history of atrial pacing, atrial sensing, and atrioventricular (AV) conduction. At least two test paces are required to verify capture or loss of capture. Failed, inconclusive, or aborted threshold tests are repeated after a delay. This method cannot measure atrial capture during atrial paced–ventricular paced (VP) rhythms or rhythms with irregular atrial or ventricular cycle lengths. A, Atrial Chamber Reset method is used if recent history indicates primarily atrial sensed events (AS). A premature atrial test pace (APt) is delivered, and the resulting atrial timing is observed. An atrial refractory event (AR) within 10 bpm after the prior intrinsic atrial rate suggests loss of capture (top panel). The lack of an atrial refractory event in this period suggests resetting of the atrial timing and atrial capture (middle and bottom panels). B, The AV conduction check method is used if the recent history indicates that AV conduction is present. The average AV conduction time is measured before delivery of the APt. A backup atrial pace at the operating atrial output is also delivered 70 msec after the APt. The algorithm looks for ventricular sensed events (VS) in one of two capture verification windows (40 msec in duration) that are placed relative to the APt and the backup atrial paced events based on the average AV conduction time. A ventricular event sensed in the first capture verification window suggests capture by the APt (top panel). Lack of a sensed ventricular event in the first capture verification window and presence of a ventricular event in the second window is evidence of noncapture by the APt (bottom panel).

n

n

SVT-VT Discriminators

Initial detection y (V rate and duration)

Rate y zone VT

SVT-VT Discriminators

y ATP

Rx

Redetection y (V rate and duration)

n

Episode termination

y

VF

n

n

Shock

Confirmation after charging

y

n

Figure 3-48  Overview of ICD detection algorithm. Algorithms apply varying degrees of supraventricular tachycardia–ventricular tachycardia (SVT-VT) discrimination to redetection. ATP, antitachycardia pacing; n, no; Rx, antitachycardia therapy; V, ventricular; VF, ventricular fibrillation; y, yes.



3  Sensing and Detection

85

Current Interval

Figure 3-49  Interval classification based on current interval and average interval (St. Jude). The table shows classification of ventricular intervals by St. Jude ICDs based on both the value of the current interval and the average of the current interval with the preceding three intervals (average interval). Detection zones from slowest to fastest are Sinus, Tach A (slower ventricular tachycardia [VT] zone), Tach B (faster VT zone), and Fib (ventricular fibrillation [VF]). If both the current and the average interval are in the same zone, the current interval is classified in that zone. If they are in different VT or VF zones, the current interval is classified in the faster zone. If one interval is in the sinus zone and the other is in a VT or VF zone, the current interval is not classified (Not Binned).

Fib

Tach B

Tach A

Tach

Sinus

Fib

Fib

Fib

Fib

Not Binned

Tach B

Fib

Tach B

Tach B

N/A

Not Binned

Tach A

Fib

Tach B

Tach A

N/A

Not Binned

Tach

Fib

N/A

N/A

Tach

Not Binned

Sinus

Not Binned

Not Binned

Not Binned

Not Binned

Sinus

Average Interval Fib

number of intervals required for episode termination is programmable in St. Jude ICDs. Programming a short duration is advisable when ATP terminates VT, but it reinitiates promptly after termination. This permits repeating the first sequence of programmed ATP rather than escalating to subsequent therapies that include shocks.

SVT-VT Discrimination in Ventricular ICDs BUILDING BLOCKS FOR DISCRIMINATION The ICDs analyze information derived from a sequence of sensed atrial and ventricular EGMs to detect VT/VF and discriminate ventricular arrhythmias from SVT. These algorithms operate in a stepwise manner, using a series of physiologically relevant, logical “building blocks” (Table 3-1) based on the timing relationships and morphology of sensed EGMs. We focus on the “tool kit” provided by these building blocks rather than on the specific details of proprietary algorithms, reviewed elsewhere in detail.113 Detection algorithms combine complementary building blocks to form the final detection decision. Each building block has advantages and limitations. Some are redundant, and some interact. Interactions vary depending on the order in which blocks are applied. Clinicians and algorithm designers must consider these issues to understand trade-offs in clinical performance. Single-Chamber Ventricular Building Blocks The first five building blocks in Table 3-1 apply to single-chamber ICDs or the ventricular component of dual-chamber ICDs. The R-R interval + duration analysis building block classifies ventricular intervals into zones by programmable cycle length (or rate) thresholds. All singleand dual-chamber ICDs use cycle length or rate in combination with tachyarrhythmia duration as the most basic method of detection. When used alone, R-R interval + duration analysis provides the highest sensitivity for detection of VT/VF, but cannot discriminate VT/VF from SVT. The R-R regularity building block is used to discriminate between regular ventricular intervals caused by monomorphic VT and irregular ventricular intervals caused by rapidly conducted AF. The R-R onset building block is used to discriminate sudden-onset VT from gradual-onset sinus tachycardia. The VEGM morphology building block classifies tachyarrhythmias as SVT if morphologic characteristics of the ventricular EGM are similar to those of beats of known supraventricular origin. Otherwise, it classifies the rhythm as VT.

Dual-Chamber Building Block: Atrial vs. Ventricular Rate Direct or indirect comparison of atrial and ventricular rates is the cornerstone of most dual-chamber algorithms. In most studies, the ventricular rate exceeds the atrial rate in more than 80% of VTs in the VT zone of dual-chamber ICDs and a higher fraction of VTs in the VF zone.68,114 Thus, algorithms that compare atrial and ventricular rates as their first step (Boston Scientific Rhythm ID, St. Jude, Biotronik) apply SVT discriminators to fewer than 20% of VTs; this reduces the risk that they will misclassify VT as SVT, provided that the atrial rate is measured correctly. The Medtronic algorithm indirectly compares atrial and ventricular rates using dual-chamber pattern analysis as the first step to achieve a comparable result. The Sorin algorithm uses a conceptually different approach, by initially detecting tachyarrhythmia based on cycle length, then further classifying the arrhythmia as VT or SVT based on the stability of R-R intervals and an analysis of AV association and tachycardia onset. Dual-Chamber Building Blocks The next four building blocks in Table 3-1 are based on combinations of atrial and ventricular information. Their primary role is to discriminate VT with 1 : 1 ventricular-atrial (V-A, VA) conduction from SVT. Their secondary roles are to classify rhythms with stable N:1 atrialventricular (A-V, AV) relationships (stable ratio of N atrial events for each ventricular event) as SVT and to classify isorhythmic tachycardias (with AV dissociation and similar ventricular rate) as VT. The P-R dissociation building block can detect the presence of VT during SVT. The P-R patterns/relationships building block applies to stable associations of atrial and ventricular events. For tachycardias with 1 : 1 AV relationships, it analyzes the relative timing of P-R and R-P intervals to classify the rhythm as SVT or VT. It also identifies consistent N:1 AV patterns that occur primarily during atrial flutter. The chamber of origin building block discriminates between VT and SVT with 1 : 1 P-R association by identifying whether the tachycardia originates in the atrium or in the ventricle. In ICD patients, SVT usually begins with an intrinsic atrial event in the interval between the last ventricular event in the sinus rate zone and the first ventricular event in the VT zone. Conversely, at the start of spontaneous VT, there is usually no atrial event in this interval. The response of the opposite chamber to atrial or ventricular pacing has long been a critical tool in the electrophysiology laboratory for diagnosing tachycardias with 1 : 1 AV relationship. A novel ICD algorithm based on this premise has been shown to

86

SECTION 1  Basic Principles of Device Therapy

Atrial B

777

738

773

P

P

V

133

623

B

P

V

133

600

133

601

1

0

719

727

P

V

RV-LV

B

734

742

B

719

719

P

V

141

586

2

B

711

719

P

V

133

578

3

402 V

4

*

DD

S

S 367

T

B

695

680

125 515

R

R

P

R

141

F

344

371

V

R

676

F

R

645

R

F 648

125 520

R

R

R

157

340

348

V

R

652

R

R

9

R

R

8

F

125 527

R

652

547

7

F

125 523

R

8

P

F

6

F

25 527

664

128 523

5

4

T

B

656

R

F 652

125 531 R

F

R

R

10

652

125 527 R

125 R

11

12

Trigger F 660

527 R

F 664

125 535 R

676

125 539

R

R

12

F

723

570

P

R

187

R

R

** S

676

125 547

R

R

734

R

187

R

P

R

187

R

17

R

P

R

187

16

18

S 762

125 605 R

125 R

S 738

125 605 R

695

125 547

R

S 730

125 609

R

15

S

P

16

R

14

125 598 R

672

125 551

13

R

R

D

P

R

179

125 637 R

R

19

20

DDD

S

P 187

20

R

B

801

125

125 617

R

R

21

R

797 P 133

B 797

777 P

V

133

664

22

B 773

816 P

V

133

664

23

B 812 V 683

24

Figure 3-50  Illustration of interval classification based on current interval and average interval; T-wave oversensing initiates R-wave doublecounting in St. Jude ICD. The figure shows continuous recording of atrial EGM, event markers, and extended bipolar ventricular EGM (between Y-adapted left ventricular [LV] and right ventricular [RV] tip electrodes). The ICD is programmed with a single ventricular tachycardia (Tach) zone at 345 msec and a ventricular fibrillation (Fib) zone at 290 msec. The top panel shows atrial sensed, ventricular paced rhythm. In the second panel, the first ventricular EGM is an interpolated premature ventricular complex (PVC). Ventricular pacing is inhibited after the next P wave because the resultant PVC-V paced interval would have been less than the interval corresponding to the programmed upper rate limit (~450 msec). This results in a conducted R wave that is double-counted at the ventricular blanking period of 125 msec, but this interval is not classified in the VF zone because the interval average of (719 + 402 + 367 + 125)/4 = 403 msec exceeds the Tach detection interval. The third and fifth beats show postpacing T-wave oversensing (down arrows). The interval ending with the first oversensed T wave is classified in the Tach zone because the interval average is less than 345 msec: (367 + 125 + 516 + 344)/4 = 338 msec. The next ventricular interval, corresponding to the subsequent double-counted R wave, is classified in the Fib zone because the interval average is in the Tach zone ([516 + 344 + 371 + 125]/4 = 339 msec) but the current interval is in the Fib zone. Mode switching to the DDI pacing mode occurs after the counter of Tach + Fib beats equal 4 (DDI, asterisk). The third and fourth panels show conducted sinus rhythm after mode switching, with alternate intervals classified in the Fib zone. VF is detected when the Fib counter reaches 12. This counter increments for each interval classified in the Fib zone and is reset to zero by five consecutive sinus intervals. The count of Fib intervals reaches 12 after the third interval in the fourth panel, and Fib is detected (Trigger, D marker), resulting in capacitor charging. However, sinus slowing results in an increase in the average interval, so that the interval average is no longer in the Tach zone. This occurs at the second R wave in the fifth panel (S marker, double asterisk; interval average = [125 + 570 + 125 + 596]/4 = 354 msec). Once this occurs, alternate detected intervals are classified as “Sinus” or “Not Binned.” The shock is aborted when the count of consecutive binned Sinus intervals reaches 5 at the beginning of the bottom panel (RS = return to sinus, up arrow), and this is followed by mode switch to DDD pacing. Note that St. Jude ICDs have a “Bigeminal Avoidance” counter that prevents bigeminal rhythms from being classified as Tach. This counter does not apply in the Fib zone. R, Ventricular sensed event; V, ventricular paced event.

VT (monitor) T

A

347

T 347

T 345

T 347

17s

VS VS

B

383

347

VS 367

VS 365

18s

F

295

T

* 442

344

65s

VS

343

VS

363

263

* 343

66s

VS 367

VS

363

19s

VS

271

VS

VS

343

343

VS

343

20s

VS

VS

363

VS

367

67s

253

VS

VS

340

359

21s

F 434

*

68s

VS

343

VS

343

C

344

VS

VS

357

106s

344

*

VS 263

VS

240

104s

345

VS 347

VS 342

107s

VS 249

F

*

367

441

363

108s

329

VS 343

100s

343

24s

VS

VS

VS

VS F

359

367

359

387

363

301

VS 367

359

*

70s

*

359

VS

VS

69s

VS

350

VS

23s

347

VS F 289

110s

426

75s

VF *

VS

22s

VS

358

VS

453

72s

*

*

*

*

*

F

F

*

343

375

111s

347

371

112s

Figure 3-51  Inappropriate detection of ventricular fibrillation (VF) caused by isolated premature ventricular complexes (PVCs) during sinus tachycardia in a monitoring zone. A, Sinus tachycardia gradually accelerated, triggering an episode recorded as ventricular tachycardia (VT) in the monitoring zone of a St. Jude ICD. B, Occasional PVCs are binned in the VF zone (F), adding to a cumulative counter. C, On the 12th such premature ventricular beat, VF is detected, leading to charging and an inappropriate shock (not shown) for sinus tachycardia. (From Mansour F, Khairy P: ICD monitoring zones: intricacies, pitfalls, and programming tips. J Cardiovasc Electrophysiol 19:568-574, 2008.)

88

SECTION 1  Basic Principles of Device Therapy

Tiered therapy: variable # ATP attempts followed by # shocks of increasing energy Bradycardia upper rate limit

Shock only; ATP not applied

Sinus

VT

FVT

VF

SVT discrimination zone

τToo fast for ATP (~240 ms) τExpect VF undersensing

Fastest SVT rejected

Different ATP or fewer trials (~320 ms)

Figure 3-52  Rate detection zones for implantable cardioverter-defibrillators. Some ICDs permit programming of an additional monitor-only zone; ATP, antitachycardia pacing. FVT, Fast VT; SVT, supraventricular tachycardia; VF, ventricular fibrillation; VT, ventricular tachycardia.

τ ~400 ms or 40 ms >slowest VT τ Consider SVT specificity

terminate or discriminate 1 : 1 tachycardias by using simultaneous atrial and ventricular ATP.115 Single-Chamber Atrial Building Blocks The final four detection building blocks are the atrial correlates of the single-chamber ventricular building blocks: P-P interval (atrial cycle length), P-P regularity, P-P onset, and AEGM morphology. Their primary role is to identify the presence (or absence) of atrial tachyarrhythmias and to invoke (or inhibit) the application of single chamber ventricular building blocks such as interval stability and/or EGM morphology. To date, atrial EGM morphology has not been applied in ICDs to discriminate between antegrade and retrograde conduction. SVT-VT DISCRIMINATION IN SINGLE-CHAMBER ICDS R-R Interval Regularity Measures of R-R interval regularity usually are referred to as measures of R-R interval “stability” or “stability algorithms.” Technical details and optimal programmed values differ among manufacturers. Specific measures of R-R regularity interact with the method of counting R-R

intervals and the duration required for detection. Requiring consecutive R-R intervals or a higher number of intervals to fulfill the rate and regularity criteria improves rejection of AF but increases the risk that detection of VT will be delayed.107,108,116-120 Regularity criteria can reject AF with ventricular rates slower than 170 beats per minute (bpm) in the absence of antiarrhythmic drugs. At faster rates, these criteria cannot discriminate AF from VT reliably, because R-R intervals in AF are more regular;116-120 and the criteria may prevent detection of VT in the presence of amiodarone or type IC antiarrhythmic drugs.117,119 These drugs may cause regular VT to become irregular, or they may cause rapid polymorphic VT to slow from the VF zone, where discriminators do not apply, to the VT zone, where regularity discriminators do apply. R-R regularity may also be used to select the first VT therapy: ATP for regular VT and shock for irregular and presumed VF or polymorphic VT. Sudden Onset Measures of abruptness of onset of a tachycardia have high specificity for rejecting sinus tachycardia,116,118-120 but may prevent detection of VT that originates during SVT or VT that starts abruptly with an initial

Shock

AS

VF 265

AS 1713 VF 233

VF 255

VF 240

VF 243

VF 243

VF 228

VF 255

AS 1713 VF 230 Detct Chrg

AS 855 VS 563

VF 255

VF 253

AS VF 858 VF 235 253 VF VF 230 255

AS 855

VF 270

VP 858

AS 855

AS 858 VF 858

VP 858

AS 855

AS 858 VP 858

VP 858 –– 23 Dvrt Chrg

70 min–1 70 min–1 Post–attempt EGM (10 sec max) Post–attempt Avs A Rate Post–attempt Avs V Rate

RV Tip-Coil

Attempt 1 Attempt Type Elapsed Time Therapy Delivered

Diverted Reconfirm 80.03 VF Shock 1

RA

–– 855

(AS) 858 VP 858

PVP+

Figure 3-53  Confirmation (“reconfirmation”) and aborted shock. Ventricular tachycardia (VT) in the ventricular fibrillation (VF) detection zone is detected and initiates capacitor charging (Chrg) before it terminates spontaneously. The noncommitted shock is diverted (Dvrt Chrg). AS, Atrial sensed event; VP, ventricular paced event.



89

3  Sensing and Detection Coil-Can

RV tip-ring

2 4 0

F D

V V V V V V V V S S S S S S S S 2 2 2 2 2 2 2 2 1 1 1 2 2 2 3 3 0 0 0 0 0 0 0 0 VF VF Rx 1 Defib

5 2 0

V S

4 5 0

V S

3 1 0

V S

4 9 0

V S

3 9 0

V S

3 8 0

V S

3 8 0

V S

3 8 0

V S

3 8 0

V S

3 9 0

V S

3 9 0

C V E S

3 9 0

C D 29.9J

7 2 0

V S

3 2 0

V S

Figure 3-54  Confirmation failure. Two ventricular EGMs and event markers are shown from a single-chamber ICD. The programmed ventricular tachycardia (VT) and ventricular fibrillation (VF) detection intervals are 380 and 320 msec, respectively. Detection of rapid VT as VF results in capacitor charging (VF Rx 1 Defib). After the charging cycle ends (CE), Medtronic ICDs deliver the shock (CD) if the ventricular cycle length after charging is less than the programmed VT interval + 60 msec. In St. Jude and Boston Scientific ICDs, shocks for VF are confirmed if the ventricular cycle length is less than the VT interval. RV, Right ventricular. (From Swerdlow CD, Friedman PA: Advanced ICD troubleshooting. Part II. Pacing Clin Electrophysiol 29:70-96, 2006.)

TABLE

3-1 

Tachyarrhythmia Detection Building Blocks

Tachyarrhythmia Detection Building Blocks Purpose/Information Single-Chamber Ventricular Building Blocks Identifies sustained high ventricular rates R-R interval + duration R-R regularity Discrimination of monomorphic VT (regular cycle lengths) from rapid AF (irregular cycle lengths) R-R onset

Identifies sudden ventricular rate changes

VEGM morphology

Abnormal VEGM morphology may indicate ventricular tachyarrhythmias Intervals after entrainment of VT by burst pacing are less variable than intervals after burst pacing during SVT

Burst ventricular pacing

Key Dual-Chamber Building Block Comparison of atrial vs. VT diagnosed if atrial rate is less than ventricular ventricular rate rate Dual-Chamber Building Blocks P-R dissociation P-R dissociation usually indicates VT P-R patterns/relationships

Consistent P-R patterns/relationships usually indicate SVT Chamber of acceleration Identifies whether tachycardia initiates in atrium or ventricle Atrial or ventricular pacing, Discrimination of 1 : 1 rhythms using ventricular response in opposite chamber response to atrial extrastimuli Single-Chamber Atrial Building Blocks P-P intervals Identifies high atrial rates P-P regularity Regular atrial rate indicates organized atrial activity P-P onset Identifies sudden atrial rate changes AEGM morphology

Identifies atrial tachyarrhythmias and/or retrograde conduction

Potential Weaknesses SVT with high ventricular rates that overlap with VT/VF rates May lose effectiveness as ventricular rates during AF increase; 2 : 1 atrial flutter has regular R-R intervals; may cause underdetection of VT with irregular R-R intervals Not specific for atrial or ventricular tachyarrhythmias; may miss VT arising during sinus tachycardia Confounded by conduction aberrancy or changes in “normal” VEGM morphology Sensitive to single interval measurement, potential detection time delay, and potential proarrhythmia

Confounded by atrial undersensing or far-field R-wave oversensing

AV reentrant tachycardia; VT with 1 : 1 retrograde conduction; AF that conducts rapidly with apparent P-R dissociation AV reentrant tachycardia and VT with 1 : 1 retrograde conduction A single oversensed/undersensed event may result in misclassification. Primarily aids diagnosis for 1 : 1 rhythms; concerns for VT detection delay and proarrhythmia High atrial rates may be present during true VT/VF. Minimal benefit for ventricular tachyarrhythmia characterization Not specific for atrial or ventricular tachyarrhythmias (e.g., VT with 1 : 1 retrograde association) Confounded by far-field R waves and changes in “normal” AEGM morphology

AEGM, Atrial electrogram; AF, atrial fibrillation; AV, atrioventricular; SVT, supraventricular tachycardia; VEGM, ventricular electrogram VF, ventricular fibrillation; VT, ventricular tachycardia.

90

SECTION 1  Basic Principles of Device Therapy

rate below the VT detection limit. In the latter case, the ICD misclassifies the “onset” of the arrhythmia as the gradual acceleration of the VT rate across the VT rate boundary. This criterion does not prevent SVT with sudden onset from being treated inappropriately. Ventricular EGM Morphology Analysis of ventricular EGM morphology,114,120-123 alone or in combination with stability, probably provides the best single-chamber SVT-VT discrimination for initial detection of VT. The morphology building block is the key element of single-chamber algorithms and the central single-chamber component of dual-chamber algorithms with this feature. For this reason, a more detailed analysis is provided. VENTRICULAR EGM MORPHOLOGY FOR SVT-VT DISCRIMINATION General Electrogram morphology algorithms are the most complex and effective building blocks in single-chamber detection algorithms. All morphology algorithms share common steps (Fig. 3-55): (1) record a template EGM of baseline rhythm; (2) construct and store a quantitative representation of this template; (3) record EGMs from an unknown tachycardia; (4) time-align the template and tachycardia EGMs; (5) construct a quantitative, normalized representation of each tachycardia EGM; (6) compare the representation of each tachycardia EGM with that of the template to determine its degree of morphologic similarity; (7) classify each tachycardia EGM as a morphology match or nonmatch with the template; and (8) classify the tachycardia rhythm as VT or SVT based on the fraction of EGMs that match the template. Steps 3 through 8 are performed in real time. Morphology algorithms differ according to EGM source or sources, methods of filtering and alignment, and details of quantitative representations. The features of specific algorithms are described in Figure 3-56. Limitations of Morphology Algorithms The START study (SAFARI trial) of arrhythmias recorded at ICD implant reported individual differences for the performance of singlechamber discrimination algorithms based primarily on EGM morphology.124 Morphology algorithms share common failure modes for inappropriate detection of SVT as VT: (1) inaccurate template, (2) EGM truncation, (3) alignment errors, (4) oversensing of pectoral

Extracted features stored in ICD memory

Template EGM (baseline rhythm)

(1)

(4)

(2)

Compare features

Time align EGMs

Match % = 1 – Area of Difference Area of Template

Tachycardia Template

(2)

Extracted features calculated in real time

(4)

(3)

Tachycardia EGM Figure 3-55  General steps in all morphology algorithms. See text for details.

myopotentials, (5) rate-related aberrancy, (6) SVT soon after shocks, and (7) inappropriate classification of VT as SVT. Inaccurate Template.  The template may be inaccurate because the baseline EGM changed (e.g., postimplantation lead maturation, intermittent bundle branch block) or because the template was recorded from an abnormal rhythm (e.g., idioventricular or bigeminal PVCs). Accurate SVT-VT discrimination requires periodic automatic or manual template updates. Most modern ICDs include an automatic template updating feature, except for cardiac resynchronization ICDs, which are intended to pace the ventricles continuously. If automatic updates are not available, the morphology algorithm should be updated when the EGM becomes chronic. However, the template cannot be updated without intrinsic AV conduction. If software permits, the template match should be verified initially and during follow-up. Electrogram Truncation.  EGM truncation (“clipping”) occurs when the recorded EGM signal amplitude exceeds the range of the EGM amplifier so that the maximum or minimum portion of the EGM is clipped. This removes EGM features for analysis and alters the timing of the tallest peak, which can affect alignment. The amplitude scale in Medtronic and St. Jude ICDs should be adjusted so that the EGM used for morphology analysis is 25% to 75% of the dynamic range (Fig. 3-57). Alignment Errors.  Alignment errors prevent match between a tachycardia EGM and a morphologically similar stored EGM. Mechanisms depend on the method used for EGM alignment (Fig. 3-58). Accurate alignment in the St. Jude algorithm is sensitive to the value of the sensing threshold at the onset of the ventricular EGM, as determined by Automatic Sensitivity Control. If a template EGM is acquired at the most sensitive setting of Automatic Sensitivity Control (either because of a slow sinus rate or after a ventricular paced beat), a low-amplitude peak at the onset of the ventricular EGM may be used for alignment. During tachycardia, the next R wave may occur before Automatic Sensitivity Control reaches its sensitive value. In this case, the lowamplitude peak at the onset of the ventricular EGM may not be used for alignment. If identical template and tachycardia EGMs are then compared, their representations in the morphology algorithm will not match. Usually, they are assigned morphology match scores of 0% (see Fig. 3-58). In patients who have dual-chamber ICDs and intact AV conduction, the most reliable template is acquired or verified during atrial pacing at a rate close to the VT rate. In single-chamber ICDs, options may include acquiring or verifying the template during exercise testing and altering the minimum sensitivity, Threshold Start, or Threshold Delay. If a template is acquired during atrial pacing or exercise testing, automatic template updating should be disabled to prevent overwriting the template with one acquired in baseline rhythm. Medtronic ICDs align EGMs based on their tallest (positive or negative) peaks. If an EGM has two peaks of near-equal amplitude, or if such peaks are caused artificially by truncation of large EGMs that exceed the programmed dynamic range, minor variations in their relative amplitudes may result in an alignment error.120 An alternative EGM source should be selected. The Boston Scientific morphology algorithm (Rhythm ID) simultaneously collects data from two different channels: the local bipolar rate-sense EGM and shock EGM.125,126 It considers the vector of depolarization wavefront (with shock EGM as the reference), the timing of the peak signal recorded on the rate-sense EGM, and alignment of eight characteristic points of the shock EGM. A correlation equation aligns peaks on the rate-sense EGM for each QRS complex of the unknown rhythm with the rate-sense EGM peak of the sinus template, then compares the eight captured points with the template. Oversensing of Pectoral Myopotentials.  In Medtronic ICDs, oversensing of pectoral myopotentials may prevent an SVT from matching the sinus template if the RV coil-to-can EGM is used for morphology analysis and the R-wave amplitude is small. The effect of myopotentials



3  Sensing and Detection

91

100 Shock

50 0 Template

50 B

A

C

Tachycardia EGM

A

–

B –

= A’

C’ B’

C

0

B’ =

– A’

100

= C’ 1

% Match = 

10



B

A

60 40 20 0 −20 −40

30

40

50

60

70

Rate NSR VT 0

10

Wavelet Wavelet Amplitude Shape

20

30

40

50

60

70

 ci*i[n]

mV

Analog electrogram

20

Align by rate EGM

0

200 msec Digitize Cumulative electrogram reconstruction

Wavelet transform

mV

Digitized electrogram (x[n]) 0

200 msec Smallest amplitude wavelets

C

− 0 +

0

200 msec 0

200 msec

Figure 3-56  Specific morphology algorithms. A, St. Jude MD algorithm. The positive and negative deflections in the sensing EGM are normalized and modeled as a series of three polygons (A, B, and C in the template EGM; A’, B’, and C’ in the tachycardia EGM). The normalized areas of these polygons are then computed. Each tachycardia EGM is compared with the template EGM in three steps. First, the difference in area of corresponding polygons is computed. Second, the absolute values of these differences are summed. Third, a match score is constructed to be inversely proportional to the sum of these differences. If a programmable number (= 4) of 8 complexes in a sliding window exceed the programmable threshold (nominally 60%), the rhythm is classified as supraventricular tachycardia (SVT). If not, it is classified as ventricular tachycardia (VT). B, Boston Scientific Vector Timing and Correlation (VTC) algorithm. This algorithm aligns shocking EGMs of the tachycardia and template based on the peak of the rate-sensing EGM. This method takes advantage of spatiotemporal differences between activation sequences in VT and baseline rhythm that cannot be detected from a single EGM. In this example, the peak of the shock EGM has similar timing to the peak of the rate-sensing EGM in sinus rhythm, but much later timing in VT. The amplitude of the shocking EGM (upper panel) is computed at each of 8 points selected on the basis of their timing relative to the peak of the sensing EGM (lower panel) and extracted as an eight-element “feature set,” corresponding to an eightdimensional vector. Feature sets of each tachycardia EGM are compared with the template EGM by computing the product-moment correlation coefficient between the two feature sets. This value, named the feature correlation coefficient (FCC), is a measure of mean spatiotemporal difference in ventricular activation between tachycardia and baseline rhythm. A threshold value for the feature correlation coefficient was selected to optimize SVT-VT discrimination on a test data set. This value is neither published nor programmable. If at least 3 of 10 complexes in a sliding window exceed the threshold, the rhythm is classified as SVT; if not, it is classified as VT. C, Medtronic Wavelet algorithm. The algorithm expresses the morphology of ventricular EGMs using the wavelet-transform. Wavelets are functions of constant shape and limited time duration.* They form the basis of a mathematical transformation that represents signals efficiently if they are both highly localized in time and preceded and followed by isoelectric intervals. Wavelets are therefore well suited for representing transient biomedical signals such as ventricular EGMs. The algorithm compares the morphology of ventricular EGMs during a tachycardia with a template recorded during baseline rhythm. This comparison is expressed as a percent-match score that describes the degree of morphologic similarity of the baseline and tachycardia EGMs using a programmable source. In general, the EGM recorded between right ventricular and superior vena cava coils is preferred as a default. This signal combines far-field sensitivity to morphology differences between VT and SVT with resistance to pectoral myopotentials. The algorithm begins processing when a tachycardia fulfills the programmed rate criterion for detection of VT and 8 beats remain to fulfill the programmed duration criterion for detection of VT. Percentmatch scores are calculated for each of the last 8 beats before detection. Beats with match scores less than a programmable threshold (nominally 70%) are classified as ventricular. Nominally, a tachycardia is classified as VT if 6 or more of the 8 analyzed EGMs are classified as ventricular. Otherwise, it is classified initially as SVT. If the tachycardia is classified as SVT, the algorithm is applied to each successive 8-beat sliding window until the rate criterion for VT is no longer fulfilled. (*Meyer Y: Wavelets: algorithms and applications. Philadelphia, 1993, Society for Industrial and Applied Mathematics.)

92

SECTION 1  Basic Principles of Device Therapy

Range 9.8 mV

Range 14.4 mV

A

T S

5 9 0

V S

6 5 0

V S

4 5 0

No match 64%

V S

5 2 0

V S

3 4 0

T S

3 5 0

T S

T T 3 S 3 S 2 1 0 0

No match 64%

3 4 0

T S

3 4 0

T S 3 6 0

T S

T 3 S 3 0

3 2 0

No match 61%

T S 3 3 0

T S

3 4 0

T S

T 3 S 3 4 4 0 0

T S 3 3 0

T S

3 7 0

T S

Figure 3-57  Electrogram truncation as source of error for morphology algorithms. A, St. Jude MD template EGM is truncated (arrow) with an amplifier range of 9.8 mV. Truncation was corrected by increasing the range to 14.4 mV. Inconsistent truncation may prevent supraventricular tachycardia (SVT) morphology from matching the template. B, Medtronic Wavelet algorithm. EGMs in rapidly conducted atrial fibrillation exceed the maximum amplitude range of 8 mV, resulting in varying degrees of truncation (“clipping”) of the right ventricular (RV) coil-to-can + superior vena cava (SVC) signal compared with the template. Inappropriate detection of ventricular tachycardia (VT) occurs at right. Complexes below show the last eight EGMs before detection at higher resolution. These tachycardia EGMs are clipped (arrow) so that the peaks are cut off. The rhythm is classified as VT because six of the last eight EGMs have less than 70% match. This problem was corrected by expanding the EGM scale ±16 mV AS, Atrial sensed event; VP, ventricular paced event.

T 3 D 3 6 0 0 VT 0

No match 64%

4 mV 20 ms QRS Template

No match 67%

Match 76%

No match 61%

Match 76%

B

SVT

X

SINUS

X

X

T

386 397

S

T

100

0

0

0

417

382

397

401

394

858 862 A 394

0

100 866

862 A

R

862 A

R 233

629 R

100 866

229 R R Sensitivity

S

R 229

633

637

R

10

Figure 3-58  Alignment error in morphology algorithm. Interaction of Automatic Sensitivity Control and morphology analysis in St. Jude MD algorithm. Left panel, Stored EGM of supraventricular tachycardia (SVT) inappropriately detected as ventricular tachycardia (VT). Right panel, Programmer strip of validated template in sinus rhythm. Despite identical ventricular EGMs, morphology match scores are 0% in SVT and 100% in sinus rhythm. Slanted line denotes slope of Automatic Sensitivity Control. In sinus rhythm, Automatic Sensitivity Control reaches minimum value before the next ventricular EGM, so that the small peak at onset of EGM (arrows) is used for alignment. In SVT, Automatic Sensitivity Control does not reach minimum, and the small peak is not used for alignment.



3  Sensing and Detection

93

degrees of aberration often distort the terminal portion of the EGM sufficiently that the percent match is less than the nominal threshold. In St. Jude ICDs, reducing the fraction of EGMs required to exceed the match threshold from 5 of 8 beats to 3 or 4 of 8 beats may reduce this problem without compromising detection of monomorphic VT. Reducing the match percent required to exceed the match threshold may also prevent misclassification of aberrantly conducted SVT as VT, but it results in a greater chance of misclassifying monomorphic VT as SVT than does reducing the fraction of EGMs.

on match percent can be tested by pectoral muscle exercise. Select an alternative EGM source (e.g., distal coil to proximal coil) to prevent such oversensing. Pectoral myopotentials also pose a source of error in Boston Scientific ICDs, which necessarily incorporate the high-voltage EGM in morphology analysis. Oversensing of pectoral myopotentials is not a problem for St. Jude ICDs, which use near-field EGMs for morphology analysis. Rate-Related Aberrancy.  If complete bundle branch aberrancy occurs reproducibly, the template may be recorded during rapid atrial pacing (Fig. 3-59). However, subtle and varying aberrancy can confound templates acquired during baseline rhythm (Fig. 3-60). If a template is acquired at a fast rate, automatic template updating should be deactivated to prevent subsequent auto-acquisition of a slow, baseline template without aberrancy. During rapidly conducted AF, subtle

Supraventricular Tachycardia Soon after Shock.  After a shock, ICD detection algorithms reclassify the rhythm as “sinus” and revert to their initial detection mode within a few seconds, but postshock distortion of EGM morphology may persist for 30 seconds to several minutes.60,120 No SVT-VT discrimination algorithm relies on EGM morphology

V.C.6 TEMPLATE IN LBBB WITH ATRIAL PACING A. Capture confirmed: 1.0 V @ 0.5 ms 1.0 V

A. Capture lost: 0.75 V @ 0.5 ms 0.75 V

Return: 3.5 V

ECG

x

x

x

x

x

x

34

40

37

37

40

31

S 664

664 660

A

664 664

664

A R

A R

297

297 383

664 668

A R 297 367

664

289

A

A

A

R 297

367

664 664

A

R

281 367

664

S 100

100

1001

A

P

R

R

R

281 367

242 383

751

RA

RV

ECG

x 100 750 750 A R 289 461

RA

100 750 750 A R 881 469

x 40 750

A 281

R

R 469

100 750 750 A R 281 469

100 750 754 A R 281 469

100 750 750 A R 289 461

100 750 750 A R 289 461

100 750 750 A R 289 461

100 750 746 A R 289 461

100 750 750 A R 889 461

RV

Baseline

Atrial pacing LBBB

Press here for Active Template Scoring

Now Scoring

Figure 3-59  Left bundle branch aberrancy error in morphology algorithm. Programmer strips show electrocardiogram (ECG), event markers, right atrial EGM, and right ventricular true bipolar EGM. Top panel, Measurement of atrial pacing threshold. Captured beats are conducted with rate-related left bundle branch aberrancy resulting in failure of morphology to match template collected in sinus rhythm. The last two ventricular EGMs at the slower sinus rate show 100% template match. A new template was acquired during atrial pacing. Middle panel, Near 100% morphology match to new template during conduction with left bundle branch aberrancy. Bottom panel, EGM morphology templates recorded during baseline sinus rhythm (left) and atrial pacing (right). LBBB, Left bundle branch block; RA, right atrium; RV, right ventricle.

94

SECTION 1  Basic Principles of Device Therapy

DD

RA

Trigger X S T T T T T T T T T T T T T T T T ATP ATP ATP ATP ATP 46 44 36 39 38 51 37 49 39 35 57 43 24 28 50 D= 355 348 355 352 348 352 355 348 348 352 348 348 352 348 348 343 343 343 359 343 355 352 352 352 352 352 352 352 348 352 352 348 348 348 348 348 X

R

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

X

R

R

ATP ATP ATP ATP ATP

R

RV

* R

* R

* R

* R

* R

* R

* R

* R

* R

* R

* R

* R

H V

* R

R R R D 332 340 332 336 336 332 340 336 336 336 336 340 336 336 340 340 336 336 336 332 336 336 336 336 336 336 336 340 336 336 344 340 R

R

R

R

R

R

R

R

R

R

R

ECG

R

R

R

R

X S

X S

0

S 100

703 543 P

R

156

RA

RV

S 0

S 100

527 P

P R

R

520

559 P

S 100

754 P

R 156

673

S 0

100

668

828

156 689

X

684

843 P

R

309 301 250 367 297

R

V

R

R

R

ECG

X 100

S 649V

485

660 P

P

P

R

R

R

70

156

156

698

500

X

X

X

X

X

X

X

61 62 0 21 38 51 34 0 0 52 398 398 398 398 398 398 398 398 398 398 402 406 402 402 402 406 402 402 395 398 A A A A A A A A A A R

R 243

R 243

R 273

R 273

R 281

R 297

R 289

303

R R R 297 297

528

RA

RV

Figure 3-60  Error in morphology algorithm caused by subtle rate-related aberrancy. Top panel and middle panel, Dual-chamber stored EGM from inappropriately treated sinus tachycardia. Right atrial (RA) EGMs, event markers, and true bipolar right ventricular (RV) EGMs are shown. Values immediately below event markers, corresponding to EGMs in ventricular tachycardia (VT) zone (labeled “T”), indicate the percent match between EGM morphology in VT and sinus morphology (seen in lower left panel). Corresponding “X” labels above event markers indicate that the morphology algorithm classifies the beat as VT because the match is less than 60%. Burst antitachycardia pacing (ATP) is delivered at the right of the first panel. Dotted arrow indicates that panels are not continuous. After several trials of ATP (not shown), a shock is delivered toward the end of the second panel (HV). “Trigger” at right of upper panel indicates (inappropriate) detection of VT. “D =” at right of upper panel indicates that the atrial rate is equal to the ventricular rate. S denotes intervals in the sinus zone above the VT detection interval of 360 msec. Time line is in seconds. Bottom panels show real-time programmer strips. Bottom left panel, 100% template match in sinus rhythm (arrows) and 0% match on premature ventricular complexes (PVCs). However, the bottom right panel, recorded during atrial pacing at a cycle length of 400 msec, shows only two EGMs with adequate match (check marks, arrows). Note that the surface electrocardiogram (ECG) does not show identifiable aberrancy despite sufficient changes in EGM to prevent template match.



3  Sensing and Detection

after shocks until the arrhythmia episode terminates. However, algorithms revert to their initial detection mode within a few seconds after a shock. If postshock SVT starts after the rhythm has been classified as sinus but before postshock EGM distortion dissipates, any morphology algorithm may misclassify SVT as VT.120 Therefore, distortion of the EGM after a shock could result in a repetitive sequence of inappropriate classification of SVT as VT, inappropriate shocks for SVT, and perpetuation of postshock EGM changes in SVT by each successive shock.

95

about whether comparable features are required for Medtronic and Boston Scientific algorithms. SVT-VT DISCRIMINATION IN DUAL-CHAMBER AND CARDIAC RESYNCHRONIZATION ICDS The integration of dual-chamber building blocks into detection algorithms may be considered in terms of the relative rates of the atrium and ventricle (Fig. 3-62). Operation for Atrial Rate Less Than Ventricular Rate

Inappropriate Classification of Ventricular Tachycardia as Supraventricular Tachycardia.  The St. Jude morphology algorithm, which analyzes only the rate-sensing electrode, continuously misclassifies up to 6% of VTs as SVT (Fig. 3-61). However, if it is restricted to tachycardias (with ventricular rate ≤ atrial rate in dual-chamber ICDs), only 2% of VTs are misclassified.114 The Medtronic morphology algorithm, which usually analyzes high-voltage EGMs, misclassifies about 1% of VTs as SVT.127 If misclassification occurs, an alternative EGM source may provide adequate discrimination. Limited data indicate that the corresponding error rate for the Boston Scientific algorithm is comparable or lower. When the St. Jude morphology algorithm is used in a single-chamber ICD, the sustained-duration time-out (Maximum Time to Diagnosis, Section V.F) should be programmed unless the algorithm is known to classify all clinical VTs correctly. Opinions differ

Dual-chamber detection algorithms revert to single-chamber operation when the atrial rate is slower than the ventricular rate and generally do not apply any single-chamber discriminators. Operation for Atrial Rate Equal to Ventricular Rate The vast majority of tachycardias with 1 : 1 AV relationship are SVT, primarily sinus tachycardia. VT with 1 : 1 VA conduction accounts for less than 10% of VTs detected by ICDs. The building blocks used by each manufacturer for distinguishing 1 : 1 AV conduction of SVT from 1 : 1 VA conduction are summarized in Table 3-2. A dual-chamber onset rule that evaluates both P-R and R-R interval onset improves specificity of R-R interval onset-type building blocks for sinus tachycardia with minimal loss of sensitivity for VT.128 Sorin ICDs classify

V.C.7 VT 3 DAYS POSTDISCHARGE ECG

T

T

T 100

T 100

T 100

T 100

T 100

T 100

T 100

T 100

T

438

434

441

438

438

445

445

445

441

441

445

441

445

R

R

R

R

R

R

R

R

R

R

R

R

R

R

R

X

Sinus rhythm T 100

438

434

R

R

S

S

100

R

691

691

R

R

T

100

T

438

T

100

T

441

100

100

T

430

T

100

T

95

RV

100

T

0

X T

100

X T

X T

0 0 0 VT: Predischarge EPS

10

379

379

383

R

R

R

0

11

Figure 3-61  Failure to detect ventricular tachycardia (VT) because of inappropriate classification of VT as supraventricular tachycardia (SVT) by morphology algorithm (St. Jude MD). Upper panel, Programmer strip from symptomatic tachycardia classified as SVT 3 days after implantation. Electrocardiogram (ECG), event markers, and right ventricular (RV) true bipolar EGM are displayed. Morphology match is 100% on most beats. The 12-lead ECG showed a left bundle branch block–type pattern, a broad R wave in V1 (distinctly different from conducted sinus QRS complexes), and atrioventricular (AV) dissociation. Lower panel, Event markers and RV EGM during tachycardia (left), sinus rhythm after manually delivered antitachycardia pacing (center), and induced VT at predischarge electrophysiologic study (EPS) (right). EGM morphology during spontaneous VT and sinus rhythm are similar and distinct from induced VT at predischarge EPS. True bipolar EGMs fail to distinguish VT from SVT in 5% to 10% of VTs.

96

SECTION 1  Basic Principles of Device Therapy

nonconducted, it is considered ventricular in origin. Individual examples are shown in Figures 3-63 to 3-66. As in the electrophysiology laboratory, pacing methods may also be used to discriminate 1 : 1 tachycardias (see Active Discrimination).

300 VF

AF/VF

Ventricular rate (bpm)

250 (A-rate, V-rate)

(A=V) ST/VT/VF

200 VT 150

VF Interval (V>A)

100

AT/VT

VT Interval

(A>V) Sinus

50

AF/VT

AT

AF

Operation for Atrial Rate Greater Than Ventricular Rate The building blocks used by each manufacturer for distinguishing rapidly conducted AF and atrial flutter from VT during atrial arrhythmias are summarized in Table 3-3. Although various combinations of these building blocks successfully discriminate VT from SVT in VT zones, most VT during AF is sufficiently rapid to be detected in the VF zone,129 where some discriminators lose specificity or may not be applied at all. For example, R-R regularity cannot be applied in the VF zone because polymorphic VT has irregular R-R intervals, and undersensing of VF exaggerates the irregularity of measured R-R intervals. AV dissociation occurs uniformly during rapidly conducted AF,68 and morphology templates acquired during sinus rhythm often misclassify aberrantly conducted beats. Individual examples are shown in Figures 3-67 to 3-69. Specific Algorithms

0 0

100

200

300

Atrial rate (bpm) Figure 3-62  Dual-chamber “rate plane” highlights power of atrial versus ventricular rate. Dual-chamber rhythm classification can be visualized as a graph that plots atrial rate (A-rate) on the abscissa and ventricular rate (V-rate) on the ordinate. All points above the horizontal line representing the ventricular tachycardia (VT) intervals will be detected as VT or ventricular fibrillation (VF) on the basis of ventricular rate alone. Points that are both above this line and above and to the left of the line of identity are VT, and no additional discriminators need to be applied in this region, provided that atrial sensing is reliable. These discriminators can be restricted to rhythms with 1 : 1 atrioventricular (AV) relationship on the line of identity and those in which the atrial rate exceeds the ventricular rate in the region below and to the right of the line of identity. AF, Atrial fibrillation; AT, atrial tachycardia; ST, sinus tachycardia. (Modified from Morris M, Marcovecchio A, KenKnight B, et al: Retrospective evaluation of detection enhancements in a dualchamber implantable cardioverter defibrillator: implications for ICD programming [abstract]. Pacing Clin Electrophysiol 22:849, 1999.)

the 1 : 1 tachycardias based on “chamber of acceleration”: the first accelerated cycle is classified as “supraventricular” if two ventricular events are classified as “conducted,” if the R-R interval is greater than 75% of the preceding P-P interval. If the two ventricular events defining the first accelerated interval are ‘ ‘conducted,’ ’ the origin of the acceleration is declared “atrial.” Conversely, if the first accelerated beat is

TABLE

3-2 

Figures 3-70 to 3-74 show block diagrams of the principal dualchamber detection algorithms in clinical use today. Legends identify unique features of each algorithm. Single-Chamber vs. Dual-Chamber Discriminators Nominal programming of dual-chamber algorithms is safe.130,131 Dualchamber stored EGMs provide higher diagnostic accuracy for troubleshooting than single-chamber stored EGMs. However, dual-chamber discriminators cannot be implemented without the complications inherent in atrial leads. Also, dual-chamber ICDs introduce unique risks for underdetection of VT caused by cross-chamber ventricular blanking after atrial pacing (see Intradevice Interactions). In addition, with early dual-chamber algorithms, optimal values of programmable parameters were not known; initial approaches to the problem of atrial blanking versus FFRW oversensing had limited success; and atrial sensing problems and specific design flaws degraded performance. Not surprisingly, clinical studies of early dual-chamber algorithms reported no benefit over single-chamber algorithms.67,68,132,133 More recent, randomized prospective studies demonstrate moderate superiority in SVT-VT discrimination for dual-chamber over single-chamber algorithms.134,135 However, no agreement exists as to when the incremental implant complexity, price, risk of atrial lead complications, and reduced longevity of a dual-chamber ICD are justified for SVT-VT discrimination alone. Generally, dual-chamber ICDs should be considered in patients who are likely to have rapidly conducted SVT, those in whom monomorphic VT and sinus tachycardia rates are likely to overlap, and those who will benefit from additional diagnostics for atrial arrhythmias. Text continued on page 101

Discrimination of Tachycardias with Atrial Rate Equal to Ventricular Rate

Building Blocks Single chamber R-R stability P-P stability Sudden onset VEGM morphology Dual Chamber A rate vs. V rate P-R patterns AV association Chamber of acceleration

GDT Rhythm ID

Medtronic PR Logic

X

X [X] {X}

St. Jude Rate Branch

Sorin Parad+

Biotronik SMART

X

X

(X) X (X) [X]

X X

X X X X

X X X

X

GDT, Boston Scientific; VEGM, ventricular electrogram; A, atrial; V, ventricular; AV, atrioventricular. X, Algorithm uses this building block; [X], new PR Logic ST rule (Entrust) uses sudden R-R and P-R onsets; (X), “implicit” use of these building blocks via pattern analysis; {X}, Protecta ICDs (investigational) integrate Wavelet VEGM morphology into dual-chamber interval analysis.



3  Sensing and Detection

97

Date Time Type 17 - MAR - 2003 12:18 Spontaneous tial Detection Parameters 20 VF: 00 VT: SVT Inhibit = On, SRD 3:00 m:s 50 VT-1: SVT Inhibit = On Nonsutained Rhythm Average V Rate

SVT 158 bpm

End of Episode

25 cm/s

RA RV Tip–RV Coil

Shock AS ––

VS ––

AS 503

VS 543

VS 430

AS 508 VS 510

AS 415

AS 348 VS 440

VS 420

AS 375 VT-1 380

AS 363

AS 320

VT-1 365

(AS) 350

(AS) 378

VT-1 VS-Hy 335 405

(AS) 375

AS 398

AS 355

AS 338

(AS) 355 (AS) 318

VT-1 VT-1 VT-1 353 VT-1 365 VT-1 385 358 370

VT-1 383 VT-1 328 Epsd

Figure 3-63  Appropriate rejection of supraventricular tachycardia (SVT) with 1 : 1 atrioventricular (AV) conduction by AV relationship and morphology algorithm. Right atrial (RA), right ventricular (RV) rate-sensing, and Shock EGMs are shown in order with dual-chamber event markers. SVT begins with gradual warm-up, accelerating from a cycle length of approximately 540 msec to 380 msec in 3 seconds. The Boston Scientific Rhythm ID algorithm classifies morphology as SVT based on 1 : 1 AV association combined with constant shock morphology and constant timing relationship between peaks of two ventricular EGMs. The label ATR at bottom of event markers indicates that the rhythm is classified as SVT. Upper panel shows episode summary classifying rhythm as SVT.

TABLE

3-3 

Discrimination of Tachycardias with Atrial Rate Greater than Ventricular Rate

Building Blocks Single Chamber R-R stability P-P stability VEGM morphology Dual Chamber A rate vs. V rate P-R patterns AV association

GDT Rhythm ID

Medtronic PR Logic

St. Jude Rate Branch

Sorin Parad+

Biotronik SMART

X

X X {X}

X

X

X X

X X X

X

X X

X

X

X X

X

A, Atrial; AV, atrioventricular. GDT, Boston Scientific; X, Algorithm uses this building block; {X}, Protecta ICDs (investigational) integrate Wavelet VEGM morphology into dual-chamber interval analysis; V, ventricular; VEGM, ventricular electrogram.

98

SECTION 1  Basic Principles of Device Therapy

SINUS TACHYCARDIA

VT WITH 1:1 RETROGRADE CONDUCTION

P R

P R A Programmable 1:1 VT-ST boundary (nominally 50% R-R interval)

N Programmable 1:1 VT-ST boundary (nominally 50% R-R interval) Junctional Retrograde Antegrade

A Sinus tachycardia

VT with 1:1 retrograde conduction

1 1 1 1 1 1 1 1 1 1 3 2 2 3 2 2 3 3 3 3 3 3 3 3 7 6 6 7 7 7 7 7 7 7 5 2 9 8 1 8 8 3 1 1 0 0 0 0 0 A 0 A 0 A 0 A0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 S S S S S S S S S S S S S S S S S S S S S S S S S

P-R (ms) Marker events R-R (ms)

V V V V V V V V V V V T T T T T T T T T T T T T T T T S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 3 S3 S3 S 3 S 3 S 3 S 3 S 3 S 4 S4 S 3 S 3 S 3 S3 S 3 S 3 D 9 9 9 9 9 9 7 8 5 7 8 6 6 6 6 6 4 3 9 9 6 9 6 6 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

300 P-R (ms) 200 100 500 R-R (ms) 400 300

B

1:1 A:V conduction

P-R expected range

Sudden P:R change

R-R expected range VT/VF therapy zone

Gradual R:R change

VT DETECTED

Figure 3-64  A, Discrimination of 1 : 1 tachycardias by P-R pattern using the original sinus tachycardia criterion in Medtronic PR Logic (GEM III, Marquis, Maximo, InSync Marquis, InSync Maximo) ICDs. PR Logic uses patterns of A-V, V-A, V-V, and A-A intervals from consecutive ventricular events to form couple codes describing supraventricular tachycardias (SVTs). These couple codes are based on the number of atrial (A) events within the ventricular (V) interval and their relative timing. Discrimination of sinus tachycardia (ST) from ventricular tachycardia (VT) with 1 : 1 retrograde conduction is critically dependent on the programmable 1 : 1 VT-ST boundary, which is defined nominally as 50% of the current R-R interval (with optional values of 35%, 66%, 75%, and 85%). P-R intervals less than the defined percentage of the current R-R interval and greater than 70 msec are considered antegrade (left panel), and P-R intervals equal to or greater than that percentage of the R-R interval and also greater than 40 msec are considered retrograde (right panel). Rhythms in the detection zone with 1 : 1 pattern and antegrade P-R intervals are classified as ST, and therapies are withheld. Rhythms with 1 : 1 pattern and retrograde P-R intervals are classified as VT. B, New adaptive ST rule in PR Logic (Medtronic Entrust DR ICD) no longer uses 1 : 1 VT-ST boundary to discriminate ST from VT with 1 : 1 retrograde conduction. Rather, it uses a combination of pattern, sudden R-R onset, and sudden P-R onset. Operation of the new adaptive ST criterion is illustrated by this example of a spontaneous episode of ST that converted into VT with 1 : 1 retrograde conduction. During the ST, the R-R and P-R intervals occurred within their expected ranges. After initiation of VT, the R-R and P-R intervals occurred outside their expected ranges. Evidence of ST was lost by the third beat of VT. The sudden change in R-R intervals was small (460 msec), so the R-R intervals during the VT occurred within twice the R-R interval expected range, and adaptation of the RR interval expected range continued. Eventually, the R-R interval expected range adapts to accept the R-R intervals of the VT. Conversely, the P-R intervals occurred outside of twice the P-R expected range, and adaptation was inhibited. VT is appropriately detected after 16 consecutive R-R intervals in the VT detection zone despite gradual R-R onset of a 1 : 1 rhythm, because the P-R intervals had sudden onset and were no longer within the expected P-R interval range. VF, Ventricular fibrillation. (From Stadler RW, Gunderson BD, Gillberg JM: An adaptive interval-based algorithm for withholding ICD therapy during sinus tachycardia. Pacing Clin Electrophysiol 26:1189-1201, 2003.)



3  Sensing and Detection

99

AEGM

VEGM

P-R Intervals A S

V

R-R Intervals

1 5 A0 S

1 5 A0 S V S

7 7 0

1 9 A 0 R V S

4 0 0

V S

3 5 0

1 6 A 0 R T S

3 3 0

1 9 T 0 S T F

3 6 0

1 8 A 0 R T S

3 6 0

1 6 A0 R T S

3 4 0

1 5 T0 S T S

3 2 0

1 6 T 0 S T S

3 4 0

1 6 T0 S T S

3 4 0

1 7 T0 S T S

3 5 0

1 6 T 0 S T S

3 4 0

1 6 T 0 S T S

3 4 0

T S

Interval (ms)

Detection Burst

1 2 T0 S

1 2 T0 S

T 3 F 0 0

3 0 0

1 1 T0 S

T T F 3 F 0 0

1 6 T 0 S

3 6 0

1 1 T0 S T S

4 T0 S

T T 2 F 2 P 9 6 0 0 FVT

Term.

1500 1200 900 600 400 200

ATP

212

210

28

26

24

22 0 2 Time (sec)

4

6

8

10

12

Figure 3-65  Appropriate detection of ventricular tachycardia (VT) with 1 : 1 ventricular-atrial (VA) conduction by abrupt change in P-R pattern and ventricular rate. Upper panel, Dual-chamber stored EGMs and dual-chamber EGM markers. Note that upper numerical values indicate P-R interval, not P-P interval. Lower panel, Interval plot. VT starts in the ventricle with a premature ventricular complex, followed by abrupt change in ventricular rate, ventricular EGM morphology, and the PR-RR relationship (Medtronic PR Logic). Fast VT (FVT) detection at right of EGM is followed by burst antitachycardia pacing (VT Rx 1 Burst), designated by ATP on interval plot. This results in abrupt termination of VT. Note that older versions of this algorithm, which discriminated VT from SVT based only on the PR-RP percentage, may have classified this long-RP tachycardia incorrectly as SVT. AEGM, Atrial electrogram; TF, interval in FVT zone; TS, interval in VT zone; VEGM, ventricular (true bipolar) electrogram; VS, ventricular sensed event.

Figure 3-66  Classification of 1 : 1 tachycardias by chamber of origin. The Sorin Parad algorithm classifies 1 : 1 tachycardias by chamber of onset. Stored ventricular EGM is shown with dual-chamber event markers (top, atrial; bottom, ventricular). Event log and Event summary are shown above each stored EGM. Upper panel, Supraventricular tachycardia (SVT) is diagnosed by atrial onset. Lower panel, Ventricular tachycardia (VT) is diagnosed by ventricular onset.

100

SECTION 1  Basic Principles of Device Therapy

Figure 3-67  Ventricular tachycardia (VT) during rapidly conducted atrial flutter discriminated by morphology of ventricular EGM. VT occurs during atrial flutter with 2 : 1 atrioventricular (AV) conduction. Time line marks indicate that the ventricular rate had been in the VT zone for 24 seconds at the beginning of the panel. VT therapy is withheld because of both the 2 : 1 AV relationship and the morphology match of ventricular EGMs to baseline sinus-rhythm EGMs (not shown). Numbers below event markers indicate 98% to 100% morphology match in atrial flutter, compared with 40% to 47% match in VT; “<” (box) marks indicate that ventricular rate is less than atrial rate. VT is detected by AV dissociation and morphology match percentage less than the threshold value of 60%. Morphology classification of each beat as SVT (check marks) or VT (X) is indicated above event markers. (From Swerdlow C, Shivkumar K: Implantable cardioverter defibrillators: clinical aspects. In Zipes DP, Jalife J, editors: Cardiac electrophysiology: from cell to bedside, ed 4, Philadelphia, 2004, Saunders.)

Figure 3-68  Inappropriate detection of rapidly conducted atrial fibrillation (AF) despite rejection by morphology. Right atrial (RA) EGM, event markers, and true bipolar right ventricular (RV) EGM are shown. Values immediately below event markers corresponding to EGMs in ventricular tachycardia (VT) zone (marked T) indicate the percent match between EGM morphology in tachycardia and sinus morphology. Corresponding check marks above event markers indicate that the morphology algorithm classifies the beats as supraventricular tachycardia (SVT) because the match is greater than 60%. Stability and morphology algorithms are combined with “AND” logic in this St. Jude ICD, so that VT is diagnosed if either discriminator classifies the rhythm as VT. The stability algorithm incorrectly classifies the rhythm because the ventricular cycle lengths regularize. The rhythm would have been classified correctly if the morphology discriminator alone had been programmed. F markers indicate ventricular intervals in ventricular fibrillation (“Fib”) zone. S denotes intervals in the “Sinus” zone above the VT detection interval. T denotes intervals in VT zone. DDI, Mode switch to DDI pacing. (From Swerdlow CD, Friedman PA: Advanced ICD troubleshooting. Part I. Pacing Clin Electrophysiol 28:1322-1346, 2005.)



3  Sensing and Detection A-A

Interval (msec)

1800 1500 1200 900 600

101

V-V FVT=240 msec VT=400 msec VF=320 msec

400 200

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Time (sec) [0=Collection Start] AEGM VEGM

Marker 2 1 1

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 0 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 A 0 A 0 A 0 A 0 A 0 A 0 A 0 A0 A 0 A0 A 0 A0 A0 A0 A0 A0 A0 A0 A 0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A0 A 0 A0 A 0 A0 A 0 A R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S R S 3 9 0

T S

4 0 0

V S

V 4 S 0 0

3 9 0

T S 3 8 0

T S 3 8 0

T S

3 8 0

T S

3 9 0

T S

3 9 0

T S

3 9 0

T S

3 8 0

T S 3 8 0

T S

3 8 0

T S

3 9 0

T S

3 9 0

T S AF

3 8 0

T S AF

3 8 0

T S AF

3 8 0

T S AF

3 9 0

T S 3 9 0 AF

T S AF

3 8 0

6 3 0

T S AF

6 3 0

A P 7 3 0

V P

6 3 0

A P 6 3 0

V P

Figure 3-69  Appropriate rejection of rapidly conducted atrial flutter by pattern analysis. Upper panel, Interval plot. Lower panel, Dualchamber stored EGM with event markers. Atrial flutter is identified by the consistent 2 : 1 PR association of the regular atrial and ventricular rhythms. AF annotations indicate that the number of intervals in the ventricular tachycardia (VT) rate zone required for detection (16) has been reached, but that therapy is withheld because atrial flutter is diagnosed. Interval plot displays 2 : 1 atrioventricular (AV) association until termination of atrial flutter after 12 seconds. AR, Atrial intervals in pacing refractory period; TS, ventricular intervals in VT zone.

Unknown rhythm detected in VT or VT-1 rate zone

V rate > (A rate + 10 bpm)

ACTIVE DISCRIMINATION

Yes

VT

No VTC rhythm No correlated? Yes SVT

A rate >200 bpm and No V rate unstable (>20 ms)

VT

Yes SVT

Figure 3-70  Boston Scientific Rhythm ID algorithm. The central features of this algorithm are comparison of atrial (A) and ventricular (V) rates (first step) and analysis of ventricular EGM morphology (Vector Timing and Correlation, or VTC). If the V rate exceeds the A rate by at least 10 bpm, the rhythm is classified as ventricular tachycardia (VT). If at least 3 of the last 10 beats are classified as supraventricular by morphology analysis, the rhythm is classified as supraventricular tachycardia (SVT). If morphology analysis does not classify the rhythm as SVT, the A rate and the regularity of the V rate are evaluated. The rhythm is classified as SVT if the A rate exceeds 200 bpm and the ventricular rhythm is irregular (measured ventricular interval stability >20 msec). Otherwise, it is classified as a VT.

Active discrimination represents a paradigm shift in the design of detection algorithms, from “diagnose before intervening” to “treat first; analyze only those tachycardias that persist after treatment.” Although active discrimination presents the risk of proarrhythmia (Fig. 3-75), it can be valuable in discriminating tachycardias with 1 : 1 AV association (Figs. 3-76 and 3-77). One such algorithm was designed and implemented by Biotronik (and incorporated into the SMART-II algorithm) but is not commercialized in Biotronik ICDs.136 Feasibility investigations recently demonstrated a new algorithm using simultaneous atrial and ventricular ATP either to terminate or to discriminate 1 : 1 tachycardias. If the tachycardia persists after the simultaneous AV ATP, the discrimination algorithm considers the rhythm ventricular in origin, if the first sensed event after pacing is on the ventricular channel, and supraventricular in origin otherwise. In 62 ambulatory dual-chamber ICD patients, the algorithm terminated or correctly classified 1379 of 1381 SVT sequences (specificity 99.9%) and 23 of 26 VTs (sensitivity 88.5%).115 FEATURES TO OVERRIDE DISCRIMINATORS Programmable duration-based “safety net” features deliver therapy if an arrhythmia satisfies the ventricular rate criterion for a sufficiently long duration even if discriminators indicate SVT. The premise is that VT will continue to satisfy the rate criterion for the programmed duration, whereas the ventricular rate during transient sinus tachycardia or AF will decrease below the VT rate boundary before the programmed duration is exceeded. The limitation is delivery of inappropriate

102

SECTION 1  Basic Principles of Device Therapy

A-V RATE BRANCH Median atrial rate/ median ventricular rate

V
V=A

Morphology discrimination (MD) Interval stability

Morphology discrimination (MD) Sudden onset

VA

AFib/flutter SVT w/multiblock

VT

ST/SVT

VT

VT/VF

Inhibit therapy

Deliver therapy

Inhibit therapy

Deliver therapy

Deliver therapy

Additional discriminators Diagnosis Figure 3-71  St. Jude A-V Rate Branch + Morphology Discrimination (MD) algorithm. Similar to the Rhythm ID, the central features of this algorithm are a comparison of the atrial (A) and ventricular (V) rates (first step) and analysis of ventricular EGM morphology (MD). Rhythms are classified into three Rate Branches: ventricular rate less than atrial rate (V < A), ventricular rate equal to atrial rate (V = A), and ventricular rate greater than atrial rate (V > A). If V < A, the algorithm applies morphology discrimination (and/or both interval stability and N:1 AV association). If V = A, it applies morphology discrimination (and/or sudden onset). All rhythms in the V > A rate branch are treated as ventricular tachycardia (VT). ST, Sinus tachycardia; SVT, supraventricular tachycardia; VF, ventricular fibrillation.

BIOTRONIK SMART

V rate > A rate

V rate = A rate

V rate < A rate

V unstable

V stable

N:1 multiplicity

A unstable

No N:1 multiplicity

V unstable

V stable

A stable

AV trend

VT

AFlut

VT

AFib

VT

VT

AV irregular

AV regular

No AV trend

Sudden onset

No sudden onset

VT

Sinus T

VT

1:1 SVT

Figure 3-72  Biotronik SMART algorithm. The high-level structure of this algorithm is similar to that of the St. Jude ICD. SMART first compares atrial (A) and ventricular (V) rates. If the V rate is faster, ventricular tachycardia (VT) is diagnosed. If the V rate is slower, ventricular interval stability and A : V ratio analysis results in discrimination of atrial fibrillation (AFib; unstable ventricular rhythm), atrial flutter (AFlut; stable rhythm, N:1 association), and VT (stable rhythm, AV dissociated). If the A rate and V rate are equal, SMART analyzes the interval stability. If the R-R interval is stable and the P-P interval is unstable, VT is diagnosed. If the PP interval is stable, the algorithm sequentially analyzes AV association (“AV Trend”) and sudden onset as discriminators. Sinus T, Sinus tachycardia; SVT, supraventricular tachycardia.



3  Sensing and Detection

A rate < V rate (Many RRs don’t have Ps) A R

Building blocks

Possible classification

T S

T S

A rate = V rate (Most RRs have only 1 P)

A R T S

T S

VT/VF (not SVT)

A R T S

A R T S

A R T S

A R T S

T S

A R T S

T S

A R

A R

A R

T S

A A R R T S

A R T S

A A R R T S

ST/AT

VT/VF + SVT

Other 1:1 SVT

Atrial fib/flutter

VT/VF (not SVT)

ST/AT (w/FFRW OS) VT/VF

• R-R intervals • PR patterns

• RR intervals • PR patterns

Get more data

A rate > V rate (Most RRs have more than 1 P)

A R

103

Process PR logic building blocks (up to 24 R-R intervals and P:R patterns)

A R T S

VT/FVT/VF detection by RR intervals? Yes

No

Yes Median RR < SVTLimit? No

Yes

Double tachycardia identified? No

• RR intervals • PP intervals • PR patterns • RR regularity • PR dissociation • PP regularity

AFib/AFlutter?

Yes

No Sinus tach?

Yes

No Other 1:1 SVT?

Yes

No VT/FVT/VF DETECTION

A

B

Figure 3-73  Medtronic PR Logic algorithm. A, Clinical decision process. The rhythm types are represented using P-R marker diagram examples (top), from least complex (left) to most complex (right). A list of possible PR Logic decisions and the building blocks used are also shown for each of the rhythm types. Note that PR Logic implicitly employs a ventricular (V) rate > atrial (A) rate override (first column), because all rhythms with A rate < V rate and V rate in one of the detection zones are classified as ventricular tachycardia/fibrillation (VT/VF). For tachycardias with A rate = V rate (i.e., 1 : 1 tachycardias, center column), the original PR Logic uses P-R patterns and discriminates 1 : 1 rhythms with critical P-R interval timing zones (see Fig. 3-64, A). The new sinus tachycardia (ST) criterion in PR Logic (Entrust and later) uses the P-R pattern along with P-R and R-R suddenonset criteria (see Fig. 3-64, B). For rhythms with A rate > V rate, PR Logic uses P-R patterns along with R-R regularity, P-R dissociation, and P-P regularity to ensure detection of double tachycardia (VT or VF during atrial fibrillation [AFib]) and to withhold therapy for 2 : 1 atrial flutter, rapid AFib, and ST with far-field R-wave oversensing (FFRW OS). In the newest Medtronic ICDs (Protecta, currently investigational), EGM morphology analysis (Wavelet) is applied for rhythms with A rate ≥ V rate that are identified by SVT by PR Logic pattern analysis alone. In addition, detection of double tachycardia in the Protecta devices requires that abnormal EGM morphology be present. Integration of Wavelet EGM morphology with PR Logic is designed to improve detection specificity compared to PR Logic interval analysis alone. B, PR Logic computational flow diagram. On each ventricular event, PR Logic processes the new P-R, R-P, P-P, and R-R patterns and timing information for the building blocks. If VT/fast VT (FVT) or VF rate detection criteria are satisfied, the ventricular rate override criterion is checked first. If the median R-R interval is less than the supraventricular tachycardia (SVT) limit, detection occurs through the single-chamber detection criteria without considering the PR Logic discrimination algorithm. If the median R-R interval is greater than the SVT limit, and if double tachycardia (VT/FVT/VF + SVT) is not detected, the three PR Logic criteria for identifying SVTs are tested in the order shown. If any one of the PR Logic SVT criteria is satisfied, inappropriate detection is avoided. If an SVT is not positively identified by PR Logic pattern analysis and the A rate ≥ V rate, EGM morphology analysis (Wavelet) is applied and classify the rhythm as SVT if the EGM morphology during tachycardia matches the template. If none of the SVT discrimination criteria is satisfied, VT/FVT/VF is detected when the R-R interval–based criterion is satisfied. If SVT is identified, the entire process repeats itself on each ventricular event until VT/FVT or VF is detected or the rhythm slows out of the ventricular rate detection zones.

therapy when SVT exceeds the programmed duration, which occurs frequently for durations of 1 minute or less and in up to 10% of SVTs at 3 minutes, depending on the VT detection interval and AV conduction.116 Because SVTs are much more common than VTs, programming of discriminator override duration to 3 minutes results primarily in inappropriate therapy of SVT. Programmed durations of 5 to 10 minutes are required to minimize such inappropriate therapy.137 The decision to use a discriminator override should be based on clinical factors, including the probability that discriminators will prevent detection of VT, the likely consequences of failure to detect VT, and the likelihood that SVT in the VT rate zone will persist long enough to trigger inappropriate therapy because of the override. For example, override features may be considered whenever a morphology algorithm is programmed without inducing VT at electrophysiologic study. The Medtronic Protecta ICDs incorporate an additional, separately programmable “VF Zone High Rate Time Out.” It applies only to rhythms that are consistently in the VF rate detection zone. This new algorithm allows SVT discriminators to be applied with

longer-duration (or no) time-out for slower rhythms, with a separate override duration for rhythms with rates in the VF zone. SVT-VT DISCRIMINATORS IN REDETECTION The SVT-VT discrimination during redetection serves two purposes: (1) to prevent inappropriate therapy for SVT after appropriate therapy for VT (Fig. 3-78) and (2) to provide a second chance for the algorithm to classify SVT correctly after inappropriate therapy. Biotronik ICDs (Fig. 3-79) and sorin-ELA ICDs provide essentially equivalent SVT-VT discrimination in initial detection and redetection, except that algorithm building blocks related to tachycardia onset are disabled. Boston Scientific algorithms permit programming discriminators after shocks, but not after ATP, when it is more useful and reliable. In Medtronic ICDs, the single-chamber stability discriminator applies to redetection only if it is “on” for initial detection. The user interface does not indicate that it applies in redetection, and it is rarely programmed for this purpose. St. Jude ICDs do not apply discriminators to redetection.

104

SECTION 1  Basic Principles of Device Therapy

Tachyarrhythmia detected

Unstable

RR Stability

Diagnosis AF No VTLC No Diagnosis VT

Inappropriate Detection, Inappropriate Therapy, and Inappropriate Shocks All failures of SVT-VT discrimination algorithms do not have equivalent clinical outcomes. ATP is delivered immediately after detection so the numbers of detections and therapies are equivalent. In contrast, shock delivery requires capacitor charging, during which therapy may be aborted. However, inappropriate ATP is often unnoticed. It terminates about 40% of SVTs and reduces the ventricular rate below the VT detection interval in another 20%.139 In contrast, inappropriate shocks adversely affect quality of life.140 Active discrimination blurs the distinction between detection and therapy because only tachycardias that persist immediately after diagnostic pacing are classified.

Stable

Associated PR Yes Yes

Diagnosis No AF Diagnosis AFlutter

PR Association 1:1 Gradual

Diagnosis ST

IS VENTRICULAR THERAPY FOR SVT ALWAYS INAPPROPRIATE?

Acceleration Sudden Origin of acceleration Atrial

Diagnosis AT

Ventricular Diagnosis VT

Figure 3-74  Sorin Parad+ algorithm. If most of the detected R-R intervals are in the ventricular tachycardia (VT) zone, ventricular interval stability is analyzed in a first step, using a histogram of R-R intervals. If the rhythm is irregular, atrial fibrillation (AF) is diagnosed and therapy is withheld. If the rhythm is regular, the atrioventricular (AV) association is assessed by comparing peak amplitudes of R-R and P-R interval histograms. If the rhythm is AV dissociated, VT is diagnosed, unless the Long Cycle Search is activated, which inhibits therapy if a long ventricular cycle (VTLC, characteristic of AF) is identified. If N:1 P-R association is identified, the rhythm is classified as supraventricular tachycardia (SVT). In the presence of 1 : 1 P-R association, the Parad+ evaluates the rate of acceleration of the ventricular rate. If acceleration is gradual, sinus tachycardia (ST) is diagnosed. If acceleration is sudden, Parad+ identifies the chamber of origin and withholds therapy if it is the atrium. AFlutter, Atrial flutter; AT, atrial tachycardia.

Neither Medtronic nor St. Jude ICDs provide any discriminators to reject sinus tachycardia in redetection. MEASURING PERFORMANCE OF SVT-VT DISCRIMINATION ALGORITHMS Valid assessments and comparisons of algorithm performance require consideration of multiple ICD-related and clinical factors. A comprehensive assessment requires analysis of all tachycardia episodes, including those not stored in ICD memory and those in the VF zone to which discriminators may not apply.68,69,130 Programmed detection parameters may influence reported algorithm performance.69 In most studies, a few patients contribute a large number of SVT or VT episodes. Therefore, statistical methods such as the generalized estimating equation (GEE)138 should control for such clustered, nonindependent data. Quantitative Considerations Detection algorithms must maintain almost 100% sensitivity for detection of VT; but detection of hemodynamically-stable asymptomatic VT is not necessarily synonymous with therapy. If patient populations and programmed detection boundaries are equivalent, positive predictive accuracy may be the most useful statistical measure of algorithm performance.68 However, it is highly dependent on the ratio of SVT to VT episodes and therefore on the programmed detection rate and patient population (prevalence of SVT and VT). However, it is almost impossible to obtain a clinically meaningful comparison of different detection algorithms based only on their performance on different sets of data.

Persistent, rapidly conducted atrial arrhythmias can cause hemodynamic compromise in patients with LV dysfunction or ischemia in patients with severe coronary artery disease. Thus, algorithmically inappropriate ventricular therapy may fortuitously terminate clinically significant SVT, although inappropriate ventricular therapy for SVT may also be proarrhythmic.141 Further, in patients with ICDs, rapid conduction in AF is often transient, and symptoms are often mild, but ventricular shocks delivered shortly after detection do not permit spontaneous termination of AF or slowing of the ventricular rate. Therefore, shocks will be delivered for AF that may have spontaneously terminated or slowed. Inappropriate shocks for AF may place patients at risk for thromboembolism if they are not anticoagulated. Also, early recurrence is common after transvenous cardioversion of AF.142 Experts differ about whether algorithmically inappropriate ventricular therapy of SVT may be clinically appropriate in specific clinical situations. ICDs designed to deliver both atrial and ventricular therapies may be implanted in patients who are likely to benefit from ICD-based therapy of SVT.

Detection: Programming and Troubleshooting The multiple programmable parameters that affect detection directly or indirectly provide opportunities both for customizing detection and for operator error. A prospective study reported that empirical programming of dual-chamber ICDs provided comparable performance to individualized programming.131 Nevertheless, it is important to understand the many trade-offs and compromises inherent in ICD detection strategies. DETECTION ZONES AND DURATION Zones and Zone Boundaries In patients receiving secondary prevention therapy, typical values for rate zone boundaries are 400 to 360 msec for the sinus-VT boundary, 330 to 240 msec for VT–fast VT boundary, and 300 to 240 msec for the upper limit of the VF zone boundary, with longer cycle lengths for the last boundary usually found in two-zone programming. In primary prevention patients and those whose only arrhythmia is VF, typically one or two zones are programmed, with the sinus boundary set at 330 to 300 msec.143,144 This approach lowers the risk of inappropriate therapy but increases the risk of not treating VT. Programming that permits delivery of ATP is desirable for most patients, even those undergoing implantation for primary prevention and those whose only clinical arrhythmia is VF, because most spontaneous VF begins with rapid VT, and most rapid VT can be terminated by ATP.145-147 Three zones permit different ATP therapies for two distinct rates of VT, as well as ATP for monomorphic VT that overlaps in rate with polymorphic VT. In the largest primary prevention trial,144 ICDs were programmed to a single detection zone at a cycle length of 320 msec, without SVT-VT discriminators, but approximately one



105

3  Sensing and Detection

RA ATP

ATP ATP

413

373

S

S

R

ATP ATP

T

T

T

T

T

422 422 422 422 422 422 418 434 422 418 426 422 422 410

493 P

ATP

T

R

R

R

R

R

R

ATP ATP ATP ATP ATP ATP ATP ATP D 423 423 413 431 399 443 423

R

ATP ATP ATP ATP ATP ATP ATP ATP

RV 32

33

34

35

36

37

38

39

40

DDI

Proarrhythmia ATP in 1:1 SVT (rapidly conducted AF)

T

F

F

T

R

R

40 DDI

41

F

F

F

42

F

F 8V

F

F

F

43

F

F

F

328 293 301 289 305 371 426 344 430 414 397 P P P R R R R R R

48

49

* R

* R

* R

* R

F

F

F

F

* R

* R

* R

* R

* R

* R

* R

H V

* R

R R D 309 301 281 285 324 465 309 297 461 473 309 309 320 297 305 324 316 355 262 289 301 270 426 277 242 246 242 254 316 383 281 281 301 270 281 293 387 309 P R R R R R R R R R R R R R R R R R R R R R R

320 332 293 348 305 441 R

F

* R

50

* R

* R

* R

51

* R

R

R

44

* R

* R

* R

45

* R

* R

* R

46

* R

* R

* R

47

* R

* R

* R

* R

48

* R

* R

D 26 293 289 309 305 230 297 320 277 293 273 277 285 273 293 258 324 336 418 328 293 297 273 258 309 305 324 277 313 35 P P R R R R R R R R R R R R R R R R

52

53

54

55

56

52

53

54

55

56

H V 830V

6 262 445 281 648 309 289 2 324 285 254 285 285 266 297 313 273 R

48

R

R

R

49

R

R

R

50

R

R

51

Figure 3-75  Atrial proarrhythmia caused by ventricular antitachycardia pacing in 1 : 1 supraventricular tachycardia (SVT). Continuous stored EGM shows right atrial (RA) EGM, event markers, and true bipolar right ventricular (RV) EGM. In the top panel, antitachycardia pacing (ATP) is delivered after rate-only, inappropriate detection of sinus tachycardia as ventricular tachycardia. Ventricular-atrial conduction occurs, initiating atrial fibrillation (AF), which is detected as ventricular fibrillation because redetection does not utilize discriminators. AF requires two shocks (HV) before termination. The first shock is delivered at the end of the middle panel and the second in the middle of the lower panel. Recording is suspended for approximately 1 second after each shock.

106

SECTION 1  Basic Principles of Device Therapy

EGM1: Atip to Aring

EGM2: Can to HVB 3 1 0

A-A interval (ms) Marker annotation

T S

V-V interval (ms)

3 1 0

3 1 0

A A S S

A S

3 2 0

A S

T T T S S S 3 3 3 1 1 1 0 0 0

3 2 0

3 3 3 2 2 2 0 0 0 A A A A S S S S

6 4 0

A S

T T T T T T T S S D P P P P 3 3 3 2 2 2 2 1 2 2 7 7 7 7 0 0 0 0 0 0 0

3 2 0

A S

3 2 0

3 1 0 A A S S

2 7 0

T T T T P P P P 2 2 2 2 7 7 7 7 0 0 0 0

third of shocks were inappropriate, most often for rapidly conducted AF. The sinus-VT rate boundary should be slow enough to ensure detection of all hemodynamically compromising VTs. To prevent underdetection of irregular VT, the VT detection interval should be set with a safety margin at least 40 to 50 msec longer than the slowest predicted VT for consecutive-interval counting and 30 to 40 msec longer for “X out of Y” or “interval + interval-average” counting.134 This safety margin should be greater if rapidly conducted SVT is unlikely or SVT-VT discrimination is reliable at long cycle lengths (Sorin ICDs). The boundary between the two VT zones should be based on the cycle length at which different types or fewer trials of ATP are preferred. The VT-VF rate boundary is based on the cycle length below which ATP or ATP before charging should not be delivered. In Medtronic ICDs, which use consecutive-interval counting above the VF interval and “X out of Y” counting below it, this boundary should be set to prevent underdetection of irregular, polymorphic VT by consecutive-interval counting.

A S

3 6 0

7 1 0

A S

3 1 0

V S

3 1 0

A A S S

3 1 0

T T S F 3 2 6 7 0 0

Figure 3-76  Effect of ventricular antitachycardia pacing on supraventricular tachycardia (SVT) with 1 : 1 atrioventricular (AV) relationship. Atrial EGM (Atip to Aring), high-voltage ventricular EGM (Can to HVB), and dual-chamber event markers are shown. Burst ventricular antitachycardia pacing at cycle length 270 msec is applied to SVTs with cycle lengths of 310 to 320 msec. The atrial interval after the last paced beat is accelerated to the pacing rate, probably indicating entrainment of the atrium. The A-A-V response at termination of pacing is diagnostic of atrial tachycardia.

Duration for Detection of Ventricular Tachycardia Detection duration before ATP should rarely be decreased from nominal values, because therapy is immediate after detection, and undersensing of monomorphic VT is rare. It should be increased in patients who have long episodes of nonsustained VT. Substantial increases in duration for detection of VT probably are safe in St. Jude and Boston Scientific ICDs, which use counting methods that are insensitive to occasional long ventricular intervals or undersensing. In contrast, consecutive-interval counting used by Medtronic ICDs in the VT zone and the Sorin persistence counter (nominally set to 12 consecutive intervals for VT and 6 for VF) may underdetect VT if occasional, long ventricular intervals or undersensing occurs.119 Duration for Detection of Ventricular Fibrillation Duration for detection of VF generally should not be reduced from nominal to prevent inappropriate therapy or aborted shocks for nonsustained VT.146,148 A prospective study of primary prevention patients demonstrated that long-duration detection (30/40 intervals) did not

A-EGM

V-EGM

A R T S

3 6 0

3 6 0

A R

T S

3 6 0

3 6 0

T S

A R

3 6 0

3 6 0

T S

3 6 0

A R

3 6 0

A R T S

3 6 0

3 6 0

A R T S

3 6 0

3 6 0

A R

T S

3 7 0

3 7 0

T S

A R

3 6 0

3 4 0

3 3 3 4 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 8 8 9 2 1 1 1 1 2 2 3 2 2 2 2 7 6 6 4 6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 A A A A A A A A A A A A A A A A A A A A R R R R S S S S S S S S S S S S R R R R T S

3 6 0

T S

3 7 0

T S

3 6 0

T S

3 7 0

T P

3 2 0

T P

3 2 0

T T T T T T T T T T T P P P P P P P P P P P 4 3 3 3 3 3 3 3 3 3 3 9 2 2 2 2 2 2 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0

V S

3 9 0

T S

3 8 0

T S

3 8 0

Figure 3-77  Atrial response to ventricular antitachycardia pacing during ventricular tachycardia (VT) with 1 : 1 ventricular-atrial (VA) conduction. Stored atrial (A) and ventricular (V) EGMs are shown with event markers. During antitachycardia pacing, atrial rate accelerates to ventricular rate. The V-A-V response at termination of pacing is characteristic of VT, although atrioventricular (AV) nodal and AV reciprocating tachycardias cannot be excluded.



3  Sensing and Detection

107

RV Tip-RV Ring

RV Coil-Can T F 3 2 0

3 1 0

T F 3 2 0

T F 3 2 0

T F 3 3 0

VT

T F 3 3 0

T F 3 3 0

T F 3 3 0

T F 3 4 0

T F 3 3 0

T F 3 5 0

T F 3 4 0

T F 3 3 0

T F 3 4 0

T F 3 3 0

T F 3 4 0

ATP

T F 3 6 0

T F 3 6 0

T P

T P

T P3 6 0

T P2 9 0

T T P2 P 2 9 9 0 0

T P2 9 0

T P2 9 0

Sinus Tachycardia T F2 9 0

T F 2 9 0

T P2 9 0

T P

T S

8 1 0

ATP T• F

4 3 0

T• F

T• F

4 3 0

4 4 0

T• F

T• F

4 4 0

4 5 0

T• F

T P

4 4 0

T P

3 3 6 6 0 0 FVT Rx 1/Sec 2

T P

3 6 0

T P

3 6 0

3 6 0

T P

3 6 0

T F

4 6 2

T F

4 5 0

T F

4 5 0

T F 4 4 0

4 4 0

T F

Sinus Tachycardia T P

3 6 0

T F

6 0 0

3 6 0

T P

3 6 0

T P

T P

3 6 0

V S

8 7 0

4 1 0

T• F

V S

5 0 0

4 4 0

T• F

T• F

4 4 0

T• F

4 4 0

T• F

4 3 0

Shock 4 3 0

V S

4 4 0

V S

4 6 0

V S

4 6 0

V S

3 7 0

C E

5 3 0

V S

4 6 0

C D

8 3 0

V S

T• F

4 3 0

5 6 0

V S

5 8 0

V S

V S

8 1 0

4 1 0

T• F

5 2 0

V S

3 3 0

T• F

5 4 0

V S

4 2 0

T• F

4 2 0

T• F

4 1 0

T• F

4 1 0

T• F

4 1 0

14.9 J

A V-V 1,800

VF = 300 ms Burst

V-V interval (ms)

1,500

FVT = 360 ms 20.1 J

VT = 470 ms 35.1 J

34.8 J

14.9 J

35.1 J

1,200 900 600 Sinus Tach 400

VT

200

240

B

220

ATP

0

20

40

60

80

100

*

*

Time (sec) [0 = detection]

Figure 3-78  Redetection. Inappropriate therapy of sinus tachycardia after appropriate therapy for ventricular tachycardia (VT) in a singlechamber ICD. Ventricular sensing and high-voltage leads are shown with event markers. A, Continuous stored EGM strips after detection of VT. The top strip shows successful antitachycardia pacing (ATP) of VT followed by sinus tachycardia in the Fast VT (FVT) zone (TF on event markers). The second strip shows the first inappropriate sequence of ATP. The third strip shows the first of five shocks delivered after ATP. B, Interval plot shows the entire episode. No U.S. ICD manufacturer provides for VT-supraventricular tachycardia (SVT) discrimination after ATP. RV, Right ventricular; VF, ventricular fibrillation. (From Swerdlow CD, Friedman PA: Advanced ICD troubleshooting. Part II. Pacing Clin Electrophysiol 29:70-96, 2006.)

108

AFlut 399

AFlut 398

AFlut 399

VT1 390

VT1 398

VT1 399

AS 719 Ars 195 AS 203 AS 196 Ars 195 AS 203 AS 195 Ars 196 AS 203 Ars 195 AS 196 AS 203 Ars 195 VS 1844

AS Ars 109 VT2 320

20 J 81Ohm

25 AS 985 VS 984

AS 984 VS 984

VS 985

AS 985

AS 975

AS 985 VS 977

AS 984

Shock

VS 984

VS 984

AS 984

AS 985 VS 985

AS 726 VS 992

AFlut 391

AFlut 390

AFlut 391

AFlut 391

AFlut 398

AFlut 398

AS 195 AS 204 Ars 195 AS 195 AS 203 Ars 196 AS 203 Ars 195 AS 195 AS 203 Ars AS 125

25 mm/s

VS 984

Charge

VT2 328

VT2 321

VT2 328

VT2 351

AS 351

AS 352

VT2 352

AS 351

VT1 351

VT2 352

VT2 352

AS 704

AS 1617 VT2 320

VT2 328

VT2 320

VT2 321

VT2 328

AS 586 VT2 351

VT2 320

VT1

VT2 320

VT2 320

VT2 328

AS 750

AS 1617

SECTION 1  Basic Principles of Device Therapy

Figure 3-79  Supraventricular tachycardia/ventricular tachycardia (SVT-VT) discrimination in redetection. Dual-chamber EGM markers, atrial EGM, and true bipolar EGM are shown in this continuous strip from a Biotronik Lexos ICD, Model 347000. Rhythm at beginning of upper panel is VT with ventricular-atrial (VA) dissociation. Vertical dotted line indicates detection and start of capacitor charging (Charge). Black horizontal line indicates period of capacitor charging followed by successful shock. Postshock nonsustained atrial flutter begins toward right side of upper panel, continues into lower panel, and shows transient atrial flutter followed by conversion to sinus rhythm. Ventricular rhythm is classified by the lower row of markers as VT2 (faster VT zone) before shock, VT1 (slower VT zone) for the first four ventricular EGMs of atrial flutter, and conducted atrial flutter (Aflut) beginning at the fifth conducted ventricular EGM during atrial flutter (arrowhead). Without SVT-VT discrimination in redetection, VT would have been redetected after 10 intervals.

increase risk of syncope compared to historical controls.143 A significant reduction in heart failure hospitalization (as well as shocks) was reported in a controlled study of primary-prevention, nonischemic heart failure patients comparing detection duration of 12/16 with 30/40 intervals.149

redetection may prevent inappropriate redetection of delayed termination of VT (type II break) or postshock nonsustained VT. ICDs misclassify effective therapy as ineffective if VT/VF recurs before the ICD identifies episode termination and reclassifies the posttherapy rhythm as “sinus” (Fig. 3-80). Misclassification may also occur if SVT begins after successful VT therapy but before ICD-defined episode termination because of frequent premature beats or nonsustained tachycardia. Decreasing the duration for redetection of sinus rhythm (St. Jude) may correct this classification error.

Duration for Redetection Inappropriate therapy for nonsustained VT or SVT may be delivered after ATP or shocks (see Fig. 3-78). Increasing the duration for

5 3 0

5 5 0

A R T F* 3 0 0

T F* 3 0 0

T F*

3 1 0

5 5 0

A S V P

4

5 5 0

A R

T F*

5 5 0

T F* 3 1 0

3 0 0

5 4 0

A S V P

5

5 2 0

A R

3 3 0

A R T S

0

T F*

5 2 0

A R 3 1 0

5 4 0

T F*

5 5 0

A R T P

A R

T P

T 2 P 6 0

FVT FVT Rx 1 Burst

A S V S

7 0 0

1

5 5 0

5 5 0

A S 6 2 0

V P

2

3 5 0

5 3 0

A R T S

0

5 0 0

V S

1

4 9 0 6 2 0

A R

5 5 0

2 T 5 F* 0

3 2 0

5 6 0

A S T P

1

5 6 0

T P

2

5 6 0

A R

2 T 2 8 F* 8 0 0

T 2 F* 9 0

A R T S

5 2 0

A S

5 3 0

A S 5 4 0

T S

3

5 5 0

A R

T 2 F* 9 0

T 3 F* 0 0

T S

3 4 0

A R V S

5 5 0

A S V P

7 1 0

0

5 5 0 T F

5 3 0

A R

1

5 4 0

A R

V S

V S

FVT FVT Rx 2 CV

3 5 0

T S

V S

V S

3 0 0

V S

5 9 0

1

5 6 0

A R

5 5 0

A R

3 7 0

0

5 2 0 3 0 0

5 3 0

A R

3 0 0

5 4 0

A R V S

3 0 0

6 5 0

3

1600

A R V S

V S

5 7 0

2

5 5 0

A R

V 1 C S 9 E 0

4 2 0

V S

3 0 0

C D 15.0

Figure 3-80  Failure to identify post-therapy sinus rhythm because of rapid reinitiation of ventricular tachycardia (VT) after successful therapy. Atrial EGM, ventricular true bipolar EGM, and EGM markers classify the rhythm as sinus (8 consecutive intervals). Therefore, VT is inappropriately redetected instead of being detected de novo for the second time. This results in delivery of the second programmed Fast VT (FVT) therapy, cardioversion, rather than repeat delivery of the previously successful antitachycardia pacing (ATP) stimulus, which is both painless and more energy efficient. Redetection marker (FV Rx 2 CV) indicates onset of capacitor charging for the second VT therapy. Shock is not shown. Large numbers below right side of upper panel and left side of lower panel show value of sinus rhythm counter, which increments for each interval in the sinus zone (VS) and is reset to zero by premature ventricular complexes (PVCs) with a coupling interval of less than the VT detection interval of 400 msec (TS). VS markers indicate unclassified ventricular intervals during capacitor charging. AS, Atrial sensed event; AR, atrial intervals in pacing refractory period.



3  Sensing and Detection

Recommended Programming of SVT-VT Discriminators in Dual-Chamber ICDs

RANGE OF CYCLE LENGTHS TO WHICH SVT-VT DISCRIMINATORS APPLY

TABLE

The SVT-VT discriminators apply in a range of cycle lengths bounded on the slower end by the VT detection interval and on the faster end by a minimum cycle length that varies among manufacturers (see Fig. 3-51). Usually, SVT-VT discriminators will not withhold inappropriate therapy for SVT if the majority of ventricular intervals (typically 70%80%) are shorter than the SVT limit. Therefore, rapidly conducted AF may be classified as VT even if the mean cycle length is 20 to 40 msec longer than the SVT limit. Programming a sufficiently short, minimum cycle length for SVT-VT discrimination is critical to reliable rejection of SVT. When discriminators are programmed, approximately 25% of inappropriate therapy is caused by SVT with ventricular cycle lengths shorter than that minimum cycle length.68,137,150 In some ICDs, the SVT discriminators can be programmed only in the VT detection zone if two-zone programming is used or in the slowest zone with three-zone programming. In currently approved Medtronic ICDs, the SVT limit is programmable independently, but the performance of SVT-VT discriminators is linked implicitly to the VT/VF zone boundary. AF is not rejected by RR regularity at cycle lengths shorter than the programmed VF detection interval; thus rapidly conducted AF cannot be distinguished from VF in dualchamber and cardiac resynchronization ICDs before the (now investigational) Protecta models. In nominal programming, the “VF Detection Interval” forms the boundary between the VT and Fast VT zones. Therefore, this degradation in discrimination of VT from rapidly conducted AF usually occurs between the VT and Fast VT zones. In these ICDs, conducted AF in the Fast VT zone may be discriminated by programming “Fast VT via VT” rather than the nominal “Fast VT via VF.” The risk is delay in detection of unusual, markedly irregular fast VT with occasional cycle lengths in the sinus zone.

Medtronic PR Logic AFib/AFlutter ON Sinus Tach ON*

Atrial View AFib Rate Threshold 200 bpm

Other 1 : 1 SVTs

Onset 9%

{Wavelet ON Match Threshold = 70%}, Protecta devices only (investigational)

Inhibit if unstable 10%

PROGRAMMING OF SVT-VT DISCRIMINATORS Single-Chamber Discriminators Technical details vary among manufacturers, as do corresponding recommended programmed values, which are summarized in Table 3-4. See earlier Ventricular EGM Morphology for SVT-VT Discrimination for programming and troubleshooting of morphology algorithms. Dual-Chamber Discriminators Dual-chamber algorithms should be programmed “on” in any patient with intact AV conduction and a functioning atrial lead. Specific considerations for each manufacturer are summarized in Table 3-5. In St. Jude ICDs, discriminators may be combined using either the “any” or “all” operators. Using “any,” the algorithm detects VT if any discriminator classifies the tachycardia as VT, resulting in higher sensitivity and lower specificity. Conversely, using “all,” the algorithm detects VT only if all discriminators classify the tachycardia as VT, resulting in lower sensitivity and higher specificity. The “all” operator corresponds to the addition of discriminators in other algorithms.

3-5 

109

Boston Scientific Rhythm ID ON

St. Jude Rate Branch Rate Branch ON A = V Branch: Morphology A > V Branch Morphology; may combine Stability† with “ANY” logic

V rate > A rate ON Sustained rate duration = 3 minutes *In older models before Entrust (Model D153DRG) (*1:1 VT-ST Boundary = 66%). †Stability at 80 msec with AV Association of 60 msec. A, Atrial; AFib, atrial fibrillation; Tach, tachycardia; V, ventricular.

St. Jude Rate Branch.  Morphology should be programmed in both the “V = A” and “V < A” rate branches. Recommended programming adds the stability discriminator in the V < A branch using the “any” operator. This results in a minor increase in sensitivity for detection of VT (98% to 99%) and a similarly minor decrease in specificity (82% to 79%). Addition of the stability discriminator using the “all” operator reduces inappropriate detection of aberrantly conducted AF, but may also reduce sensitivity for detection of VT.114 Boston-Scientific Rhythm ID.  This algorithm has no programmable features. Medtronic PR Logic.  At implantation, rejection rules should be programmed “on” for sinus tachycardia and atrial fibrillation/flutter. The 1 : 1 SVT rejection rule should not be programmed until the atrial lead is stable, because its dislodgement to the ventricle may result in misclassification of VT as a 1 : 1 SVT. This potential problem also applies to the St. Jude Rate Branch algorithm without additional discriminators.

Failure to Deliver Therapy: Undersensing and Underdetection Undersensing and underdetection may be caused by ICD system performance, programmed values (including human error), or a combination of the two. They result in failure to delivery therapy or delay in therapy. UNDERSENSING

TABLE

3-4 

Recommended Programming of SVT-VT Discriminators in Single-Chamber ICDs

Stability* Onset Morphology

Medtronic 40-50 msec, NID = 16 84%-88% 3 of 8 electrograms ≥70% match

Boston Scientific 24-40 msec, duration 2.5 sec 9% Not programmable†

St. Jude 80 msec 150 msec 5 of 8 electrograms ≥60% match

*Less strict values are required for patients taking type I or III antiarrhythmic drugs. †3 of 10 electrograms with Feature Correlation Coefficient greater than threshold. ICDs, Implantable cardioverter-defibrillators; NID, number of intervals to detect VT; SVT-VT, Supraventricular tachycardia–ventricular tachycardia.

Ventricular fibrillation may be undersensed because of combinations of programming (sensitivity, rate, or duration), low-amplitude EGMs, rapidly varying EGM amplitude, drug effects, and postshock tissue changes. At present, the most common causes of VF undersensing are drug or hyperkalemic effects that slow VF into the VT zone, ischemia, and rapidly varying EGM amplitude48,71 (Fig. 3-81). ICDs that adjust dynamic range based on the amplitude of the sensed R wave (Boston Scientific) may be the most vulnerable to rapidly varying EGM amplitude (Fig. 3-82). ICD features that reduce sensitivity to prevent T-wave oversensing may also result in undersensing of VF.60 Prolonged ischemia from sustained VT slower than the VT detection interval may cause deterioration of signal quality, resulting in undersensing of VF. Lead, connector, or generator problems may also manifest as undersensing.

110

SECTION 1  Basic Principles of Device Therapy

Near field V

VF 158

Pre-attempt EGM (10 sec max) Initial Detection VF Zone Pre-attempt AVS Rate 176 bpm

VF 248

Far field V

VF 253 Epsd Grad 1

VF 163

VF 265

VF 163

VF 263 VF 155

VF 280

VF 155

VF 270

VF 270 VF 168

VF 163

VF 265

VF 158

VF VF 283 270 VF VF 163 165

VF 278 VF 143

VF 303 VF 135

VF 305 VF 165

VF 280 VF 168

VF 278 VF 165

VF 290 VF 165

VF 278

VF 175

VF 278

VF 160

VF 300

VF 163

VF 298

VF 168

–– 533

VF 373 –– 98

VF 138 VS 465

VS 335 Dvrt

Chrg

A

End of Episode 00.25

Pre-attempt EGM (10 sec max) Initial Detection Pre-attempt AVS Rate 218 bpm

25 mm/s

VF –– 228 VF 165 230

VS 365

VS 478

VF 140

VS 345

VF 143

VS 345 VF 145

VS 353

VF 153

VS 353

VF 145

VT 310

VF 170

VS 355

VF 145

VS 368

VF 138

VT 315

VF 135 VS 425

VT 310

VF 173

VS 345

VF 145

VF 158 VS 355

VS 368

VS 543

VS 625

VS 578

VF 230

VF 228 Detct Chrg

VF 218

VF 190

VF 188

VF VF VF 135 223 225 VF VF VF VF 188 258 155 195

VS 383

VF 288

VF 243

VF 188

VF 178

VF 280

VF 218

VF 243

–– 170

Chrg

–– 223

VF 170

1

VF 260

VF 180

Shock

Attempt

VF 230

Attempt Type Elapsed Time Therapy Delivered

VF 208

14J Biphasic 00:01 VF Shock 1

Far field V

Pre-attempt EGM (10 sec max) Initial Detection Pre-attempt AVS Rate 60 bpm

Near field V

–– 1363

VS 1573

B Figure 3-81  Underdetection of ventricular fibrillation (VF) caused by hyperkalemia (potassium level, 6.7 mg/dL) in the setting of chronic amiodarone therapy. A, Near-field and far-field ventricular (V) EGM and event markers of a Boston Scientific Prizm VR ICD. The top panel shows a sine-wave ventricular tachycardia (VT) in the far-field channel, which is detected as VF because local EGMs on the near-field channel are doublecounted. At right of upper panel, four intervals greater than the programmed VF detection interval of 316 msec (190 bpm) result in an aborted shock. The lower panel shows persistence of VF after the shock is aborted. Too few intervals are sensed in the VF zone to permit detection of VF. The patient was resuscitated by external shock. B, ICD system testing after correction of hyperkalemia. Induced VF is sensed reliably and is terminated by an ICD shock. The near-field EGM is narrow, indicating that double EGMs present during the clinical arrhythmia were caused by functional conduction block. (Courtesy Dr. Felix Schnoell.)



3  Sensing and Detection

111

ECG

RA

RV (Tip-Coil)

(AS) 1343

PVC 303 VF 265

(AS) 1268

(AS) 1215 PVC 580

VS PVC 305 310

PVP

PVC 283

PVC 483

PVP

(AS) 1185

AS 1158

PVC VP-MT 320 VF 523 170 PVP

VP 555

PVC PVC 288 VF 330 273 PVP

VS 31

PVP

Figure 3-82  Undersensing of ventricular fibrillation (VF) despite normal R wave in sinus rhythm (18.5 mV). Programmer strip recorded at implantation testing of a Boston Scientific Prizm ICD shows electrocardiogram (ECG), right atrial (RA) EGM, and integrated bipolar right ventricular (RV) sensing EGM (Tip-Coil) during implantation testing. The VF EGMs have highly variable amplitudes, resulting in undersensing of low-amplitude EGMs immediately after high-amplitude ones (arrows). Intermittent ventricular pacing (VP) introduces postpacing blanking periods. Slow Automatic Gain Control may contribute to this type of undersensing. AS, atrial sensed event; PVC, premature ventricular complex; PVP→, extension of postventricular atrial refractory period (PVARP); VP, ventricular paced event. (Modified from Dekker LR, Schrama TA, Steinmetz FH, et al: Undersensing of VF in a patient with optimal R wave sensing during sinus rhythm. Pacing Clin Electrophysiol 27:833-834, 2004.)

ICD INACTIVATION If detection is programmed “off ” for surgery using electrocautery, reprogramming must be performed at the end of the procedure, a fact that is easily forgotten, especially with outpatient surgery. One study reported an unexplained 11% annual incidence of transient suspension of detection.151 This problem is addressed in Medtronic ICDs with an audible patient alert that sounds if programmed detection or therapy is “off ” for longer than 6 hours. VENTRICULAR TACHYCARDIA SLOWER THAN PROGRAMMED DETECTION INTERVAL In most ICD patients, VT with cycle lengths greater than 400 to 450 msec are tolerated well, but repeated inappropriate therapies are not. SVT-VT discrimination algorithms, except those in Sorin models,71,134,152 deliver fewer inappropriate therapies if the VT detection interval is programmed to a shorter cycle length, simply because fewer SVTs are evaluated. However, slow VT can be catastrophic in patients with severe LV dysfunction or ischemia,153 and a long VT detection interval is important in some patients with advanced heart failure (Fig. 3-83). The VT detection interval should be increased if antiarrhythmic drug therapy is initiated, particularly with amiodarone or a sodium channel–blocking (type IA or IC) drug.15 It may be prudent to measure the cycle length of induced VT at electrophysiologic testing after initiation of drug therapy.154 However, spontaneous VT often is slower than induced VT.155 SVT-VT DISCRIMINATORS The SVT-VT discriminators may prevent or delay therapy if they misclassify VT or VF as SVT.114,116,119,156 Discriminators that reevaluate the rhythm diagnosis during an ongoing tachycardia (e.g., stability, most dual-chamber algorithms) reduce the risk of underdetection of VT compared with discriminators that withhold therapy if the rhythm is

not classified correctly by the initial evaluation (e.g., onset, chamber of origin algorithms). The minimum cycle length for SVT-VT discrimination should be set to prevent clinically significant delay in detection of hemodynamically unstable VT. PACEMAKER-ICD INTERACTIONS Interactions between ICDs and separate pacemakers have become rare since ICDs incorporated dual-chamber bradycardia pacing. Potential interactions have been reviewed.157-159 The principal interaction that may delay or prevent ICD therapy is oversensing of high-amplitude pacemaker stimulus artifacts. If this occurs during VF, repetitive autoadjustment of sensitivity may prevent detection of VF. INTRADEVICE INTERACTIONS In intradevice interactions, bradycardia pacing features of dualchamber ICDs may interact with and impair detection of VT or VF.54 During high-rate, atrial or dual-chamber pacing, sensing may be restricted to short periods of the cardiac cycle because of the combined effects of ventricular blanking after ventricular pacing and crosschamber ventricular blanking after atrial pacing, which is needed to avoid crosstalk. If a sufficient fraction of the cardiac cycle is blanked, systematic undersensing of VT or VF may occur. When pacing and blanking events occur at intervals that are multiples of a VT/VF cycle length, ventricular complexes are repeatedly undersensed, delaying or preventing detection52-54 (Fig. 3-84). Intradevice interactions have been reported most frequently with the use of the rate-smoothing algorithm.52-54 This algorithm is intended to prevent VT/VF initiated by sudden changes in ventricular rate.160 Rate smoothing prevents sudden changes in ventricular rate by pacing both the atrium and the ventricle at intervals based on the preceding (baseline) R-R interval. As an unintended consequence, it may prevent sensing of VT/VF in some patients, because rate smoothing introduces

112

SECTION 1  Basic Principles of Device Therapy

Atrial EGM RV Coil-Can

Interval (ms) 1800 VF Detected

1720

3 5 0

A P T S

6 8 0

VV SP

4 2 0

V S

F F F F F F S S S S S S 2 1 1 2 1 1 1 8 2 0 2 6 0 0 0 0 0 0

4 6 0

V S

2 1 0

1600

A P

1760 F S

7 2 0

VV SP

4 7 0

V S

1 7 0

F S

4 7 0

V F S S 1 3 0

4 6 0

V S

2 1 0

F S

1 8 0

F S

1 8 0

F S

2 3 0

F S

2 2 0

F S

F F F F V V S S S S S S 2 1 1 1 4 2 5 3 8 8 4 0 0 0 0 0 0 0 VF Rx 1 Defib

5 1 0

V S

4 6 0

V S

1400 1200 1000

3.7 minutes

800 600

TDI

400

FDI 200 0 600

400

0

200

Time Before VF Detection (Seconds)

VF Detected

Figure 3-83  Ventricular tachycardia (VT) slower than the programmed detection interval. The lower panel is a “Flashback Interval” plot of R-R interval cycle lengths before detection of ventricular fibrillation (VF), which occurs at the right side of each panel. The interval number before detection is plotted on the abscissa, and the corresponding interval is plotted on the ordinate. Horizontal lines indicate the VT detection interval (TDI) of 400 msec and the VF detection interval (FDI) of 320 msec. Shortly after the 500th interval preceding detection, regular tachycardia begins abruptly. The constant cycle length indicates reliable ventricular sensing. Atrial flashback intervals (not shown) demonstrated atrioventricular (AV) dissociation. This VT is not detected despite reliable sensing, because the cycle length is greater than the programmed TDI. VT persists for 3.7 minutes until approximately interval 280 before detection, when sensed intervals become highly variable. This indicates degeneration of the rhythm to VF with undersensing that delays detection. During VT and VF, atrial Flashback Intervals (not shown) indicated lower rate limit bradycardia pacing at 40 bpm (1500 msec). The upper panel shows stored atrial and far-field ventricular EGMs immediately before detection with atrial and ventricular channel showing event markers. Specific undersensed EGMs cannot be identified because the rate-sensing EGM was not recorded. However, long sensed R-R intervals ending with ventricular sense (VS) markers indicate undersensing and correspond to long intervals in the upper panel. VF Rx 1 Defib at lower right (arrow) denotes “VF detected.” AP, Atrial paced event; FD, VF detected; FS, intervals in VF zone. (From Swerdlow C, Friedman P: Advanced ICD troubleshooting. Part I. Pacing Clin Electrophysiol 28:1322-1346, 2005.)

repetitive postpacing blanking periods. The algorithm applies rate smoothing to baseline intervals independent of their cycle length, including intervals in the VT or VF zones. Intradevice interactions that result in delayed or absent detection of VT/VF are most common and most dangerous when VT is fast. The parameter interrelationships that result in delayed or absent detection of VT/VF are complex and difficult to predict, but usually elicit a programmer warning. Generally, aggressive rate smoothing (a small, allowable percentage change in RR intervals), a high upper pacing rate, and a long and fixed AV interval favor undersensing and should be avoided. If rate smoothing is required, the AV delay should be dynamic, the upper rates should be 125 bpm or less, and parameter combinations that result in warnings should be avoided. This programming reduces, but does not eliminate, the risk of undersensing.52-54

Detection of SVT/VT as Diagnostic Tool and Basis for Atrial Antitachycardia Pacemakers and Atrial ICDs Detection of SVT and VT provides diagnostics that are useful for pacemaker management.161 Atrial antitachycardia pacing and shocks provide a therapeutic option for some patients with paroxysmal atrial

tachycardia/flutter (AT) and atrial fibrillation (AF). Appropriate delivery of this therapy requires accurate detection and discrimination AT and AF independent of ventricular rate. PACEMAKER DIAGNOSTICS Monitoring for Ventricular Tachycardia Some pacemakers have ventricular high-rate diagnostics that trigger EGM and marker storage of nonpaced rhythms that are faster than a specific rate. Triggers based on ventricular rate alone store episodes that may be rapidly conducted SVT, ventricular oversensing, or VT. Studies of these diagnostics demonstrate the importance of stored EGMs to confirm the diagnosis, because the false-positive detection rate is high.162 Newer dual-chamber pacemakers and antitachycardia pacemakers incorporate tachyarrhythmia detection algorithms that are identical or substantially similar to those in dual-chamber ICDs (Fig. 3-85). The performance of these algorithms may be influenced by differences in pacemaker and ICD atrial sensing characteristics (fixed atrial sensitivity, automatically adjusting sensitivity, or intermediate case) and atrial blanking periods (Fig. 3-86). Even with accurate atrial sensing, Bayes theorem predicts that the fraction of false-positive VT detection in patients with pacemakers is large, because the incidence of true VT is low.



3  Sensing and Detection

Surface ECG Atrial EGM Vent EGM

PABP VBP

AS 1875 VS 935

VP 350

VS 350

VP 350

VP 350

AP 863 VF 283 VF 280

AS 970

VP 350

VP 350

VP 350

Surface ECG Atrial EGM Vent EGM

25-FEB-00 19:30

AP 268 VP 560

VP 570

PVC 448

VP 230

VF 308

VT 415

AP 875

AP 723

VF 305

VP 560

AP 863 VF 283

AP 863 VS 575

VF 283

VF 285

AP 1118

VF 280

VP 570

VF 278

AP 860

AP 260 VP 560

VF 298

VF 285

VP 570

AP 850 VP 560

AP 1135

AP 865

VF 288

VP 580

GUIDANT

VP 570

VF 280

Surface ECG Atrial EGM Vent EGM

25-FEB-00 19:30

VENTAK PRIZM

VS 575

VF 283

VP 270

VP 250

Surface ECG Atrial EGM Vent EGM

25-FEB-00 19:30

AP 1630 VP 350

AP 863

AP 863 VF 293

25 mm/s

VENTAK PRIZM

VP 560

VF 280

113

AP 870 VF 300

AP 855 VF 275

AP 853 VS 573

VF 278

AP 858

AP 260

VF 283

AP 560

VF 788

VP 570

External rescue

AP 878 VP 570

VP 580

VF 298

AP 880 VF 290

AP 8737 VS 583

VF 288

VF 293

AP 260 [VS]

VP 560

[AS] (AS) 733 VF 308

Figure 3-84  Failure to detect ventricular tachycardia (VT) caused by intradevice interaction. The rate-smoothing algorithm introduced atrial and ventricular pacing complexes with associated blanking periods that prevented detection of VT during postimplantation testing. An external rescue shock was required. Top to bottom, Surface electrocardiogram (ECG), atrial EGM, ventricular EGM, and event markers. At top, VT is induced by programmed electrical stimulation with a drive cycle length of 350 msec and premature stimuli at 270, 250, and 230 msec (intervals labeled next to event markers). The first sensed ventricular event occurs 448 msec after the pacing drive (PVC 448). The rate-smoothing algorithm drives pacing to prevent a pause after the premature ventricular complex (PVC), labeled AP↓ 1638. A ventricular paced event does not follow the first AP↓ because a ventricular event is sensed (VT 415). Subsequent rate smoothing generated atrial and ventricular pacing pulses (indicated by AP↓ and VP↓ markers, respectively). The resultant postpacing blanking periods are shown on the figure as horizontal bars. PABP denotes cross-chamber (postatrial pacing) ventricular blanking period. VBP denotes same-chamber (postventricular pacing) blanking period. Together, they prevent approximately four of every six VT complexes from being sensed. Because the VT counter must accumulate 8 of 10 consecutive complexes in the VT zone for detection of VT to occur, VT is not detected. (From Swerdlow C, Friedman P: Advanced ICD troubleshooting. Part II. Pacing Clin Electrophysiol 29:70-96, 2006.)

V-V

A-A

VTM=400 ms

Interval (ms)

Detection

1500 1200 900 600

Term. 9 sec

AEGM VEGM

400 A P

200

230

225

220

215

210

Time (sec)

25

0

5

V S

0

A R

1180 5 6 0

1020

V 3 V 4 V S 7 S 5 S 0 0

6 9 0

9 8 0

A S

A R

9 4 0

A R

9 6 0

A R

9 2 0

A R

8 9 0

A R

8 7 0

A R

EGM for

V 5 V 3 V 3 V 3 V 3 V3 V 3 V3 V 3 V 3 V 3 V 3 V 3V 3 V 3 V3 V 3 V S 0 S 8 S 9 S 7 S 8 S3 S 4 S5 S 4 S 6 S 6 S 7 S 4S 6 S 9 S3 S 6 T 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VTM

A V-V

A-A

VTM=400 ms

Interval (ms)

Detection

1500 1200 900 600

Term. 1.4 min

AEGM

0.5mV

VEGM

400 .2000

200 230

225

220

215

210

Time (sec)

25

0

5

0

V S

5 6 0

V S

5 1 0

A b

.2000

A b

EGM for 1

V V V V V V V V V V V V V V V V V V S 4 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 S 3 T 1 7 8 7 9 8 7 7 6 8 7 9 5 0 0 8 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VTM

B Figure 3-85  Pacemaker diagnostics for monitoring of ventricular tachycardia (VT), showing stored intervals, atrial electrogrm (AEGM), ventricular electrogram (VEGM), and markers from a patient with a Medtronic EnRhythm DR pacemaker. The left panels show the A-A and V-V intervals plotted against time before VT detection, which requires 16 consecutive intervals at less than the VT monitoring interval of 400 msec (horizontal line). The right panels show dual-chamber EGM and markers. A, Onset of spontaneous VT occurs with several premature ventricular complexes (PVCs) and sudden acceleration of ventricular rate with little or no change in A-A intervals (left panel). The VT cycle length is initially 340 msec and progressively lengthens to greater than 400 msec after several seconds. After 8 consecutive intervals of 400 msec or longer, the ICD declares the episode to be “terminated” despite clear atrioventricular (AV) dissociation and ongoing VT (right-hand side of interval plot). The duration of VT is reported as 9 seconds, representing the time that the RR intervals remained less than 400 msec after initial detection. Dual-chamber EGM and markers leading up to detection of VT indicate appropriate sensing in both chambers and AV dissociation (right panel). B, Rapidly conducted atrial fibrillation with severe atrial undersensing reported as VT. The interval plot shows fast and irregular R-R intervals and long A-A intervals (1500 msec), with sporadic A-A intervals shorter than 200 msec. Dual-chamber EGMs indicate appropriate ventricular sensing but severe atrial undersensing of small-amplitude atrial fibrillation, resulting in false-positive detection of VT. AB, Atrial sensed event in postventricular atrial blanking period; AR, atrial refractory sense; AS, atrial sensed event; VS, ventricular sensed event; VT, VT detected.

114

SECTION 1  Basic Principles of Device Therapy

False-positive VT/VF episodes (%)

100%

80%

Patients with AT/AF history and no VT/VF history

60%

40%

20%

Secondary prevention ICD patient population

0% Higher incidence of true VT/VF relative to SVT Figure 3-86  Rate of inappropriate ventricular tachycardia/fibrillation (VT/VF) detection depends on the patient population. Bayes theorem predicts that patients with a higher incidence of true VT/VF relative to supraventricular tachycardia (SVT) will have fewer inappropriate detections than patients with a lower incidence of VT/VF. The receiver operator curve shows the Bayes theorem prediction of detection performance of an algorithm with a fixed sensitivity and specificity. The curve plots percentage of false-positive detections of VT/VF on the ordinate and estimated incidence of true VT/VF on abscissa. Two data points are plotted from clinical studies of two different patient populations with implanted ICDs running the same VT/SVT discrimination algorithm (Medtronic GEM DR68 and AT500 ICDs* with PR Logic). (*Willems R, Morck ML, Exner DV, et al: Ventricular high-rate episode in pacemaker diagnostics identify a high-risk subgroup of patients with tachy-brady syndrome. Heart Rhythm 1:414421, 2004.)

Monitoring for Atrial Tachycardia and Atrial Fibrillation Traditional pacemaker diagnostics for atrial high-rate episodes and automatic mode switches have been validated as a means of monitoring AT/AF.163,164 Diagnostic accuracy of these methods depends on the specific detection algorithm used and the accuracy of atrial sensing. Mode-switching algorithms and their diagnostics have been used as a surrogate marker for AT/AF detection in patients with dual-chamber pacemakers.161,163 A Holter monitoring study of 40 patients with bipolar pacemakers demonstrated that mode-switching diagnostics appropriately identified 53 of 54 true AT/AF episodes (98.1%) with only one short (13-second) false mode-switching episode.163 Other studies have reviewed stored pacemaker EGMs and found high percentages of inappropriate mode switching caused by atrial oversensing.162,165 Most modern pacemakers and ICDs store atrial EGMs for mode-switching events; and important clinical decisions, such as starting anticoagulation, should be based on analysis of atrial EGMs rather than mode-switching events. Further, absence of mode-switching events is not equivalent to absence of AT/AF in pacemakers with long PVAB periods or low atrial sensitivity. The AT/AF detection algorithms in some pacemakers and ICDs provide substantial additional information, including atrial EGMs, classification of AT versus AF, and integrated displays of data from multiple episodes. These include histograms of episode duration and ventricular rate during AT/AF that may be of value in managing atrial antiarrhythmic drugs and AV nodal blocking drugs (Fig. 3-87). The former histogram, combined with patient-activated ICD interrogations, may permit discontinuation of anticoagulation in some patients. A prospective study of 2486 patients with one or more stroke risk factors and an implantable pacemaker or ICD with continuous AT/AF monitoring evaluated the risk of thromboembolic events as a function of AT/AF burden (hours of AT/AF per day). More than 5.5 hours of AT/AF on any day doubled a patient’s risk of stroke.166 Other studies have demonstrated similar increased risk associated with monitored AT/AF episodes.166,167 Computer modeling predicts that home monitoring of patients with automatic ICD-generated alerts for detected AT/AF may reduce the risk of stroke.168 A multicenter randomized trial is designed to test the hypothesis that initiation and withdrawal of oral anticoagulation therapy guided by continuous AT/

AF monitoring reduces the risk of stroke, embolism and major bleeding compared with conventional management.169 DETECTION OF ATRIAL TACHYCARDIA AND ATRIAL FIBRILLATION Principles Bradycardia pacemakers must detect AT/AF rapidly so that mode switching will avoid uncomfortable pacing at the upper rate limit. To determine the atrial rate and rhythm accurately, atrial blanking must be minimized. As long as the atrial rate exceeds the upper tracking limit, accurate determination of atrial rate and rhythm is not important. Ventricular ICDs must discriminate VT from rapidly conducted AF quickly, to permit rapid detection of hemodynamically compromising VT. Discrimination of AT versus AF is less important. In contrast, atrial antiarrhythmic pacemakers and ICDs must detect AF with high specificity to minimize painful and potentially proarrhythmic therapy. Rapid detection is not important, because AF usually is clinically stable and may terminate spontaneously after hours to days. Therefore, atrial antiarrhythmic ICDs should be capable of permitting therapy for long-duration AT/AF while withholding therapy from self-terminating AT/AF. To achieve this goal, they must be capable of detecting AF continuously for extended periods, to discriminate between repetitive self-terminating episodes and persistent episodes. Because atrial EGMs in AF have low and variable amplitudes and slew rates, antiarrhythmic ICDs must have high (automatically adjusting) atrial sensitivity and apply algorithms that are tolerant of some atrial undersensing. They must also discriminate between AT and AF to deliver ATP for AT. Detection of AT/AF for Atrial Therapy High specificity in AT/AF detection has been achieved by multistep methods for detection of AT/AF. Initial detection is based on the presence of an atrial tachyarrhythmia and absence of VT. This is achieved by a measure of atrial rate combined with either comparison of atrial and ventricular rates (Boston Scientific)170 or use of A-V patterns to identify N:1 rhythms (Medtronic) (Fig. 3-88). The trade-off between atrial undersensing and oversensing of FFRWs that applies to dualchamber ICD algorithms is even more important when considering



115

3  Sensing and Detection VENTRICULAR RESPONSE (IN AF)

Long-term trends May 00

Jul 00

Program/interrogate

Sep 00

Nov 00

P

Drug change

Jan 01

Mar 01

P

# beats

May 01 I

Sotalol

CV/ablation/other AT/AF patient check AT/AF total hrs/day

AT/AF episodes/day

24 20 16 12 8 4 0 .25 20 15 10 5 0

ATP change

% ATP success

.25 20 15 10 5 0

% Pacing/day

(0%)

80-100 bpm

3

(0%)

100-120 bpm

124

(4%)

120-140 bpm

175

(6%)

140-160 bpm

344

(12%)

160-180 bpm

912

(33%)

180-200 bpm

880

(32%)

>200

319

(12%)

100

100 75 50 25 0

ATP ON 80

Antici-Pace Change % Pacing/day — A.total — A. ARS/APP

0

DATA - AT/AF EPISODE DURATION HISTOGRAM

Episodes (%)

Treated AT/AF episodes/day

<80 bpm

100 75 50 25 0 100 75 50 25 0

60 40 20 0 < 1 min 10 min 1 hr 4 hr 12 hr 24 hr 72 hr

May 00

Jul 00

Sep 00

Nov 00

Jan 01

Mar 01

May 01

>

Episode duration

Figure 3-87  Diagnostic data stored in atrial antiarrhythmic pacemakers and ICDs assist medical management of atrial arrhythmias. Data are taken from three patients with Medtronic AT500 pacemakers. Left panels, Long-term trend data over 1 year. Panels from top to bottom show total hours per day in atrial tachycardia/flutter (AT) or atrial fibrillation (AF), total AT/AF ICD-detected episodes per day, number of daily episodes treated by antitachycardia pacing (ATP), percentage of ATP therapies classified as “successful” by the ICD, percent atrial pacing, and percent ventricular pacing. ATP ON denotes activation of atrial ATP. Note that, although the many episodes of AT/AF are treated and this treatment is usually classified as successful, there is no detectable change in the number of hours per day of AT/AF until sotalol therapy is initiated. Sotalol decreases the total hourly “burden” of AT/AF more by shortening episodes rather than by preventing them. Percent ventricular pacing is high throughout but increases after sotalol treatment to almost 100%. Top right panel, Ventricular rate during AT/AF as percentage of time spent in AT/ AF; 77% of intervals are shorter than intervals corresponding to 160 bpm, and 12% are shorter than intervals corresponding to 200 bpm, indicating inadequate control of ventricular rate. Lower right panel, Histogram of durations of AT/AF episodes since the last follow-up visit. This patient had 10 episodes of AF since the last visit, but only one episode lasted longer than 10 minutes.

detection of AT/AF for atrial therapy. Minimization of atrial blanking is important to prevent undersensing of AF, and rejection of FFRWs is important to prevent inappropriate detection of AT/AF (see earlier Atrial Sensing in Dual-Chamber ICDs and Atrial ICDs). Once initial detection occurs, the episode timer begins, initiating a sustained-detection mode in which AT/AF remains detected despite a moderate degree of undersensing (Fig. 3-89). When this timer expires, atrial therapy is delivered if AT/AF still persists (Fig. 3-90). Atrial episodes must be interrupted if true VT occurs. The final step in detection is discrimination of AT from AF or, alternatively, determining whether the rhythm is likely to respond to atrial ATP. As shown in Figure 3-88, Medtronic atrial ICDs track dynamic changes in atrial tachyarrhythmia (e.g., transitions between AT and AF) based on the median rate and regularity of the atrial rhythm. Boston Scientific atrial ICDs use a more complex algorithm based on maximum rate, standard deviation, and range of the 12 most recent atrial cycle lengths to plot a point in a three-dimensional space. A decision boundary divides the space into two regions: faster/irregular

atrial cycle lengths (AF) and slower/regular cycle lengths (AT). Classifications are made on a sliding window of 12 consecutive cycles until the end of the episode is reached.170,171 Typically, there may be one timer for ATP and one for shock therapy. In newer Medtronic ICDs, the “reactive antitachycardia pacing” algorithm resets the ATP timer to permit repeat attempts at ATP if changes in atrial rate or atrial rhythm regularity are detected, or after a preprogrammed duration of sustained AT/AF. Changes in rate or regularity of the atrial rhythm are classified as a shift to a new rhythm, which may be more susceptible to ATP termination (Fig. 3-91). Detection Considerations for Atrial Shocks In addition to permitting therapy after hours of continuous AF, atrial ICDs may withhold therapy if the episode duration is sufficiently long that patients may be at risk for thromboembolism if they are not adequately anticoagulated, typically 24 hours. R-wave-synchronized atrial shock therapy is restricted to R-R intervals greater than 400 to 500 msec. This minimizes the risk that a therapeutic atrial shock can

116

SECTION 1  Basic Principles of Device Therapy

Median P-P interval

Auto discrimination zone

AF detection zone

Atrial blanking (100 mS)

AFDI: 280 mS AFDI: 320 mS

ATDImin: 180 mS AT detection zone

AF/AT evidence counter

Atrial fibrillation

P R

A

B

D Count: +1 Count: 28

+1 29

+1 30

A=A range

−1 29

+1 30

+1 31

+1 32

SD

Figure 3-88  Criteria for detection of atrial tachyarrhythmias. A, Medtronic atrial therapy ICDs (Jewel AF, GEM III AT, AT500, and EnRhythm DR) use a combination of atrial cycle length and atrial/ventricular (A : V) patterns to detect atrial fibrillation and atrial flutter. The atrial tachycardia (AT) and atrial fibrillation (AF) detection zones are based on median atrial cycle length (12 P-P intervals) and may overlap. The overlap region is the “autodiscrimination” zone, where regularity of the PP intervals determines whether rhythm classification is AT (regular P-P intervals) or AF (irregular P-P intervals). Detection of AT or AF requires that (1) the median P-P interval is in one of the detection zones and (2) the rhythm is N:1 as determined by the AF/AT evidence counter. The AF/AT evidence counter is an up-down counter (minimum value, 0; maximum value of detection threshold, +15). The counter increments by 1 on each ventricular event if there are two or more atrial events and there is no pattern-based evidence of far-field R-wave oversensing on the atrial channel (see Fig. 3-25, A), and it decrements by 1 if there is strong evidence of lack of N:1 rhythm (e.g., two consecutive 1 : 1 beats). Isolated 1 : 1 beats contribute AF/AT evidence if they are preceded by a confirmed N:1 beat. The AF/AT counter detection threshold is between 24 and 32, depending on the specific ICD. AFDI, Atrial fibrillation detection interval; mS, milliseconds. B, Atrial Rhythm Classification (ARC) algorithm (Boston Scientific) discriminates AF from atrial flutter (AFL) based on the atrial rate and two measurements of variability of atrial rate: the range of the atrial intervals (i.e., the difference between the longest and shortest A-A intervals [A-A range]) and the standard deviation of A-A intervals (SD). The values of these three variables define a point in a three-dimensional space. A curved surface separates the AF region from the AFL region. Points in the AF region have higher atrial rates, a higher range of A-A intervals, and a greater standard deviation of A-A intervals. (From Morris MM, KenKnight BH, Lang DJ: Detection of atrial arrhythmia for cardiac rhythm management by implantable ICDs. J Electrocardiol 33(Suppl):133-139, 2000.)

be delivered into the vulnerable period of the preceding cardiac cycle, but it may prevent shock therapy for rapidly conducted AF. Early or immediate recurrence of AF after shock is an important clinical problem in patients with atrial ICDs. Early recurrence of AF before postshock redetection of sinus rhythm will result in incorrect classification of shock success (Fig. 3-92).

Sensing and Detection Using the Subcutaneous Electrocardiogram IMPLANTABLE SUBCUTANEOUS MONITORING Implantable loop recorders (ILRs) offer patient-activated recordings of subcutaneous ECGs as well as arrhythmia detection algorithms to automatically trigger storage for asystole, bradycardia/tachycardia, and AF. Two sensing electrodes are built into the ILR shell and record a single-lead bipolar ECG that is retrieved with a programmer or remote-monitoring ICD. ECG signals are stored in a circular buffer. Multiple, automatically triggered events may be stored. The memory buffer may also be activated by a hand-held system to record the ECG preceding and following activation. Automated triggers for storage of arrhythmic events in ILRs require robust R-wave sensing and detection algorithms based on RR intervals. The amplitude of R waves recorded by an ILR averages about 0.3 mV, versus 1 to 2 mV recorded in the precordial leads of a surface ECG.

Unlike EGMs, the amplitude of subcutaneous ECGs increases over time to about 0.35 mV at 4 to 6 months, then remains stable.172 R-wave sensing in an ILR uses the same principles as shown in Figure 3-13 with band-pass filtering tuned for lower frequencies and either fixed or auto-adjusting sensitivity. Sensing problems were common with early models that used a fixed sensing threshold, including undersensing caused by abrupt, unexplained decreases in R-wave amplitude and ICD amplifier saturation, as well as oversensing of T waves, myopotentials, and other sources of noise.173-175 Sensing enhancements such as better noise rejection and auto-adjusting threshold reduce both false-positive triggers caused by oversensing and problems related to undersensing.176 Figures 3-93 and 3-94 show examples of rhythms recorded by ILRs. Monitoring of AF burden has been a recent addition to the Medtronic Reveal XT ILRs. The algorithm detects the irregularly irregular ventricular response to conducted AF by analyzing the difference between the present and previous R-R intervals (δRR). Pattern analysis is performed using Lorenz plots, or scatter plots of δRR(i) vs. δRR(i-1) over a duration of 2 minutes.177 The algorithm can distinguish patterns associated with AF and regular AT from sinus rhythm, as shown in Figure 3-95. This algorithm was shown to have sensitivity of 96.1% and specificity of 85.4% for identifying patients with or without AF in a study of 247 patients using Holter ECGs as a “gold standard.”178 AF burden as measured by this algorithm was highly correlated with the Holter standard.



3  Sensing and Detection 13:26:26-1

117

AF - - MS delta

ECG

AEGM

AP

AP

AR FS FS FS FS FS

FS FS FS FS FS FS FS FS FD FD FD

Marker VP PP Median Atrial Evidence

VP 750 0

VS 750 1

VP 750 2

VS 200 30

VP 200 31

VP 210

VP 210 *A

A

ECG

AEGM 1 sec Marker

FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD FD VS VS PP Median Atrial Evidence

VS 170

VS 170

VP 170

VS 180 *A

FD FDFDFD FD FDFD FD FD FD FD VP 170

VS 170

VS 170

VS 170 *A

B Figure 3-89  Holter recording illustrates continuous detection of atrial fibrillation (AF). A, Onset of AF and initial detection of AF after 32 ventricular events (arrow). Double atrial markers (FS) change to triple markers (FD), and the symbol *A appears on the atrial evidence channel to indicate AF episode in progress. B, Rhythms after 5 hours of continuous recording. AP, Atrial paced event; VP, ventricular paced event; VS, sensed R wave. (From Swerdlow CD, Schsls W, Dijkman B, et al: Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverterdefibrillator. For the Worldwide Jewel AF Investigators. Circulation 101:878-885.)

SUBCUTANEOUS ICDS Investigational subcutaneous ICD (S-ICD) systems, with no transvenous or epicardial leads, are undergoing clinical trials. They rely on subcutaneous ECGs for sensing and detection of VF. The present S-ICD (Cameron Health) uses a 69-cc pulse generator placed in the left midaxillary line over the lower thorax. A single subcutaneous lead is tunneled medially to the left parasternal position and then superiorly along the sternum. It includes two widely spaced sensing electrodes and a defibrillation coil (Fig. 3-96). Sensing The S-ICD automatically selects the best sensing vector based on QRS amplitude and signal-to-noise ratio from among three choices: (1) proximal electrode ring on the lead to the active surface of the pulse generator, (2) distal electrode ring on the lead to the pulse generator, or (3) distal ring to proximal ring. The S-ICD automatically selects one of two amplifier gains (±2 mV unless QRS amplitude is clipped at this setting; otherwise, ±4 mV) and the sensing vector least likely to oversense T waves (Fig. 3-97; see also Fig. 3-96). As in ICDs with intracardiac leads, the S-ICD uses automatic adjustment of sensitivity. Sensitivity increases when rapid rates are detected. In addition to this event detection phase of sensing, the S-ICD has a certification phase that examines sensed events and classifies them as certified QRS complexes or as suspect events. This ensures that accurate ventricular rate is passed to the detection algorithm. An event is

classified as “suspect” if its pattern or timing suggests oversensing, according to specific oversensing rules intended to reject myopotentials, R-wave double-counting, and T-wave oversensing. Sensing and Tachyarrhythmia Detection The detection algorithm (decision phase) examines all certified events and calculates a continuous, running, “four R-to-R interval average” (4 RR average), which is used as a measure of ventricular rate. Rate-based therapy zones include a mandatory rate-only VF (“shock”) zone and an optional VT (“conditional”) zone. In the VT zone the S-ICD uses stable QRS morphology and QRS width to discriminate VT from SVT, as well as varying QRS morphology to identify polymorphic VT. The “START” study compared SVT-VT discrimination using tachyarrhythmias recorded at ICD or S-ICD implant.124 The S-ICD detection algorithm had equivalent sensitivity for VT to the best ICD algorithm (100%), and insignificantly better specificity for rejection of SVT (100% vs. 92%). The S-ICD detection process begins when the “4 RR average” enters either therapy zone. VT or VF detection is a two-step process. The initial detection step uses X of Y counting (18/24 for the first therapy), and the “persistence” step requires that the X of Y criterion remain fulfilled for additional consecutive intervals (nominally two, but automatically increased if shocks are aborted). Capacitor charging begins if persistence is met and if the last two certified sensed events are in a therapy zone. Shock confirmation, redetection, and episode termination function similar to these features in ICDs with intracardiac leads.

118

SECTION 1  Basic Principles of Device Therapy

Onset

Detection 12 sec

First Rx

Termination 19 sec

1 min

Marker 5 0 0

P P

2 1 1 1 1 1 1 1 1 7 9 8 9 9 8 9 7 9 A 0 T 0 T0 T 0 T0 T 0 T0 T0F0 T R S F F F F F F S F

V P

220

210

0

230

220

Time (sec)

210

V S

4 4 0

0

V S

4 1 0

T S

3 5 0

T S

3 7 0

3 5 0

T S

2 8 0

3 7 0

Onset

Atip-Vring EGM

Marker

1 2 1 1 1 1 1 1 1 2 2 1 1 2 1 1 2 1 2 1 1 1 1 1 1 2 2 2 8 1 9 9 9 9 9 8 7 1 0 9 9 0 9 9 0 9 0 8 7 6 5 5 5 6 2 2 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 T 0 A 0 A 0 A 0 A 0 A0 A 0 A 0 T 0 T 0 T D D D D D D D D D D D D D D D D D D D S P P P P P P S F F V S

4 4 0

6 0 0

V P

V S

4 4 0

V S

5 5 0

V P

6 2 0

V S

6 2 0

V S

4 8 0

V S

4 4 0

V S

4 3 0

First Rx

V S

4 1 0

3 4 0

V S

4 9 0

6 7 0

A P V P

6 0 0

6 6 0

A P 5 9 0

A P

V S

V P

7 4 0

Figure 3-90  Atrial tachycardia (AT) detection and therapy after 1 minute of sustained detection. Spontaneous episode of AT from an atrial therapy ICD. Upper left panel, P-P intervals (open squares) and R-R intervals (closed circles) for this episode. Onset of the AT episode is labeled on the interval plot and on the stored marker channel (top right). The interval plot also labels the initial detection of AT (Detection), delivery of the first therapy (First ATP Rx), and ICD recognition of episode termination (Termination). In this case, therapies were programmed to begin 1 minute after initial detection. Top right panel, Dual-chamber EGM markers preceding detection of AT. Dots indicate discontinuous recording between top and bottom panels. Bottom panel, Composite EGM recorded between the atrial tip electrode (Atip) and the ventricular ring electrode (Vring) and dualchamber EGM markers immediately preceding delivery of successful antitachycardia pacing (First Rx, fast AP events). TS, FS, and TF events refer to atrial intervals in the AT, atrial fibrillation (AF), and overlap zones, respectively. TD (atrial marker), Atrial tachycardia detected; VP, ventricular paced event; VS, ventricular sensed event.

2 2 0

T D

2 1 0

T D

V S

2 1 0

T D

2 1 0

T D

2 1 0

2 1 0

T D

T D

V S

8 1 0

2 3 0

T D

2 4 0

2 5 0

T D

T D

2 4 0

V S

9 4 0

T D

2 3 0

T D

2 2 0

T D

2 1 0

T D

V S

7 9 0

2 1 0

T D

2 2 0

T D

2 2 0

V S

6 6 0

T D

2 2 0

T D

6 8 0

Successful atrial ATP 3 7 0

T S V S

3 7 0

T S

7 5 0

3 7 0

T S V S

3 7 0

T S

7 6 0

3 7 0

T S V S

3 7 0

T S

7 7 0

3 7 0

A S V S

3 4 0

A P

7 8 0

3 3 0

A P V S

3 2 0

A P

3 1 0

7 4 0

A P

3 0 0

V S

A P

2 9 0

A P

7 5 0

2 8 0

A P V S

2 7 0

A P

2 6 0

6 7 0

A P

2 5 0

V S

A P

1 0 0

6 3 0

1373

A S V S

6 0 0

V S

1 0 0

A P

9 0 0

V P

1 0 0

A P

9 8 0

V P

Figure 3-91  Example of successfully terminated atrial tachycardia/fibrillation (AT/AF). Top panel, Atrial EGM and marker diagram from AT/ AF episode (median atrial interval, 220 msec) that was initially detected and treated unsuccessfully with antitachycardia therapy (ATP). Bottom panel, After 2.1 hours, the atrial rate slowed, and the reactive ATP algorithm recognized the presence of a slower, regular AT/AF rhythm with a median atrial interval of 370 msec. Atrial ATP was delivered and successfully terminated the AT/AF. AP, atrial paced event; TD, AT/AF detected; TS, AT/AF sensed event; VP, ventricular paced event; VS, ventricular sensed event. (From Mainardi L, Sornmo L, Cerutti S: Understanding atrial fibrillation: the signal processing contribution, San Rafael, Calif, 2008, Morgan & Claypool.)



3  Sensing and Detection

119

Lead II

Shock

Atip-Aring

ERAF

Markers A A A A AAA R R S R S RS

V S

V S

V C V S E S

A A A AC S S S SD

V R

A S

A S

V P

V S

A S

V S

A A A R R R

V S

V S

A A A A A A AAAA A AA R R RS R RSRSR S RR

V S

V S

V S

V P

V S

V S

V P

Figure 3-92  Postshock early recurrence of atrial fibrillation (ERAF) recorded at implantation occurs three RR intervals after shock. Because the ICD requires five consecutive postshock beats of sinus or atrial paced rhythm to detect termination of atrial fibrillation (AF) and store intervals, no data were stored for this clinically unsuccessful shock. Lead II of the surface electrocardiogram, the atrial EGM, and the atrial and ventricular channels with event markers are shown. AR, Atrial refractory event; AS, atrial sensed event; CD, charge delivered; CE, charge end; VP, ventricular paced event, VS, ventricular sensed event. (From Swerdlow CD, Schwartzman D, Hoyt R, et al: Determinants of first-shock success for atrial implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 13:347-354, 2002.)

11:32:07

11:32:20

11:32:33

11:32:46

11:32:59

Figure 3-93  Stored EGM recorded by an implantable loop recorder (Reveal, Medtronic) shows about 45 seconds of asystole, some myopotentials, perhaps one depolarization in the middle of the asystole, very small deflections throughout that are probably P waves, and relative bradycardia on the bottom panel. The amplitude of the subcutaneous electrocardiogram is approximately 0.25 mV.

120

SECTION 1  Basic Principles of Device Therapy

12:22:47 P

12:23:00

230 bpm (260 msec) Figure 3-94  Stored EGM recorded by an implantable loop recorder (Reveal, Medtronic) shows nonsustained tachycardia at about 230 bpm with duration of 8 seconds. The underlying rhythm is reset by the high-rate segment. The patient did activate this stored strip, as indicated by the dark triangle and the “P” marker.

RR 670 435 900 520 800 1030 700 675 760 650 515 625 925 δRR

−235 525 −440 280 250 −350 −25 85 −110 −135 110 300

1

2

3 4 5 6 7 δRR(i-1) (msec)

8

9

10

11

2 4

5 8

11

7

9

10 6

A

δRR(i) (msec)

3

1

B Figure 3-95  Algorithm for detection of atrial fibrillation (AF) by implantable loop recorder based on pattern of R-R intervals. A, Illustration showing how R-R intervals derived from a short strip of subcutaneous ECG during AF populate the numerical equivalent of a Lorenz plot of ΔRR intervals. Each point in the Lorenz plot is derived from four R waves that provide three R-R intervals and thus a [δRR(i), δRR(i-1)] value. The markers near the top of each R wave indicate the time at which each R wave is sensed. The magnitude of the vector from the origin of the Lorenz plot to each point encodes the irregularity, and the magnitude coupled with phase encodes the incoherence, of changes in R-R intervals. B, ECG tracings (2-minute duration) of AF (top panel), two examples of atrial flutter (middle and bottom panels), and the corresponding patterns they map to in a Lorenz plot of δRR intervals (right-hand side of each tracing). Note that a collection of δRR intervals on the Lorentz plot during atrial fibrillation/ flutter results in characteristic signatures, including the clustering of points for periods of regularity. These signatures form the basis for the detection/ discrimination algorithm.



3  Sensing and Detection

QRS: T wave: Ratio:

QRS: T wave: Ratio:

1.6 mV 0.4 mV 4

QRS: T wave: Ratio:

0.9 mV 0.1 mV 9

121

1.6 mV 1.0 mV 1.6

Figure 3-96  Electrode system for subcutaneous ICD (S-ICD).

Future Directions: Hemodynamic Sensors for ICDs Current ICDs do not differentiate directly between hemodynamically stable and unstable tachycardias. Morbidity associated with unnecessary shocks for hemodynamically stable VT and repetitive shocks caused by SVT may be reduced using implantable hemodynamic sensors integrated in the therapy decision process. Mixed-venous oxygen saturation, right atrial pressure, RV pressure, subcutaneous photoplethysmography, endocardial accelerometers, and cardiac impedance sensors have been proposed as methods of discriminating hemodynamically stable from unstable tachycardias.57,179-183 Subcutaneous photoplethysmography has been tested in acute and chronic animal models as well as acute human studies. There is a good

correlation between mean arterial pressure and photoplethysmography pulse amplitude; discriminating perfusing (stable) from nonperfusing (unstable) tachycardias is feasible169,184 (Fig. 3-98). An implantable system for ambulatory hemodynamic monitoring using RV pressure has been studied in clinical trials.185 A recent clinical trial studied an ICD with the capability of recording RV pressure waveforms during tachycardias detected using “rate + interval” analysis. Episodes of recorded spontaneous VT-VF demonstrate substantial changes in RV pressure waveforms (Fig. 3-99). Although this clinical trial was terminated because of an unacceptable failure rate of the pressure sensor, it provided valuable data to assist in developing metrics that discriminate hemodynamically stable versus hemodynamically unstable tachyarrhythmias for integration into ICD algorithms.186

Amp mV1

3 0

3 0

0.05

0.1

0.35

0.4

0.15 Time

0.2

0.25

0.3

Amp mV2

3 0

3 0.3

0.45 0.5 0.55 0.6 Time Figure 3-97  Automatic selection of best sensing vector for subcutaneous ICD (S-ICD). The potential sensing vectors for S-ICD are shown. The S-ICD uses the ratio of R-wave amplitude to T-wave amplitude to choose the optimal sensing vector.

122

SECTION 1  Basic Principles of Device Therapy

O2 index

Pressure (mm Hg)

ECG (mV)

1 0.5

LED

0

Photodiode

–0.5 200

LED

150 100 50 0 0.02 0 –0.02 –0.04

O2 index

Pressure (mm Hg)

ECG (mV)

0

5

10

15 Time (sec)

25

20

1.5 1 0.5 0 –0.5 –1 –1.5 200 150 100 50 0 0.02 0 –0.02 –0.04 0

2

4

6

8

10 12 Time (sec)

14

16

18

20

Figure 3-98  Recordings from investigational sensor during electrophysiology laboratory testing. The sensor is mounted on the housing of an ICD emulator placed in the pocket during implant testing. Inset shows light-emitting diodes (LED) and light-receiving photodiode on housing of ICD emulator. Each panel shows surface ECG (upper tracing), arterial pressure (middle tracing), and photoplethysmographic oxygen (O2) index of tissue perfusion (lower tracing). The first panel shows the onset of atrial pacing at cycle length 400 msec. The arterial pressure remains stable, and the O2 index retains its phasic component with a mean value near the baseline-normalized value of zero. The second panel shows the onset of VF induced by 50-Hz current. With the onset of 50-Hz stimulation, the arterial pressure drops abruptly, and the O2 index loses its phasic component. About 2 seconds later, the O2 index begins a steep, monotonic decline. (Modified from Kroll MW, Swerdlow CD: The future of the implantable defibrillator. In Efimov I, Kroll M, Tchou P, editors: Cardiac bioelectric therapy: mechanisms and practical implications, Berlin, 2008, Springer Verlag.)



3  Sensing and Detection

123

RV pressure (mm Hg)

100

A

80 VS

60

563

VS

578

VS

578

VS

563

VS

VS

578

563

VS VS TS TF TF TS TF TF TS TF TF TF TF TF TF TF TF TF TF TF T 438 328 313 297 344 313 313 344 297 313 313 297 297 297 297 297 313 297 297 313

40 20 0

VT no syncope

RV pressure (mm Hg)

100

B

80 60

VS

625

VS

703

VS

625

VS

703

VS

750

VS

VS VS

719

484

516

VS TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TFT

297 266 266 266 266 250 266 250250 266 250 266250250 250 266234 250 250

40 20 0

VT syncope

RV pressure (mm Hg)

100

C

80 VS VS VS VS VS TF VS VS VS VS VS VSTF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TF TFTPTP TPTP 60 VS 375 375 391 375 375 250 469 391 375 391 375 375 266 250 266 250 266266 266 266 250 266266266 201 266 266 266 266 234 219 234 234

40 20 0

Rapidly-conducted AF 0

1

2

3

4

5

6

7

8

9

10

Figure 3-99  Stored EGM and pressure tracing from investigational ICD with hemodynamic sensor (Medtronic Chronicle ICD). In each panel, the upper tracing shows the shock electrogram recorded between right ventricular (RV) coil and left pectoral ICD housing. The marker channel below it shows interval classification and interval duration in milliseconds. The lower tracing shows RV pressure recorded from the implanted hemodynamic sensor in mm Hg. Horizontal axis shows time in seconds. Intervals are labeled VS (sinus zone), TS (VT zone), and TF (fast VT zone). A, Onset of VT at cycle length 300 msec. The patient was asymptomatic prior to antitachycardia pacing. RV systolic pressure falls by less than half. B, Onset of VT at cycle length 250 msec. The patient presented with syncope. RV systolic pressure drops abruptly and remains below a third of the baseline value. C, Rapidly conducted atrial fibrillation at cycle length 260 msec. Inappropriate antitachycardia pacing (TP markers) occurs for the last four beats. There is only a slight reduction in RV systolic pressure at shorter cycle lengths. The patient had no alteration of consciousness. (Tracings courtesy Dr. Michael Sweeney. From Kroll MW, Swerdlow CD: The future of the implantable defibrillator. In Efimov I, Kroll M, Tchou P, editors: Cardiac bioelectric therapy: mechanisms and practical implications, Berlin, 2008, Springer Verlag.)

REFERENCES 1. Parsonnet V, Myers GH, Kresh YM: Characteristics of intracardiac electrograms. II. Atrial endocardial electrograms. Pacing Clin Electrophysiol 3:406-417, 1980. 2. Saxonhouse SJ, Conti JB, Curtis AB: Current of injury predicts adequate active lead fixation in permanent pacemaker/ defibrillation leads. J Am Coll Cardiol 45:412-417, 2005. 3. Sweeney MO, Ellison KE, Shea JB, Newell JB: Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 12:402-410, 2001. 4. Weretka S, Michaelsen J, Becker R, et al: Ventricular oversensing: a study of 101 patients implanted with dual chamber defibrillators and two different lead systems. Pacing Clin Electrophysiol 26:65-70, 2003. 5. Cao J, Koyrakh L, Gillberg J, et al: A new automatic electrogram template updating algorithm: enhancing VT/SVT discrimination in ICDs. Pacing Clin Electrophysiol 24:706, 2001. 6. Platia EV, Brinker JA: Time course of transvenous pacemaker stimulation impedance, capture threshold, and electrogram amplitude. Pacing Clin Electrophysiol 9:620-625, 1986.

7. DeCaprio V, Hurzeler P, Furman S: A comparison of unipolar and bipolar electrograms for cardiac pacemaker sensing. Circulation 56:750-755, 1977. 8. Cornacchia D, Jacopi F, Fabbri M, Finzi C: [Comparison between active screw type and passive electrodes in permanent intraventricular pacing]. Minerva Cardioangiol 32:101-103, 1984. 9. Ceviz N, Celiker A, Kucukosmanoglu O, et al: Comparison of mid-term clinical experience with steroid-eluting active and passive fixation ventricular electrodes in children. Pacing Clin Electrophysiol 23:1245-1249, 2000. 10. Danilovic D, Ohm OJ: Pacing impedance variability in tined steroid eluting leads. Pacing Clin Electrophysiol 21:1356-1363, 1998. 11. Hua W, Mond HG, Strathmore N: Chronic steroid-eluting lead performance: a comparison of atrial and ventricular pacing. Pacing Clin Electrophysiol 20:17-24, 1997. 12. Crossley GH, Brinker JA, Reynolds D, et al: Steroid elution improves the stimulation threshold in an active-fixation atrial permanent pacing lead: a randomized, controlled study. Model 4068 Investigators. Circulation 92:2935-2939, 1995.

13. Wish M, Swartz J, Cohen A, et al: Steroid-tipped leads versus porous platinum permanent pacemaker leads: a controlled study. Pacing Clin Electrophysiol 13:1887-1890, 1990. 14. Ellenbogen KA, Wood MA, Gilligan DM: Evaluation of “inappropriate” ICD shocks in an asymptomatic patient following myocardial infarction. Pacing Clin Electrophysiol 19:254-255, 1996. 15. Goldschlager N, Epstein A, Friedman P, et al: Environmental and drug effects on patients with pacemakers and implantable cardioverter/defibrillators: a practical guide to patient treatment. Arch Intern Med 161:649-655, 2001. 16. Rajawat YS, Patel VV, Gerstenfeld EP, et al: Advantages and pitfalls of combining device-based and pharmacologic therapies for the treatment of ventricular arrhythmias: observations from a tertiary referral center. Pacing Clin Electrophysiol 27:1670-1681, 2004. 17. Theres H, Stadler RW, Stylos L, et al: Comparison of electrocardiogram and intrathoracic electrogram signals for detection of ischemic ST segment changes during normal sinus and ventricular paced rhythms. J Cardiovasc Electrophysiol 13:990-995, 2002.

124

SECTION 1  Basic Principles of Device Therapy

18. Centurion OA, Isomoto S, Shimizu A, et al: The effects of aging on atrial endocardial electrograms in patients with paroxysmal atrial fibrillation. Clin Cardiol 26:435-438, 2003. 19. Frohlig G, Schwerdt H, Schieffer H, Bette L: Atrial signal variations and pacemaker malsensing during exercise: a study in the time and frequency domain. J Am Coll Cardiol 11:806-813, 1988. 20. Ross BA, Zeigler V, Zinner A, et al: The effect of exercise on the atrial electrogram voltage in young patients. Pacing Clin Electrophysiol 14:2092-2097, 1991. 21. Schuchert A, Kuck KH, Bleifeld W: Stability of pacing threshold, impedance, and R wave amplitude at rest and during exercise. Pacing Clin Electrophysiol 13:1602-1608, 1990. 22. Shandling AH, Florio J, Castellanet MJ, et al: Physical determinants of the endocardial P wave. Pacing Clin Electrophysiol 13:1585-1589, 1990. 23. Rosenheck S, Schmaltz S, Kadish AH, Morady F: Effect of rate augmentation and isoproterenol on the amplitude of atrial and ventricular electrograms. Am J Cardiol 66:101-102, 1990. 24. Varriale P, Chryssos BE: Atrial sensing performance of the single-lead VDD pacemaker during exercise. J Am Coll Cardiol 22:1854-1857, 1993. 25. Chan CC, Lau CP, Leung SK, et al: Comparative evaluation of bipolar atrial electrogram amplitude during everyday activities: atrial active fixation versus two types of single pass VDD/R leads. Pacing Clin Electrophysiol 17:1873-1877, 1994. 26. Furman S, Hurzeler P, De Caprio V: Cardiac pacing and pacemaker. III. Sensing the cardiac electrogram. Am Heart J 93:794801, 1977. 27. Ellenbogen KA, Wood MA, Stambler BS, et al: Measurement of ventricular electrogram amplitude during intraoperative induction of ventricular tachyarrhythmias. Am J Cardiol 70:10171022, 1992. 28. Taneja T, Goldberger J, Parker MA, et al: Reproducibility of ventricular fibrillation characteristics in patients undergoing implantable cardioverter defibrillator implantation. J Cardiovasc Electrophysiol 8:1209-1217, 1997. 29. McAlister HF, Klementowicz PT, Calderon EM, et al: Atrial electrogram analysis: antegrade versus retrograde. Pacing Clin Electrophysiol 11:1703-1707, 1988. 30. Wainwright R, Davies W, Tooley M: Ideal atrial lead positioning to detect retrograde atrial depolarization by digitization and slope analysis of the atrial electrogram. Pacing Clin Electrophysiol 7:1152-1158, 1984. 31. Timmis GC, Westveer DC, Bakalyar DM, et al: Discrimination of anterograde from retrograde atrial electrograms for physiologic pacing. Pacing Clin Electrophysiol 11:130-140, 1988. 32. Davies DW, Wainwright RJ, Tooley MA, et al: Detection of pathological tachycardia by analysis of electrogram morphology. Pacing Clin Electrophysiol 9:200-208, 1986. 33. Roithinger FX, SippensGroenewegen A, Karch MR, et al: Organized activation during atrial fibrillation in man: endocardial and electrocardiographic manifestations. J Cardiovasc Electrophysiol 9:451-461, 1998. 34. Konings KT, Smeets JL, Penn OC, et al: Configuration of unipolar atrial electrograms during electrically induced atrial fibrillation in humans. Circulation 95:1231-1241, 1997. 35. Wood MA, Moskovljevic P, Stambler BS, Ellenbogen KA: Comparison of bipolar atrial electrogram amplitude in sinus rhythm, atrial fibrillation, and atrial flutter. Pacing Clin Electrophysiol 19:150-156, 1996. 36. Ropella KM, Sahakian AV, Baerman JM, Swiryn S: The coherence spectrum: a quantitative discriminator of fibrillatory and nonfibrillatory cardiac rhythms. Circulation 80:112-119, 1989. 37. Baerman JM, Ropella KM, Sahakian AV, et al: Effect of bipole configuration on atrial electrograms during atrial fibrillation. Pacing Clin Electrophysiol 13:78-87, 1990. 38. Karagueuzian HS, Khan SS, Peters W, et al: Nonhomogeneous local atrial activity during acute atrial fibrillation: spectral and dynamic analysis. Pacing Clin Electrophysiol 13:1937-1942, 1990. 39. Lewalter T, Schimpf R, Kulik D, et al: Comparison of spontaneous atrial fibrillation electrogram potentials with the P-wave electrogram amplitude in dual chamber pacing with unipolar atrial sensing. Europace 2:136-140, 2000. 40. Ropella KM, Sahakian AV, Baerman JM, Swiryn S: Effects of procainamide on intra-atrial [corrected] electrograms during atrial fibrillation: implications [corrected] for detection algorithms. Circulation 77:1047-1054, 1988. 41. Bellardine Black CL, Stromberg K, van Balen GP, et al: Is surface ECG a useful surrogate for subcutaneous ECG? Pacing Clin Electrophysiol 33:135-145, 2010. 42. Van Dam P, van Groeningen C, Houben RP, Hampton DR: Improving sensing and detection performance in subcutaneous monitors. J Electrocardiol 42:580-583, 2009. 43. Beeman AL, Deutsch G, Rea RF: Paradoxical undersensing due to quiet timer blanking. Heart Rhythm 1:345-347, 2004. 44. Willems R, Holemans P, Ector H, et al: Paradoxical undersensing at a high sensitivity in dual chamber pacemakers. Pacing Clin Electrophysiol 24:308-315, 2001. 45. Castro A, Liebold A, Vincente J, et al: Evaluation of autosensing as an automatic means of maintaining a 2:1 sensing safety margin in an implanted pacemaker. Autosensing Investigation Team. Pacing Clin Electrophysiol 19:1708-1713, 1996. 46. Nowak B, Kampmann C, Schmid FX, et al: Pacemaker therapy in premature children with high degree AV block. Pacing Clin Electrophysiol 21:2695-2698, 1998. 47. Inama G, Santini M, Padeletti L, et al: Far-field R wave oversensing in dual chamber pacemakers designed for atrial arrhythmia

management: effect of pacing site and lead tip to ring distance. Pacing Clin Electrophysiol 27:1221-1230, 2004. 48. Dekker LR, Schrama TA, Steinmetz FH, Tukkie R: Undersensing of VF in a patient with optimal R wave sensing during sinus rhythm. Pacing Clin Electrophysiol 27:833-834, 2004. 49. Callans DJ, Hook BG, Kleiman RB, et al: Unique sensing errors in third-generation implantable cardioverter-defibrillators. J Am Coll Cardiol 22:1135-1140, 1993. 50. Callans DJ, Hook BG, Marchlinski FE: Paced beats following single nonsensed complexes in a “codependent” cardioverterdefibrillator and bradycardia pacing system: potential for ventricular tachycardia induction. Pacing Clin Electrophysiol 14:1281-1287, 1991. 51. Callans DJ, Hook BG, Marchlinski FE: Effect of rate and coupling interval on endocardial R wave amplitude variability in permanent ventricular sensing lead systems. J Am Coll Cardiol 22:746-750, 1993. 52. Glikson M, Beeman AL, Luria DM, et al: Impaired detection of ventricular tachyarrhythmias by a rate-smoothing algorithm in dual-chamber implantable defibrillators: intradevice interactions. J Cardiovasc Electrophysiol 13:312-318, 2002. 53. Cooper JM, Sauer WH, Verdino RJ: Absent ventricular tachycardia detection in a biventricular implantable cardioverterdefibrillator due to intradevice interaction with a rate-smoothing pacing algorithm. Heart Rhythm 1:728-731, 2004. 54. Shivkumar K, Feliciano Z, Boyle NG, Wiener I: Intradevice interaction in a dual chamber implantable cardioverter-defibrillator preventing ventricular tachyarrhythmia detection. J Cardiovasc Electrophysiol 11:1285-1288, 2000. 55. Gunderson BD, Gillberg JM, Wood MA, et al: Development and testing of an algorithm to detect implantable cardioverterdefibrillator lead failure. Heart Rhythm 3:155-162, 2006. 56. Zhang X, Volosin K, Kumar A, et al: Withholding ICD shocks for detected lead fractures. Heart Rhythm 6:S249, 2009. 57. Ellenbogen KA, Wood MA, Kapadia K, et al: Short-term reproducibility over time of right ventricular pulse pressure as a potential hemodynamic sensor for ventricular tachyarrhythmias. Pacing Clin Electrophysiol 15:971-974, 1992. 58. Leitch J, Klein G, Yee R, et al: Feasibility of an implantable arrhythmia monitor. Pacing Clin Electrophysiol 15:2232-2235, 1992. 59. Swerdlow CD: Implantation of cardioverter-defibrillators without induction of ventricular fibrillation. Circulation 103:2159-2164, 2001. 60. Michaud J, Horduna I, Dubuc M, Khairy P: ICD-unresponsive ventricular arrhythmias. Heart Rhythm 6:1827-1829, 2009. 61. Ruetz L, Koehler JL, Jackson TE, Belk P: Sinus rhythm R-wave amplitude does not predict undersensing of ventricular fibrillation by implantable cardioverter-defibrillators. Circ Arrhythm Electrophysiol 120:S650, 2009. 62. Tung L, Tovar O, Neunlist M, et al: Effects of strong electrical shock on cardiac muscle tissue. Ann NY Acad Sci 720:160-175, 1994. 63. Winkle RA, Bach SM, Jr, Echt DS, et al: The automatic implantable defibrillator: local ventricular bipolar sensing to detect ventricular tachycardia and fibrillation. Am J Cardiol 52:265-270, 1983. 64. Goldberger JJ, Horvath G, Donovan D, et al: Detection of ventricular fibrillation by transvenous defibrillating leads: integrated versus dedicated bipolar sensing. J Cardiovasc Electrophysiol 9:677-688, 1998. 65. Yee R, Jones DL, Jarvis E, et al: Changes in pacing threshold and R wave amplitude after transvenous catheter countershock. J Am Coll Cardiol 4:543-549, 1984. 66. Jung W, Manz M, Moosdorf R, et al: Changes in the amplitude of endocardial electrograms following defibrillator discharge: comparison of two lead systems. Pacing Clin Electrophysiol 18:2163-2172, 1995. 67. Kuhlkamp V, Dornberger V, Mewis C, et al: Clinical experience with the new detection algorithms for atrial fibrillation of a defibrillator with dual chamber sensing and pacing. J Cardiovasc Electrophysiol 10:905-915, 1999. 68. Wilkoff BL, Kuhlkamp V, Volosin K, et al: Critical analysis of dual-chamber implantable cardioverter-defibrillator arrhythmia detection: results and technical considerations. Circulation 103:381-386, 2001. 69. Swerdlow CD: Supraventricular tachycardia–ventricular tachycardia discrimination algorithms in implantable cardioverterdefibrillators: state-of-the-art review. J Cardiovasc Electrophysiol 12:606-612, 2001. 70. Gunderson B, Patel A, Bounds C: Automatic identification of implantable cardioverter-defibrillator lead problems using intracardiac electrograms. Comput Cardiol 29:121-124, 2002. 71. Swerdlow C, Shivkumar K: Implantable cardioverterdefibrillators: clinical aspects. In Zipes DP, Jalife J, editors: Cardiac electrophysiology: from cell to bedside, ed 4, Philadephia, 2004, Saunders, pp 980-993. 72. Pinski SL: 2:1 tracking of sinus rhythm in a patient with a dualchamber implantable cardioverter-defibrillator: what is the mechanism? J Cardiovasc Electrophysiol 12:503-504, 2001. 73. Hsu SS, Mohib S, Schroeder A, Deger FT: T-wave oversensing in implantable cardioverter-defibrillators. J Interv Card Electrophysiol 11:67-72, 2004. 74. Cao J, Shrivastav M, Koehler J, et al: Automatic identification of T-wave oversensing by patterns of alternating amplitude and frequency content in implantable cardioverter defibrillator electrograms [abstract]. Heart Rhythm 5:S094, 2008.

75. Garcia-Moran E, Mont L, Brugada J: Inappropriate tachycardia detection by a biventricular implantable cardioverterdefibrillator. Pacing Clin Electrophysiol 25:123-124, 2002. 76. Gunderson B, Swerdlow C, Wilcox J, et al: Causes of ventricular oversensing in implantable cardioverter-defibrillators: implications for diagnosis of lead fracture. Heart Rhythm 7:626-633, 2010. 77. Lloyd M, Hayes D, Friedman P: Troubleshooting. In Cardiac pacing and defibrillation: a clinical approach, Armonk, NY, 2000, Futura, pp 347-452. 78. Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008. 79. Cheung JW, Iwai S, Lerman BB, Mittal S: Shock-induced ventricular oversensing due to seal plug damage: a potential mechanism of inappropriate device therapies in implantable cardioverter-defibrillators. Heart Rhythm 2:1371-1375, 2005. 80. Kallinen LM, Hauser RG, Lee KW, et al: Failure of impedance monitoring to prevent adverse clinical events caused by fracture of a recalled high-voltage implantable cardioverter-defibrillator lead. Heart Rhythm 5:775-779, 2008. 81. Chung EH, Casavant D, John RM: Analysis of pacing/ defibrillator lead failure using device diagnostics and pacing maneuvers. Pacing Clin Electrophysiol 32:547-549, 2009. 82. Hauser RG, Hayes DL: Increasing hazard of Sprint Fidelis implantable cardioverter-defibrillator lead failure. Heart Rhythm 6:605-610, 2009. 83. Pinski S, Eguia L, Sgarbossa E, Trohman R: Incidence and causes of commited shocks in noncommited implantable defibrillators [abstract]. J Am Coll Cardiol 39:93A, 2002. 84. Sweesy MW, Holland JL, Smith KW: Electromagnetic interference in cardiac rhythm management devices. AACN Clin Issues 15:391-403, 2004. 85. Lau CP, Leung SK, Tse HF, Barold SS: Automatic mode switching of implantable pacemakers. II. Clinical performance of current algorithms and their programming. Pacing Clin Electrophysiol 25:1094-1113, 2002. 86. Israel CW: Analysis of mode switching algorithms in dual chamber pacemakers. Pacing Clin Electrophysiol 25:380-393, 2002. 87. Lam CT, Lau CP, Leung SK, et al: Improved efficacy of mode switching during atrial fibrillation using automatic atrial sensitivity adjustment. Pacing Clin Electrophysiol 22:17-25, 1999. 88. Leung SK, Lau CP, Lam C, et al: Programmed atrial sensitivity: a critical determinant in atrial fibrillation detection and optimal automatic mode switching [in process citation]. Pacing Clin Electrophysiol 21:2214-2219, 1998. 89. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 107:2932-2937, 2003. 90. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial [see comment]. JAMA 288:3115-3123, 2002. 91. Melzer C, Sowelam S, Sheldon TJ, et al: Reduction of right ventricular pacing in patients with sinus node dysfunction using an enhanced search AV algorithm. Pacing Clin Electrophysiol 28:521-527, 2005. 92. Sweeney M, Nsah E, McGrew F, et al: Reduction in ventricular pacing and its long-term clinical outcomes: preliminary results of the Save Pace Trial [abstract]. Heart Rhythm 2:S322, 2005. 93. Olshansky B, Day J, McGuire M, Pratt T: Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV): design and clinical protocol. Pacing Clin Electrophysiol 28:62-66, 2005. 94. Deering T, Wilensky M, Tondato F, et al: Auto intrinsic conduction search algorithm: a prospective analysis [abstract]. Pacing Clin Electrophysiol 26:1080, 2003. 95. Savoure A, Frohlig G, Galley D, et al: A new dual-chamber pacing mode to minimize ventricular pacing. Pacing Clin Electrophysiol 28:S43-S46, 2005. 96. Sweeney MO, Shea JB, Fox V, et al: Randomized pilot study of a new atrial-based minimal ventricular pacing mode in dualchamber implantable cardioverter-defibrillators. Heart Rhythm 1:160-167, 2004. 97. Pascale P, Pruvot E, Graf D: Pacemaker syndrome during managed ventricular pacing mode: what is the mechanism? J Cardiovasc Electrophysiol 20:574-576, 2009. 98. Mansour F, Talajic M, Thibault B, Khairy P: Pacemaker troubleshooting: when MVP is not the most valuable parameter. Heart Rhythm 3:612-614, 2006. 99. Gillis AM, Purerfellner H, Israel CW, et al: Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Pacing Clin Electrophysiol 29:697-705, 2006. 100. De Voogt WG, Vonk BF, Albers BA, Hintringer F: Understanding capture detection. Europace 6:561-569, 2004. 101. Schuchert A, Frese J, Stammwitz E, et al: Low settings of the ventricular pacing output in patients dependent on a pacemaker: are they really safe? Am Heart J 143:1009-1011, 2002. 102. Splett V, Trusty JM, Hayes DL, Friedman PA: Determination of pacing capture in implantable defibrillators: benefit of evoked response detection using RV coil-to-can vector. Pacing Clin Electrophysiol 23:1645-1650, 2000.



103. Crossley GH, Mead H, Kleckner K, et al: Automated left ventricular capture management. Pacing Clin Electrophysiol 30:1190-1200, 2007. 104. Sperzel J, Binner L, Boriani G, et al: Evaluation of the atrial evoked response for capture detection with high-polarization leads. Pacing Clin Electrophysiol 28:S57-S62, 2005. 105. Sperzel J, Milasinovic G, Smith TW, et al: Automatic measurement of atrial pacing thresholds in dual-chamber pacemakers: clinical experience with atrial capture management. Heart Rhythm 2:1203-1210, 2005. 106. Olson W: Safety margins for sensing and detection: programming tradeoffs. In Kroll M, Lehmann M, editors: Implantable cardioverter-defibrillator therapy: the engineering-clinical interface, Norwell, Mass, 1996, Kluwer Academic Publishers, pp 389-420. 107. Anderson MH, Murgatroyd FD, Hnatkova K, et al: Performance of basic ventricular tachycardia detection algorithms in implantable cardioverter-defibrillators: implications for device programming. Pacing Clin Electrophysiol 20:2975-2983, 1997. 108. Murgatroyd F, Anderson M, Hnatkova K, et al: Comparison of misdiagnosis of atrial fibrillation as ventricular tachycardia by algorithms employed in current implantable cardioverterdefibrillators. Circulation 88:I-353, 1993. 109. Mansour F, Khairy P: ICD monitoring zones: intricacies, pitfalls, and programming tips. J Cardiovasc Electrophysiol 19:568-574, 2008. 110. Mansour F, Thibault B, Dubuc M, et al: Shocking truths about implantable cardioverter-defibrillator monitoring zones. Pacing Clin Electrophysiol 30:1146-1148, 2007. 111. Grimm W, Menz V, Hoffmann J, Maisch B: Failure of thirdgeneration implantable cardioverter defibrillators to abort shock therapy for nonsustained ventricular tachycardia due to shortcomings of the VF confirmation algorithm. Pacing Clin Electrophysiol 21:722-727, 1998. 112. Raedle-Hurst TM, Wiecha J, Schwab JO, et al: Clinical performance of a specific algorithm to reconfirm self-terminating ventricular arrhythmias in current implantable cardioverterdefibrillators. Am J Cardiol 88:744-749, 2001. 113. Gillberg J, Olson W: Dual-chamber sensing and detection for implantable cardioverter-defibrillators. In Singer I, editor: Interventional electrophysiology, ed 2, Philadelphia, 2001, Lippincott– Williams & Wilkins. 114. Glikson M, Swerdlow CD, Gurevitz OT, et al: Optimal combination of discriminators for differentiating ventricular from supraventricular tachycardia by dual-chamber defibrillators. J Cardiovasc Electrophysiol 16:732-739, 2005. 115. Saba S, Volosin K, Yee R, et al: Combined atrial and ventricular antitachycardia pacing as a novel method of rhythm discrimination: the Dynamic Discrimination Download Study. Circulation 121:487-497, 2010. 116. Brugada J, Mont L, Figueiredo M, et al: Enhanced detection criteria in implantable defibrillators. J Cardiovasc Electrophysiol 9:261-268, 1998. 117. Le Franc P, Kus T, Vinet A, et al: Underdetection of ventricular tachycardia using a 40 ms stability criterion: effect of antiarrythmic therapy. Pacing Clin Electrophysiol 20:2882-2892, 1997. 118. Neuzner J, Pitschner HF, Schlepper M: Programmable VT detection enhancements in implantable cardioverter defibrillator therapy. Pacing Clin Electrophysiol 18:539-547, 1995. 119. Swerdlow CD, Ahern T, Chen PS, et al: Underdetection of ventricular tachycardia by algorithms to enhance specificity in a tiered-therapy cardioverter-defibrillator. J Am Coll Cardiol 24:416-424, 1994. 120. Swerdlow CD, Chen PS, Kass RM, et al: Discrimination of ventricular tachycardia from sinus tachycardia and atrial fibrillation in a tiered-therapy cardioverter-defibrillator. J Am Coll Cardiol 23:1342-1355, 1994. 121. Gronefeld GC, Schulte B, Hohnloser SH, et al: Morphology discrimination: a beat-to-beat algorithm for the discrimination of ventricular from supraventricular tachycardia by implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 24:15191524, 2001. 122. Boriani G, Biffi M, Frabetti L, et al: Clinical evaluation of morphology discrimination: an algorithm for rhythm discrimination in cardioverter-defibrillators. Pacing Clin Electrophysiol 24:994-1001, 2001. 123. Gold MR, Shorofsky SR, Thompson JA, et al: Advanced rhythm discrimination for implantable cardioverter-defibrillators using electrogram vector timing and correlation. J Cardiovasc Electrophysiol 13:1092-1097, 2002. 124. Gold MR, Theuns DA, Knight BP, et al: Comparison of arrhythmia discrimination by subcutaneous versus dual chamber transvenous ICD systems: Primary results from START. Circulation 120:S649, 2009. 125. Corbisiero R, Lee MA, Nabert DR, et al: Performance of a new single-chamber ICD algorithm: discrimination of supraventricular and ventricular tachycardia based on vector timing and correlation. Europace 8:1057-1061, 2006. 126. Lee MA, Corbisiero R, Nabert DR, et al: Clinical results of an advanced SVT detection enhancement algorithm. Pacing Clin Electrophysiol 28:1032-1040, 2005. 127. Klein G, Manolis A, Viskin S, et al: Clinical performance of Wavelet morphology discrimination algorithm in a worldwide single chamber ICD population [abstract]. Circulation 110:III345, 2003.

3  Sensing and Detection 128. Stadler RW, Gunderson BD, Gillberg JM: An adaptive intervalbased algorithm for withholding ICD therapy during sinus tachycardia. Pacing Clin Electrophysiol 26:1189-1201, 2003. 129. Stein KM, Euler DE, Mehra R, et al: Do atrial tachyarrhythmias beget ventricular tachyarrhythmias in defibrillator recipients? J Am Coll Cardiol 40:335-340, 2002. 130. Aliot E, Nitzsche R, Ripart A: Arrhythmia detection by dualchamber implantable cardioverter-defibrillators: a review of current algorithms. Europace 6:273-286, 2004. 131. Wilkoff B, Sterns L, Morgan JM, et al: Preventing shocks after ICD implantation: can a strategy of standardized ICD programming match physician tailored? (Late breaking clinical trial presentation). Heart Rhythm 2005. 132. Deisenhofer I, Kolb C, Ndrepepa G, et al: Do current dual chamber cardioverter defibrillators have advantages over conventional single chamber cardioverter defibrillators in reducing inappropriate therapies? A randomized, prospective study. J Cardiovasc Electrophysiol 12:134-142, 2001. 133. Theuns DA, Klootwijk AP, Goedhart DM, Jordaens LJ: Prevention of inappropriate therapy in implantable cardioverterdefibrillators: results of a prospective, randomized study of tachyarrhythmia detection algorithms. J Am Coll Cardiol 44:2362-2367, 2004. 134. Bansch D, Steffgen F, Gronefeld G, et al: The 1+1 trial: a prospective trial of a dual- versus a single-chamber implantable defibrillator in patients with slow ventricular tachycardias. Circulation 110:1022-1029, 2004. 135. Friedman P, McClelland R, Bamlet W, et al: Dual chamber versus single chamber detection enhancements for implantable defibrillator rhythm diagnosis (The Detect SVT Study). Circulation 113:2871-2879, 2006. 136. Sinha AM, Stellbrink C, Schuchert A, et al: Clinical experience with a new detection algorithm for differentiation of supraventricular from ventricular tachycardia in a dual-chamber defibrillator. J Cardiovasc Electrophysiol 15:646-652, 2004. 137. Klein GJ, Gillberg JM, Tang A, et al: Improving SVT discrimination in single-chamber ICDs: a new electrogram morphologybased algorithm. J Cardiovasc Electrophysiol 17:1310-1319, 2006. 138. Zeger SL, Liang KY, Albert PS: Models for longitudinal data: a generalized estimating equation approach. Biometrics 44:10491060, 1988. 139. Wathen MS, Volosin KJ, Sweeney MO, et al: Ventricular anti­ tachycardia pacing by implantable cardioverter-defibrillators reduces shocks for inappropriately detected supraventricular tachycardia [abstract]. Heart Rhythm 1, 2004. 140. Irvine J, Dorian P, Baker B, et al: Quality of life in the Canadian Implantable Defibrillator Study (CIDS). Am Heart J 144:282289, 2002. 141. Birgersdotter-Green U, Rosenqvist M, Lindemans FW, et al: Holter documented sudden death in a patient with an implanted defibrillator. Pacing Clin Electrophysiol 15:1008-1014, 1992. 142. Schwartzman D, Musley SK, Swerdlow C, et al: Early recurrence of atrial fibrillation after ambulatory shock conversion. J Am Coll Cardiol 40:93-99, 2002. 143. Wilkoff BL, Williamson BD, Stern RS, et al: Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 52:541-550, 2008. 144. Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352:225-237, 2005. 145. Schaumann A, von zur Muhlen F, Herse B, et al: Empirical versus tested antitachycardia pacing in implantable cardioverterdefibrillators: a prospective study including 200 patients. Circulation 97:66-74, 1998. 146. Wathen MS, Sweeney MO, DeGroot PJ, et al: Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease. Circulation 104:796-801, 2001. 147. Wathen MS, DeGroot PJ, Sweeney MO, et al: Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 110:2591-2596, 2004. 148. Gunderson BD, Gillberg JM, Olson WH, Swerdlow C: Effect of programmed number of intervals to detect ventricular fibrillation on implantable cardioverter defibrillator longevity and unnecessary shocks [abstract]. Circulation 106:322, 2002. 149. Gasparini M, Menozzi C, Proclemer A, et al: A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter-defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT study (Role of Long Detection Window Programming in Patients with Left Ventricular Dysfunction, Non-ischemic Etiology in Primary Prevention Treated with a Biventricular ICD). Eur Heart J 30:2758-2767, 2009. 150. Daubert JP, Wojciech Z, Cannom DC, et al: Frequency and mechanisms of inappropriate ICD therapy in MADIT II [abstract]. J Am Coll Cardiol 2004. 151. Kolb C, Deisenhofer I, Weyerbrock S, et al: Incidence of anti­ tachycardia therapy suspension due to magnet reversion in

125

implantable cardioverter defibrillators. Pacing Clin Electrophysiol 27:221-223, 2004. 152. Shukla HH, Flaker GC, Jayam V, Roberts D: High defibrillation thresholds in transvenous biphasic implantable defibrillators: clinical predictors and prognostic implications. Pacing Clin Electrophysiol 26:44-48, 2003. 153. Bansch D, Castrucci M, Bocker D, et al: Ventricular tachycardias above the initially programmed tachycardia detection interval in patients with implantable cardioverter-defibrillators: incidence, prediction and significance. J Am Coll Cardiol 36:557-565, 2000. 154. Brode SE, Schwartzman D, Callans DJ, et al: ICD-antiarrhythmic drug and ICD-pacemaker interactions. J Cardiovasc Electrophysiol 8:830-842, 1997. 155. Monahan KM, Hadjis T, Hallett N, et al: Relation of induced to spontaneous ventricular tachycardia from analysis of stored far-field implantable defibrillator electrograms. Am J Cardiol 83:349-353, 1999. 156. Weber M, Bocker D, Bansch D, et al: Efficacy and safety of the initial use of stability and onset criteria in implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 10:145-153, 1999. 157. Cohen AI, Wish MH, Fletcher RD, et al: The use and interaction of permanent pacemakers and the automatic implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 11:704-711, 1988. 158. Geiger MJ, O’Neill P, Sharma A, et al: Interactions between transvenous nonthoracotomy cardioverter-defibrillator systems and permanent transvenous endocardial pacemakers. Pacing Clin Electrophysiol 20:624-630, 1997. 159. Glikson M, Trusty JM, Grice SK, et al: A stepwise testing protocol for modern implantable cardioverter-defibrillator systems to prevent pacemaker-implantable cardioverter-defibrillator interactions. Am J Cardiol 83:360-366, 1999. 160. Wietholt D, Kuehlkamp V, Meisel E, et al: Prevention of sustained ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators: the PREVENT study. J Interv Card Electrophysiol 9:383-389, 2003. 161. Pollak WM, Simmons JD, Interian A, Jr, et al: Pacemaker diagnostics: a critical appraisal of current technology. Pacing Clin Electrophysiol 26:76-98, 2003. 162. Hammel E, Bertrand B, et al: Appropriate detection of guidant pacemaker stored electrograms assessed by centralized arrhythmia workstation [abstract]. Pacing Clin Electrophsyiol 23:680, 2000. 163. Passman RS, Weinberg KM, Freher M, et al: Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias. J Cardiovasc Electrophysiol 15:773-777, 2004. 164. Seidl K, Rameken M, Breunung S, et al: Diagnostic assessment of recurrent unexplained syncope with a new subcutaneously implantable loop recorder. REVEAL Investigators. Europace 2:256-262, 2000. 165. Israel CW, Gascon D, Nowak B, et al: Diagnostic value of stored electrograms in single-lead VDD systems. Pacing Clin Electrophysiol 23:1801-1803, 2000. 166. Glotzer TV, Daoud EG, Wyse DG, et al: The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol 2:474-480, 2009. 167. Capucci A, Santini M, Padeletti L, et al: Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. J Am Coll Cardiol 46:1913-1920, 2005. 168. Ricci RP, Morichelli L, Gargaro A, et al: Home monitoring in patients with implantable cardiac devices: is there a potential reduction of stroke risk? Results from a computer model tested through Monte Carlo simulations. J Cardiovasc Electrophysiol 20:1244-1251, 2009. 169. Ip J, Waldo AL, Lip GY, et al: Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: rationale, design, and clinical characteristics of the initially enrolled cohort. The IMPACT study. Am Heart J 158:364370, 2009. 170. Morris MM, KenKnight BH, Lang DJ: Detection of atrial arrhythmia for cardiac rhythm management by implantable devices. J Electrocardiol 33(Suppl):133-139, 2000. 171. Schuchert A, Boriani G, Wollmann C, et al: Implantable dualchamber defibrillator for the selective treatment of spontaneous atrial and ventricular arrhythmias: arrhythmia incidence and device performance. J Interv Card Electrophysiol 12:149-156, 2005. 172. Krahn AD, Klein GJ, Yee R, Norris C: Maturation of the sensed electrogram amplitude over time in a new subcutaneous implantable loop recorder. Pacing Clin Electrophysiol 20:16861690, 1997. 173. Thaker JP, Patel MB, Jongnarangsin K, et al: Electromagnetic interference in an implantable loop recorder caused by a portable digital media player. Pacing Clin Electrophysiol 31:13451347, 2008. 174. Trigano A, Blandeau O, Dale C, et al: Risk of cellular phone interference with an implantable loop recorder. Int J Cardiol 116:126-130, 2007. 175. Gimbel JR, Zarghami J, Machado C, Wilkoff BL: Safe scanning, but frequent artifacts mimicking bradycardia and tachycardia during magnetic resonance imaging (MRI) in patients with an

126

SECTION 1  Basic Principles of Device Therapy

implantable loop recorder (ILR). Ann Noninvas Electrocardiol 10:404-408, 2005. 176. Brignole M, Bellardine Black CL, Thomsen PE, et al: Improved arrhythmia detection in implantable loop recorders. J Cardiovasc Electrophysiol 19:928-934, 2008. 177. Sarkar S, Ritscher D, Mehra R: A detector for a chronic implantable atrial tachyarrhythmia monitor. Biomed Eng IEEE Trans 55:1219-1224, 2008. 178. Hindricks G, Pokushalov E, Urban L, et al: Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: results of the XPECT Trial. Circ Arrhythm Electrophysiol 3:141-147, 2010. 179. Bordachar P, Garrigue S, Reuter S, et al: Hemodynamic assessment of right, left, and biventricular pacing by peak endocardial acceleration and echocardiography in patients with

end-stage heart failure. Pacing Clin Electrophysiol 23:1726-1730, 2000. 180. Hegbom F, Hoff PI, Oie B, et al: RV function in stable and unstable VT: is there a need for hemodynamic monitoring in future defibrillators? Pacing Clin Electrophysiol 24:172-182, 2001. 181. Kaye G, Astridge P, Perrins J: Tachycardia recognition and diagnosis from changes in right atrial pressure waveform: a feasibility study. Pacing Clin Electrophysiol 14:1384-1392, 1991. 182. Sharma AD, Bennett TD, Erickson M, et al: Right ventricular pressure during ventricular arrhythmias in humans: potential implications for implantable antitachycardia devices. J Am Coll Cardiol 15:648-655, 1990. 183. Ellenbogen KA, Lu B, Kapadia K, et al: Usefulness of right ventricular pulse pressure as a potential sensor for hemo­

dynamically unstable ventricular tachycardia. Am J Cardiol 65:1105-1111, 1990. 184. Turcott R: Detection of hemodynamically unstable arrhythmias using subcutaneous photoplethysmography [abstract]. Heart Rhythm 2:S83, 2005. 185. Bourge RC, Abraham WT, Adamson PB, et al: Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 51:1073-1079, 2008. 186. Kroll MW, Swerdlow CD: The future of the implantable defibrillator. In Efimov I, Kroll M, Tchou P, editors: Cardiac bioelectric therapy: mechanisms and practical implications, Berlin, 2008, Springer Verlag, pp 551-570.

4 

Engineering and Construction of Pacemaker and ICD Leads HARIS M. HAQQANI  |  LAURENCE M. EPSTEIN  |  JOSHUA M. COOPER*

Tremendous advances have occurred in implanted cardiac device

therapy, from the evolution of pacemakers to the modern era of highvoltage defibrillation and resynchronization devices. Advances in the components, integrated circuitry, size, and software of the implantable pulse generator are readily apparent, but the revolutionary progress in the design and manufacture of device leads is often not appreciated. In any device system, the lead is the critical interface linking the pulse generator and the myocardium; it allows for communication of electrical signals from the heart to the pulse generator through the sensing circuitry, and in the reverse direction, it allows for bradycardia pacing or tachyarrhythmia therapy. Although leadless pacing1 and defibrillation2 device systems are being actively developed, leads clearly will remain an integral component of device therapy for the foreseeable future. Whether used for pacing, resynchronization, or defibrillation, and regardless of their internal structural design, all leads contain several common components, including electrodes, conductors, insulators, fixation mechanisms, and connector pins. Defibrillation leads also contain shock coils for the delivery of high-voltage, high-current electrical discharges to terminate ventricular fibrillation. This chapter examines each of these elements as well as the overall design, construction, and evolution of pacemaker and implantable cardioverterdefibrillator (ICD) leads.

Pacing Leads HISTORICAL MILESTONES IN DEVELOPMENT Permanently implantable pacing leads evolved from the temporary pacing wires that were first used to provide bradycardia support.3 The initial permanent transvenous leads were unipolar and consisted of a basic conductor, an insulator, and a connector pin. The electrodes were large and polished with high-polarization properties, low electrodetissue impedance, and excessive current drain. No lumen was present in these leads to allow for stylet insertion, so lead implantation was a long, difficult task. Also, no fixation mechanism was present, so lead displacement rates were high. The development of bipolar pacing leads minimized far-field oversensing,4 requiring a major reconsideration of lead body design and structure, because two longitudinal conductors needed to coexist inside the lead, separated only by a thin layer of insulation. This and subsequent increases in complexity required advances in materials science so as not to compromise reliability. The development of passive-fixation tines was a huge step forward and dramatically reduced the rate of reoperation for lead dislodgement compared with existing flange-tipped pacing leads.5-7 Active-fixation helices were introduced subsequently and further improved the stability of implanted leads. Modern electrodes were developed with small geometric surface area but large effective area as a result of porous surfaces, and these optimized the trade-off between high current *Disclosures: Dr. Haqqani is the recipient of a Training Fellowship from the National Health and Medical Research Council of Australia (544309) and the Bayer Fellowship from the Royal Australasian College of Physicians. Drs. Cooper and Epstein have received modest honoraria from Boston Scientific, Medtronic, St. Jude Medical, Biotronik, and Spectranetics.

density and low polarization. Chronic threshold rises and late exit block were still major problems in cardiac pacing at that stage, however, and remained so until the revolutionary incorporation of an elutable dexamethasone reservoir into a porous-tip electrode, essentially eliminating this complication.8 Although this likely resulted from the glucocorticoid and not the redesigned porous titanium-tip electrode, this remained unproved until a pioneering randomized double-blind trial compared two otherwise identical leads and electrodes, with and without steroid elution.9 This unequivocally demonstrated the benefit was the result of the dexamethasone. Subsequent advances have included the universal standardization of connector pins (and consequently device headers), improving lead longevity through the use of better component materials, and improving sensing through the use of narrower bipoles. LEAD STRUCTURE AND POLARITY The basic functions of any cardiac device lead—pacing and sensing— require conductors for current flow between the pulse generator and myocardium and insulators to prevent short-circuiting of this current. These elements may be configured in two ways. First, a pace/sense circuit may be composed of a lead containing one conductor that connects to a negatively charged tip electrode, the cathode, from which electrons flow through the myocardium and thoracic cavity back to the active, positively charged pulse generator (IPG), the anode (Fig. 4-1, A). Such a lead, with only one conductor and electrode, is called a unipolar lead because only one electrode is in contact with the heart (although it is part of a bipolar circuit). It has been established that pacing thresholds are lower at most pulse widths when the intracardiac pacing electrode is configured as the cathode rather than as the anode10 (see Chapter 1). Although once the only option, unipolar leads have largely been replaced by bipolar leads. The alternative system consists of a lead body containing two conductors (separated and surrounded by insulation) that connect to a cathode-tip electrode and an anode ring electrode located several millimeters more proximally (Fig. 4-1, B). The IPG is not an active electrode in a bipolar circuit, and such leads are said to have bipolar configuration. Unipolar systems have a large interelectrode distance from the tip of the intracardiac lead to the IPG, and this large field of view makes them vulnerable to the oversensing of myocardial signals (T waves or electrograms from another chamber, known as “crosstalk”) and farfield nonmyocardial signals such as pacing artifacts (another form of crosstalk), skeletal myopotentials, and nonphysiologic electrical “noise” in up to 38% of patients.11 Electrical signal oversensing can have significant consequences on pacing behavior, including ventricular output inhibition and inappropriate mode switching caused by far-field ventricular oversensing on the atrial channel.12,13 Because of the additional consequence of inappropriate shock delivery if oversensing were to occur in an ICD, it is particularly important for ICD leads to have bipolar sensing circuitry. Since the IPG itself serves as one of the electrodes in a unipolar system, skeletal muscle capture and pectoral muscle stimulation may result in the setting of a higher programmed pacing output. Bipolar leads have been shown to have similar but slightly higher, acute and chronic stimulation thresholds to unipolar leads.4 Bipolar leads also carry an element of redundancy in that they

127

128

SECTION 1  Basic Principles of Device Therapy

Unipolar

Bipolar

+

RV lead

RV lead +

–

A

–

B

Figure 4-1  A, Unipolar pacing circuit, with an intracardiac cathode located on the lead tip in the right ventricle (RV). The circuit is completed by the active pulse generator, which forms the anode. B, In a bipolar circuit, both cathode and anode are located on the lead, with the anode generally formed by a ring electrode proximal to the tip cathode.

can be used in either the bipolar or the unipolar configuration, as in isolated failure of the proximal, anodal conductor, with no demonstrated difference in performance between the two pacing configurations.14 In addition, the much lower amplitude of the bipolar pacing artifact greatly reduces the likelihood of crosstalk and oversensing. The great advantage of bipolar leads is related to their superior sensing properties. These factors have led to the near-universal adoption of the bipolar lead as the configuration of choice in cardiac device systems.15 The only potential disadvantage of bipolar leads is that reliability is lower than with the less complicated unipolar lead,16 although some studies have not supported this contention.15,17 However, insulation failure usually has negligible effects on unipolar lead performance, a clear reliability advantage. In terms of the structure of the lead body, the simple, single-conductor design of unipolar leads had to be modified to accommodate the greater number of components and increased complexity of the bipolar lead body. There are two main bipolar lead designs, coaxial and coradial (Fig 4-2). Coaxial leads have an inner conductor that extends down the length of the lead to the tip electrode, the cathode, arranged in a coil configuration with a central lumen to allow for passage of a stylet at implantation. This coil is covered by a cylindrical length of inner insulation, which in turn

is wrapped by another coil conductor that also runs down the lead to the ring electrode, the anode. A second, outer layer of insulation and lead covering protect the ring conductor from the outside environment, thereby completing the design. Although this coaxial model has been the industry standard for pacing leads for many years, the resulting bulk and stiffness of this four-layer design are significant compared with the simpler unipolar leads. Coradial bipolar leads addressed some of these concerns with new conductor and insulator technology that was subsequently used in ICD lead design. In coradial leads, a single coil extends down the length of the lead (again with a central lumen to allow for stylet insertion) and consists of two parallel, alternating conductor strands, one of which connects to the cathode and the other to the anode. Each conductor strand is individually coated with a bonded layer of ethylene tetrafluoroethylene (ETFE) fluoropolymer insulation (originally by DuPont, Wilmington, Del), which serves to insulate each strand from the other, despite being intertwined. The single, two-component coil is surrounded by a single, outer insulation covering.18 These leads have comparable bulk (~5F diameter) and flexibility to unipolar leads, often with tines or a fixed, nonretractable helix to minimize size; electrical parameters and reliability have not been demonstrably inferior to coaxial leads.18-21 Defibrillator leads have even greater complexity, with two, three, or four conductors that connect to the pacing/sensing electrodes as well as to the high-voltage shocking coil(s), depending on the specific type of lead. Because of the prohibitive bulk that would result from a coaxial design with more than two conductors, ICD leads generally have a different type of structure, known as a multilumen design. This type of ICD lead consists of a long cylinder of insulating material, with separate internal channels running down its length (Fig. 4-3). Each conductor runs down an individual channel, usually with its own additional covering tube of insulation. The configuration and number of channels differ, depending on the number of conductors, the specific manufacturer, and whether air-filled channels are also

Urethane ETFE

Sense

COAXIAL DESIGN Ring Tip

A

Outer insulation Inner insulation

CORADIAL DESIGN

Compression lumen

Defib

Tip

PTFE

B

Ring

Outer insulation

Figure 4-2  A, Coaxial lead body design consists of two nested coil conductors to the tip and ring electrodes, each wrapped in a separate layer of insulation. The inner coil connects to the tip cathode and contains a central lumen for stylet passage; the outer coil connects to the ring anode. B, In coradial design, a single coil contains the parallel conductor strands to the tip and ring electrodes, with each strand covered by a fluoropolymer insulator. A surrounding layer of outer insulation covers the lead body.

HP silicone

Pace

Figure 4-3  Multilumen ICD lead design consists of a single body of insulation with several internal channels that contain the conductor elements (central pace/sense coil and outer high-voltage cables), each covered by its own layer of fluoropolymer insulation. A surrounding layer of outer polyurethane-based insulation is present. HP, Highperformance. (Courtesy Medtronic, Minneapolis.)



4  Engineering and Construction of Pacemaker and ICD Leads

Deflectable delivery catheter

129

DFT conductor strands are then formed into multifilar (i.e., multiple strands or filaments) coils with a central lumen in coaxial leads, as described earlier, or further coated in a layer of ETFE fluoropolymer before being arranged in bifilar coradial coils,28 again with a central lumen. The alternative way of forming a composite-wire conductor is the drawn brazed strand (DBS) method, generally consisting of six strands of a high-resistance material (e.g., MP-35N) that are tightly molded over a central strand of silver, such that the inner, low-resistance metal is forced between and around the strong outer strands (Fig. 4-5, Drawn filled tube

Figure 4-4  Isodiametric, lumenless, 4.1F pacing lead (Model 3830 SelectSecure). There is no central lumen for stylet passage, so the lead is deployed through an 8.5F steerable catheter delivery system (SelectSite C304) at implantation. (Courtesy Medtronic, Minneapolis.)

incorporated into the design to improve lead handling and protect the conductors from flexion-related damage in the dynamic intracardiac and intravascular environment. One other lead body structure worth mentioning are small (4.1F diameter), isodiametric, lumenless pacing leads (Model 3830 SelectSecure; Fig. 4-4). The lack of a central lumen and the use of a conductor cable (rather than coil) allows for increased insulation redundancy, high tensile strength, and reduced bulk. It also means that the activefixation helix is nonextendable because there is no central coil conductor to transmit torque from the connector pin to extend or retract the helix. Fixation of such leads to the myocardium is achieved by turning the entire lead body. To enable implantation without a stylet, the lead is deployed through an 8.5F steerable catheter delivery system (SelectSite C304). Short-term results from this lead have been reasonable, with no signs of increased lead displacement or fracture risk.22,23 The small external diameter of this lead has been considered to be of some benefit in pediatric patients24 and patients with congenital heart disease,25 but the suggestion of a resulting improvement in chronic venous patency from the smaller size is yet to be substantiated in longterm follow-up. In addition, selective site pacing, in both the atria and the ventricles, is facilitated by the deflectable sheath, although steerable and preformed stylets can also be used with conventional leads to achieve this. No published experience with extraction of chronically placed lumenless leads exists, and the lack of a lumen to accommodate a lead-locking device may be a significant disadvantage of this design.

Silver core

MP−35N

A Drawn brazed strand

CONDUCTORS Both the coaxial and the coradial bipolar pacing lead body designs have been in widespread use and proved to be relatively fracture resistant over time. This durability is at least partially related to the materials and design of the conductor elements used in pacing leads. One study found conductor fracture over a 17-year follow-up in 19 of 561 right ventricular pacing leads (3.4%) and then generally at points of high stress, such as at the lead anchoring sleeve and the costoclavicular ligament (subclavian crush).26 The basic material used for most conductors over the last 3 to 4 decades has been MP-35N (SPS Technologies, Cleveland), an alloy of nickel, cobalt, chromium, and molybdenum. The main advantage of MP-35N is its high strength and resistance to corrosion.27 Its main disadvantage is its high electrical resistance, but this has been overcome with the development of composite-wire conductors that incorporate low-resistance metals such as silver and stainless steel with high-strength materials such as titanium, platinum, and platinum-iridium alloy. In pacing leads, these materials are generally incorporated into a drawn filled tube (DFT) composite-wire conductor strand consisting of a thick, strong body of MP-35N or titanium that has been filled with a central core of softer, low-resistance metal such as silver, often encased in a further outer shell of platinum alloy (Fig. 4-5, A). The

Silver

MP−35N

B Figure 4-5  Composite-wire conductor design. A, Drawn filled tube (DFT) composite wire; thick body of MP-35N is filled with softer, lowresistance silver. B, Drawn brazed strand (DBS) wire; six strands of MP-35N are tightly molded over a central strand of silver. DFT and DBS composite wire can then be further fashioned into multifilar coil and cables. (Courtesy St Jude Medical, Sylmar, Calif.)

130

SECTION 1  Basic Principles of Device Therapy

B). This results in a low-resistance, durable composite conductor wire that can once again be formed into a multifilar coil for use in pacing leads.29 However, it is also used to form strong, multifilar, braided cables that are employed as the conductors for the high-voltage circuitry of ICD leads. DBS cables are discussed later.

Environmental stresss cracking

INSULATION Pacing lead insulation is a critical and vulnerable component that is often the cause of lead failure.30,31 One of the problems with the major materials used for lead insulation (polyurethane, silicone rubber, fluoropolymers) is that they were not originally designed specifically for this purpose, and each has disadvantages when used as part of a biologic pacing system. They were incorporated by early lead engineers into their designs for lack of any purpose-built alternatives, and it is only recently that any viable, tailored alternatives have been developed. Poly(ether)urethane is a synthetic, segmented polymer with very high tensile strength and resistance to mechanical abrasion. From a physical perspective, this means that a thinner layer of insulation can be used to cover the lead conductors, thereby reducing the overall lead diameter. Also, polyurethane has excellent lubricity and handling characteristics, with a low frictional coefficient, which can facilitate implantation of two or three lead systems by decreasing the physical interactions between the leads. However, polyurethane leads are stiffer and not fully biostable, being subject to in vivo polymer degradation that can cause insulation and late lead failure.32 The two main types of polyurethane are Pellethane 80A and Pellethane 55D (Upjohn, CPR Division, Torrance, Calif), with 80A particularly prone to biodegradation. Two mechanisms of in vivo, biologically mediated degradation of polyurethane predominate: environmental stress cracking (ESC) and metal ion oxidation (MIO)33 (Fig. 4-6). When polyurethane is subjected to repeated mechanical stresses in the presence of surface-active agents provided by macrophages and α2-macroglobulin, parallel polymer molecules are disordered and interchain bonds weakened. This is the mechanism of ESC,34 manifesting as a deep surface cracking visible with electron microscopy, particularly at the anchoring sleeve and venous entry portions of the lead. By comparison, no mechanical stress is required for MIO to develop because this is a chemical reaction that occurs particularly at the conductor-insulator interface.35 Biologic oxidants, such as peroxide from surrounding inflammatory cells,36 can result in the release of metal cations from the conductor, especially cobalt and nickel ions. These cations cause oxidation of the soft zones in the polymer, starting at the α-carbon of the ether bond and resulting in chain break. The harder Pellethane 55D is much less susceptible to both ESC and MIO than 80A but is significantly stiffer. Nevertheless, the long-term performance of Pellethane 55D has been much better than Pellethane 80A, a material notoriously prone to failure. Silicone rubber (polysiloxane) has none of the disadvantages of polyurethane. It is completely inert and biostable over extended periods and thus not vulnerable to MIO or ESC. Silicone is more flexible, which may decrease the risk of damage to cardiac structures, including lead perforation. It is also more thermally resistant to the effects of electrocautery, which can be a significant advantage during pulse generator replacement or system revision.37 Initially, a softer peroxide-catalyzed silicone rubber, MDX4-4515-50A, was used for pacing leads, but new versions with higher tensile strength and abrasion resistance have been developed. These include high-performance (HP) silicone, extra-tear-resistant (ETR) silicone, and Novus (Med4719, Nusil Technologies, Carpinteria, Calif), produced by hybridizing HP and MDX4 silicone. Unfortunately, no variety of silicone rubber has the positive characteristics of polyurethane, including surface lubriciousness and ease of handling. Although these friction-related problems of silicone can be addressed by an outer layering of polyurethane, the main problem with silicone relates to its lower tensile strength and susceptibility to abrasion and tears (Fig. 4-7, A). This means that silicone insulation is more prone to damage during

A Metal ion oxidation

B Figure 4-6  Mechanisms of polyurethane insulation failure on electron microscopy. A, Environmental stress cracking (ESC) results from mechanical stress, leading to disruption of polymer molecule arrays and interchain bonds. B, Metal ion oxidation (MIO) of the polymer soft segments causes polymer chain break. (Courtesy St Jude Medical, Sylmar, Calif.)

implantation and subsequent interactions in the device pocket, and that a thicker insulation layer must be used to maintain lead reliability, thereby increasing lead bulk. Also, as with glass, silicone is a fluid material and thus prone to a gradual flowing process away from pressure points, known as “cold flow,” which can lead to thinned, denuded, and abraded troughs or depressions adjacent to areas of thickened rubber polymer32 (Fig. 4-7, B). The fluoropolymers polytetrafluoroethylene (PTFE) and ETFE (DuPont) have some of the advantages of both silicone and polyurethane, with good abrasion resistance and biostability.38 Unfortunately, their great stiffness excludes them from functioning as the primary insulating material in any lead, but they can be used, as outlined earlier, as a thin coat on conductor strands, particularly in coradial leads. This inner insulating layer can prevent electrical communication between conductor strands and can also protect them from interacting with an adjacent outer layer of polyurethane, thereby reducing MIO. Recently, the development of a specific insulation material for cardiac leads has suggested that the deficiencies of the standard insulators in pacing leads may finally be addressed. The material is a copolymer hybrid composed of 48% silicone, 40% polyurethane hard segment, and 12% polyhexamethylene oxide soft segment; it is called Elast-Eon (Aortech Biomaterials, Clayton, Victoria, Australia). This



4  Engineering and Construction of Pacemaker and ICD Leads

Abrasion: 4 years

A

Silicone abrasion

Cold flow: 1 year

B

Silicone cold flow

Figure 4-7  Mechanisms of silicone rubber insulation failure. A, Weaker molecular structure of silicone makes it more prone to abrasions and tears at points of higher mechanical stress. B, Glasslike fluid composition of silicone renders it susceptible to cold flow away from areas of higher pressure. (Courtesy St Jude Medical, Sylmar, Calif.)

blending of insulating materials results in the product having the strength, lubricity and abrasion resistance of polyurethane, but the flexibility and biostability of silicone.39 Early bench and clinical testing have been promising to date, with little evidence of cold flow, ESC, or MIO phenomena, the main weaknesses of silicone and polyurethane. The material has been used in the St. Jude Medical Optim family of pacing (Models 1888T and 2088T) and ICD leads (Durata), but no long-term data on its chronic performance are yet available.

131

although vitreous carbon cathodes have particular strength, inertness, and long-term electrical reliability.45 More important than the precise material composition of electrodes seems to be their geometry, particularly the surface area. A large cathodal surface area in contact with the endocardium results in a low current density at the electrode-tissue interface and consequently a higher capture threshold. As tip electrodes were reduced in surface area, apart from better thresholds, higher tissue-electrode impedances were also seen, and this increased pulse generator longevity.46,47 Against this beneficial effect of a smaller electrode is the adverse effect on tissue polarization seen with a smaller electrode surface area. Polarization refers to the electrical afterpotential generated at the electrode-tissue interface by ionic movement induced by the pacing stimulus. At pacing pulse delivery, a layer of positively charged cations is attracted to and surrounds the negatively charged cathode (and a larger layer of negatively charged anions surrounds the cation layer), which opposes current flow from the pacing electrode. This polarization potential is recorded as an afterpotential following the stimulus artifact. To maximize the advantages of small-radius electrodes, yet minimize the disadvantage of the polarization effect more prominent with smaller electrode surface area, current electrodes are small in size but have a complex, porous microscopic surface (Fig. 4-8). Regardless of the method of achieving a complex, highly textured surface, such as coating the electrode with microspheres or a woven mesh of microscopic metallic fibers, the resulting large surface area has proved beneficial with regard to pacing and sensing performance. Titanium nitride–coated or iridium-coated cathodes with fractal surface structure achieve the goal of enhanced surface area with a negligible polarization signal48 (Fig. 4-9). Such electrodes have permitted the development of beat-by-beat automatic capture threshold and pacing output management systems that measure the evoked myocardial response following every pacing stimulus. By verifying myocardial capture for each paced beat, with the immediate delivery of a backup higher-output pulse if capture is lost (Fig. 4-10), the pacemaker can maintain a pacing output only marginally above the capture threshold, thereby prolonging pulse generator battery life.49 Another type of automatic threshold algorithm does not verify beat-to-beat capture, but performs an automatic threshold test daily and adjusts the pacing output accordingly (with larger safety margin above capture

ELECTRODES Electrodes represent the final common electrical and mechanical interface between the lead and myocardium. The design and construction of the electrodes influence the acute and chronic electrical performance of the lead. Because the electrode type also determines the fixation mechanisms employed and the lead tip pressure generated, however, mechanical problems such as lead dislodgement and cardiac perforation can also be affected by the tip electrode. The materials used for lead electrodes have evolved over the past 40 years and have included titanium, anodized platinum, platinumiridium alloys, Elgiloy (an alloy of cobalt, iron, chromium, molybdenum, nickel, and manganese), and vitreous carbon. All these display relative inertness in vivo, which minimizes inflammatory reactions and corrosion over the long term. Minor corrosion is seen, however, with Elgiloy and platinum alloys when in situ for extended periods, although this is of uncertain clinical significance.40 While attempting to control for other differences, several human and animal studies have compared these materials, but the results are conflicting.41-44 In general, applications have been found for these materials in electrode composition, with most having reasonable in vivo performance and longevity,

Figure 4-8  Sintered porous electrode (left) and laser porous electrode (right). (From Hirshorn MS, Holley LK, Skalsky M, et al: Characteristics of advanced porous and textured surface pacemaker electrodes. PACE 6:525-536, 1983.)

132

SECTION 1  Basic Principles of Device Therapy

A

B

Figure 4-9  Magnified view (A) and electron micrograph (B) of fractally coated, titanium nitride electrode tip, which optimizes surface area and minimizes polarization resistance. (Courtesy St Jude Medical, Sylmar, Calif.)

threshold). These types of automatic capture-detection algorithms can be unreliable in the setting of a significant polarization afterpotential, because a large polarization signal cannot be distinguished from the local myocardial evoked response.50 Electrodes implanted in myocardium elicit a strong foreign body granulomatous reaction that results in the formation of a local fibrous A

B

capsule at the lead tip, which can have a profound effect on electrical performance. Smooth-surfaced electrodes elicit the formation of a thick, electrically insulating capsule of fibrous and granulation tissue that may impede electrode fixation to the endocardium.51 Complex, porous electrodes, in contrast, are manufactured to have extremely small (20-50 µ in diameter) surface pores that allow for endocardial C

D

II

V5

B 2 1

3

Figure 4-10  Automatic loss of capture algorithm (Autocapture). The atrioventricular (AV) delay is shortened to ensure ventricular pacing (A). The pacing output is automatically decreased until loss of capture is detected by failure to sense a myocardial-evoked response at B2. A backup 5-V pulse is delivered at B3, followed by an automatic gradual increase in pacing output that restores myocardial capture (C), and then resumption of dual-chamber pacing is seen, with the programmed AV delay (D). Modern leads produce negligible polarization afterpotential and thus allow for high-fidelity sensing of the myocardial-evoked response. (Courtesy St Jude Medical, Sylmar, Calif.)



4  Engineering and Construction of Pacemaker and ICD Leads

Steroid plug

133

1699T Optisense, St. Jude Medical) with a standard 10-mm spacing, the close-spaced bipole showed minimal far-field ventricular sensing at a sensitivity of 0.3 mV, compared to 30% 1-year incidence in the standard-bipole group.56 This translated into a large reduction in inappropriate mode switch events, from 23% in the control group to 4% in the narrow-bipole group. FIXATION MECHANISMS

A

Steroid plug

B Figure 4-11  Dexamethasone-eluting reservoirs in passive-fixation (A) and active-fixation (B) leads. (Courtesy St Jude Medical, Sylmar, Calif.)

attachment by way of tissue ingrowth into these regions, which yields a mechanical advantage in addition to the electrical benefits mentioned earlier. A fibrous reaction also occurs with highly textured electrodes, but a lesser insulating effect is observed because the electrically active myocardium is closer to the electrode,51 resulting in improved electrical parameters over time.52 To curtail further the fibrous reaction elicited by the electrode and to decrease the incidence and magnitude of chronic threshold rises, a pharmacologic anti-inflammatory strategy was pursued with glucocorticoid-eluting porous electrodes (Fig. 4-11). These leads showed excellent long-term capture and sensing parameters, with a dramatic reduction in late exit block (i.e., loss of myocardial capture).8 In an elegant and seminal double-blind randomized trial, Mond et al.9 conclusively proved the beneficial effect of steroid elution by comparing two otherwise identical porous titanium electrodes, only one of which incorporated dexamethasone in its tip. There was no difference in capture threshold seen at implant. Although there was an expected late rise in threshold in the standard leads starting at 2 weeks, this was completely abolished in the steroid-eluting lead, both during the trial period and in long-term follow-up.53 Animal studies confirmed that the biologic basis of this electrophysiologic effect was through the glucocorticoid-induced attenuation of the inflammatory reaction, with thinner, less cellular fibrous capsules.54 In bipolar leads, another factor affecting electrical performance, particularly far-field sensing, is the interelectrode distance between the tip cathode and the ring anode. Narrow-spaced bipolar electrodes in atrial leads have been shown to reduce far-field ventricular electrogram sensing without compromising atrial sensing.55 In a randomized trial that compared an atrial lead with a 1.1-mm tip-to-ring spacing (Model

Initial pacemaker leads had no fixation mechanisms, so lead dislodgement rates were high. The first solutions to this problem were wedgeshaped flanges and fins, but these had limitations. The development of scalloped tines was the first robust solution to the problem of lead displacement,5 and comparisons with earlier methods of passive fixation were favorable.57 Tines are usually constructed from the same material as the covering insulation of the lead, typically silicone rubber, and protrude backward from the base of the tip electrode. Their orientation is designed to allow advancement of the lead for initial implantation but to prevent retraction and dislodgement by engaging the myocardial trabeculae of the right atrial appendage and right ventricular apex (Fig. 4-12, A). Although passive-fixation tined leads perform well, with low rates of dislodgement, they are less reliable for pacing at nontraditional sites, and the development of active-fixation leads with a helix at the tip improved the options for pacing site selection (Fig. 4-12, B). These leads generally have an extendable-retractable screw made of platinumiridium or similar alloy that is usually electrically active as part of the cathode. This terminal helix is deployed (i.e., extended out of lead) with clockwise rotation of the connector pin, which transmits torque via the central coil conductor to the helix mechanism at the other end of the lead. A small number of leads use a stylet-driven extension-retraction mechanism. Some smaller-diameter leads have a fixed helix that requires rotation of the entire lead body around the stylet for deployment into the myocardium. Steroid elution from a reservoir at the base of the helix helps to dampen the inflammatory reaction produced by traumatic engagement of the myocardium by the screw. Active- and passive-fixation leads perform similarly overall,58 with some differences related to their construction. Active leads tend to be easier to extract, whereas passive leads tend to have lower chronic thresholds with higher impedances that prolong pulse generator longevity. The clinician must always consider the potential for perforation59 and trauma to surrounding structures60 when using active-fixation leads.61

A

Passive fixation

B

Active fixation

Figure 4-12  Lead fixation mechanisms. A, Passive-fixation tined lead. The tines are constructed of outer insulation material and facilitate advancement of the lead but prevent its retraction by engaging myocardial trabeculae in the right ventricle or right atrial appendage.  B, Extendable-retractable helix is deployed to screw directly into the myocardium in an active-fixation lead. (Courtesy St Jude Medical, Sylmar, Calif.)

134

SECTION 1  Basic Principles of Device Therapy

Figure 4-13  Lead anchoring sleeves. Each sleeve contains up to three grooves to allow for suturing the sleeve to the lead body, then to the underlying deep fascia in the pocket. (Courtesy St Jude Medical, Sylmar, Calif.)

IS-1 (pace/sense)

A

LEAD ANCHORING SLEEVES Securing the lead body to the fascia or muscle at the floor of the device pocket at implantation is an important step to prevent lead dislodgement. The sutures used must be fastened firmly but, given the relative fragility of lead insulation as previously outlined, must not be allowed to compromise the lead structure or integrity (Fig. 4-13). Although the anchoring sleeve provides a mechanism to achieve this balance, there has been little development in this area. After being tied down tightly, sleeves made of MDX silicone were found to produce much lower lead deformation than ETR silicone,62 but no long-term in vivo data are available. Suture sleeves that grasp the lead by snapping into place (rather than relying on circumferential deformation of sleeve by encircling suture) have been proposed but are not in current use. CONNECTOR TERMINAL PINS The connector terminal pin forms the interface of the lead with the header of the pulse generator and has gone through significant evolution. With successive generations of pulse generator and lead technology, various standards for connector terminal pins for pacing leads have been used,63,64 as well as two different pin-fixation mechanisms within the device header, the side lock, and the now-universal set screw. Reliability has been high with both pin-header fixation interfaces, although the more forgiving tolerance of the set-screw platform has led to its widespread adoption.65 This design requires a self-sealing grommet to cover the head of the set screw and prevent corrosion of the pin or header connections because pocket fluid enters the header. Sealing fins are required around the lead body or within the header channel to prevent fluid leaking into the header at that site, regardless of the fixation mechanism. Different patterns of connector pins include the 5- and 6-mm-long pins, the 3.2-mm low-profile pin, the VS-1 pin, and the current standard IS-1 connector pin (Fig. 4-14). Compatibility CONNECTOR SIZE OR STANDARD

6 mm, 5/6 mm, 5 mm

3.2 mm

IS−1 Figure 4-14  Evolution of pace/sense connector pins, culminating in current IS-1 standard (bottom).

• 3.2 mm diameter • no sealing rings in header • short receptacle for B lead terminal

IS-1

Figure 4-15  A, IS-1 pace/sense connector pin terminal. B, Cross section of IS-1 header.

between terminal pin type and header channel type is still of major concern when changing pulse generators in patients with older leads. Modern pulse generator headers conform to IS-1 specifications (Fig. 4-15) and are backwards-compatible with VS-1 pins. Occasionally, for example, adapters may be required to downsize a long pin connector to an IS-1 header.

  Resynchronization Leads The symptomatic and prognostic benefits of cardiac resynchronization therapy (CRT) in congestive heart failure patients with electrical dyssynchrony (asynchrony), usually in the form of native left bundle branch block (LBBB) or right ventricular pacing, have been repeatedly demonstrated in those already receiving maximal medical therapy.66,67 Leads used for providing CRT are exposed to different implant conditions than conventional pacing leads and thus have different design parameters. The benefits of CRT were first demonstrated with the placement of left ventricular (LV) epicardial leads. CRT leads can be implanted directly on the epicardium by an open or video-assisted thoracotomy. These leads are, or have similar characteristics to, standard epicardial pacing leads (Fig. 4-16). They are generally sutured or screwed in place on the lateral LV wall. Increasingly, patients who undergo cardiac surgery for coronary disease or valve dysfunction, but who also have heart failure, LV dysfunction, or a chronic need for pacing because of heart block, are having LV epicardial leads implanted at surgery, with the terminal pin end tunneled up to the left infraclavicular fossa for future connection to a CRT device. However, a transvenous approach to LV epicardial lead placement avoids the morbidity and mortality of an open surgical approach and is usually the preferred initial implantation method for patients not otherwise scheduled for cardiac surgery. Therefore, most candidates for CRT therapy have their LV lead implanted transvenously into one of the venous tributaries of the coronary sinus. Compared with standard endocardial pacing, this technique has two challenges:(1) placing the lead into a desirable location despite venous tortuosities, acutely angled branch ostia, obstructive venous valves, patches of myocardial scar with high capture threshold, and regions of phrenic nerve capture, and (2) once placed, achieving stable lead fixation within the thinwalled coronary vein (vs. relative ease of standard tined electrode or active-fixation helix obtaining purchase on endocardial wall of cardiac chamber).



4  Engineering and Construction of Pacemaker and ICD Leads

Figure 4-16  Epicardial active-fixation steroid-eluting leads, implanted surgically. Lead on the left has an active-fixation helix, whereas two electrodes on the right are sutured to the epicardium. (Courtesy St Jude Medical, Sylmar, Calif.)

LEAD PLACEMENT AND FIXATION MECHANISMS For accessing the stimulation site, CRT lead systems come with a range of outer guide introducers to facilitate coronary sinus cannulation and provide support during lead placement. Although the initial transvenous CRT leads were stylet driven, over-the-wire leads were rapidly introduced because of difficulty negotiating venous tortuosities and acute takeoff angles. The development of an over-the-wire system was a major advance,68 and such leads are routinely required to select and place leads in the best possible target venous branches, usually over the posterolateral left ventricle. These leads allow for front or back loading of a 0.014-inch angioplasty wire into the stylet lumen. With or without the assistance of inner guiding catheters, the wire may be used to subselect target venous branches (including those with acute takeoff angles) and the lead may then be tracked over the pre-positioned wire. Obtaining distal vascular access with a wire also allows for venoplasty to facilitate lead placement in the setting of stenotic vascular segments.

135

Once at the target site, and with retraction of the wire or stylet back into the lead body, most lead tips have some degree of memory and assume the form of a preshaped curvature, which may be a smooth curve, an angled cant, or a spiral (Fig. 4-17). These distal lead shapes provide some degree of stability in the target vein by exerting modest lateral pressure on the inner vein surface, thereby increasing friction and a resistance to forward or backward migration. LV lead models that have no distal curvature use small, distal tines to engage the venous wall, but these tines likely have a reduced ability to fix the lead passively in place, particularly in larger vein branches. Thus, stability of tined leads probably relies more on lead flexibility and the cumulative friction along the lead length wherever it is in contact with the venous wall. These straight leads seem to have a higher risk of dislodgement, and subsequent generations of CRT leads have not incorporated tines. In most cases the major contributor to LV lead fixation in the coronary venous system has been the extent to which the outer lead diameter is circumferentially opposed to the inside wall of a venous tributary of given caliber. If the lead has been advanced snugly into a vein branch, significant fixation friction forces may be generated, but lead stability remains variable. The risk of dislodgement also depends on upstream factors, including the number and size of redundant loops and tortuosities in the proximal course of the lead body, cardiac motion, tricuspid valve regurgitation, and interactions with other intracardiac hardware, which can each generate traction forces on the LV lead. Consequently, there is a significant rate of CRT lead displacement of up to 1% to 5% that may require surgical lead revision if there is a significant change in electrode position, ventricular capture threshold, or phrenic capture.66,69,70 The concept of active-fixation leads in the coronary venous system has been brought to clinical practice with the Attain StarFix lead (Model 4195, Medtronic, Minneapolis), which has three sets of deployable lobes that fold out and protrude from the lead body just proximal to the tip (Fig. 4-18). These 12 circumferential lobes are extended by an external sliding-push tubing mechanism, and radiopaque markers are used to indicate whether one, two, or all three sets of lobes are extended or retracted. In a recent multicenter study of 408 implants, Crossley et al.71 found a very low lead dislodgment rate of 0.7% with stable electrical parameters over a mean follow-up of 23 months. Phrenic nerve capture with this unipolar lead required lead revision in 11 patients (2.5%). This reasonable performance must be weighed, however, against potential difficulties of extraction, which fortunately has not been a major issue in the other LV lead models to date. In this study of the active-fixation LV lead, 26 patients (6.4%) underwent an

Figure 4-17  Representative variety of currently available resynchronization leads with differing passive-fixation curvatures. (Courtesy Medtronic, Minneapolis; St Jude Medical, Sylmar, Calif; and Boston Scientific, St Paul, Minn.)

136

SECTION 1  Basic Principles of Device Therapy

output is inadvertently programmed below the true LV capture threshold, because RV anodal capture is mistaken for LV cathodal capture during threshold testing.75 No significant differences have been noted in the short-term and long-term complication rates after CRT implantation among the various leads and CRT systems commercially available.76

ICD Leads

Figure 4-18  Active-fixation resynchronization lead (Attain StarFix, Model 4195) with deployable lobes to grip the lumen of the coronary venous tributary in which it is implanted. (Courtesy Medtronic, Minneapolis.)

attempt at lead revision. In two patients, no attempt to remove the lead was made, and in the remaining 24 revisions, five attempts failed (21%). These patients had maximum implant duration of only 941 days. Of the seven patients who had a lead in situ for more than 1 year, four (57%) were unable to be extracted. This study is similar to the experience of Nagele et al.,72 who encountered extraction difficulty caused by immobile lobes in two patients. The ability to un-deploy the lobes seems to be independent of the duration of implant and may be related to local branch vein thrombosis or an ingrowth of fibrous tissue through the lobe loops. Although both these studies were small and represented early experience with this lead, the difficulties with extraction of the StarFix lead contrast with the relative ease of extraction of chronic LV leads, even after extended periods since implantation.73 DESIGN OF CRT LEADS The original CRT leads were exclusively unipolar because of size considerations, given that LV leads had to be advanced through a long, smaller-caliber sheath that was used to engage the coronary sinus selectively. An early example was the EasyTrak lead family (Models 4510/11/12/13, Guidant, St. Paul, Minn.), which had a 6F lead body diameter and an LV-1 connector terminal pin compatible only with LV-1 headers on Guidant CRT pulse generators. Since then, numerous developments in lead size, polarity, and CRT device programmability have greatly increased the options available to the implanting operator, including lead and device options to manage the problem of phrenic nerve capture, as well as to find suitable pacing configurations in the setting of myocardial scar. Most significantly, bipolar CRT leads were developed that were no larger in diameter than the previous generation of unipolar leads and that could therefore be deployed through the same sheath delivery systems and into venous branches of the same caliber. Newer LV lead versions include 4F to 5F leads that can be advanced through smaller venous subselection sheaths, into more diminutive vein branches, which increases the number of lead positioning options. The interelectrode distance in bipolar CRT leads varies from 8 to 21 mm. The great advantage of bipolar leads is the option of programming between multiple different pacing electrode permutations, including true bipolar and extended bipolar configurations, with the option of selecting whether to use the LV tip or the LV ring electrode as the pacing cathode (Fig. 4-19). These programming options may be invaluable in the patient with posterolateral LV fibrosis or a large field of phrenic nerve capture, where an alternate pacing polarity may obviate the need for lead revision. True bipolar LV pacing also eliminates the problem of simultaneous right ventricular (RV) anodal capture, which can be seen in the setting of unipolar LV lead use and can sometimes partially undermine the benefit of LV pacing.74 Anodal capture from the RV ring or coil electrode can hinder proper CRT delivery by eliminating the ability to stimulate the left before the right ventricle, and occasionally by leading to absent LV pacing if the pacing

The development of the implantable cardioverter-defibrillator was a revolutionary step in the history of medicine.77 Sudden-death prevention became an achievable goal, initially in those who had survived cardiac arrest or malignant ventricular arrhythmias,78 but then in patients at risk of dying suddenly (primary prevention).79,80 Modern ICD systems are extremely sophisticated devices, frequently combined with CRT capability, that feature advanced rhythm-discrimination software, antitachycardia pacing (ATP) during capacitor charging, and high-voltage biphasic shocks, all in a pectorally implanted device of 40 cc or less. Advances in pulse generator technology and reliability are important but of limited relevance if progress cannot be matched in ICD lead design, development, and particularly durability. The reductionist view of ICD leads as simply being “pacemaker leads with additional shock coils” ignores the exponential rise in complexity as more components are added. This complexity puts pressure on long-term reliability in a device expected to cope repeatedly with 800-V highcurrent discharges and move with the heartbeat 37 million times annually. As longer follow-up data are published on both older and newer ICD leads, despite the innovations and developments in recent years, clearly this most vulnerable part of the ICD system continues to be prone to late failure.81-84 HISTORICAL EVOLUTION OF ICD LEADS Epicardial patches placed through thoracotomy were the leads first used in human ICD systems.77 The pulse generators in these systems were large and required placement in an abdominal pocket. Shock energy was delivered through a free-floating 12F nonpacing endovascular titanium spring coil that served as the anode, with the patch as the cathode. Sensing was accomplished initially by epicardial patches (or apical cup electrode in the first implant), but this sensing mechanism proved to be unreliable, and dedicated epicardial and endocardial leads were adopted early. These first-generation ICD systems had a high risk of complications, particularly in the large endovascular coil,

6

4

2

5

1 LV lead

RV lead

3

Figure 4-19  Multiple different pacing polarity configurations are possible with modern bipolar resynchronization leads and generators. Each arrow originates at the cathode and ends at the anode of current left ventricular (LV) lead pacing configurations. RV, Right ventricular.



4  Engineering and Construction of Pacemaker and ICD Leads

including superior vena cava thrombosis, coil fracture, insulation failure, and coil retraction into the subclavian vein caused by lack of a lead anchoring sleeve. Consequently, the second-generation ICD devices in the late 1980s were fully epicardial systems, with shock delivery between two epicardial patches and tachyarrhythmia sensing through an epicardial lead. Epicardial patches also had problems, however, including an ongoing infection and pericarditis risk,85 a possible adverse effect on transthoracic external defibrillation threshold, and a perioperative mortality of up to 4% at implantation in these patients, who were generally at high risk for thoracotomy or median sternotomy.86,87 These patch electrodes also displayed poor in vivo durability over time, with a failure rate of up to 28% at 4 years. More than half of patients with obvious lead failure or fracture were asymptomatic. The epicardial pace/sense leads incorporated in these systems were also suspect, with a failure rate of 14.1% at 8.5 years in one study, with lead fracture accounting for half these failures.88 In contrast to patch failure, patients with epicardial pace/sense lead failure were likely to develop multiple inappropriate ICD shocks from oversensing.89 By the early 1990s, advances in pulse generator design and technology allowed miniaturization for infraclavicular pectoral implantation, although this would require an entirely endocardial defibrillation, sensing, and pacing lead system. The initial transvenous leads were implanted with the pulse generator in an abdominal pocket, and the leads were tunneled subcutaneously from their pectoral vascular insertion site down to the abdomen. Such leads, including the Transvene family (Medtronic), were initially based on coaxial pacing lead platforms. Their development added ATP capability to ICD systems, but also new lead-related problems. Apart from the large bulk of these leads (up to 12F), predisposing to venous occlusion and subclavian crush,90 lead failure was frequent, demonstrating a progressive late incidence related to both conductor fracture and insulation defects.91 Addressing these problems required paradigm shifts in lead body design as well as advancements in materials technology, which ushered in the modern era of multilumen, narrow-caliber transvenous ICD leads. ICD LEAD STRUCTURE The basic elements in pacing leads are also found in transvenous ICD leads: conductors, insulation, electrodes, fixation mechanisms, and connector terminals. In addition, however, ICD leads contain the highvoltage circuitry that links the pulse generator with one or two highvoltage shock coils located on the lead body (Fig. 4-20). One of these coils is located in the right ventricle, a variable distance proximal to the tip pace/sense electrode, whereas the other coil, if present, is positioned on the part of the lead located in the superior vena cava.

A

137

Two basic lead body architectures can be used to incorporate all these elements into an ICD lead. First, the coaxial structure, a design essentially borrowed from the pacing platform of the same name, consists of concentric coiled conductors (to tip electrode, ring electrode, and shock coils) layered inside one another and separated by intervening layers of insulation, with the whole assembly housed in an outer covering layer of insulation. The innermost coil connected down to the tip conductor contained a lumen for stylet insertion that assisted with endocardial lead implantation. The best known examples of this design were the Medtronic Transvene and the Ventritex TVL families of ICD leads, first used in the early 1990s. Although initial reports were positive,92 subsequent longitudinal data showed that these leads were prone to early and late failure, caused by a combination of conductor and insulation problems.83,91 Whether these failures were mainly related to the limited durability of the conductor and insulation (polyurethane 80A) materials, or resulted from an inherent weakness of the bulky coaxial architecture in situations of increased complexity as found in ICD leads, will never be known; this design was no longer in use by the late 1990s. The second main paradigm for ICD lead structure, and still the dominant architecture for modern ICD leads, is the multilumen design, in which parallel cable and coil conductors run to the tip, with ring and shock electrodes in separate channel lumens, all within a single frame of insulation; some models also have additional, empty decompression lumens. The conductor to the tip electrode is conventionally coiled and contains the central lumen for stylet insertion. The coil also permits the transfer of torque when the implanting physician rotates the pace/sense connector terminal pin to deploy an active-fixation helix at the distal lead tip. Each conductor, both cable and coil, is invested with an inner layer of insulation, typically of fluoropolymer type, and the entire lead body is encased in a further outer insulation layer (see Fig. 4-3). ICD LEAD SENSING DESIGN Sensing function is critical in ICD systems to allow for accurate rhythm discrimination and to prevent inappropriate shocks from oversensing as well as failure of tachyarrhythmia treatment caused by undersensing. Therefore, unipolar ICD leads were not developed because of the prohibitive risk of oversensing noncardiac potentials, such as pectoral and diaphragmatic myopotentials. Bipolar ICD lead sensing can be arranged according to one of two paradigms: integrated bipolar and dedicated bipolar (also called true bipolar) designs. Sensing in integrated bipolar leads occurs between the tip electrode and the RV shock coil, which doubles as the sensing anode, the distal extent of which is located 6 to 15 mm proximal to the tip. By comparison, dedicated bipolar leads additionally include a conventional ring electrode (the

B

Figure 4-20  A, Dual-coil ICD lead with second high-voltage shock coil residing in the superior vena cava. B, Single-coil ICD lead with one shock coil in the right ventricle only. The active ICD pulse generator generally serves as the cathode or anode for the first phase of biphasic shocks.

138

SECTION 1  Basic Principles of Device Therapy

Integrated bipole lead

12 mm RV high-voltage electrode

A Dedicated bipole lead RV high-voltage electrode

B

25 mm

Ring for pacing and sensing

Figure 4-21  Design pullback. “Pullback” refers to the distance between the lower active edge of the right ventricular (RV) defibrillation electrode and the RV apex. Design pullback should be minimized for lower defibrillation thresholds. The diagrams show the impact of sensing methods on catheter design and the magnitude of the RV electrode pullback. A, Leads using integrated bipolar sensing/pacing methods (from tip to RV defibrillation electrode) typically have a shorter pullback distance (e.g., 12 mm here). B, Leads using dedicated bipolar sensing/ pacing methods have larger distances from catheter tip to active RV defibrillation electrode because of sensing ring (e.g., 25 mm here).

anode) 10 to 15 mm back from the tip, similar to a bipolar pacing lead (Fig. 4-21). The additional electrode means that an extra conductor is required in dedicated bipolar leads, but the smaller anode in these leads confers superior sensing performance with reduced far-field oversensing.93,94 The larger sensing anode (the distal shock coil) in integrated bipolar leads may be of particular concern in patients with small right ventricles, where the proximal end of the coil may extend across the tricuspid anulus and thereby pose a risk of far-field atrial oversensing.93 Integrated bipolar leads may be more prone to oversensing highfrequency respirophasic noise transients (i.e., diaphragmatic myopotentials), which may cause pacing inhibition and inappropriate shocks.95 The increased current density at the smaller anode of a dedicated bipolar lead does, however, increase the likelihood of anodal myocardial stimulation in CRT systems in which LV pacing is programmed in an “extended bipolar” fashion, with the RV ring doubling as the LV pacing anode,75 although in the current era of bipolar LV leads and pacing vector programmability, this is less of a concern. The main theoretical advantage of integrated bipolar leads, apart from their greater simplicity (which may reduce the chance for component failure), relates to the smaller distance between the RV shock coil in these leads and the RV apex, because there is no intervening ring electrode between the shock coil and the lead tip. This is known as the pullback distance, and data suggest a modestly improved defibrillation threshold with shorter pullback distance,96,97 although this was more important before the current era of high-output, biphasic devices and greater defibrillation safety margins. Theoretical concerns about differences in R-wave amplitudes between the two lead designs have not been borne out by comparative studies,98 but some studies suggest longer sensing latency98 with integrated bipolar leads, as well as the potential for undersensing of postshock ventricular fibrillation, presumably from local myocardial stunning around the shock coil and its proximity to the tip cathode.99,100 This phenomenon was not seen when the shock coil was more than 6 mm from the tip electrode. However, in terms of sensing de novo ventricular fibrillation, no significant differences have been demonstrated between the two lead platforms,101 and both are in clinical use today, although dedicated bipolar systems are implanted more frequently. CONDUCTORS As with pacing leads, similar materials are used in ICD lead conductor construction, with MP-35N being the dominant metal alloy employed. As outlined earlier, its advantages include its corrosion and fracture

resistance, but MP-35N–based conductors can still fracture at points of high stress (e.g., costoclavicular ligament). Recent testing suggests that this risk may be related to the presence of contaminant titanium inclusions, although this is controversial.102 In ICD systems, however, low-resistance conductors are essential to minimize voltage drops across the lead during high-voltage shock delivery. This requirement mandates the use of composite wire technology in which individual conductor strands combine higher-resistance MP-35N with a lowresistance metal such as silver in one of two patterns. The DFT pattern (see Fig. 4-5, A) produces conductor strands that are generally formed into coils, whereas in the DBS pattern (see Fig. 4-5, B), strands are twisted into multifilar braided cables (Fig. 4-22). The latter are particularly important in ICD leads because they have very high tensile strength and are more fracture resistant than coils. Failed ICD leads frequently demonstrate intact high-voltage cables with fractured pace/sense coil conductors. One conductor coil strand is generally required, as outlined earlier, to create a lumen for stylet insertion and to permit active-fixation helix deployment. However, the use of multiple parallel cables in a multilumen ICD lead design produces a stronger lead of smaller diameter than would be possible if only coiled conductors were used (as in the now-obsolete coaxial configurations). Each cable generally is housed in its own lumen of the multilumen lead by coating it with stiff, fluoropolymer insulation, preventing abrasion and damage to the soft, silicone-based insulation of the lead body (see Fig. 4-3). Decompression spaces, either within the lumen that houses a conductor or as separate channels in the housing insulation, may reduce the stress on the conductors, particularly in the setting of repeated lead flexion. ELECTRODES AND HIGH-VOLTAGE COILS Electrode composition and design in ICD leads conform to the same basic principles as outlined earlier for pacing leads, with steroid elution, current density, and polarization considerations again dictating the material composition of the tip cathode and ring anode in dedicated bipolar leads. Fixation mechanisms are also similar, with either electrically active extendable-retractable helices or flexible tines being employed. The high-voltage defibrillation shock coil is the defining feature of the ICD lead. All models include at least one shock coil, wrapped around the distal lead body, 5 to 6 cm in length and positioned in the right ventricle, whereas dual-coil leads have a second shock coil located either 17 cm or 21 cm proximal to the shaft end of the RV coil, with this superior vena cava (SVC) coil being slightly longer, 7 to 8 cm (see Fig. 4-20). The RV coil serves as the defibrillation anode or cathode during phase 1 of a biphasic shock, depending on how the ICD is programmed to deliver high-voltage therapy, with the SVC coil and active pulse generator casing together serving as the other shock cathode or anode. With single-coil ICD leads, the pulse generator solely functions as the second high-voltage electrode. Dual-coil leads may assist in lowering the defibrillation threshold (DFT), although the improvement in DFT with the addition of an SVC coil may be modest

Cable

ICD lead Coil Figure 4-22  Filar composition of unraveled high-voltage conductor cable alongside multifilar central pace/sense conductor coil in dissected ICD lead.



4  Engineering and Construction of Pacemaker and ICD Leads

and of greater benefit when the electrical impedance during single-coil shock delivery is higher.103 Because the high-voltage shock vector plays a role in DFT, some ICDs permit programming changes to eliminate either the SVC coil or the pulse generator itself from the shocking circuit, thereby improving the DFT in certain patients. Shocking coil– only leads are also available for implantation in the coronary sinus or azygous vein, or subcutaneously around the left thorax to improve the shock vector in patients with an elevated DFT and unreliable defibrillation with standard shock configurations. The materials used in shock coil construction are generally platinumiridium alloy or platinum alloy–clad tantalum, because titanium coils produce metallic oxides during high-voltage shocks that prevent their use in ICD leads. Polarization also affects the design of shock electrodes, as it does for pacing electrodes, but unlike the situation described earlier with pacing leads, fractally coating the shock coils does not improve defibrillation efficacy.104 However, some data suggest that iridium oxide coating may improve lead porosity and reduce polarization, even to the point of seeing a clinically meaningful reduction in DFT.105,106 Although an essential part of the ICD lead, the presence of endovascular defibrillation coils poses distinct physical problems, especially related to fibrous tissue ingrowth, which can make lead extraction difficult and potentially hazardous, as discussed later. INSULATION Essentially the same materials used in the manufacture of pacing lead insulation are also used in the context of ICD leads, and their respective advantages and disadvantages are discussed earlier. The multilumen design of ICD leads relies on a single, large-caliber body of insulation that contains the conductor lumens. Other insulation elements may include the jackets investing the conductor cables or an additional outer insulation covering, but the mechanical characteristics of the lead will largely be determined by the material used to construct the lead body. Because ICD leads are larger and more complex than pacemaker leads, silicone rubber is the dominant option for ICD lead body insulation; polyurethane 55D and fluoropolymers are too stiff for this purpose, and polyurethane 80A is too susceptible to biodegradation. The relative structural advantages of polyurethane 55D, lubriciousness and high tear strength, can be used to good advantage instead as an outer insulation layer surrounding the lead body. In this location it is far away from the metal conductors within the thick silicone rubber casing and a fluoropolymer jacket. This barrier prevents exposure to metal ions from the MP-35N conductor that can trigger the oxidative degradation of the soft, polyurethane segment. Likewise, although the major structural weaknesses of fluoropolymers (related especially to rigidity) preclude their use as the primary insulator, inner insulation of the coil and cable conductors is well suited to these highly biostable, abrasion-resistant materials. Generally, ETFE is used for coating of the cable conductors, and PTFE is used to line the central lumen lead body that houses the coil conductor. Although silicone rubber may be biostable and flexible enough to be used as the dominant material for ICD lead body insulation, its softness and high frictional coefficient make lead implantation difficult if the outermost surface of the ICD lead is silicone. Outer coverings of polyurethane may address this disadvantage to some extent, but the longterm mechanical risks related to silicone’s softness remain, as well as its susceptibility to abrasion and cold flow, and require the use of thicker silicone layers and thus increased lead caliber. This weakness is particularly marked at high-stress points such as at the costoclavicular ligament or in the pocket next to the pulse generator, where harsh local mechanical forces can lead to progressive insulation abrasion and local silicone thinning at pressure points. If lead insulation is sufficiently thinned or denuded that a low-impedance dielectric is created, particularly where a high-voltage conductor strand closely opposes the metal casing of the pulse generator in the device pocket, a short circuit with arcing can result during shock delivery, leading to ineffective defibrillation and permanent damage to the lead, the ICD circuitry, or both.107

139

As mentioned in the section on pacing leads, newer insulation materials are being developed for specific application in cardiac device leads, including one already in clinical use, Elast-Eon (Aortech Biomaterials, Clayton, Victoria, Australia). This substance is a hybrid copolymer composed of near-equal amounts of silicone and polyurethane and, in extensive laboratory experience, combines advantages of each.39 A family of pacing and ICD leads uses this material as an outer insulator (Optim, St. Jude Medical), but as yet no leads use this material for the primary lead body insulation. ICD LEAD CONNECTOR TERMINALS As with the initial CRT leads, early ICD leads had high-voltage circuitry that terminated proximally in connector pins compatible only with pulse generators made by the same vendor. This was a major problem, particularly at generator change procedures, when lack of hardware cross-compatibility could limit device selection options and increase procedural complexity. The first solutions involved developing a wide range of adapters and extenders that could be used to switch connector pin design. However, this added further complexity to the system, increased the number of electrical connection points, and introduced another component that was subject to similar modes of failure as the rest of the lead. Eventually, industry-wide standardization occurred in ICD systems, such that the pace/sense coil conductor terminates in a standard IS-1 pacing pin that is placed in the IS-1 port of the ICD header, and each high-voltage shock coil terminates in a standard DF-1 (ISO-11318) connector pin. In a dual-coil ICD lead, therefore, three tails ending in one IS-1 pin and two DF-1 pins emerge from a trifurcation yoke attached to the main lead body (Fig. 4-23). Three separate connector ports are found on the ICD header to accommodate the trifurcated end of a dual-coil ICD lead (one IS-1 port and two DF-1 ports). The yoke and lead tails of the ICD lead are subject to insulation and

A

IS−1

B

DF−1

Trifurcation yoke

C

Dual-coil ICD lead

Figure 4-23  ICD lead connector terminals. A, Standard IS-1 pace/ sense connector terminal. B, High-voltage DF-1 pin connects shock coil(s) to generator header. C, Proximal end of dual-coil ICD lead, with central IS-1 pace/sense pin, two high-voltage DF-1 pins, and trifurcation yoke to interface the three terminal pins with lead body.

140

SECTION 1  Basic Principles of Device Therapy

Pin geometry Low voltage

EXTRACTION CONSIDERATIONS

High voltage DF4−LLHH

Low

A

Low

High

Low = pacing/sensing

B

High High = cardioversion/defribrillation DF−4

Figure 4-24  Schematic representation and photograph of the IS-4/ DF-4 connector pin incorporating high-voltage and low-voltage elements in the one pin and thus obviating the need for an external trifurcation yoke. (Courtesy St Jude Medical, Sylmar, Calif.)

conductor failure, just as in the rest of the lead system. They also increase pocket bulk and may contribute to erosion risk, particularly in the setting of a dual-chamber or biventricular device system, with atrial and LV leads also present. Additional abandoned lead ends might also be present in the device pocket, if nonfunctional or redundant leads remain in place in the setting of lead failure or device upgrade. Besides increasing pocket bulk and interaction between device system components, the greater number of connector pins in a standard ICD lead allows inadvertent connector pin reversal in the device header, and the thick fibrous tissue that frequently encapsulates the lead trifurcation yoke can make a generator change or system revision more challenging. The development of the new IS-4/DF-4 standard connector pin has allowed the integration of two DF-1 high-voltage terminals and one bipolar IS-1 pace/sense terminal, all into one connector pin (Fig. 4-24). This new design addresses the mechanical issues associated with current multiterminal ICD leads, but the long-term reliability of these connector pins is currently unknown.108 In addition, this all-in-one connector pin design precludes the ability to replace a single component of the ICD lead, such as the pace/sense or a shocking coil component, in the setting of pace/sense malfunction or elevated DFT.

A

C

Increasingly, ICD systems are being implanted in younger patients with evolving indications outside the context of acquired cardiomyopathy. Channelopathies, arrhythmogenic RV dysplasia, congenital cardiac abnormalities, and sarcoidosis are indications for implant that affect younger patients, often children, who are expected to live with their ICD leads (since generators are changed at regular intervals) over their lifetime. Because ICD lead failure rates continue to accrue over time with current lead and materials technology,81 and lead infection can occur at any time without warning,109 lead manufacturers and physicians must give due consideration to this aspect of device therapy at implant. In addition, abandoned sterile leads are increasingly being removed to allow for reduced intravascular hardware burden, avoidance of inappropriate oversensing,110 and potentially increased longterm venous patency.111 Lead extraction, even with the modern tools and expertise,112 remains a potentially hazardous endeavor,113,114 particularly in young patients with long-standing dual-coil ICD leads, in which tissue ingrowth into the interstices between the helical turns of the shock coil wire may be causing dense, fibrous adhesions and tissue encapsulation of the lead body (Fig. 4-25). With some data indicating that defibrillation efficacy may not be significantly improved with the addition of the SVC coil,115 one approach is to consider implanting only single-coil ICD leads in patients expected to have longer implant duration.116 However, the real solution lies in the manufacture of shock coils that are easier to extract. All newer ICD lead bodies are isodiametric, with the same or a smaller maximal external diameter as proceeding from the proximal to the distal end of the lead (Fig. 4-26), and are 8-Fr size or smaller, which already improves the ease of extraction over previous transvenous ICD lead systems. Manufacturers also have taken different approaches to the problem of shock coil adhesion to the venous and cardiac walls102 (Fig. 4-27). Silicone backfilling of the interstices between the coils has been used in Medtronic leads to reduce fibrous tissue ingrowth. This approach may be effective117 but is limited by the

B

D

Figure 4-25  A, Chronically implanted ICD lead shows extensive adhesions binding the lead tip and shock coil to the trabeculated ventricular endocardium. B, After lead extraction, extent of shock coil–associated fibrosis is evident. C and D, Cross-sectional photomicrographs of a chronically implanted lead show fibrous tissue invasion into interstices between helical turns of the shock coil. (C and D courtesy St Jude Medical, Sylmar, Calif.)



4  Engineering and Construction of Pacemaker and ICD Leads

141

tissue ingrowth into, and local adherence of, the shocking coils over time. This has made ICD lead extraction easier in animal models, compared with an identical lead without covering sleeves.117 Recent clinical data have corroborated the potential benefit of modified ICD lead shock coils to improve the ease of extraction.119

Step up in diameter

ICD LEAD FAILURE

Figure 4-26  Lead body diameter may not be uniform throughout (top) or may be isodiametric (bottom), which improves the ability to extract chronically implanted leads. (Courtesy Medtronic, Minneapolis.)

surface area of the outer curvature of the round coil strands; the interstices cannot be fully obliterated because a large, exposed coil surface area is required for effective defibrillation. In Biotronik and St. Jude Medical leads, use of flatwire technology allows complete backfilling of the interhelix turns with silicone, allowing for a completely isodiametric shock coil segment while still reducing fibrous tissue ingrowth, as demonstrated in animal testing.102 A third strategy, employed in Boston Scientific leads, is to cover the defibrillation coils with a thin, encapsulating jacket of semiporous expanded polytetrafluoroethylene (ePTFE; Gore-Tex, Gore and Associates, Flagstaff, Ariz). As with all fluoropolymers, this material is abrasion and tear resistant as well as biostable, but it has been molecularly modified to make it semiporous. This allows for free fluid and ion flow so as not to significantly alter high-voltage electrical conductance during shocks from the underlying defibrillation coils. Consequently, no significant difference in clinical defibrillation efficacy has been demonstrated with the use of ePTFE coils.118 In the setting of an integrated bipolar sensing ICD lead and additional abandoned leads in the right ventricle, mechanical interactions between the large RV coil and adjacent lead materials may occasionally result in sensed electrical artifacts. Oversensing from this type of lead-on-lead interaction may be reduced or eliminated if the metal strands of the RV coil are covered by an ePTFE sleeve.110 The real advantage of the semiporous sleeve, however, is that cellular migration cannot occur into the covered underlying coil interstices, thus reducing Figure 4-27  Solutions to the problem of shock coil fibrous tissue ingrowth. Top panel shows the shock coil interstices backfilled with silicone. Middle two panels demonstrate effective backfilling between flatwire helix turns. Bottom two panels show an ePTFE covering sleeve over the shock coil. (Courtesy Medtronic, Minneapolis; St Jude Medical, Sylmar, Calif; and Boston Scientific, St Paul, Minn.)

The ICD lead is one of the most complex and vulnerable parts of the ICD system, and lead failure is a significant problem (Box 4-1). ICD lead failure, perhaps more so than with pacing lead failure, can lead to sudden death. This can occur not only by loss of pacing support in pacemaker-dependent patients, but as most often seen, also by causing recurrent inappropriate shocks due to oversensing of lead noise. These shocks can induce ventricular fibrillation, which the system may then not be able to defibrillate successfully.120 Early data from the transvenous lead experience held great promise,121 but late lead failure was seen at longer-term follow-up across all lead designs and manufacturers.81 Patient-related factors, such as excessive upper body activity, can contribute to ICD lead failure, as can procedural factors at implant, including subclavian (rather than cephalic) access,122,123 rough handling, traumatic transvenous insertion, overtorquing of active-fixation helices, and kinking of lead loops in the pocket. However, none of these factors is positively identified in most cases; the difficulty in extracting ICD leads (possibly with additional lead damage during its extraction) means that the failure mechanism usually remains obscure. A systematic solution to this problem must involve better ICD lead design and manufacture, with advances in materials technology. The Transvene family (Medtronic) of coaxial ICD leads had a structural failure rate of 38% at 8 years,83 which was more often caused by fracture of the outer high-voltage coil conductor than disruption of the polyurethane 80A insulation. Despite changes in design and materials, however, newer generations of ICD leads are also prone to late failure. Kleemann et al.81 found that cumulative survival of 990 ICD leads implanted between 1992 and 2005 was only 60% at 8 years, mainly from insulation defects, including in silicone-based leads. One in five leads implanted for a decade or longer failed. This study was weighted toward the older lead models, however, and 95% of implants were through subclavian access, which may have affected failure rates and mechanisms.

INGROWTH SOLUTIONS

Silicone backfill

Flatwire design and backfill

ePTFE covering sleeve

142

SECTION 1  Basic Principles of Device Therapy

Box 4-1 

SYMPTOMS AND SIGNS OF LEAD PROBLEMS Pacing/Sensing Oversensing (most common) caused by detection of noise Inappropriate shocks Inappropriate aborted shocks Inhibition of pacing Change in pacing impedance Prolonged oversensing immediately after shock delivery Undersensing in sinus rhythm Undersensing or nonsensing of VT/VF, with failure to deliver therapy Elevated pacing thresholds or noncapture Defibrillation Ineffective defibrillation Change in high-voltage impedance Sudden death VT/VF, Ventricular tachycardia/ventricular fibrillation.

In an industry-wide push for increasing miniaturization, smallcaliber ICD leads were introduced in the mid-2000s. Again, although early data gave no cause for alarm,124 more recently125 the small-caliber (6.6F) Sprint Fidelis lead (Models 6930/6931/6949/6948, Medtronic)

has been identified as much more prone than other contemporary lead models to early and late failure, usually presenting with conductor fracture, noise oversensing, and inappropriate shocks. Initial failure rate was 1.29% at 21 months,126 but risk appears to increase with time, up to 5.7% to 12.1% at 3 years,127-129 a failure rate of 3.75% per year, versus 0.58% per year or less for other contemporary ICD lead models.129,130 The mechanism in most cases is a fracture of the pace/ sense hexafilar cathode conductor, either proximally, near the lead anchoring sleeve, or distally, near the anode ring electrode.102,131 Although no longer being implanted, the problem of failure with this lead is ongoing because of the large number of patients with this model in place.

Conclusion The remarkable progress in lead technology over more than four decades has contributed greatly to the modern era of implantable cardiac rhythm devices. Advances such as fixation mechanisms, steroid elution, and transvenous defibrillation lead development have been milestone events, facilitated by ongoing improvements in materials science and lead design. However, the ideal of a small-caliber, easily implanted-extracted lead with reliable long-term performance does not yet exist. Future advances in lead engineering and construction that allow physicians to approach this goal are eagerly awaited.

REFERENCES 1. Wieneke H, Konorza T, Erbel R, Kisker E: Leadless pacing of the heart using induction technology: a feasibility study. Pacing Clin Electrophysiol 32:177-183, 2009. 2. Santini M, Cappato R, Andresen D, et al: Current state of knowledge and experts’ perspective on the subcutaneous implantable cardioverter-defibrillator. J Interv Card Electrophysiol 25:83-88, 2009. 3. Mond HG, Hunt D, Vohra J, Sloman JG: Cardiac pacing: memories of a bygone era. Pacing Clin Electrophysiol 31:1192-1201, 2008. 4. Breivik K, Ohm OJ, Engedal H: Long-term comparison of unipolar and bipolar pacing and sensing, using a new multiprogrammable pacemaker system. Pacing Clin Electrophysiol 6:592-600, 1983. 5. Mond H, Sloman G: The small-tined pacemaker lead: absence of dislodgement. Pacing Clin Electrophysiol 3:171-177, 1980. 6. Richardson JV, Wright CB, Ehrenhaft JL: Tined transvenous endocardial electrodes: results of a randomized prospective study. Ann Thorac Surg 31:289, 1981. 7. Snow N: Elimination of lead dislodgement by the use of tined transvenous electrodes. Pacing Clin Electrophysiol 5:571-574, 1982. 8. Kruse IM: Long-term performance of endocardial leads with steroid-eluting electrodes. Pacing Clin Electrophysiol 9:12171219, 1986. 9. Mond H, Stokes K, Helland J, et al: The porous titanium steroideluting electrode: a double-blind study assessing the stimulation threshold effects of steroid. Pacing Clin Electrophysiol 11:214219, 1988. 10. Mehra R, Furman S: Comparison of cathodal, anodal, and bipolar strength-interval curves with temporary and permanent pacing electrodes. Br Heart J 41:468-476, 1979. 11. Secemsky SI, Hauser RG, Denes P, Edwards LM: Unipolar sensing abnormalities: incidence and clinical significance of skeletal muscle interference and undersensing in 228 patients. Pacing Clin Electrophysiol 5:10-19, 1982. 12. Zimmern SH, Clark MF, Austin WK, et al: Characteristics and clinical effects of myopotential signals in a unipolar DDD pacemaker population. Pacing Clin Electrophysiol 9:1019-1025, 1986. 13. Echeverria HJ, Luceri RM, Thurer RJ, Castellanos A: Myopotential inhibition of unipolar AV sequential (DVI) pacemaker. Pacing Clin Electrophysiol 5:20-22, 1982. 14. Schuchert A, Cappato R, Kuck KH, Meinertz T: Programmable polarity: effects on pacing and sensing of bipolar steroid-eluting leads. Pacing Clin Electrophysiol 19:2099-2102, 1996. 15. Mond HG: Unipolar versus bipolar pacing: poles apart. Pacing Clin Electrophysiol 14:1411-1424, 1991. 16. Helguera ME, Pinski SL, Maloney JD, et al: Durability of bipolar coaxial endocardial pacemaker leads compared with unipolar leads. Cleve Clin J Med 61:25-28, 1994. quiz 80-22. 17. Wiegand UK, Bode F, Bonnemeier H, et al: Incidence and predictors of pacemaker dysfunction with unipolar ventricular lead configuration: can we identify patients who benefit from bipolar electrodes? Pacing Clin Electrophysiol 24:1383-1388, 2001. 18. Breivik K, Danilovic D, Ohm OJ, et al: Clinical evaluation of a thin bipolar pacing lead. Pacing Clin Electrophysiol 20:637-646, 1997.

19. Mond HG, Grenz D: Implantable transvenous pacing leads: the shape of things to come. Pacing Clin Electrophysiol 27:887-893, 2004. 20. Belott PH, Rizo-Patron C, Brownstein SL, et al: Clinical experience with passive-fixation coradial bipolar endocardial pacing leads. Thinline clinical investigators. Pacing Clin Electrophysiol 21:2291-2299, 1998. 21. Tang C, Yeung-Lai-Wah JA, Qi A, et al: Initial experience with a co-radial bipolar pacing lead. Pacing Clin Electrophysiol 20:18001807, 1997. 22. Gammage MD, Lieberman RA, Yee R, et al: Multi-center clinical experience with a lumenless, catheter-delivered, bipolar, permanent pacemaker lead: implant safety and electrical performance. Pacing Clin Electrophysiol 29:858-865, 2006. 23. Bai R, Kam R, Ching CK, et al: Implantation of lumenless pacing leads at the inter-atrial septum and right ventricular outflow tract with deflectable catheter-sheath. J Huazhong Univ Sci Technol Med Sci 28:639-644, 2008. 24. Kenny D, Walsh KP: Noncatheter-based delivery of a singlechamber lumenless pacing lead in small children. Pacing Clin Electrophysiol 30:834-838, 2007. 25. Chakrabarti S, Morgan GJ, Kenny D, et al: Initial experience of pacing with a lumenless lead system in patients with congenital heart disease. Pacing Clin Electrophysiol 32:1428-1433, 2009. 26. Kazama S, Nishiyama K, Machii M, et al: Long-term follow-up of ventricular endocardial pacing leads: complications, electrical performance, and longevity of 561 right ventricular leads. Jpn Heart J 34:193-200, 1993. 27. Stokes K: Implantable pacing lead technology. IEEE Eng Med Biol Mag 9:43-49, 1990. 28. Tyers GF, Mills P, Clark J, et al: Bipolar leads for use with permanently implantable cardiac pacing systems: a review of limitations of traditional and coaxial configurations and the development and testing of new conductor, insulation, and electrode designs. J Invest Surg 10:1-15, 1997. 29. Kruse I, Peters P, Ryden L: A new transvenous lead for both atrial and ventricular pacing. Pacing Clin Electrophysiol 6:953-956, 1983. 30. Raymond RD, Nanian KB: Insulation failure with bipolar polyurethane pacing leads. Pacing Clin Electrophysiol 7:378-380, 1984. 31. Antonelli D, Rosenfeld T, Freedberg NA, et al: Insulation lead failure: is it a matter of insulation coating, venous approach, or both? Pacing Clin Electrophysiol 21:418-421, 1998. 32. Bruck SD, Mueller EP: Materials aspects of implantable cardiac pacemaker leads. Med Prog Technol 13:149-160, 1988. 33. Phillips R, Frey M, Martin RO: Long-term performance of polyurethane pacing leads: mechanisms of design-related failures. Pacing Clin Electrophysiol 9:1166-1172, 1986. 34. Byrd CL, McArthur W, Stokes K, et al: Implant experience with unipolar polyurethane pacing leads. Pacing Clin Electrophysiol 6:869-882, 1983. 35. Stokes K, Urbanski P, Upton J: The in vivo auto-oxidation of polyether polyurethane by metal ions. J Biomater Sci Polym Ed 1:207-230, 1990. 36. Wiggins MJ, Wilkoff B, Anderson JM, Hiltner A: Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads. J Biomed Mater Res 58:302-307, 2001.

37. Lim KK, Reddy S, Desai S, et al: Effects of electrocautery on transvenous lead insulation materials. J Cardiovasc Electrophysiol 20:429-435, 2009. 38. De Voogt WG: Pacemaker leads: performance and progress. Am J Cardiol 83:187D-191D, 1999. 39. Jenney C, Tan J, Karicheria A, et al: A new insulation material for cardiac leads with potential for improved performance. Heart Rhythm 2:S318-S319, 2005. 40. Parsonnet V, Villanueva A, Driller J, Bernstein AD: Corrosion of pacemaker electrodes. Pacing Clin Electrophysiol 4:289-296, 1981. 41. Mugica J, Duconge B, Henry L, et al: Clinical experience with new leads. Pacing Clin Electrophysiol 11:1745-1752, 1988. 42. Molajo AO, Bowes RJ, Fananapazir L, et al: Comparison of vitreous carbon and Elgiloy transvenous ventricular pacing leads. Pacing Clin Electrophysiol 8:261-265, 1985. 43. Adler S, Spehr P, Allen J, Block W: Chronic animal testing of new cardiac pacing electrodes. Pacing Clin Electrophysiol 13:18961900, 1990. 44. Hirshorn MS, Holley LK, Hales JR, et al: Screening of solid and porous materials for pacemaker electrodes. Pacing Clin Electrophysiol 4:380-390, 1981. 45. Mugica J, Henry L, Attuel P, et al: Clinical experience with 910 carbon tip leads: comparison with polished platinum leads. Pacing Clin Electrophysiol 9:1230-1238, 1986. 46. Moracchini PV, Cornacchia D, Bernasconi M, et al: High impedance low energy pacing leads: Long-term results with a very small surface area steroid-eluting lead compared to three conventional electrodes. Pacing Clin Electrophysiol 22:326-334, 1999. 47. Berger T, Roithinger FX, Antretter H, et al: The influence of high versus normal impedance ventricular leads on pacemaker generator longevity. Pacing Clin Electrophysiol 26:2116-2120, 2003. 48. Bolz A, Hubmann M, Hardt R, et al: Low polarization pacing lead for detecting the ventricular-evoked response. Med Prog Technol 19:129-137, 1993. 49. Erdinler I, Akyol A, Okmen E, et al: Long-term follow-up of pacemakers with an autocapture pacing system. Jpn Heart J 43:631-641, 2002. 50. Luria D, Gurevitz O, Bar Lev D, et al: Use of automatic threshold tracking function with non-low polarization leads: risk for algorithm malfunction. Pacing Clin Electrophysiol 27:453-459, 2004. 51. MacGregor DC, Wilson GJ, Lixfeld W, et al: The porous-surfaced electrode: a new concept in pacemaker lead design. J Thorac Cardiovasc Surg 78:281-291, 1979. 52. Djordjevic M, Stojanov P, Velimirovic D, Kocovic D: Target lead– low threshold electrode. Pacing Clin Electrophysiol 9:1206-1210, 1986. 53. Mond HG, Stokes KB: The steroid-eluting electrode: a 10-year experience. Pacing Clin Electrophysiol 19:1016-1020, 1996. 54. Radovsky AS, Van Vleet JF: Effects of dexamethasone elution on tissue reaction around stimulating electrodes of endocardial pacing leads in dogs. Am Heart J 117:1288-1298, 1989. 55. De Groot JR, Schroeder-Tanka JM, Visser J, et al: Clinical results of far-field R-wave reduction with a short tip-ring electrode. Pacing Clin Electrophysiol 31:1554-1559, 2008. 56. Fung JW, Sperzel J, Yu CM, et al: Multicenter clinical experience with an atrial lead designed to minimize far-field R-wave sensing. Europace 11:618-624, 2009.



4  Engineering and Construction of Pacemaker and ICD Leads 57. Kertes P, Mond H, Sloman G, et al: Comparison of lead complications with polyurethane tined, silicone rubber tined, and wedge tip leads: clinical experience with 822 ventricular endocardial leads. Pacing Clin Electrophysiol 6:957-962, 1983. 58. Hidden-Lucet F, Halimi F, Gallais Y, et al: Low chronic pacing thresholds of steroid-eluting active-fixation ventricular pacemaker leads: a useful alternative to passive-fixation leads. Pacing Clin Electrophysiol 23:1798-1800, 2000. 59. Geyfman V, Storm RH, Lico SC, Oren JW: Cardiac tamponade as complication of active-fixation atrial lead perforations: proposed mechanism and management algorithm. Pacing Clin Electrophysiol 30:498-501, 2007. 60. Van Herendael H, Willems R: Contralateral pneumothorax after endocardial dual-chamber pacemaker implantation resulting from atrial lead perforation. Acta Cardiol 64:271-273, 2009. 61. Vlay SC: Complications of active-fixation electrodes. Pacing Clin Electrophysiol 25:1153-1154, 2002. 62. Li H, Helland J: In vitro evaluation of new design lead anchoring sleeves. Pacing Clin Electrophysiol 15:2005-2010, 1992. 63. Brown S: Connectors for implantable pacemaker leads. Pacing Clin Electrophysiol 3:620-621, 1980. 64. Doring J, Flink R: The impact of pending technologies on a universal connector standard. Pacing Clin Electrophysiol 9:11861190, 1986. 65. Tyers GF, Sanders R, Mills P, Clark J: Analysis of set screw and side-lock connector reliability. Pacing Clin Electrophysiol 15:2000-2004, 1992. 66. Cleland JG, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005. 67. Bristow MR, Saxon LA, Boehmer J, et al: Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004. 68. Purerfellner H, Nesser HJ, Winter S, et al: Transvenous left ventricular lead implantation with the Easytrak lead system: the European experience. Am J Cardiol 86:157K-164K, 2000. 69. Linde C, Abraham WT, Gold MR, et al: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 52:1834-1843, 2008. 70. Beshai JF, Grimm RA, Nagueh SF, et al: Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 357:2461-2471, 2007. 71. Crossley GH, Exner D, Mead RH, et al: Chronic performance of an active-fixation coronary sinus lead. Heart Rhythm 7:472-478, 2010. 72. Nagele H, Azizi M, Hashagen S, et al: First experience with a new active fixation coronary sinus lead. Europace 9:437-441, 2007. 73. Hamid S, Arujuna A, Khan S, et al: Extraction of chronic pacemaker and defibrillator leads from the coronary sinus: laser infrequently used but required. Europace 11:213-215, 2009. 74. Freedman RA, Petrakian A, Boyce K, et al: Performance of dedicated versus integrated bipolar defibrillator leads with CRTdefibrillators: results from a prospective multicenter study. Pacing Clin Electrophysiol 32:157-165, 2009. 75. Thibault B, Roy D, Guerra PG, et al: Anodal right ventricular capture during left ventricular stimulation in CRT-implantable cardioverter defibrillators. Pacing Clin Electrophysiol 28:613-619, 2005. 76. Nof E, Gurevitz O, Carraso S, et al: Comparison of results with different left ventricular pacing leads. Europace 10:35-39, 2008. 77. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322-324, 1980. 78. Connolly SJ, Hallstrom AP, Cappato R, et al: Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator Study. Cardiac Arrest Study Hamburg. Canadian Implantable Defibrillator Study. Eur Heart J 21:20712078, 2000. 79. Moss AJ, Zareba W, Hall WJ, et al: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346:877-883, 2002. 80. Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352:225-237, 2005. 81. Kleemann T, Becker T, Doenges K, et al: Annual rate of transvenous defibrillation lead defects in implantable cardioverterdefibrillators over a period of >10 years. Circulation 115:2474-2480, 2007. 82. Ellenbogen KA, Wood MA, Shepard RK, et al: Detection and management of an implantable cardioverter defibrillator lead

failure: incidence and clinical implications. J Am Coll Cardiol 41:73-80, 2003. 83. Dorwarth U, Frey B, Dugas M, et al: Transvenous defibrillation leads: high incidence of failure during long-term follow-up. J Cardiovasc Electrophysiol 14:38-43, 2003. 84. Luria D, Glikson M, Brady PA, et al: Predictors and mode of detection of transvenous lead malfunction in implantable defibrillators. Am J Cardiol 87:901-904, 2001. 85. Chevalier P, Moncada E, Canu G, et al: Symptomatic pericardial disease associated with patch electrodes of the automatic implantable cardioverter defibrillator: an underestimated complication? Pacing Clin Electrophysiol 19:2150-2152, 1996. 86. Echt DS, Armstrong K, Schmidt P, et al: Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator. Circulation 71:289-296, 1985. 87. Gartman DM, Bardy GH, Allen MD, et al: Short-term morbidity and mortality of implantation of automatic implantable cardioverter-defibrillator. J Thorac Cardiovasc Surg 100:353-357, 1990. discussion 357-359. 88. Almassi GH, Olinger GN, Wetherbee JN, Fehl G: Long-term complications of implantable cardioverter defibrillator lead systems. Ann Thorac Surg 55:888-892, 1993. 89. Daoud EG, Kirsh MM, Bolling SF, et al: Incidence, presentation, diagnosis, and management of malfunctioning implantable cardioverter-defibrillator rate-sensing leads. Am Heart J 128:892-895, 1994. 90. Gallik DM, Ben-Zur UM, Gross JN, Furman S: Lead fracture in cephalic versus subclavian approach with transvenous implantable cardioverter defibrillator systems. Pacing Clin Electrophysiol 19:1089-1094, 1996. 91. Hauser RG, Cannom D, Hayes DL, et al: Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads. Pacing Clin Electrophysiol 25:879-882, 2002. 92. Golino A, Pappone C, Panza A, et al: Clinical experience with the transvenous Medtronic Pacer Cardioverter Defibrillator (PCD) system. Tex Heart Inst J 20:264-270, 1993. 93. Weretka S, Michaelsen J, Becker R, et al: Ventricular oversensing: A study of 101 patients implanted with dual chamber defibrillators and two different lead systems. Pacing Clin Electrophysiol 26:65-70, 2003. 94. Gradaus R, Breithardt G, Bocker D: ICD leads: design and chronic dysfunctions. Pacing Clin Electrophysiol 26:649-657, 2003. 95. Sweeney MO, Ellison KE, Shea JB, Newell JB: Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverter defibrillators. J Cardiovasc Electrophysiol 12:402-410, 2001. 96. Rashba EJ, Bonner M, Wilson J, et al: Distal right ventricular coil position reduces defibrillation thresholds. J Cardiovasc Electrophysiol 14:1036-1040, 2003. 97. Lang DJ, Heil JE, Hahn SJ, et al: Implantable cardioverter defibrillator lead technology: Improved performance and lower defibrillation thresholds. Pacing Clin Electrophysiol 18:548-559, 1995. 98. Frain BH, Ellison KE, Michaud GF, et al: True bipolar defibrillator leads have increased sensing latency and threshold compared with the integrated bipolar configuration. J Cardiovasc Electrophysiol 18:192-195, 2007. 99. Callans DJ, Swarna US, Schwartzman D, et al: Postshock sensing performance in transvenous defibrillation lead systems: analysis of detection and redetection of ventricular fibrillation. J Cardiovasc Electrophysiol 6:604-612, 1995. 100. Natale A, Sra J, Axtell K, et al: Undetected ventricular fibrillation in transvenous implantable cardioverter-defibrillators: prospective comparison of different lead system-device combinations. Circulation 93:91-98, 1996. 101. Goldberger JJ, Horvath G, Donovan D, et al: Detection of ventricular fibrillation by transvenous defibrillating leads: Integrated versus dedicated bipolar sensing. J Cardiovasc Electrophysiol 9:677-688, 1998. 102. Haqqani HM, Mond HG: The implantable cardioverterdefibrillator lead: principles, progress, and promises. Pacing Clin Electrophysiol 32:1336-1353, 2009. 103. Lubinski A, Lewicka-Nowak E, Zienciuk A, et al: Comparison of defibrillation efficacy using implantable cardioverterdefibrillator with single- or dual-coil defibrillation leads and active can. Kardiol Pol 63:234-241, 2005. discussion 242-243. 104. Gradaus R, Bocker D, Dorszewski A, et al: Fractally coated defibrillation electrodes: is an improvement in defibrillation threshold possible? Europace 2:154-159, 2000. 105. Niebauer MJ, Wilkoff B, Yamanouchi Y, et al: Iridium oxide– coated defibrillation electrode: reduced shock polarization and improved defibrillation efficacy. Circulation 96:3732-3736, 1997.

143

106. Niebauer MJ, Yamanouchi Y, Hills D, et al: Voltage dependence of ICD lead polarization and the effect of iridium oxide coating. Pacing Clin Electrophysiol 23:818-823, 2000. 107. Sweeney MO: Exploding implantable cardioverter defibrillator. J Cardiovasc Electrophysiol 12:1422-1424, 2001. 108. Hauser RG, Almquist AK: Learning from our mistakes? Testing new ICD technology. N Engl J Med 359:2517-2519, 2008. 109. Klug D, Balde M, Pavin D, et al: Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation 116:1349-1355, 2007. 110. Cooper JM, Sauer WH, Garcia FC, et al: Covering sleeves can shield the high-voltage coils from lead chatter in an integrated bipolar ICD lead. Europace 9:137-142, 2007. 111. Zartner PA, Wiebe W, Toussaint-Goetz N, Schneider MB: Lead removal in young patients in view of lifelong pacing. Europace 12:714-718, 2010. 112. Wazni O, Epstein LM, Carrillo RG, et al: Lead extraction in the contemporary setting: the Lexicon Study: an observational retrospective study of consecutive laser lead extractions. J Am Coll Cardiol 55:579-586, 2010. 113. Hauser RG, Katsiyiannis WT, Gornick CC, et al: Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction. Europace 12:395-401, 2010. 114. Saad EB, Saliba WI, Schweikert RA, et al: Nonthoracotomy implantable defibrillator lead extraction: results and comparison with extraction of pacemaker leads. Pacing Clin Electrophysiol 26:1944-1950, 2003. 115. Rinaldi CA, Simon RD, Geelen P, et al: A randomized prospective study of single-coil versus dual-coil defibrillation in patients with ventricular arrhythmias undergoing implantable cardioverter defibrillator therapy. Pacing Clin Electrophysiol 26:16841690, 2003. 116. Cooper JM, Stephenson EA, Berul CI, et al: Implantable cardioverter-defibrillator lead complications and laser extraction in children and young adults with congenital heart disease: implications for implantation and management. J Cardiovasc Electrophysiol 14:344-349, 2003. 117. Wilkoff BL, Belott PH, Love CJ, et al: Improved extraction of ePTFE and medical adhesive modified defibrillation leads from the coronary sinus and great cardiac vein. Pacing Clin Electrophysiol 28:205-211, 2005. 118. Koplan BA, Weiner S, Gilligan D, et al: Clinical and electrical performance of expanded polytetrafluoroethylene–covered defibrillator leads in comparison to traditional leads. Pacing Clin Electrophysiol 31:47-55, 2008. 119. Hackler JW, Sun Z, Lindsay BD, et al: Effectiveness of implantable cardioverter defibrillator lead coil treatments in facilitating ease of extraction. Heart Rhythm 7:890-897, 2010. 120. Undavia M, Fischer A, Mehta D: Fatal outcome in a pacemakerdependent patient. Pacing Clin Electrophysiol 32:550-553, 2009. 121. Fahy GJ, Kleman JM, Wilkoff BL, et al: Low incidence of leadrelated complications associated with nonthoracotomy implantable cardioverter-defibrillator systems. Pacing Clin Electrophysiol 18:172-178, 1995. 122. Roelke M, O’Nunain SS, Osswald S, et al: Subclavian crush syndrome complicating transvenous cardioverter-defibrillator systems. Pacing Clin Electrophysiol 18:973-979, 1995. 123. Kron J, Herre J, Renfroe EG, et al: Lead- and device-related complications in the antiarrhythmics versus implantable defibrillators trial. Am Heart J 141:92-98, 2001. 124. Kupper B, Yee R, O’Hara G, et al: Do small (6.6 Fr) active and passive fixation defibrillation leads perform as well as larger sized leads? A multi-centre analysis. Europace 9:657-661, 2007. 125. Hauser RG, Kallinen LM, Almquist AK, et al: Early failure of a small-diameter high-voltage implantable cardioverterdefibrillator lead. Heart Rhythm 4:892-896, 2007. 126. Krahn AD, Champagne J, Healey JS, et al: Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: a report from the Canadian Heart Rhythm Society Device Advisory Committee. Heart Rhythm 5:639-642, 2008. 127. Faulknier BA, Traub DM, Aktas MK, et al: Time-dependent risk of Fidelis lead failure. Am J Cardiol 105:95-99, 2010. 128. Beukema RJ, Misier AR, Delnoy PP, et al: Characteristics of Sprint Fidelis lead failure. Neth Heart J 18:12-17, 2010. 129. Hauser RG, Hayes DL: Increasing hazard of Sprint Fidelis implantable cardioverter-defibrillator lead failure. Heart Rhythm 6:605-610, 2009. 130. Porterfield JG, Porterfield LM, Kuck KH, et al: Clinical performance of the St. Jude Medical Riata defibrillation lead in a large patient population. J Cardiovasc Electrophysiol 21:551-556, 2010. 131. Cannom DS, Fisher J: The Fidelis recall: how much pressure can the ICD world bear? Pacing Clin Electrophysiol 31:1233-1235, 2008.

144

5 

SECTION 1  Basic Principles of Device Therapy

Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring CHU-PAK LAU  |  CHUNG-WAH SIU  |  HUNG-FAT TSE

Implantable sensors monitor changes in the body’s physiologic con-

ditions. Detection of pathophysiologic changes has been used either to modify the pacing rate of a rate-adaptive pacing system or to allow continuous monitoring of medical conditions such as heart failure or ischemia. This chapter reviews the principles and types of sensors that have been investigated and their clinical applications.

SENSORS FOR RATE-ADAPTIVE PACING Basis of Sensor-Driven Pacing Chronotropic incompetence may occur in up to 30% of patients with sinus node disease. It may also develop over time as a result of degeneration, medications, or comorbidities. In addition, for patients whose atrium is unreliable for pacing, such as during atrial fibrillation, an alternative means is required to simulate the response of the sinus node to exercise or emotion. Implantable sensors for cardiac pacing allow a pacing system to respond to exercise and nonexercise requirements for an increase in heart rate. Sensors are now a programmable option of almost all bradycardia pacemakers. Atrioventricular (AV) synchrony enhances cardiac output by augmenting the stroke volume by 20% to 30% during exercise. However, this increase is relatively small compared with the threefold to fourfold increase achieved by an increase in heart rate. The relative contribution of AV synchrony and rate increase in patients with complete AV block was studied in dual-chamber (DDD) and a rate-matched ventricular pacing (VVI) mode.1 At rest, the cardiac output during DDD pacing was 18% higher than during VVI pacing because of AV synchrony. During exercise, however, the net cardiac output was only 8% higher during DDD pacing compared with VVI pacing at an identical rate. An equivalent exercise capacity was reported in another study,2 and both DDD and rate-matched VVI pacing were superior to fixed-rate VVI pacing during exercise. Cardiac output was similar in the two modes at near-maximal exercise, but at lower workload levels, cardiac output was maintained by an increased arteriovenous oxygen saturation difference and arterial lactate level. In addition, systolic and mean blood pressures were lower when exercise was performed without AV synchrony. These findings suggest that rate response is the primary driver for exercise cardiac hemodynamics, with a much smaller contribution of AV synchrony. EXERCISE RESPONSE IN HEART FAILURE In a patient with heart failure, because the left ventricular (LV) filling pressure is elevated and the heart is working at the flat portion of the Frank-Starling curve, an increase in heart rate is the most important means to increase the cardiac output. In a study of 22 patients with poor LV function and implanted rate-adaptive pacemakers, the benefit of rate adaptation to exercise capacity was greatest in those with the poorest LV function.3 In patients with implanted cardiac resynchronization therapy (CRT) devices,4 chronotropic incompetence (maximum heart rate <70% of age-predicted maximum) was found in 70% of heart failure patients.

144

In this group, sensor-driven CRT pacing improved maximum oxygen consumption and work capacity compared with CRT pacing without rate adaption. This increment is independent of A-V interval shortening during exercise. These data suggest that rate modulation plays a critical role in some patients with impaired LV function who require pacing therapy, even in those with CRT. HEART RATE MODULATION FOR NONEXERCISE NEEDS Exercise is only one of the many physiologic requirements for variation in heart rate. Other changes, such as mental stress, can lead to a rate increase. The sinus rate is also higher when a person assumes the upright posture. Isometric exercise also results in an increase in cardiac output and heart rate in most people. The changes in heart rate that occur during various physiologic maneuvers (e.g., Valsalva) and baroreceptor reflexes may also be important. An appropriate compensatory heart rate response may be especially important in pathophysiologic conditions such as anemia, acute blood loss, or other causes of hypovolemia, and during febrile illness.

Ideal Sensor Characteristics Based on the physiology of the normal sinus node, a sensor system to overcome chronotropic incompetence needs to be sensitive to both exercise and nonexercise needs. It also should be specific, unaffected by internal or external changes that can cause an inappropriate rate change. The sensor should achieve rate modulation at an appropriate speed, with its response proportional to the level of exercise load. The sensor system should be easy to implement (preferably with standard device casing and lead system), should be stable in the body’s internal environment, and should not significantly increase battery consumption. CLASSIFICATION OF SENSORS In a sensor-driven pacing system, a sensor (or combination of sensors) must first detect a physical or physiologic parameter that is related to metabolic demand5 (Fig. 5-1). Second, the rate-modulating circuit in the pulse generator must have an algorithm that relates changes in the sensed parameter to a change in pacing rate. Third, because the magnitude of the physical or physiologic changes monitored by a sensor may differ between patients, clinician input may be necessary to adjust the algorithm, generally by programming one or more rate-responsive variables, to achieve the clinically desired rate response. This requirement for adjustment has decreased with automatic optimization of the rate-responsive settings. Most sensors operate in an open-loop algorithm; that is, the induced rate changes do not induce a negative feedback on the sensed parameter. In a closed-loop sensor system, the induced hemodynamic changes will induce an opposite change in the level of the sensed parameter that is responsible for the initial rate adaptation (negative feedback loop). Theoretically, minimal programming is required in a closed-loop system (see Fig. 5-1). Furthermore, the actual rate response is calculated using rate-response curves after programming a threshold of sensor detection (Fig. 5-2).



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring CLOSED LOOP

OPEN LOOP

Sensor

Sensor

∆ Physiologic parameters

∆ Physiologic/ physical parameters

Algorithm

145

Algorithm

Ph

Ph

ys inp ician ut

ys inp ician ut

∆ Rate

∆ Rate

Figure 5-1  Design of a rate-adaptive system. Closed loop, The physiologic change detected by the sensor is converted to a change (Δ) in rate using an algorithm. The resultant rate change induces a change in the physiologic parameter in the opposite direction, thereby establishing a negative feedback loop. Open loop, The physiologic or physical change detected by the sensor is converted to a change in rate using an algorithm. The resultant rate change does not have a negative feedback effect on the physiologic/physical parameter.

Technical Classification A practical classification is to categorize sensors according to the technical methods that are used to measure the sensed parameter (Table 5-1). Body movements during exercise result in changes in acceleration forces that are transmitted to the pacemaker. Sensors that are capable of measuring the acceleration or vibration forces in the pulse generator Figure 5-2  Types of rate-responsive curves used in rate-adaptive pacemakers employing a single sensed parameter (sensor level). An appropriate filter (F) eliminates unwanted raw signals (e.g., high- or low-pass frequency filters and thresholds). The filtered signals are then appropriately modified (M; e.g., with gains and rectification) before being converted to a rate change. The curves can be linear (A), curvilinear (B), or complex (C and D). The physician can select an appropriate rate-responsive slope from a family of curves (see text). IR, Interim rate.

are broadly referred to as activity sensors. Technically, detection of body movement can be achieved using a piezoelectric crystal, an accelerometer, a tilt switch, or an inductive sensor. Each of these devices transduces motion of the sensor either directly into a voltage or indirectly into measurable changes in the electrical resistance of a piezoresistive crystal. Activity sensing is the most widely used control parameter LINEAR

∆ Rate

F

CURVILINEAR

∆ Rate

M

∆ Sensor

A

F

M

∆ Sensor

B COMPLEX

∆ Rate

∆ Rate

IR

– F

C

M

∆ Sensor

F

D

+

0 M

∆ Sensor

146

TABLE

5-1 

SECTION 1  Basic Principles of Device Therapy

Major Classes of Sensors Used in Implanted Devices, Classified According to Method of Technical Realization Examples

Methods Vibration and acceleration sensing

Physiologic Parameter Body movement

Impedance sensing

Minute ventilation Ventricular inotropic parameter Evoked QT interval* Physical parameters Central venous temperature dP/dt Right ventricular pressure Pulmonary arterial pressure Peak endocardial acceleration Chemical parameters pH Mixed venous oxygen saturation Catecholamine

Ventricular evoked response Special sensors on pacing electrode

Models Sigma, Kappa, EnRhythm Talent Miniswing, Neway Insignia, Pulsar Max, Discovery Actos, Protos, Philos Identity, Integrity, Affinity Kappa 400 Talent Insignia, Pulsar Max Protos, Inos Diamond, Clarity, Selection AF

Manufacturers Medtronic Vitatron ELA-Sorin Boston Scientific Biotronik St. Jude Medical Medtronic ELA-Sorin Boston Scientific Biotronik Vitatron

Chronicle†

Medtronic

Best-Living system

ELA-Sorin

*Currently no longer available in market. †For hemodynamic monitoring only.

in rate-adaptive pacing because of its ease of implementation and its compatibility with standard unipolar and bipolar pacing leads. Additionally, activity sensors can be used for either atrial or ventricular pacing modes. Impedance is a measure of all factors that oppose the flow of electric current and is derived by measuring resistivity to an injected current across a tissue. The impedance principle has been extensively used for measuring respiratory parameters and those associated with ventricular contractility, such as relative stroke volume or the right ventricular preejection interval. Transthoracic impedance can be used to assess respiratory rate and tidal volume by measuring the continuous impedance between the pacemaker casing and an intracardiac electrode. The product of respiratory rate and tidal volume, minute ventilation (MV), is used as the sensed parameter. When using unipolar impedance from a distal electrode of a pacing lead, impedance reflects myocardial contractility, as used in the closed-loop stimulation (CLS) sensor. The intracardiac ventricular electrogram (EGM) resulting from a suprathreshold pacing stimulus has been used to provide several parameters to guide rate modulation. The total duration of depolarization and repolarization can be estimated by the interval from the pacing stimulus to the intracardiac T wave: the QT interval, or stimulus-T interval. This parameter is sensitive to changes in heart rate and circulating catecholamines and can be derived from the paced EGM with conventional pacing electrodes. This was developed as a QT-sensing pacemaker, based on the QT interval shortening during exercise and stress.5 The last group of sensors is incorporated into the pacing lead itself. These specialized leads include thermistors (used to measure blood temperature), piezoelectric crystals (right ventricular pressure), optical

TABLE

5-2 

sensors (mixed-venous oxygen level), and accelerometers at the tip of pacing leads. Some of these sensors measure highly physiologic parameters. For example, oxygen saturation is closely related to oxygen consumption during exercise. Physical activities increase cardiac output and oxygen extraction from the blood, and the tissue arteriovenous oxygen difference widens during increased tissue oxygen consumption. The fall in oxygen saturation will trigger an increase in rate that will improve cardiac output and minimize the decrease in mixed-venous oxygen saturation.6 The mixed-venous oxygen sensor is a true closedloop system, although its technical complexity limits its use for rateadaptive pacing. Sensing of changes in blood pH during exercise has also been suggested as a possible sensor, although the requirement for a specialized lead has impeded its clinical implementation.7 Using an accelerometer incorporated at the tip of a unipolar ventricular electrode, the contractile state of the right ventricle can be assessed indirectly from the endocardial pressure generated during isovolumic contraction of the heart, a parameter known as peak endocardial acceleration (PEA). PEA is significantly increased by exercise and other inotropic stimuli (e.g., mental stress). Over the years, many of these sensors have been implemented in implantable devices. Significant differences in rate response were found among sensors, notably between their sensitivity and specificity (Table 5-2). However, only activity, MV, and CLS sensors are currently used for rate response. The activity sensor has the advantage of reliability and ease of implementation; its lack of proportionality to exercise workload has not been a major clinical disadvantage for most patients. Sensors in special leads are no longer used for rate adaptation because of their uncertain long-term reliability and difficulty during pacemaker replacement. However, these sensors are now used for hemodynamic monitoring in heart failure.

Relative Performance of Different Sensors

Activity Minute ventilation QT interval PEA CLS

Speed High Moderate Low Moderate Moderate

*Refers to technical and clinical realization. CLS, Closed-loop stimulation; PEA, peak endocardial acceleration.

Proportionality Low High Moderate Moderate Moderate

Specificity Low Moderate High Moderate Moderate

Sensitivity Low Low Moderate High High

Reliability* High Moderate Low Moderate Moderate



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring 120

Activity sensing is the most widely used sensor, alone or in combination. Because activity-based pacemakers are operationally simple and do not require a special sensor outside the pulse generator casing, they work with any type of pacing lead, have excellent long-term stability, and are highly reliable. Activity-guided pacemaker implantation is the same as for conventional pacemakers. Although activity sensors may not be excellent proportional sensors, they react promptly to the start and termination of physical exercise. The first activity sensors, piezoelectric crystals, mainly respond to the frequency of vibrations transmitted to the pulse generator, with more variable response depending on the pulse generator and the pocket. The subsequent activity sensors, accelerometers, detect body accelerations and have less interpatient variability and better proportionality (Fig. 5-3). Current Activity-Sensing Devices Medtronic (Kappa 700/900/400, Adapta, Advisa, EnRhythm).  The Medtronic Activitrax and Thera devices were the first generation of activity-sensing pacemakers to use a piezoelectric crystal bonded to the inside of the pacemaker casing to detect activity. Activity levels that exceed a programmable threshold are counted, and the number of counts that exceed a programmable threshold is used to determine the rate response. The clinician adjusts the overall rate response by programming the activity threshold and the rate-response slope. Typically, this instrumentation allows a good response from the programmed lower rate to about 100 beats per minute (bpm) during daily activities. The response to the upper rate is often less accurate and depends on the patient and the programmed settings. Despite their limitations, these piezoelectric devices were clinically highly effective when first introduced. The current Medtronic activity-sensing device uses an accelerometer attached to the circuit board to detect movement in the anteroposterior (AP) plane. Instead of a fixed threshold, a rolling threshold is used to provide a count of activity that depends not only on the frequency of counts that cross a threshold value, but also on the amplitude (strength) of these counts. This rolling threshold minimizes the Electronics Piezoelectric crystal

A

Battery

Body tissue

Piezoelectric accelerometer

B

Electronics

Battery

Piezoresistive accelerometer

C

Electronics

Battery

Figure 5-3  Three types of activity sensors. A, Piezoelectric sensor is bound to the inside surface of the pacemaker case. Vibration is sensed through tissue contact. The mechanical forces are transmitted by the surrounding connective tissue, fatty tissue, and muscles. The extent of contact and the coupling mass of the mechanical forces can vary considerably. B, Piezoelectric accelerometer, and C, piezoresistive accelerometer, mounted on the pacemaker’s hybrid circuitry. The seismic mass of the accelerometer is fixed. Therefore, measured accelerations are independent of surrounding tissue and patient physical properties.

Target rate (bpm)

Current Sensor-Driven Pacemakers ACTIVITY-SENSING AND ACCELEROMETER-BASED PACEMAKERS

147

110 100 90 80

ADL 5 ER 5

70

ADL 3 ER 3

ADL 1 ER 1

60 0

8

16

24

32

40

Sensor counts Figure 5-4  Triphasic rate-responsive curve. Medtronic Kappa 600/700/900, Enrhythm, and Enpulse accelerometer activity-sensing pacemakers; ADL, activity of daily living; ER, exertion response.

detection of low-intensity but high-frequency accelerations, as during motor vehicle travel, but allows detection of high-intensity signals during physical activity. The sensor-driven rate is adjusted by the use of a triphasic rate curve that incorporates two rate ranges, activity of daily living (ADL) and exertion response (ER) programming (Fig. 5-4). The physician determines the lower rate limit (LRL), the ADL rate, and the sensor-driven upper rate limit (SURL). With the nominal ADL response of 3 (I-5), counts between 12 and 20 will give the ADL rate, during which the rate response will be stable. When counts are greater than 20, ER will occur to the maximum programmed SURL. The flat portion of the response curve corresponds to 25% of the total counts. Adjustment of the ADL and ER to a more sensitive setting will decrease the number of counts needed to reach between ADL rate and SURL, and shorten the ADL portion of the response curve. The actual number of counts to effect a change in pacing rate is not fixed and differs among patients. Rather, an ADL response of 3 implies that the patient will spend up to 30 minutes daily at a sensor rate at or above the ADL. This is achieved by adjusting the rate/count relationship to achieve this percentage of rate response, the ADL set point. Similarly, an ER response of 3 means that the patient will be spending about 20 minutes weekly at the higher rates, 105 to 120 bpm, the upper-rate set point. The acceleration signal input can be adjusted by changing the threshold (lower threshold allows detection of more acceleration signals) and slope. These two parameters affect the sensitivity to the acceleration detected. The physician can manually program these parameters to achieve a faster or slower response in both the ADL and ER ranges. With automatic rate response, rate profile optimization will adjust these rate curves automatically, using daily comparison of the rate histogram with the target-rate histogram. The device adjusts more quickly in the first 10 days after a programming change so that the new setting will be achieved more quickly (Fig. 5-5). The Kappa 400 is a combined activity/MV-sensing device. The general hardware and software implementation is similar to the Kappa 700/600 series. However, actual time spent in ADL and ER is longer in the Kappa 400 because a more aggressive rate response is allowed. St. Jude Medical (Identity, Vitality, Zephyr, Accent).  These activity devices use an Omnisense accelerometer bonded to the circuit board and are sensitive to accelerations that occur in the AP axis. Activity counts above a programmable threshold (1 = most sensitive; 7 = least sensitive) are integrated and translated to a rate response using a rateresponse slope (1 = least sensitive; 16 = most sensitive) (Fig. 5-6). The threshold level can be adjusted manually or automatically (Auto). In the Auto setting, the device measures the sensor activity level over the preceding 18 hours to determine the threshold parameter. The Auto threshold can be adjusted using “Auto threshold offset.” Similarly, the slope of response can be calibrated manually or automatically. In the slope Auto adjustment, the device records the activity variance occurring above the threshold over the last 7 days, and the slope is

SECTION 1  Basic Principles of Device Therapy

0.35 0.3 0.25 0.2 0.15 0.1 0.05 0

activity threshold (very low, low, medium-low, medium-high, high, very high); reaction time, and recovery time. Programming can be done manually or automatically using the Automatic Response Factor. In this method, the physician uses the Expert Ease feature in the programmer to decide the LRL, SURL and the sensor rate target, based on the patient’s age, gender, exercise frequency, and target heart rate during exercise, derived from a population average. After inputting these parameters, an initial nominal slope such as 8 (range, 1-16) is programmed. The Automatic Response Factor tracks the maximum sensor rate each day for a week, and the average of this maximum is compared to the sensor rate target. The response factor is then scaled to trigger either a more aggressive response or a conservative response, depending on whether the average rate is below or is above the sensor rate target by 5 bpm, respectively.

Target rate profile Sensor rate profile

LRL

ADL

130–140

120–130

100–110

90–100

80–90

70–80

Exertion response range

60–70

Indicated % of time

ADL response range

110–120

148

Other Activity Sensors.  ELA-Sorin has introduced a gravitational sensor that is used either alone (Swing) or in combination with a PEA sensor (MiniLiving). The gravitational sensor uses the vibrations from a mercury ball to measure body activity. An accelerometer activity sensor (Opus G) uses a half-bridge variable-capacitance accelerometer. The accelerometer senses the AP axis at a frequency range of 0.6 to 6.0 Hz and samples acceleration signals every 1.56 seconds. The device can be programmed manually or automatically using the Autocalibration feature. The level of acceleration at rest is reset daily based on the lowest mean acceleration of 64 consecutive measurements. The maximum mean acceleration of 8 consecutive accelerations is used to match the programmed upper sensor rate.

URL

Rate Figure 5-5  Optimization using target rate histogram. The sensor rate profile is matched against a target rate profile. The activity of daily living (ADL) range includes moderate pacing rates between the lower rate limit (LRL) and the ADL rate. The exertion rates range from the ADL rate to the upper rate limit (URL). By comparing the sensor rate profile with the target rate profile once daily, the pacemaker automatically controls how rapidly the sensor-indicated rate increases and decreases in these ranges. (From Leung SK, Lau CP, Tang MO, et al: An integrated dual sensor system automatically optimized by target rate histogram. Pacing Clin Electrophysiol 21:1559-1566, 1998.)

Clinical Results of Activity Sensors

adjusted to achieve a rate response such that almost 1% heart rate occurs beyond 23% of heart rate reserve. Typically, the slope adjusts by a factor of 2 each week. If the patient has been immobile for the previous week, as indicated by the small activity variance, the slope setting will be held constant, to avoid undue rate response when the patient resumes activity. In addition, rapid manual adjustment of the slope can be achieved by instructing the patient to perform an exercise at a prescribed slope. The Prediction Model will attempt to suggest an alternative slope based on the detected rate response. In addition, the onset and recovery kinetics are separately programmable. These devices also feature a “rest rate” that may be programmed below the LRL. The rest rate is attained when the acceleration sensor does not register significant counts (the “activity variance” level) over an extended period, implying the patient is resting or asleep.

Clinical studies have demonstrated that activity-based pacing systems improve exercise capacity and reduce symptoms compared with VVI pacemakers. In an early study of a piezoelectric vibration-based sensor pacemaker, Benditt et al.8 compared exercise tolerance during VVI and VVIR pacing using treadmill tests. Sensor-driven pacing prolonged exercise duration by 35% and led to similar increments in peak oxygen consumption and oxygen consumption at anaerobic threshold. Activity sensor–driven pacing also reduced the patient’s perception of exertion at comparable exercise levels, and the benefit was sustained when exercise testing was repeated after an average 5 months of follow-up. Further, at follow-up exercise testing, reversion of the pacing system to a VVI mode resulted in prompt deterioration of both observed oxygen consumption and exercise duration. Crossover studies comparing VVIR mode to DDD pacing found no significant difference in symptom scores, maximal exercise performance (treadmill), or plasma concentrations of epinephrine, norepinephrine, and atrial natriuretic peptide, suggesting rate adaptation was the most important factor for exercise in the patient population studied.9,10

Boston Scientific (Insignia, Pulsar Max, Altrua).  An accelerometer mounted in the circuit board is used to detect AP acceleration. In addition to LRL and URL, four other parameters are used to determine the rate response: response factor (1 = least sensitive; 16 = most sensitive); RATE RESPONSE SLOPES SURL

AUTO SLOPES

16

30% % of time

Rate response

8 20% 10%

1 LRL Low activity

A

Lower rate

High activity Sensor levels

B

Heart rate

Upper sensor rate

23% HRR Figure 5-6  Rate-response and “Auto” slopes. A, Rate-response curves from St. Jude Medical activity sensors. B, Automatic threshold (Auto) slope ensures that about 1% of the pacing rate will reach more than 23% of the heart rate reserve (HRR) over time. Note that the sensor-driven upper rate limit (SURL) may not be reached at a low slope setting. LRL, Lower rate limit.



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

In a study of the efficacy of automatic “rate profile optimization” over time, 11 patients with Kappa 700 pacemakers performed treadmill testing at 1 month, 1 year, and 2 years after implantation.11 Based on the sinus profile at follow-up, a more aggressive slope was needed to match the sinus rate profile. This required a change in ADL response from 3 to 4 and in ER from 3 to 4 at 1 year, and a change in activity threshold from medium-low to low at 2 years. These adjustments enabled better approximation of pacing rate to sinus rate during treadmill exercise. Exercise capacity was maintained during the 2 years of follow-up. Variation in activity level (Activity Variance) as detected by an accelerometer is used to determine the rest rate in the St. Jude Medical devices,12 with an overall appropriate rate response. Limitations of Activity-Sensing Devices Activity sensing may give inappropriate heart rate responses when subjected to environmental vibrations, such as from motor vehicle movement over rough terrain, air travel, or use of vibrating appliances or machinery. The piezoelectric vibrational sensor also responds to the application of static pressure on the pulse generator, which may cause inappropriate rate increase when the patient lies prone. This falsepositive response to pressure is no longer a problem with pacemakers that incorporate an accelerometer. The effects of various means of locomotion on pacing rate were assessed for different activity-based pacemakers.13 Three different activity-based pacing systems (peak counting algorithm, integration type, and accelerometers) were strapped to the chests of volunteers. Bicycling on the street resulted in higher pacing rates than did stationary bicycling for each type of pacemaker, although none of the pacemakers reached the heart rate achieved by the normal sinus node. During driving, the pacemakers increased the pacing rate, although the intrinsic sinus rate continued to be higher. In passively riding passengers, the pacemakers tended to produce a higher pacing rate than that of the normal sinus node. Independent of the sensor, activity-initiated rate response depends on the manner in which activity is performed rather than the exercise workload, and proportionality is generally limited.14 Activity sensors typically produce a higher heart rate walking downhill than uphill because of the greater force of heel-strike in the descending direction. Nonexercise stresses such as emotional changes are not detected. MINUTE VENTILATION SENSING Although a respiratory rate–sensing pacemaker was in use as early as 1983, it was limited by the need for an auxiliary subcutaneous electrode, as well as easy interference by arm movement because of unipolar impedance sensing.15 All subsequent generations of respiratory sensor detect impedance as a surrogate measure of minute ventilation for rate adaptation. Again, MV is the product of tidal volume and respiratory rate. Although MV is not actually measured, both the amplitude of changes in transthoracic and intravenous impedance (correlating with tidal volume) and the frequency of changes in these parameters (correlating with respiratory rate) can be measured by injecting a very-low-amplitude and short-duration electrical stimulus between an electrode on a pacemaker lead and the pulse generator casing. Thus, changes in MV can be estimated by changes in minute impedance. The advantage of this sensor is that it only requires a standard bipolar pacing lead in either the right atrium or right ventricle, without the need for additional hardware. The response of MV during exercise is proportional to oxygen consumption (below anaerobic threshold) and responds at a reasonable speed; battery drain is not excessive. Current Minute Ventilation–Sensing Devices Medtronic (Kappa 400).  The Medtronic MV pacer was marketed as a dual-sensor device. The MV component requires a bipolar lead. Subthreshold, 30-µV biphasic pulses at 1 millisecond (msec) are injected between the electrode (atrial or ventricular) and pacemaker case at 16 Hz, and the resulting impedance is measured between the

149

lead tip and the case. Changes in MV are measured as MV counts over a 32-second, short-term moving average to avoid transient changes in impedance, such as those caused by coughing and speech. The shortterm average is compared over an 18-hour, long-term average to effect a change. Medtronic Kappa 400 has been evaluated using symptom-limited treadmill testing.16 All patients had cardiopulmonary gaseous analysis in conjunction with simultaneous recording of MV-induced impedance changes. Calibrations were made during resting, supine, sitting, and different types of exercise (bicycle or treadmill). The impedancederived MV was smaller for sitting versus supine position, for shallow versus slow breathing, and for bicycle versus treadmill exercise, possibly because of change in chest cage geometry. Correlation coefficients of the best-fit line for measured and device-based MV were high (>0.9 in first-, second-, and third-order polynomial equations).17 Furthermore, the calibration between measured MV and impedance MV changes over time (1 week to 1 month). However, the changes were not correlative, with implications for the need of continual automatic adaptation. These findings also suggest the potential use of the sensor for MV monitoring. Boston Scientific (Pulsar Max, Insignia, Altrua).  In the Boston Scientific devices, MV is available in conjunction with an accelerometer sensor, although either sensor can be used alone or blended with the other. MV collected by the atrial or ventricular lead (programmable) over 24 hours is used as an average against which future changes in MV are compared for a rate response. The minimum time for achieving a baseline is 4 minutes (“4 → On”). A linear response curve is used, and a total of 16 response factors can be chosen below the pacing rate estimated for anaerobic threshold. This rate is also programmable. In between the pacing rate for anaerobic threshold and the maximum predicted heart rate, a gentler “high rate response” can be programmed. The adaptation can be made faster by activating the 4-minute walk within 30-minute option, in which the subject is instructed to exercise to achieve the maximal MV change. The telemetered MV impedance signal from a Boston Scientific device was compared with measured MV in 20 patients.18 Respiratory rate was accurately measured by the device during hyperventilation, with difference less than 0.2 breath/min. During 10-minute cycle ergometry at 50 W, the correlation between MV measured directly and by the device was 0.99. Large, individual variations exist between the measured MV and the impedance MV slope, requiring individualized rate-response curves. ELA-Sorin (Chorus, Talent, Opus, Symphony, Rhapsody, Reply).  Minute ventilation is determined from a default bipolar atrial lead, with current injection from distal electrode to casing, and current collection between the proximal pole and casing. In the event of a unipolar atrial lead, the distal electrode of the ventricular lead is used as the current-injecting electrode. Sourcing and injection can also be performed with a bipolar ventricular lead. The automatic slope algorithm in the Chorus determines the resting and maximum MV values daily. If MV over 128 cycles remains below the 24-hour MV average, the lower rate will decrease to the LRL. The device calculates the exercise MV signal by looking for the maximal MV signal and recalculates this value every eighth cycle. The exercise MV value is increased or decreased in 6% intervals. The mean resting and exercise MV values are used to adjust the rate-response slope automatically over the range of values from 1 to 15 in steps of 0.1. The response of the Talent DR during exercise was compared in 81 patients. The correlation coefficient between the sensor rate and programmerderived sensor rate was 0.983 ± 0.005, and a linear relationship was observed between the heart rate reserve and MV reserve.19 Clinical Experience of MV Sensor Pacemakers Minute ventilation is an indirect but reliable marker of metabolic demand, and in the first generation of MV pacemakers (Meta MV, Telectronics), the rate response was proportional to the level of

SECTION 1  Basic Principles of Device Therapy

Limitations of Minute Ventilation Sensing As with all impedance systems, the MV sensor will likely be affected by electromagnetic interference, arm swinging, coughing, and hyperventilation.16 Artificial ventilation will induce an unphysiologic rate, so MV sensing needs to be disabled in such patients (e.g., general anesthesia, mechanical ventilation). The use of MV devices in patients with lung disease and heart failure remain controversial. Early generations of MV-sensing devices limited the maximum detectable respiratory rates to less than 48 to 60 breaths/min to minimize the cardiac effects of changes in impedance. Because of this filtering of the cardiac component of changes in impedance, MV sensors may not accurately reflect rate adaptation at very high respiratory rates, as may occur in children. A bipolar ventricular lead is needed for MV sensing in several models. The battery current for MV sensing may consume approximately 2% of the total current of a dual-chamber pacemaker. Some amplifiers may sense the small impedance pulses unless preventive steps are taken. In some products, a blanking period of about 1 msec is applied to the amplifiers to “blind” them to these pulses. In other cases, special balancing of the pulse achieves the same objective. Sensing of the impedance pulses by a surface electrocardiogram (ECG) monitor may occur, depending on the ECG machine’s frequency response as well as pulse width and balancing of the impedance pulse. Also, frequencies above a few kilohertz (kHz), such as generated by electrocautery and electrosurgery, are detected by the rate-response circuitry and could drive an MV-sensing pacemaker to its maximum rate. It is recommended that the rate-response function be inactivated whenever electrosurgery will be used. Respiration may also be influenced by phonation and coughing that have no direct relevance to change in cardiac output. UNIPOLAR VENTRICULAR IMPEDANCE: CLOSED-LOOP STIMULATION SENSOR Contractility of the right ventricle increases during catecholamine stimulation, as occurs in exercise and emotional stress. In the absence of an adequate rate response, exercise will induce a higher contractility. When rate response is adequate, the change in contractility is less, thus establishing a negative feedback loop and a new, steady contractility state. On the other hand, elevated pacing rates can increase contractility, the so-called Treppe effect, although this has not been important in clinical practice. Right ventricular (RV) impedance can be derived from a standard pacing lead and can be used to monitor heart function and catecholamine state. Sensor and Algorithm The CLS sensor is based on unipolar impedance at the tip of a pacing lead.22 Subthreshold pulses of automatically selected outputs, ranging from 100 to 400 microamperes (µA), with biphasic duration of 46 msec are emitted 50 to 300 msec after a sensed or paced ventricular event. During late diastole immediately after a ventricular paced (Vp)

or sensed (Vs) event, the blood volume of the right ventricle is highest and RV impedance is lowest. On the other hand, as contraction occurs, the walls surrounding the electrode tip draw closer, and impedance rises (Fig. 5-7, A). A baseline waveform will depend on the conduction state of the heart: AsVs, AsVp, ApVs, ApVp (As, atrial sensed; Ap, atrial paced event). Baseline CLS waveforms will be acquired only when the associated accelerometer indicates “no activity,” and a waveform will be discarded within 48 hours if not referenced. An average template of the baseline CLS waveform will take 2 to 3 days to optimize. As contractility increases during exercise, unipolar impedance will change. The time-integrated difference between the exercise and baseline impedance waveforms is converted to a pacing rate using an auto response factor, which is continually adapted and patient specific. The magnitude of rate response is then determined by a programmable exertion threshold rate (ETR; very low, low, medium, high, and very high) (Fig. 5-7, B). The ETR, acting through the auto response factor, will determine that 80% of the heart rate will occur below the ETR and 20% above the ETR. An active young individual will probably require a higher ETR than an inactive elderly patient. Again, the type of rate profile attained will be determined by the patient’s cardiac condition, physical state, and specific automatic response factor. Although not strictly a dual-sensor pacemaker, the incorporated accelerometer performs an “on-off ” function to decide on the acquisition of the baseline CLS waveform and the CLS-driven response. Full CLS-driven rate according to the programmed ETR will be allowed only if the accelerometer registers “exercise”; otherwise, only 20 bpm above the LRL is allowed to enable a nonexercise rate increase. In neurocardiogenic syncope, this rate-limiting algorithm can be inactivated for full overdrive response, as during a syncopal episode. TIME (ms) 240 Resting

200 Units

exertion and correlated with the normal sinus response.20,21 Compared with VVI pacing, MV-based VVIR pacing increased exercise capacity by 33%,21 and maximal oxygen consumption and cardiac output were significantly improved. In one study of 10 patients with the first version of MV-driven VVIR pacing, pacing rate was highly correlated with measured MV (r = 0.89), respiratory quotient (r = 0.89), Vco2 (r = 0.87), tidal volume (r = 0.87), Vo2 (r = 0.84), and respiratory rate (r = 0.84). Maximum oxygen consumption also increased from 13.4 ± 3.4 to 16.3 ± 4.1 mL/kg/min (P = .0004) using MV-driven over VVI pacing. Improvement in symptoms were also documented in the VVIR mode.21 The MV sensor has good long-term stability; programming of the sensor is relatively simple; and the rate response is appropriate during daily activities. Compared with activity pacing, MV is significantly better in achieving a near-normal pacing rate–workload relationship, whereas activity sensing tends to overpace at low-level exercise and underpace at peak exercise and in the recovery period.

160 120

Exercise

80 40 50

A

100

150

200

250

300

Milliseconds after a sensed or paced ventricular event 8

ETR = 73

7 6 Rate (%)

150

ETR = 80

ETR = 92

Very low

5 4

Medium

3

Very low

2 1 0

B

60

70

80

90

100

110

120

130

Figure 5-7  Closed-loop stimulation (CLS) sensor and algorithm. A, Changes in CLS parameter during exercise. Hatched area represents the difference between baseline and exercise CLS waveforms and is converted to a rate using the exertion threshold rate (ETR). B, Impact of ETR on rate response of CLS. “Medium” ETR corresponds to a rate of 80 beats per minute (bpm; 20 bpm above lower rate limit). Programming this rate will ensure a rate response of 80% less than this rate and 20% above this rate. A higher or lower ETR will result in different rate responses.



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

151

Micro mass PEA Pace/sense Electronics Figure 5-8  Biomechanical Endocardial Sorin Transducer. The BEST sensor (Sorin Biomedica Cardio) consists of a microaccelerometer located inside a rigid capsule at the tip of a standard ventricular pacing lead, which is connected to a triple header. PEA, Peak endocardial acceleration.

Current Closed-Loop Stimulation Devices: Biotronik (Inos, Protos, Cyclos, Entovis, Evia) Acute measurements of the CLS parameter (previously known as “ventricular inotropic index”) were taken in 82 patients with chronically implanted unipolar ventricular leads at pulse generator replacement.22 A wide fluctuation of baseline impedance was observed (500-1500 Ω), whereas CLS fluctuated by about 4 to 25 ohms (Ω), with a good correlation between CLS and the baseline impedance. A clinical study of 205 patients evaluating the CLS pacemaker included a significant number of young subjects with complete AV block caused by Chagas’ disease.23 Satisfactory rate modulation was reported in 93% of patients. In the remaining 7% of patients, rate adaptation could not be achieved because of poor exercise tolerance, severe myocardial dysfunction, and intermittent intrinsic AV conduction. In a multicenter study that included 178 VVIR (Biotronik Neos-PEP) and 84 DDDR (Biotronik Diplos-PEP, InosDR) devices, physiologic rate adaptation was possible in 93% and 96% of patients with these devices, respectively.24 Apart from exercise rate response, this study also involved mental stress testing using color-word matching and the infusion of inotropic agents. A moderate level of rate response was documented in some patients with CLS pacemakers during these nonexercise conditions that was greater than during accelerometer-guided pacing. The benefit of CLS sensor pacing during mental stress and cognitive function has also been studied.25 Considerable interest surrounds the use of the CLS sensor to detect changes in posture. Passive head-up tilt, which depletes intravascular volume, increases the inotropic state of the heart. In a multicenter study, Inotropy Controlled Pacing in Vasovagal Syncope (INVASY), 50 patients with severe vasovagal syncope and positive head-up tilt test were randomized between DDD-CLS and DDI mode at 40 bpm.26 Whereas 7 of 9 patients in the DDI arm experienced syncope within 1 year, only 4 of 41 patients in the DDD-CLS arm had presyncope. The authors suggested the efficacy of this approach, although a placebo effect of pacing was suspected in 22% of patients. In 131 patients with chronotropic incompetence, CLS pacing resulted in a higher pacing rate compared with accelerometer sensor, but no difference in 6-minute walking distance (6MWD) test.27 However, twice as many patients preferred the CLS mode. The use of CLS in the left ventricle, as in a CRT device for monitoring, may be a useful application of this technology (see later discussion).

PEAK ENDOCARDIAL ACCELERATION Sensor and Algorithm The contractile state of the heart can be identified by the maximal velocity of shortening of unloaded myocardial contractile elements, which can be measured with a catheter tip accelerometer attached to the ventricular wall. The “peak endocardial acceleration” represents the endocardial vibration measured by the accelerometer in the right ventricle during isovolumetric contraction phase of the ventricles. This signal is closely associated with the intensity of the first heart sound. The ELA-Sorin BEST (Biomechanical Endocardial Sorin Transducer) sensor is a microaccelerometer consisting of an acceleration sensor built into a nondeformable capsule on the tip of a standard unipolar ventricular pacing lead. The lead is placed against the RV wall so as to be sensitive to its acceleration and insensitive to the pressure of blood and myocardium (Fig. 5-8). This system has a frequency response up to 1 kHz and a sensitivity of 5 mV/G (1 G = 9.8 m/sec/sec). In early animal experience using an external system and an implantable radiotelemetry system, the PEA was not affected by heart rate but significantly increased by emotional stress, exercise stress testing, and inotropic stimulation.28 The PEA signal changes in parallel to the maximal LV dP/dt and appears to measure the global LV contractile performance rather than the regional mechanical function. The PEA signal that occurs 150 msec after the R wave corresponds to the isovolumetric contraction phase of the left ventricle (PEA-I)29 (Fig. 5-9). A smaller signal also occurs in the 100-msec period after the T wave,

ECG

LV dP/dt

Ao Press

LV Press

Advantages and Limitations Closed-loop stimulation appears to be a good sensor to measure cardiac contractility using a conventional ventricular pacing electrode. The demand on pacing energy is acceptable. As a contractility sensor, CLS is sensitive not only to exercise but also to nonexercise requirements, and it may therefore be used for monitoring cardiac contractility for non–rate augmentation purposes. CLS can be used only in a pacing mode that incorporates a ventricular lead. Ventricular ischemia and cardioactive medications likely influence CLS rate adaptation, although automatic adjustment may permit long-term function. A small proportion of patients are not suitable for CLS sensors because of severely impaired RV function. Such patients may be identified preoperatively, and a backup activity sensor is always available.

EA PEA-I

PEA-II

Figure 5-9  BEST tracings. Electrocardiogram (ECG), left ventricular (LV) dP/dt, aortic pressure (Ao Press), LV pressure, and endocardial accelerometer tracing (EA) recordings in a sheep with the BEST sensor (see Fig. 5-8). The peak of the accelerometer tracing during the isovolumic diastole (PEA-II) occurs in a 100-msec period after the T wave on the ECG. (From Plicchi G, Mercelli E, Parlapiano M, et al: PEA-I and PEA-II based implantable haemodynamic monitor: preclinical studies in sheep. Europace 4:49, 2002.)

152

SECTION 1  Basic Principles of Device Therapy

the so-called PEA-II, which corresponds to the isovolumetric LV relaxation. PEA-II is related to peak negative dP/dt (r = 0.92) and aortic diastolic pressure (r = 0.91).30 To enable the PEA sensor to be used in patients requiring an ICD lead, the sensor has been incorporated into a right atrial (RA) lead (SonR sensor). Preliminary results suggest that the SonR sensor is similar to the RV PEA signal and that it might be useful in patients receiving cardiac resynchronization therapy with defibrillation (CRT-D).29 This offers the potential to measure cardiac hemodynamics in heart failure patients with an ICD. Current PEA Devices: BEST Sensor Rate–Adaptive Pacemakers (Sorin Best-Living Systems: Miniliving D and S) These PEA devices use a dedicated unipolar ventricular pace/sense lead, which is IS-1 compatible. Together with the two electrodes for PEA signals, a tripolar connector is necessary. These devices also incorporate an activity sensor detecting the vibration (gravitational sensor). In the PEA mode, continuous PEA signal collected over time is used as a reference, against which the change in PEA is compared. A linear pacing rate response curve is used to relate the change in PEA signal and the rate response. In the dual-sensor mode, the combined output from both sensors is used to drive the rate to an intermediate level, and further rate increases are guided by the PEA sensor alone. In addition, prolonged absence (about 45 minutes) of signals from both the gravitational and the PEA sensor will allow the basic rate to decrease to the programmable rest rate. Clinical Results Clinical studies show good correlation between the sinus rate and PEA sensor–indicated rate during daily life activities and submaximal stress testing.31,32 Similar results were obtained in patients tested during electrophysiologic studies using an external system; changes in PEA were linearly related to the RV dp/dt during dobutamine infusion. PEA signals have been used to monitor hemodynamic function and program the A-V interval. In 13 patients with end-stage heart failure implanted with a DDD-PEA device with a custom lead arrangement, PEA level during RV, LV, and biventricular (BiV) pacing were compared.32 Both LV and BiV pacing increased stroke volume (21% and 37%, respectively) compared with RV pacing, and mean PEA changes over 15 minutes were also higher (43% and 38%). In addition, an apparent minimum PEA level at the optimal A-V interval has shown promise in automatically detecting the optimal A-V interval in a dual-chamber device.33 The algorithm is now automatic. An increase in PEA during head-up tilt-table testing has been observed, and the use of PEA-driven overdrive pacing in patients with vasovagal syncope has been reported.34 Patients randomized to DDDR have a reduced frequency of syncope compared with DDI pacing. In 15 patients with a CRT pacemaker, the PEA correctly indentified the optimal AV interval in 75% of patients.35 These data suggest the potential use of PEA sensor for hemodynamic monitoring (see later). Advantages and Limitations PEA is a proportional sensor that shows good correlation to cardiac workload, especially at higher ranges. The PEA sensor is limited by the need for a specialized lead, leading to concerns about its long-term stability and its use at pacemaker replacement (when a standard header pacemaker is used). Development of the PEA sensor in an atrial lead allows its use in patients requiring an ICD lead.

Current Combined Sensor Devices Experience with sensors has suggested that rapidly responding sensors (e.g., activity) are not proportional at higher levels of cardiac workload, whereas proportional sensors are usually slow in response. As a result, an activity sensor overpaces at low activity levels but underpaces at higher exertional levels (Fig. 5-10). Furthermore, single sensors may be limited by insensitivity to nonexercise stress and are prone to

interference by nonphysiologic causes. Thus, it is logical to enhance their rate-response profile by combining two or more sensors. Two principles guide the combining of sensors: sensor blending and sensor cross-checking. Sensor blending involves combining sensordriven rates from individual sensors in a certain ratio. This can be the “faster win” method, in which the higher rate indicated by either sensor is chosen as the pacing rate, or ratios of the individual rates are added together to compute the actual rate response. Sensor cross-checking enhances the specificity of each sensor. If a more specific sensor registers “no exercise” or physiologic stress, changes in the other, less specific sensor can be ignored or its response attenuated (Fig. 5-11). Table 5-3 summarizes instrumentation of current dual-sensor devices. Details of the combined CLS/activity and PEA/activity devices are discussed earlier. CURRENT DUAL-SENSOR DEVICES Medtronic Pacemakers Medtronic marketed two dual-sensor pacemakers: the combined activity and QT sensors (Vitatron) and the combined activity and MV sensors (Kappa 400). Both are no longer manufactured. In the activity/ QT device, a “faster win” algorithm was used, with highest rate of two sensors used to determine actual pacing rate. Since the QT sensor is more specific for physiologic changes, an increase in activity sensor level in the absence of QT documenting exercise was used as a crosscheck, resulting only in a brief and limited rate response. Using an adaptive sensor level to the SURL, the QT sensor level was continuously scaled down if, at the SURL, QT continued to shorten, suggesting the sensor level had reached the upper rate too soon. The converse was also operative. The combined sensor rate was found to be closer to the sinus rate during daily activities.36 In the Kappa 400, a piezoelectric sensor is used for activity sensing, and MV is sensed from a bipolar ventricular lead. Differential sensor blending is used. Up to the ADL rate, activity input predominates, whereas MV-driven pacing will predominate at the SURL. Activity and MV sensors were checked against one another. In the absence of piezoelectric sensor indicating exercise, MV pacing only reached the ADL rate, and vice versa. Only when both MV and activity signified exercise would pacing occur above the ADL rate. The dual-sensor rate response has been reported to be reliable for both maximal and submaximal activities, as well as resistant to nonphysiologic interference.37 Compared with MV sensor alone, dualsensor mode reduces oxygen deficit acquired during exercise by enhancing the initial rate response.38 “Quantitative rate adaptation” is also superior in the dual-sensor mode.39,40 “Rate profile optimization” was found to be a useful method for rate-adaptive programming, comparable to manual programming,41 and may be superior to accelerometer alone for rate optimization.11 Boston Scientific (Insignia, Pulsar Max, Altrua) An accelerometer activity sensor is integrated with the MV sensor, using differential sensor blending. At low heart rates, the blended sensor rate is approximately 80% accelerometer and 20% MV sensor. This ratio changes to 40%/60% near the SURL. In addition, if the MV rate is higher than the accelerometer rate, the dual-sensor rate follows the MV level. In a study involving 120 patients with Insignia, the programmed sensor modes were randomized to the accelerometer sensor alone, the MV sensor alone, or the dual-sensor mode, each for a 3-month period.42 Using the implanted Activity Log to determine the mean percentage and intensity of activity, quality of life (QOL), and New York Heart Association (NYHA) classes were assessed at the end of each period. Overall, either single-sensor DDDR mode improved Activity Log, QOL, and NYHA scores compared with DDD pacing, but with no difference between the two sensors. The dual-sensor mode did not improve these measurements. This study may have been limited by the prolonged, triple-crossover design but does suggest that clinical differences are likely minimal between sensors and their combinations.



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring 1.00

1.0

HR (normalized)

Observed

Expected Quartile 1 137%

0.25 Quartile 2 81%

Quartile 3 66%

A

0.25

0.50

1.00 Max VO2

0.75

Observed

1.0 Total area 122%

0.8

0.6

HR (normalized)

0.4 Quartile 3 100%

0.4

0.2

0.0

Metabolic equivalents (normalized)

Total area 30%

0.8

0.6

Quartile 2 166%

0.8

1.0

Expected

Observed

Quartile 1 352%

1.0

B

Metabolic equivalents (normalized)

HR (normalized)

Expected 0.4

0.0

0.00 Min VO2

0.6 Expected 0.4

Observed

0.2

Quartile 4 75%

0.0

0.0

0.00 Min VO2

C

0.6

0.2

Quartile 4 102%

0.00

0.2

Total area 85%

0.8 HR (normalized)

Total area 89%

0.75

0.50

153

0.25

0.50

0.75

1.00 Max VO2

Metabolic equivalents (normalized)

1.0

D

0.8

0.6

0.4

0.2

0.0

Metabolic equivalents (normalized)

Figure 5-10  Quantification of pacing percentage of minute volume (MV) and activity pacer during graded treadmill exercise. A, Results of the normalized heart rate and workload in one patient. There is overpacing in quartile 1 (137%), underpacing in quartiles 2 (81%) and 3 (66%), and near-ideal pacing in quartile 4. B, Near-ideal rate recovery of the MV sensor. C and D, Exercise response of an activity sensor, with overpacing most of the time, but inadequate rate recovery. (From Kay GN: Quantitation of chronotropic response: comparison of methods for rate-modulated permanent pacemakers. J Am Coll Cardiol 20:1533, 1992.)

TABLE

5-3 

Types of Dual-Sensor Pacemakers in Current Use

Manufacturer Medtronic

Models Kappa 400

Sensors ACT: piezoelectric MV: impedance

Algorithms Blending ≤ADL range: ACT + MV ADL-ER range: mainly ACT

Boston Scientific

Pulsar Max Insignia Altrua

ACT: accelerometer MV: impedance

ELA-Sorin

Chorus Talent Symphony Rhapsody Talos Cylos Entoris

ACT: accelerometer MV: impedance

Blending Low heart rate: ACT 80%, MV 20% High heart rate: ACT 40%, MV 60% No blending MV-determined rate response if ACT indicates exercise No blending No ACT rate contribution Rate response determined only by CLS

Biotronik

CLS: unipolar ventricular impedance ACT: accelerometer

Cross-checking ACT (0) and MV (+): up to ADL rate ACT (+) and MV (0): up to ADL rate ACT (0) and MV (+); and ACT (+) and MV (0): limited rate ACT (+) and MV (0): initial limited rate response ACT (0) and MV (+): rate recovery ACT (0) and CLS (+): limited rate response ACT (+) and CLS (0): no rate response

Automaticity Rate Profile Optimization

AutoLifestyle

Automatic matching MV sensor to LRL and SURL Auto Response Factor adjusts CLS data to reach rate distribution determined by the programmed Exertion Threshold Rate

ACT, Activity level; ADL, activity of daily living; CLS, closed-loop stimulation; ER, exertion response; LRL, lower rate limit; MV, minute ventilation; SURL, sensor-driven upper rate limit.

154

SECTION 1  Basic Principles of Device Therapy

TABLE

SR

5-4 

Select Patients for Dual-Sensor Pacemaker

Clinical Situation High exercise heart rate preferred

S1

Avoidance of undue rate acceleration Need for nonexercise rate response

S2

Examples Young, athletic individuals may require a more physiologic sensor. Working in a vibrational environment Vasovagal syncope Stress response

Hemodynamic or other monitoring

Exercise

Nonexercise stress

Interference

Proportionality and speed

Sensitivity

Specificity

Figure 5-11  Algorithms for sensor combinations needed to achieve better proportionality and speed of response, sensitivity, and specificity. Top to bottom, Graphs depict the responses of the sinus node (SR), sensor 1 (S1), sensor 2 (S2), and combined rate profile (S1 + S2). SR shows ideal proportionality, speed of rate response, and freedom from interference. S1 is a rapidly responding sensor, although it is neither proportional nor sensitive and is susceptible to interference. S2 is a proportional and sensitive sensor, although it has a slow response. It is also specific to exercise. Note the improved ability of the combined sensor approach in simulating the sinus rate under different conditions.

The Limiting Chronotropic Incompetence for Pacemaker Recipients (LIFE) study of 1256 patients with chronotropic incompetence found that the blended sensor improved metabolic-chronotropic slope compared with the activity sensor alone43 (Fig. 5-12). However, besides improved physical activity time/energy expenditure, there was no measurable difference in QOL between the blended sensor and the activity sensor alone. A prospective randomized parallel study on activity and MV with the primary outcome of Vo2 is planned (APPROPRIATE study).44 This study will randomize 1000 patients who will be screened for CI using a 6MWD and treadmill heart rate at 1 month. Patients with confirmed CI will have their sensors optimized with a brief walking test. Apart from Vo2 max, rate changes during daily activities will be assessed. This study will shed light in the role of different sensors on exercise oxygen uptake. (Unfortunately, the study was prematurely terminated because of suboptimal recruitment.) ELA-Sorin (Chorus, Talent, Symphony, Rhapsody, Reply) An accelerometer and a MV sensor are combined in these devices. Sensor blending and cross-checking are both operative to effect rate adaptation during exercise (Fig. 5-13). When the accelerometer is active but MV has not increased, as may occur at the beginning of exercise, rate response occurs according to a fixed activity response curve to a limited rate. When MV increases, rate response follows the MV sensor–driven rate. Persistent absence of accelerometer signal is considered the cessation of exercise, and this allows a decrease in the pacing rate using a recovery curve to the LRL, even though MV remains higher than baseline. A multicenter study involved 81 patients with the ELA dual-sensor pacemakers.19 In patients who underwent exercise stress testing at 1-month follow up, sensor-driven rate had good correlation with the sinus rate (r = 0.92 ± 0.07; P < .001), with the slope of linearity at 1.0 ± 0.2. Using metabolic reserve to relate to heart rate reserve, a slope of 1.1 ± 0.2 was obtained, suggesting a close relation between the dualsensor rate and metabolic workload. ARE DUAL SENSORS JUSTIFIED? Dual-sensor implementation is technically and clinically feasible and provides a rate profile closer to the normal sinus rate. In practice, a more specific sensor is added to the activity sensor to enhance its

specificity. However, apart from physiologic parameters such as oxygen uptake and transport kinetics, no clinical benefit over single sensor has been seen in large groups of patients, likely reflecting the limited exercise activities of most patients meeting standard indications for pacing. For select patients who are highly active, however, these dual-sensor pacemakers may provide important clinical benefits (Table 5-4).

Clinical Benefits of Sensor-Driven Pacing Controversy remains about the clinical benefits of sensor-driven pacing, especially the lack of symptomatic benefit observed in some comparative studies. Factors that may affect such comparisons include (1) definition of CI, (2) programming of sensor (extent of rate adaptation), (3) patient populations including their comorbidities, (4) pacing modes, and (5) site of ventricular pacing (Table 5-5). CHRONOTROPIC INCOMPETENCE Although factors contributing to CI can be obvious—age, coronary artery disease, sinus node dysfunction, and cardioactive medications— what constitutes CI remains uncertain. CI can vary from 9% to 84%, MCR SLOPE

1.0

Heart rate reserve (%)

S1 + S2

0.8 p <0.001

0.6

0.4

0.2

0.0 0.0

0.2

0.4

0.6

0.8

1.0

Metabolic rate reserve (%) Figure 5-12  Sensors in patients with chronotropic incompetence (CI). Overall sensor response (blended sensor [BS] and activity sensor [XL]) from 1 to 6 months in CI patients with adequate exercise tests. Blue lines indicate paired BS responses from 1 month (dashed line) to 6 months (solid line). Orange lines indicate paired XL responses from 1 month (dashed line) to 6 months (solid line). The black solid line indicates a normal metabolic-chronotropic relationship (MCR) slope; black dashed lines, 96% confidence interval CI (0.8-1.3). (From Coman J, Freedman R, Koplan BA, et al: A blended sensor restores chronotropic response more favorably than an accelerometer alone in pacemaker patients: the LIFE study results. Pacing Clin Electrophysiol 31:1433-1442, 2008.)



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring SENSOR BLENDING

155

AUTOCALIBRATION

Rate

Rate

Y SURL

SURL

LRL

X LRL

Rest

Exercise

Rest

Rest MV/ACT

B

Exercise MV/ACT

ACT

A

MV

Figure 5-13  Algorithm of dual-sensor device (ELA-Sorin). A, Combination of activity (ACT) and minute ventilation (MV) inputs during exercise. B, Autocalibration of the sensor. If the maximum sensor level is reached before the sensor-driven upper rate limit (SURL; indicated by X), then the slope is adjusted in steps to Y to match the SURL to the maximum sensor level. LRL, Lower rate limit.

TABLE

5-5 

Factors Affecting Clinical Benefit of Sensor-Driven Pacing

Issues Patient related

Device related Programming Methods of measurements

Factors Degree of chronotropic incompetence Left ventricular function Sinus vs. atrial fibrillation Age and comorbidities Sensor type Site of ventricular lead(s) Rate adaptive pacing mode Sensor programming Lower and upper rate Percentage of ventricular pacing Protocol: crossover or parallel arm Exercise Symptoms Quality of life

This study did not address whether rate adaptation improves exercise or QOL. However, patients with CI had a lower QOL (physical and mental component) than those who were chronotropic competent. With correction of CI in the DDDR mode, there was an increase in physical activity time and kilocalories expanded per week compared to baseline DDD at 1 month, with a greater tendency toward higher levels for the dual sensors than the single, activity sensor (mean change for activity score from baseline to 6 months: activity sensor = 1.45 ± 17.12, dual sensor = 2.69 ± 15.3; and energy expenditure change: activity sensor = 359 ± 367, dual sensor = 716 ± 3810

100 90

86%

87%

%

80

70%

70 Percent

depending on the definition used.43,45-57 Based on cardiac mortality, CI defined as “inability to reach 85% maximum age-predicted heart rate” will identify 2.2 times as many individuals with increased cardiac mortality.45 From the patient’s perspective, CI should be defined as a level at which its reversal by a sensor will improve exercise capacity and QOL. There are few long-term studies in pacemaker patients, although it is generally accepted that inability to reach a rate greater than 100 bpm represents severe CI.48 The metabolic-chronotropic relationship may be a scientific way to classify CI at peak and each level of exercise, with a slope value of the plot of heart rate reserve to metabolic reserve of less than 0.8 identifying CI.49 In 547 pacemaker patients, exercise testing was used to identify CI at 1 month after pacemaker implantation.43 Patients were recruited in this study if they could complete three or more stages of CAEP protocol and attained a perceived-exertion Borge scale of 16 or higher. CI is defined as a heart rate reserve less than 80% of metabolic reserve at each stage of the CAEP exercise test, and if more than 0% of these stages were incompetent, CI is identified. Based on this study, 50% of these patients had CI. The study further assessed the prevalence of CI using different definitions in the same cohort according to the previous definition, and found that the incidence is similar to using maximum predicted heart rate of less than 70% as CI. The other definitions tend to be more sensitive and identify 70% to 87% of recipients with CI (Fig. 5-14).

60 50 40

34%

35%

LIFE

70% MPHR

30 20 10 0 85% Metabolic MPHR chronotropic slope <0.8

80% HRR

Figure 5-14  Prevalence of chronotropic incompetence (CI). Results in 547 pacemaker recipients during maximum exercise according to published criteria. See text for LIFE study CI definition (Fig. 5-12). HRR, Heart rate reserve; MPHR, maximum [age] predicted heart rate. (Data from Coman J, Freedman R, Koplan BA, et al: A blended sensor restores chronotropic response more favorably than an accelerometer alone in pacemaker patients: the LIFE study results. Pacing Clin Electrophysiol 31:1433-1442, 2008.)

156

SECTION 1  Basic Principles of Device Therapy

Kcal).43 These data suggest that a more stringent criterion for CI may identify a group of pacemaker recipients who are more symptomatic and benefit from dual sensors, although the benefit of accurate rate adaptation remains controversial in large-scale studies. UPPER RATE LIMIT The peak heart rate (HR) is inversely related to age. In large studies, mean peak HR has been traditionally estimated by the formula: HRmax = 220 − age. The variance is approximately 15 bpm. This is a useful guide to prescribe physical training, but its application to pacemaker recipients remains controversial. Kindermann et al.50 exercised 49 patients with conventional DDD pacemaker using cardiopulmonary exercise results and Doppler to define the optimal upper rate. In patients with normal heart function (left ventricular ejection fraction [LVEF] ≥55%), the URL was 86% of the maximum predicted HR. In those with impaired heart function (LVEF ≤45%), a 75% maximum predicted HR was optimal, beyond which cardiac output tended to decrease. This may be related to decreased ventricular compliance and other factors, such as ischemia that could occur at higher HR. Of interest, contractility augmentation as a function of increased HR appeared to be attenuated with RV pacing. In 22 patients with heart failure and a wide QRS complex, Vollmann et al.51 found that BiV pacing restored the rate-related contractility when pacing at 80 to 140 bpm, whereas the change in RV pacing was minimal, and the changes during LV-only pacing was intermediate. Thus, the site of ventricular pacing is an important determinant of the URL. RATE-ADAPTIVE PACING MODES VVIR vs. VVI The first rate-adaptive pacing mode introduced was VVIR pacing. This mode was most extensively studied, and often applies to patients who had complete CI, as in those with complete AV block. Independent of the type of sensors, a 69% and 32% increase in heart rate and exercise capacity has been documented over VVI pacing.52 In addition, VVIR pacing has been shown to improve most aspects of QOL over fixed-rate pacing.53 AAIR vs. AAI/VVI An infrequently used pacing mode, AAIR has the theoretical advantage of preserving native conduction and avoiding ventricular pacing altogether. The disadvantages include progression of AV conduction disease, even in patients with normal AV conduction at baseline, and potential induction of Wenckebach AV block by inappropriately high atrial pacing rates. How quickly AV conduction can adapt with exercise may be an issue, because lack of AV adaptation during an appropriate sensor-driven atrial rate may prolong the P-R interval, resulting in AV dyssynchrony. If the P-R interval is greatly prolonged, the pseudo– pacemaker syndrome may result.54 An early study on AAIR pacing compared AAIR, DDDR, and VVIR mode in patients with intact intrinsic AV conduction (1 : 1 A-V ≥100 bpm; atrial-R ≤220 msec).55 Patients with VVIR pacing had worse QOL than AAIR patients, as well as more palpitations and depression despite a lower frequency of ventricular pacing than DDDR patients (39% ± 7% vs. 64% ± 11%). All patients initially had normal LV function, which may have obscured minor differences between modes. In a further study, AAIR pacing that increased the maximum heart rate to 142 bpm did not increase oxygen uptake compared with VVI backup at 40 bpm in patients with impaired LV function.55 The study was limited by an intrinsic maximum rate of 130 bpm even without rate adaptation. DDDR vs. DDD Much controversy surrounds the potential benefit of DDDR versus DDD pacing. In a small cohort of 10 patients, DDDR improved exercise capacity over DDD pacing in patients with severe CI.46 However, in a more recent trial including 873 patients, despite an increase in HR

from 101.1 ± 21.1 bpm to 113.3 ± 19.6 bpm at 6 months, there was no difference in exercise capacity between the two pacing modes.56 More than 90% of beats in the two modes were ventricularly paced, and a potential reason for lack of benefit may be related to the potentially negative effects of RV apical pacing. In a small study, van Hamel et al.57 compared DDDR versus DDD mode in 99 patients with either AV block or sinus node disease. They found no difference between DDDR and DDD mode in terms of QOL, despite significantly higher atrial pacing rate in the sensor-driven arm. Again, this study documented a high percentage of RV pacing in both sinus node patients (87.9%) and AV block patients (96.8%). Pacemaker Operations That Minimize Ventricular Pacing With the recognition of disadvantages of excessive RV pacing, most manufacturers provide some form of A-V interval extension to reduce RV pacing and allows intrinsic conduction. These features are usually inactivated during the DDDR mode. In the minimal ventricular pacing algorithm of the Medtronic, the device functions in AAI ↔ DDD, and although rate response can be programmed, it will only be operative in the DDIR mode that occurs after a mode switch for atrial fibrillation. It will be of interest to see if this mode can be sensor driven to allow rate adaptation with minimal ventricular pacing. VENTRICULAR PACING SITE The role of sensor-driven pacing in CRT/CRT-D is discussed earlier for patients with heart failure. Recent observations indicate that RV apical pacing may be associated with impaired ventricular function in the long term, especially in patients with a depressed LVEF who do not require pacing. Thus, the benefit of rate increase might be mitigated by the harmful effect of RV apical pacing. Inducing a narrower QRS complex in RV septal pacing better preserves LV function.58 A recent study in 12 patients with high-level AV block (8 of 12 with permanent atrial fibrillation) in the VVIR mode received an upgrade from chronic RV apical to RV septal VVIR pacing.59 Over 18 months, these patients showed a significant increase in LVEF (55.2 ± 2.6 to 60.4 ± 2.9%) and improvement in 6 MWD. A control group with simple pacemaker replacement had no change in LV function. This study suggests that the potentially harmful effect on LV function by VVIR pacing can be ameliorated with septal VVIR pacing.

Conclusion Sensor-driven pacing is now an integral part of virtually all pacemakers and ICDs. Activity sensing, despite several theoretical disadvantages, is widely used, followed by the closed-loop stimulation and minute ventilation sensors. The clinical benefit of dual sensor over single sensor is likely to be small, but may be useful for certain patient cohorts. The lack of observed clinical benefit of sensor-driven pacing in DDDR mode may be related to patient co-morbidities, the definition of CI, excessive RV apical pacing, and the site(s) of pacing used.

SENSORS FOR HEART FAILURE MONITORING Acute Decompensated Heart Failure About 5 million Americans suffer from heart failure, with an estimated 550,000 new cases each year and resulting in significant mortality and morbidity. Furthermore, estimated annual treatment costs $33.2 billion, most incurred during hospitalization for acute decompensated heart failure (ADHF).60 ADHF refers to a clinical condition of worsening heart failure with dyspnea and often with evidence of fluid overload.61 ADHF is often triggered by one of four main factors: atrial fibrillation, anemia, hypertension, or medication/dietary indiscretion. In the 1991–1994 Connecticut Medicare beneficiaries review, ADHF resulting in hospitalization carried an 8% in-hospital mortality.62 Importantly, of the 17,448 survivors, 44% were readmitted once, 18%



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

of these for recurrent heart failure. Overall, 24% died within 6 months of the first ADHF event, and 53% either died or were readmitted over the same period. The prognosis for heart failure admission has improved over time,60 partly because of adherence to optimal doses of evidenced-based therapy. Despite this, prevention of ADHF can have significant prognostic impact for the patient, in addition to reducing the cost of heart failure management. LIMITATIONS OF SYMPTOMS, SIGNS, AND INVESTIGATIONS Although the most common presenting complaint for hospitalization in ADHF patients, dyspnea occurs relatively late in relation to changes in hemodynamics and intravascular volume. Until the era of implantable devices, it was not possible to evaluate the hemodynamic changes leading to ADHF except by repeated catheterization. Adamson et al.63 implanted an RV pressure sensor to measure RV systolic and diastolic pressure during heart failure exacerbation in 32 patients. They found that at a mean of 4 ± 2 days before admission, RV systolic pressure started to increase in 9 of 12 heart failure events (Fig. 5-15). As a group, RV systolic pressure increased by 25% ± 4% and heart rate by 11% ± 2% during ADHF, with substantial changes also during minor exacerbation. This study suggests that intracardiac pressure changes precede symptoms of heart failure exacerbation. Likewise, an implantable intrathoracic impedance sensor to assess pulmonary fluid showed that fluid overload occurred 18.3 ± 10.1 days before dyspnea.64 Thus, 40

Percent change

30

Hospitalization

Pressure change (9 of 12)

20 10 0 –10 Baseline –7 –6 –5 –4 –3 –2

A

Recovery

Days relative to event 40 30

Percent change

–1

Pressure change

Event

20 10 0 –10 Baseline –7 –6 –5 –4 –3 –2

B

–1

Recovery

Days relative to event

Figure 5-15  Right ventricular (RV) sensor to measure RV pressure during heart failure exacerbation in 32 patients. A, Pressure changes occurred in 9 of 12 events 4 ± 2 days before hospitalization (major events). B, Pressure changes before minor exacerbations (n = 24) that did not require hospitalization. Percent changes in RV systolic pressure (black circles), estimated pulmonary artery diastolic pressure (green diamonds), and heart rate (red triangles). (From Adamson PB, Magalski A, Braunschweig F, et al. Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system. J Am Coll Cardiol 41:565-571, 2003.)

157

dyspnea is a late event and does not allow either the clinician or the patient enough time for intervention to avert hospitalization. The cardinal physical signs of congestive heart failure are a third heart sound, pulmonary crackles, raised jugular venous pressure, and pedal edema. However, these signs have poor sensitivity to detect heart failure. In a study of 50 patients with increased pulmonary artery wedge pressure (PAWP ≥22 mm Hg), lung crackles were identified in 19% of patients, and higher jugular venous pressure and peripheral edema were present in only 50% and 20% of patients, respectively.65 A third heart sound was heard in most patients, but it was also detected in those with a low PAWP. This combination of signs carries a sensitivity of 58% and specificity of 100% for congestive heart failure. Physical examination of jugular pressure is difficult and often inaccurate.66 Body weight change is both a symptom and a sign that predicts ADHF. Some suggest this may be an unreliable sign because body weight not only reflects body fluid, but also may depend on amount of food/fluid intake and other causes of weight loss or weight gain. In a recent study, 134 patients with heart failure hospitalization were compared with a case-matched group without hospitalization.67 Body weight gain 1 week before hospitalization was associated with increasing risk of hospitalization (relative risk: Δ2-5 lb = 2.77; Δ5-10 lb = 4.46; and >10 lb = 7.65). Therefore, monitoring of body weight remains useful to identify a high-risk group for intervention and provides supportive evidence for ADHF. Radiologic evidence of ADHF tends to occur late. Brain natriuretic peptide (BNP) has been proposed as a means to monitor and improve heart failure management. In a randomized study on the N-terminal BNP to guide heart failure therapy (TIMECHF) study, 499 patients 60 years or older with systolic heart failure were randomized either to monitoring of BNP to maintain a level twice or less the upper limit or to conventional management without BNP guidance.68 There was no significant difference in the probability of remaining free from all-cause hospitalization between BNP-guided and conventional therapy (41% vs. 40%). Both groups had similar quality of life (QOL). However, the secondary endpoint of heart failure hospitalization was significantly reduced (72% vs. 62%), and outcomes were better in patients age 60 to 74 but not in those 75 or older. Although vigilant monitoring of symptoms and signs (and BNP levels) is useful, this strategy is not a guarantee for accurately predicting ADHF. On the other hand, frequent monitoring of some signs and symptoms and the use of external physiologic (and implantable) data may be superior to conventional care. A meta-analysis of both cohort (2354 patients) and randomized trials (6258 patients), with 6 to 12 months of follow-up, found a significantly lower rate of mortality and hospitalization compared with conventional management.69 Relative reduction in heart failure hospitalization of 0.93 and 0.52 was seen in randomized and cohort studies, respectively, and mortality was reduced by 0.83 and 0.53. The Cochrane Database Systematic Review69a reviewed 25 studies and 5 abstracts and suggested that telephone support and telemonitoring are effective in reducing all-cause mortality and heart failure hospitalization, and thus improve QOL and reduce cost and evidence-based prescribing. Several prospective randomized studies have been published since these meta-analyses. The Randomized Trial of Phone Intervention in Chronic Heart Failure (DIAL) trial69b randomized 1518 outpatients to either nurse-led telephone-based intervention or conventional treatment. The three main supervision areas were weight, diet, and medication compliance, and nurse specialists were allowed to change diuretic doses according to specified criteria. Patients were organized to call once every 14 days for three times, and thereafter at a frequency depending on the severity of heart failure. This protracted study followed patients up to 3 years after trial completion. The primary end point (death or heart failure hospitalization) was reduced in the intervention versus conventional arm, with the main benefit being a reduction in hospitalization (28.5% vs 35.1% at 3 years). An educational effect and adherence to the above three supervision areas are considered the main reasons for improvement. The Telemedical Interventional Monitoring in Heart Failure (TIMHF) trial69c also randomized stable Class II or III heart failure patients

158

TABLE

5-6 

SECTION 1  Basic Principles of Device Therapy

Monitoring for Heart Failure Pathophysiology

Pathophysiologic Area Electrical Remodeling Atrium Ventricle Conduction Mechanical Remodeling Atrium Ventricle Pressure changes

Monitoring Examples Rate, atrial ERP, atrial fibrillation Rate, ventricular ERP, ventricular tachyarrhythmias Atrioventricular node conduction time and capacity Intra-atrial and interatrial conduction Intraventricular and interventricular conduction Size, function, structure Size, function, structure End-diastolic pressure, pulmonary artery pressure (and wedge pressure), venous pressure

Neurohormonal Changes Sympathovagal Heart rate variability imbalance ERP, Effective refractory period.

who had a history of heart failure hospitalization within 2 years to either remote data monitoring (ECG, blood pressure, body weight) and sent these data via a personal digital assistant to the monitoring center daily, with physician-led response. Over a median follow up of 26 months, there was no difference in heart failure hospitalization or death, nor in overall QOL score. However, physical functioning was improved. The study documented an 81% compliance in ≥70% daily transmission of data. The Telemonitoring in Patients with Heart Failure (TELE-HF) trial69d randomized 1653 patients who had recently been admitted with ADHF. A daily telephone-based interactive voice response system on symptoms and weight was reviewed by the patients’ physicians. At the end of 180 days there was no significant difference in the primary end point of death and heart failure hospitalization between the telephonebased intervention versus the usual care group (52.3% vs 51.5%, respectively). Again, this study shows only a 55.1% adherence to interventional therapy at the end of 26 weeks in the 85.6% of patients who made at least one call. The different efficacies of telemonitoring reported between metaanalyses and prospective studies may be attributable to differences in severity of patients involved in the studies, the types of clinical variables measured, and the intervention offered. Among these, suboptimal compliance and lack of rapid therapeutic intervention (which often varies between studies) are important drawbacks. Furthermore, these studies have mainly been limited to easily measurable clinical variables that occur relatively late in the course of ADHF. Because many patients with LV dysfunction require cardiac implantable electronic devices (CIEDs) for arrhythmia prevention or therapy (implantable cardioverter-defibrillator, ICD) or for heart failure treatment (cardiac resynchronization therapy [CRT] or CRT-defibrillation [CRTD]), implantable sensors for heart failure monitoring may be added in these devices. The use of implantable sensors allows continuous monitoring of physiologic parameters with less labor-intensive efforts. Furthermore, the ability of these sensors to detect earlier physiologic changes before ADHF may help prevent heart failure hospitalization. Such sensors can also measure hemodynamic values in different body positions and on an ambulatory basis, and may obviate the need for invasive monitoring on admission for ADHF therapy. MONITORING OF PATHOPHYSIOLOGIC CHANGES The three pathophysiologic areas for heart failure monitoring are electrical remodeling, mechanical remodeling, and neurohormonal changes that occur with heart failure (Table 5-6). Electrical remodeling in either the atrium or the ventricle will result in changes in normal automaticity, conduction properties, and refractory period and will predispose to atrial fibrillation (AF) and ventricular tachyarrhythmias. Arrhythmias are routinely monitored and treated by CIED, either by pacing or defibrillation. The effective refractory

period (ERP) can be monitored by physician-activated electrical stimulation through a programmer. Monophasic action potential duration could be assessed by telemetry in some early devices.70 Using fractalcoated iridium electrodes, the paced unipolar ventricular signal was found to correlate with acutely measured monophasic potential. However, the implications of ERP monitoring remain uncertain. Intrachamber and interchamber conduction times in heart failure are important because they are either the result or the cause of electrical remodeling in heart failure. A wide left bundle branch block (LBBB) QRS complex is associated with ventricular dyssynchrony and impaired LV function. In a postmortem series of 34 patients with premorbid serial ECGs, progressive PR and QRS prolongation occurred with worsening of heart failure. Cardiac mass index was also significantly correlated with V1-V6 R-wave amplitudes.71 Optimal left-sided atrioventricular (AV) and cross-chamber sequencing are important for the proper systolic function of the heart (see Chapter 30). Although relatively simple, these conduction parameters have not been examined as long-term predictors of cardiac decompensation. The major development of sensors in heart failure monitoring is to track mechanical remodeling, including chamber size, pressure changes, and pulmonary congestion consequent on heart failure. Such sensors use either impedance or specialized pressure-sensing leads or devices. A variety of neurohormonal changes result from the compensating mechanisms of heart failure. These changes are not easily measurable directly but may be reflected through heart rate variability and electrical repolarization such as the QT interval. This will be an interesting new area for monitoring and as a guide to therapy.

Sensors for Heart Failure Sensors for rate adaptation can be classified according to the technical instrumentation. Table 5-7 summarizes the sensors that have been used for or proposed to monitor the events of heart failure. The paced QRS complex enables the QT duration to be evaluated. In addition, the RV-evoked response, measured as the ventricular depolarization gradient, has been proposed as a marker that is sensitive to catecholamines.72 These sensors have long been used as surrogate markers of sympathetic level that increases with exercise, with a view toward rate-adaptive pacing. It is uncertain if they are also good markers of increase sympathetic tone that accompanies heart failure. Heart rate variability (HRV) can be measured in a non-pacing-dependent patient and is a well-established prognostic marker of heart failure because it reflects sympathovagal imbalance.73 Reduced HRV precedes heart failure events. Although percentage of biventricular pacing and HRV are rhythm diagnostics rather than implantable sensors, they provide important indications of the prevailing heart failure status. Piezoelectric crystals or accelerometers are used to monitor body motion. Decreased body activity is an intuitive consequence of heart failure exacerbation. Impedance can be used to measure pulmonary TABLE

5-7 

Sensors for Monitoring Heart Failure

Sensors Electrogram

Intraventricular impedance Specialized lead

Transthoracic impedance Accelerometers

Parameters Percentage of pacing ST segment AF Ventricular arrhythmias Paced QRS Paced QT interval Heart rate variability LV size and function PEA to monitor LV function PA pressures PA wedge pressures LA pressures Pulmonary edema Minute ventilation Activity level

AF, Atrial fibrillation; LA, left atrial; LV, left ventricular; PA, pulmonary artery; PEA, peak endocardial acceleration.



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

edema and MV in a transthoracic manner. Intraventricular impedance is used to monitor LV size and contractility. Direct measurements of intracardiac pressure are now possible with pressure sensors instrumented in the right ventricle, pulmonary artery, or left atrium. A decrease in the mixed-venous oxygen saturation is highly associated with reduced cardiac output (or exercise) and has been measured by implantable devices. ACTIVITY MONITORING Kadhiresan et al.74 reported the use of externally attached accelerometers at the chest wall to monitor walking distance in heart failure patients. Using an acceleration threshold of 50 mG, a walking speed of 2 mph (≅2.8 METS) could be detected in a group of 30 patients. The activity log index so defined was closely related to the walking distance and increased when patients were tested during CRT-on versus CRT-off phase. Similarly, time per day with physical activity greater than a threshold of 70 steps/min was detected in an implanted accelerometer sensor,75 and the activity level trend was similar to HRV trending during ADHF and correlated with NYHA functional class at baseline (Fig. 5-16). 350

MDPA (min/day)

300 ***

250 200

***

150 100 50 0 0

1

2

3

4

A

5

6

7

8

9

10 11 12

Week after implant NYHA at baseline II

III

IV

100

SDANN (ms)

90 80

***

70

*

60 50 40 0

B

1

2

3

4

5

6

7

8

9

10 11 12

Week after implant

Figure 5-16  Activity and heart rate variability (HRV) after CRT implantation. Trend data analysis performed weekly: A, mean daily physical activity (MDPA; mean ± SEM; ***P < .001); B, standard deviation of intrinsic intervals in 288 5-minute segments of day averaged over a week (SDANN; mean ± SEM; *P < .005). Results are grouped by preimplantation assessment of disease severity; New York Heart Association (NYHA) classification. Both activity and HRV improve with CRT; the level of improvement is related to NYHA class. (P = repeated-measures analysis of variance for differences between trends.) (From Braunschweig F, Mortensen PT, Gras D, et al: Monitoring of physical activity and heart rate variability in patients with chronic heart failure using cardiac resynchronization devices. InSync III Study Investigators. Am J Cardiol 95:1104-1107, 2005.)

159

Although a crude index, activity sensing is a good reflection of general well-being of the patient with heart failure. It is a readily available sensor in most CIEDs and uses minimal battery energy. In addition, the absence of activity signifies the patient is at rest, allowing determination of other measurements (e.g., respiration). The use of accelerometer rather than piezoelectric crystal avoids some of the external vibration interference on measuring body activity. An activity sensor is used with other sensors for heart failure monitoring. HEART RATE VARIABILITY In patients with heart failure, neurohormonal activity predicts cardiovascular outcome.74 HRV is an indirect measure of autonomic tone and predicts both sudden and nonsudden cardiac death.76,77 HRV has been proposed not only to predict heart failure severity, but also to guide treatment and perhaps predict ADHF. In a randomized study of 50 patients with an implanted CRT device, HRV was measured in the atrial sensing mode (VDD at 30 bpm) with either CRT-on or CRT-off.63 HRV, measured as the standard deviation (SD) of atrial cycle length of all atrial sensed beats, was 25% higher in the CRT-on versus the CRT-off arm and 27% higher when the patients were receiving a beta-adrenergic blocker. Thus, time-domain HRV improves with CRT, likely reflecting changes in both sympathetic and parasympathetic activities with heart failure improvement. In Boston Scientific devices, HRV is measured by the so-called SDANN, the SD of the intrinsic intervals in the 288 5-minute segments of a day, averaged over a week. If the percentage of intrinsic beats is less than 67% for 24 hours, the data for that day are discarded. Using the SDANN in 113 heart failure patients with CRT, CRT reduced the mean heart rates and increased SDANN (from 69 ± 23 msec to 93 ± 27 msec) after 3 months (see Fig. 5-16). Furthermore, lack of HRV improvement predicts nonresponders to CRT.78 The HRV can be plotted at each heart rate over a 24-hour period, resulting in a so-called footprint79 (Fig. 5-17). The normalized size of the footprint is the “footprint number,” and the graph and number give an easy understanding of the HRV level: “the larger, the better.” In another cohort study, HRV using either SDANN or footprint predicted mortality in 842 patients implanted with a CRT device during 11.8 months of follow-up.80 A clinical score was derived based on 2-week postimplant diagnostic data (SDANN <43 msec, mean heart rate >74 bpm, footprint number <29, activity percent <5%) from a 436-patient cohort in the CRT RENEWAL study.81 Using this scoring system, patients could be triaged to low, moderate, and high risk. When applied to a separate group of CRT recipients in the HF-HRV cohorts, this scoring system accurately predicted the level of mortality risk (low 2.8%, moderate 10.1%, and high 13.4%) depending on tertiles of their score. In Medtronic devices, a long-term measure of HRV, the SDAAM (SD of 5-minute median atrial sensed intervals) is used. The algorithm averages the 24-hour SD of intrinsic atrial cycle length and will exclude the day’s data if the percentage of atrial pacing exceeds 80% or an atrial high rate episode (AHRE) is detected. The change in SDAAM is compared to a rolling average of the preceding 6 months. The SDAAM, nighttime heart rate, and activity level were used to predict outcome and to detect heart failure hospitalization in 397 patients.82 Figure 5-18 shows that SDAAM less than 50 msec predicts overall mortality. Furthermore, the absolute value of SDAAM remained low in patients who were hospitalized or who died. SDAAM declined from 76 ± 27 msec to 64 ± 26 msec at hospitalization, and the change was apparent up to 3 weeks before the event. An algorithm was developed to use SDAAM to predict hospitalization (Fig. 5-19). At a threshold of 200-msec days, a sensitivity rate of 70% was associated with 2.4 false-positive events per patient-year of follow-up, at a median of 16 days before the event. The sensitivity is not affected by the use of beta blockade. The SDAAM is significantly better than the nighttime heart rate and activity level change for predicting heart failure. These data suggest that autonomic surveillance such as the use of HRV is a good way to monitor both heart failure prognosis and to predict ADHF. However, HRV is limited

160

SECTION 1  Basic Principles of Device Therapy

Counters - heart failure/Brady

Counters - heart failure/Brady

04-SEP-2008 to 15-JAN-2009

14-FEB-2009 to 28-APR-2009

Percent

Since last reset

Atrial

0% Paced 100% Sensed ATR switches Minimum duration Maximum duration Mode switch time PMT

2.9 K 14.2 M 1 00:31 m:s 00:31 m:s 0% 2

Paced Sensed ATR switches Minimum duration Maximum duration Mode switch time PMT

Atrial

Right ventricular Right paced 88% Tracked 100% BiV triggered 0% Device determined 0% Right sensed 12%

13.2 M 13.2 M 1 19.2 K 1.8 M

Amio

Left ventricular

Since last reset

Percent 67% 33%

4.9 M 2.5 M 0 00:00 m:s 00:00 m:s 0% 0

Right ventricular Right paced Tracked BiV triggered Device determined Right sensed

7.4 M 2.3 M 0 5.1 M 191.3 K

97% 31% 0% 69% 3%

Left ventricular

Left paced 88% Tracked 100% BiV triggered 0% Device determined 0% Left sensed 12%

13.2 M 13.2 M 0 19.2 K 1.7 M

Single or double PVCs Three or more PVCs

Left paced Tracked BiV triggered Device determined Left sensed

1.3 M 759

97% 31% 0% 69% 3%

7.4 M 2.3 M 0 5.1 M 199.3 K

Single or double PVCs Three or more PVCs

176.0 K 0

A HEART RATE VARIABILITY – PLOT Last measured

HEART RATE VARIABILITY – PLOT

Mean

Last measured

Variability (ms)

Variability (ms)

Amio

0

0 40

60

80 100

200

(min–1)

B

Mean

120

120

Less More frequent frequent

40

60

80 100

200

(min–1) Less More frequent frequent

Figure 5-17  Heart rate variability (HRV) and “footprint number.” A, Patient with dilated cardiomyopathy receiving chronic resynchronization therapy with defibrillation (CRT-D; Boston Renewal). Deterioration of heart failure results from loss of biventricular (BiV) pacing secondary to premature ventricular contractions (PVCs) (%Vp = 88%). After amiodarone (Amio), with reduction of PVCs, BiV pacing increased to 97% with clinical heart failure improvement. B, HRV presented at each heart rate, resulting in two-dimensional plot known as “footprint.” Overall size of the footprint reflects HRV. Footprint improved after a period of CRT, with a greater range of heart rate experienced. Atrial tracking responses (ATR) and pacemaker-mediated tachycardia (PMT) were both suppressed after amiodarone.

when there is a high percentage of atrial pacing and during atrial tachyarrhythmias, and medications may affect HRV measurements. PERCENTAGE BIVENTRICULAR PACING In a cohort retrospective analysis of two heart failure trials involving CRT-D (1812 patients), Koplan et al.82a analyzed the relationship between percentage of biventricular (BiV) pacing and the outcome of death and heart failure hospitalization. When subjects were divided

into quartiles, there was a lower event rate with an increasing percentage of BiV pacing: 44% reduction in event rates in those paced 100% of the time versus those paced less than 92%. Even subjects paced 93% to 97% had a higher event rate than those paced between 98% and 99% (22% higher). The main reason for an inadequate percentage of pacing was atrial arrhythmias. Thus, a high percentage of BiV pacing (≥98%) is an important goal to achieve in patients with CRT. A low percentage of BiV pacing is particularly the problem in those with AF, especially when AF is permanent. Because of frequent



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring 1.00

Survival

using a template matching system.83 Only 9 to 19 (47%) had adequate complete BiV pacing, the remaining had either fusion or pseudofusion beats. Patients with 86.4% ± 17.1% full capture had one or more NYHA class improvement than those fully captured at only 66.8% ± 19.1% of the time. This study suggests careful evaluation of the percentage of BiV pacing using multiple surface ECG leads will be needed in patients with AF and conducted response, and sensors to detect full BiV capture will be an interesting development.

SDAAM >100 ms SDAAM 50–100 ms

0.95

SDAAM <50 ms

0.90

RIGHT VENTRICULAR PRESSURE

0.85 SDAAM <50 ms versus SDAAM >100 ms: Hazard ratio = 3.2; p = 0.02

0.80 0

2

4

6

8

10

12

Months Figure 5-18  Kaplan-Meier survival curve for all-cause mortality in heart failure patients. Survival plot based on average value of standard deviation of 5-minute median atrial sensed intervals (SDAAM) for weeks 5 to 8 after implantation. There were 36 patients in SDAAM <50-msec group, 227 in 50- to 100-msec group, and 167 in >100-msec group. SDAAM <50 msec when averaged over 4 weeks was associated with increased mortality risk. (From Adamson PB, Smith AL, Abraham WT, et al: Continuous autonomic assessment in patients with symptomatic heart failure: prognostic value of heart rate variability measured by an implanted cardiac resynchronization device. InSync III Model 8042 and Attain OTW Lead Model 4193 Clinical Trial Investigators. Circulation 110:2389-2394, 2004.)

intrinsic conduction and fusion beats in AF, a high percentage of BiV pacing may still not reflect the percentage of true mechanically synchronized beats. In one study of 19 patients with permanent AF with diagnostic counters showing greater than 90% BiV pacing, 12-lead Holter was used to monitor “true” complete BiV capture 1

0.8

Sensitivity

161

Feasibility Study

SDAAM

0.6 Activity 0.4

Night heart rate

0.2

0

1

2

3

Pulmonary artery (PA) pressure and PAWP monitoring have been extensively studied in patients admitted with advanced heart failure.8486 An implantable sensor that measures pressure has been incorporated into a pacing electrode with an initial application for rate adaptive pacing.87 This sensor is a hermetically sealed piezoelectric crystal with a diaphragm facing the bloodstream. Early experiences showed the ability of this sensor to record RV pressure continuously when connected to an implanted hemodynamic monitor.88,89 The Medtronic Chronicle IHM (Model 9520) is a nonpacing implantable pulse generator capable of external radiofrequency connection and integration in a Web-based data system, with 128 kilobytes of RAM for continuous storage of sensor data. Piezoelectric activity from a passive-fixation lead in the RV outflow tract is sampled up to once every 2 seconds, timed to the sensed unipolar RV electrogram (EGM). The sensor frequency is linear up to 100 Hz, and a 60-Hz high-pass filter is used. The frequency and timing of RV systolic pressure sampling are programmable, often at early morning when the subject is likely to be supine and rested. In addition, instantaneous high-resolution recordings can be made using an external triggering device. RV pressures (systolic, diastolic, dP/dt) are recorded, and RV systolic reflects PA systolic pressure. Prior studies have assessed the ability to estimate PA diastolic pressure from the RV pressure waveform.90 The minimum PA pressure occurs at pulmonic valve opening. This is estimated at the time of the maximum positive RV dp/dt, which is simultaneous with the RV preejection period (Fig. 5-20). Preimplant calibration pressure is required to allow absolute pressure measurement. An external barometric pressure measurement device provides external pressure reference against which sensor data can be calibrated.

4

5

False positives per patient-year of monitoring (85.7 patient-years total) Figure 5-19  Comparison of detector performance for SDAAM, night heart rate, and patient activity. Plots show sensitivity to detect impending cardiovascular hospitalization versus number of falsepositive detections per patient-year of monitoring, as a function of detection threshold. (From Adamson PB, Smith AL, Abraham WT, et al: Continuous autonomic assessment in patients with symptomatic heart failure: prognostic value of heart rate variability measured by an implanted cardiac resynchronization device. InSync III Model 8042 and Attain OTW Lead Model 4193 Clinical Trial Investigators. Circulation 110:2389-2394, 2004.)

The long-term stability of the pressure sensor has been previously reported.89,90 In one study, serial Swan-Ganz catheterizations at 3, 6, and 12 months after implant showed a small baseline error at 12 months of less than 1 mm Hg from the time of implantation.91 Furthermore, the accuracy of pressure measured is not affected by body posture. As mentioned earlier, Adamson et al.63 studied 32 patients with heart failure who received a Chronicle IHM and found that long-term RV pressure was stable in most patients. In some, however, it showed significant variability despite measurements being taken at 4 am with no activity level registered. During a total of 36 volume-overloaded events, RV systolic pressure increased by 25% ± 4%, heart rate by 11% ± 2%, and estimated PA diastolic pressure by 26% ± 4%. In all events, pressures were increased 1 day before the required clinical intervention. In patients with heart failure hospitalization, increases in one of the pressures occurred in 9 of 12 events, whereas this occurred in 9 of 24 patients during a nonhospitalized episode (see Fig. 5-15). During a volume-depleted state in seven patients, RV pressure parameters were reduced. All patients returned to baseline levels after therapeutic intervention. The authors further reported that sustained increase in one of the pressures (>20% from baseline) occurred in patients subsequently admitted, at a mean of 4.2 days before admission. When the device data were available to the monitoring physician, a reduction in heart failure hospitalization was subsequently observed. This important study also documents the time sequence of RV pressure changes that occurred before heart failure exacerbation, suggesting that

162

SECTION 1  Basic Principles of Device Therapy

ECG, ECG: (105–2 mV/CM)

EGM, ECG: (85–10 mV/CM)

RVP, pressure: (30–10 mm Hg/CM)

RVP, derivative: 15–500 mm Hg/CM

1 EGM 3 1 = R-R interval 2 = RVDP, at QRS detection

4

3 = RVSP, at peak waveform

2

4 = ePAD, at maximum positive dP/dt RVP

dP/dt Figure 5-20  Real-time right ventricular (RV) pressure waveforms. Pressure waveforms assessed from an implantable hemodynamic monitor (IHM) system using a programmer, with illustration of how IHM determines the pressure values. ECG, Electrocardiogram; EGM, electrogram; ePAD, estimated pulmonary artery diastolic pressure; RVDP, RV diastolic pressure; RVSP, RV systolic pressure; dP/dt, contractility as measured by change in pressure over change in time. (From Adamson PB, Magalski A, Braunschweig F, et al: Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system. J Am Coll Cardiol 41:565-571, 2003.)

pressures increase for several days and reduce the patient’s “tolerable reserve” before the final increase in pressures leading to clinical heart failure exacerbation. Zile et al.92 compared the ongoing RV hemodynamics between patients with systolic and diastolic heart failure during heart failure events. RV diastolic pressure was elevated in both conditions, although there was a trend for more rapid RV diastolic pressure elevation to occur in diastolic heart failure with less compliant ventricles than during systolic heart failure. Clinical Outcome Studies The COMPASS-HF (Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure) study prospectively randomized 274 NYHA Class III or IV heart failure patients into a conventional care group or a group with therapy also guided by Chronicle-derived RV pressure parameters.93 The two safety endpoints documented no pressure sensor failure and an 8% implanted system complication. During 6-month follow-up, there was a statistically insignificant trend for reduction of either heart failure hospitalization or the need of intravenous diuretics (primary endpoint) by 21%. Later

analysis showed a 36% prolongation in time to the final heart failurerelated hospitalization in the Chronicle-guided treatment group (Fig. 5-21). Bourge et al.93 suggest that the lack of significance in the primary endpoint may be caused by the lower-than-expected number of heart failure events (predicted 1.2, actual 0.85 per 6 patientmonths), thus decreasing the power of the study. The lower event rate may result from enrollment in specialized centers with high compliance for heart failure treatment. Importantly, Chronicle-guided therapy resulted in 54% more adjustment in diuretic doses, without an increase risk in hypovolemic heart failure events. The study also included 70 of 274 patients with diastolic heart failure. A subgroup analysis found a 20% nonsignificant reduction in heart failure events when diastolic heart failure patients were managed with Chronicleguided information.94 A large outcome study involving 850 patients with Class I to III patients with a single-lead ICD integrated with IHM using weekly transmission will examine the effect on heart failure events.94a The Chronicle ICD (Model 7286, Medtronic, Inc) uses a single RV apical shock coil and a pressure sensor electrode in the RV outflow track for pressure measurement from which PA diastolic pressure is estimated.

Freedom from heart failure hospitalization



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring 1.0 0.8 0.6 HR = 0.64 (0.42–0.96), p = 0.03

0.4 0.2

Chronicle (37 patients with event) Control (57 patients with event)

0.0 0

50

100

150

200

Days from randomization Number at risk Chronicle Control

124 132

120 119

108 110

101 91

93 87

89 80

84 77

4 3

Figure 5-21  Time to first heart failure hospitalization in COMPASSHF Study. Results showed a 33% improvement in the time to the first heart failure events. Hazard ratio (HR) from Cox proportional hazards regression model. (From Bourge RC, Abraham WT, Adamson PB, et al: Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 51:1073-1079, 2008.)

OTHER PRESSURE SENSORS Left Atrial Sensor The PA diastolic pressure is an indirect assessment of the LV filling pressure, and measurement of left atrial (LA) pressure may reflect an earlier pressure change that triggers pulmonary congestion. This may allow a longer time window for physician intervention to avert ADHF. The HeartPOD LA pressure monitoring device (St. Jude Medical) comprises an implantable sensor lead that is attached to a coil antenna for telemetry of sensor signals (Fig. 5-22). The sensor has a titanium pressure-sensing membrane of 3 × 7 mm and is capable of highfidelity pressure, temperature, and EGM measurement. An external patient advisory module (PAM) sends a 125-kHz radiofrequency transmission to the antenna, which then captures 20 seconds of sensor data. The PAM has 13 megabytes of memory and can store about 3 months’ data of six recordings per day. In a single-center feasibility study, eight patients received the LA pressure device using a transseptal approach from the femoral vein.95

Venous entry at 1 cm above the inguinal ligament was achieved by conventional guidewire introduction in the femoral vein below the ligament as a landmark. After standard transseptal puncture, an 11-French sheath was placed in the LA, and the sensor was deployed until the distal set of anchors was on the left side of the interatrial septum. The sheath was then removed, and the sensor membrane was positioned 1 to 2 mm on the LA septum. All patients received dualantiplatelet therapy for 6 months (aspirin, 160 mg, and clopidogrel, 75 mg, daily). The device was calibrated over time using Valsalva maneuver, with the PAM-measured expiratory pressure to equal LA pressure. Over 6 months, the net drift was 0.2 ±1.9 mm Hg per month, although much more in one patient. The authors emphasized the need to maintain the sensor orthogonal to the septum to avoid distortion of LA pressure waveform. The Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patient (HOMEOSTASIS) trial enrolled 40 patients with NYHA Class III to IV heart failure.96 All patients had the LA pressure device implanted successfully, although sensor failure occurred in four, which was subsequently replaced in three patients. The study started after an initial 3-month period in which heart failure hospitalization, related events, and medications were documented. LA pressure data were then used to adjust the diuretic dosages. Survival without heart failure events occurred in 61% of patients at 3 years. Mean daily pressure therapy reduced LA pressure (from 17.6 to 14.8 mm Hg), frequency of high-pressure events (>25 mm Hg by 67%), and diuretic dosage, with better NYHA class, LVEF, and more frequent uptitration of angiotensinconverting enzyme (ACE) inhibitors. The role of LA pressure monitoring needs to be confirmed in prospective randomized trials. At present, issues remain about sensor stability, ease of implant (subclavian implant tools are now available), and risk of thromboembolism (which is probably low and comparable to occluder for closing atrial septal defect). Pulmonary Arterial Pressure Sensor Diastolic PA pressure is often used as a surrogate measure of PAWP. An implantable wireless PA pressure transducer (W-IHM) has been developed (Cardio-MENS, Atlanta, GA, USA), which is capable of transmitting continuous PA pressure readings when powered by radiofrequency signal from outside (Fig. 5-23, A). In one study, the device has been shown to correlate with direct PA pressure measured invasively and with echocardiographic Doppler data.97 The cardioMENS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION)97a,97b trial investigated the use of such a sensor in 550 patients in the U.S. Compared to 280 patients randomized to have the sensor information blinded and treated in the conventional manner, daily measurement of PA pressure with W-IHM in the 270-patient active group resulted in significant 39% reduction of heart failure hospitalizations (Fig. 5-23, B). There was no device failure,

Figure 5-22  Left atrial (LA) pressure sensing device. A, Patient advisory module. B, LA pressure sensing device. C, Close-up image of the sensor tip. (From Ritzema J, Melton IC, Richards AM, et al: Direct left atrial pressure monitoring in ambulatory heart failure patients: initial experience with a new permanent implantable device. Circulation 116:2952-2959, 2007.)

A

163

B

C

164

SECTION 1  Basic Principles of Device Therapy

Control group (253 hospital admissions for heart failure) Treatment group (153 hospital admissions for heart failure)

260 240 220 200 180 160 140 120 100 80 60 40 20 0

Hazard ratio 0.64 (95% CI 0.55–0.75) p <0.0001

0

B

90

90 80 70 60 50 40

Number at risk Control group 280 267 252 215 179 138 105 67 Treatment group 270 262 244 210 169 131 108 82

Hazard ratio 0.71 (95% CI 0.55–0.92) p = 0.0086

30 20 10 0

180 270 360 450 540 630

Time from implant (days)

Control group (138 patients with event) Treatment group (107 patients with event)

100 Freedom from hospital admissions or mortality

Cumulative hospital admissions

A

0

C

90

180 270 360 450 540 630

Time from implant (days) 280 223 186 146 113 80 270 226 202 169 130 104

and system-related complications occurred in only eight patients, with a 1% implant related complication. All patients were either continued on warfarin or aspirin after 1 month of dual antiplatelet therapy. No episodes of pulmonary infarction or embolism were reported related to the sensor. The CHAMPION study is the first large study to confirm the role of implantable pressure sensor data to reduce heart failure morbidity. Unlike telemonitoring that involves only clinical and non-invasive heart failure parameters, the invasively derived PA pressure allows the physician to adjust neurohormonal, diuretic, or vasodilator drugs, with an aim to reduce PA pressure. In addition to the primary end point of hospitalization rate, there are also encouraging secondary outcomes, such as reduction in mortality (Fig. 5-23, C), improvement in QOL, and shorter duration of heart failure–related hospitalizations. There were more changes in medications, and the benefit occurred in both the systolic and non-systolic heart failure groups. Other implanted PA pressure devices are also under development. For example, an external ultrasound-activated PA pressure sensor in the right pulmonary artery that is fixed with a self-expanding wire mesh has been tested in 31 patients with chronic heart failure (PAPIRUS study) (InPressure, Remon Medical Technologies, Boston Scientific). Pressure values are reported to be similar to Millar catheter–measured data with no short term acute issues.97c

57 84

39 62

Figure 5-23  Wireless implantable pulmonary arter (PA) pressure sensor. A, CardioMENS sensor for implanting in a distal branch of PA artery. B, Cumulative heart failure– related hospitalizations during entire period of randomized single-blind follow-up. C, Freedom from first heart failure–related hospitalization or mortality during the entire period of randomized follow-up. (From Abraham WT, Adamson PB, Bourge RC, et al: Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomized controlled trial. Lancet 377:658-666, 2011.)

every 20 minutes is averaged to establish a baseline impedance level. The algorithm is inactive for the first 34 days after device implantation to allow time for postimplant pocket healing and electrode stabilization. When pulmonary fluid has accumulated beyond a programmable threshold, an alarm alerts the patient (or the physician via remote monitoring) (Fig. 5-25).

INTRATHORACIC IMPEDANCE FOR PULMONARY FLUID STATUS Device Description The concept of impedance to monitor pulmonary congestion is based on a canine experiment.98 The Medtronic OptiVol fluid management system uses transthoracic impedance to measure pulmonary fluid (Fig. 5-24). Low-voltage, nonstimulating currents are injected between RV ICD electrode (e.g., InSyn Sentry) or RV bipolar pacing electrode (e.g., Advisa) to the ICD or pacemaker casing between noon and 5 pm, at a time when the subject is presumably ambulant and upright. Sampling

Figure 5-24  Intrathoracic impedance measurement by implantable system. (From Yu CM, Wang L, Chau E, et al: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 112:841-848, 2005.)



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

165

INITIAL INTERROGATION: CARDIAC COMPASS TRENDS >200

P P

P

P

I

160 OptiVol fluid index OptiVol threshold

120 80 40 Fluid

0 Sep 2008

Nov 2008

Jan 2009

BNP Normal

Mar 2009

May 2009

Jul 2009

Sep 2009

Raised BNP

Figure 5-25.  OptiVol level changes in patient with recurrent heart failure. At the nominal level of 60 ohms per day (Ω/day, Fluid), the algorithm detected an episode of impedance fall which was not corroborated with brain natriuretic peptide (BNP) level. A higher OptiVol threshold accurately detected all heart failure episodes.

Feasibility Studies Fluid index (W • days)

120

60

Impedance (W)

0 90 80 70 Reference impedance 60 0

40

A

80

120

160

200

Days after implant

Impedance (W)

90 Reference baseline

80 70

Impedance reduction

60 Duration of impedance reduction

–28

B

–21

–14

–7

0

Days before hospitalization

Figure 5-26  Intrathoracic impedance to monitor fluid status in patients with NYHA Class III or IV heart failure (MID-Heft Study). A, Operation of algorithm for detecting decreases in impedance over time. Differences between measured impedance (bottom) and reference impedance (solid line) are accumulated over time to produce fluid index (top). Threshold is then applied to fluid index to detect sustained decreases in impedance. B, Example of impedance reduction before heart failure hospitalization (arrow) for fluid overload and impedance increase during intensive diuresis during hospitalization. Label indicates reference baseline (initial reference impedance value when daily impedance value consistently falls below reference impedance line before admission). Magnitude and duration of impedance reduction are also shown. Days in hospital are shaded. (From Yu CM, Wang L, Chau E, et al: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 112:841-848, 2005.)

The feasibility of using intrathoracic impedance to monitor fluid status has been tested in 34 patients with NYHA Class III or IV heart failure in the MID-Heft Study.64 A defibrillation lead in the RV apex was connected to a special pacemaker capable of injecting and sourcing impedance. Three impedance current vectors were tested: RV lead ring to device case and sampled from coil to device case; RV coil to device case and sampled from RV coil to device case; and RV ring electrode to device case and sampled from RV tip electrode to device case. The electrode pairs that use RV coil to device case are most suitable. An initial decrease in impedance, followed by an increase to steady state, is observed during pocket healing, which peaks by about 4 weeks. During a follow-up period of 20 ± 8.4 months, 25 adjudicated heart failure hospitalizations occurred in 10 patients (Fig. 5-26). Intrathoracic impedance started to decrease before worsening symptoms at 15.3 ± 10.6 days, whereas dyspnea was reported, at the earliest, only 3 days before hospitalization. During 17 heart failure hospitalizations, PAWP was found to correlate significantly with impedance (r = −0.61, P < .001), and impedance increased as fluid removal occurred with diuresis (Fig. 5-27). An algorithm for detection of heart failure was derived from 6.2 patient-years of monitoring from 10 patients and tested in the remaining cohort (see Fig. 5-27). Depending on the set threshold for impedance crossing, a receiver-operator curve was constructed (Fig. 5-28). Lower detection thresholds lead to higher sensitivity to detect ADHF, but also to a higher false-positive rate of detection. Conversely, a higher threshold will be more specific but may underdetect some ADHF events. A level of 60 Ω/day was suggested, to give a sensitivity of 76.9% at the cost of 1.5 false-positives per patient-year of monitoring. Early warning occurred at 13.4 ± 6.2 days of heart failure hospitalization event. This landmark study shows that intrathoracic impedance is correlated with pulmonary congestion and changes days before ADHF. Clinical Outcome Studies The impact of automatic OptiVol alert to guide therapy was observed in 532 patients with heart failure in the Italian OptiVol Study.99 With the OptiVol alert “on,” 67% of heart failure patients were detected who required hospitalization or therapy adjustment. Interestingly, in the patients with OptiVol alert “off,” heart failure hospitalization was significantly more frequent (20% vs. 7%). The study also showed a falsepositive detection rate of 0.5 per patient-year of follow up. Although impedance monitoring from RV coil to device case detects lung edema, measurement of RV and LV lead vectors may be able to assess LV volumes better. In 170 patients, 43 with replacement devices, Maines et al.100 showed that a 12-week maturation period was required

PCWP (mm Hg) Impedance (W)

166

SECTION 1  Basic Principles of Device Therapy

Figure 5-27  Data form heart failure patients (MID-Heft Study). A, Example from one patient. Relationship between intrathoracic impedance, pulmonary capillary wedge pressure (PCWP), and net fluid loss (I/O) during 4 days of intensive diuresis in cardiac care unit (CCU). B, Pooled data from all patients. Relationship between intrathoracic impedance and PCWP during intense diuresis in CCU pooled from 14 heart failure hospitalizations in five patients. C, Relationship between intrathoracic impedance measurement at admission to CCU and overall amount of fluid loss that occurred during CCU stay from 17 heart failure hospitalizations in six patients. (From Yu CM, Wang L, Chau E, et al: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 112:841-848, 2005.)

70 65 60 55 30 20 10

Fluid I/O (L)

0 –2 –4 –6 0

1

A

2

3

4

Days in cardiac care unit 100 r = –61, p <.001

Impedance (W)

90 80 70 60

for the pocket and the leads in first-time implants. However, a similar adaptation, but stabilizing earlier, was still required for the replacement group, suggesting the adaptation partly results from the leads or algorithm itself. Using the RV-LV impedance vectors, this study suggests that significant differences exist in impedance in the volume responder versus nonresponder groups, with a higher BiV-measured impedance in the responders, indicating a role for impedance in tracking responders to CRT. The ability of OptiVol to reflect heart failure outcome has been examined in several cohort studies. In a multicenter studies of 558 heart failures with InSync Sentry from 34 Italian centers, devicerecorded OptiVol fluid index above 60 Ω/day was associated with a 36% increased risk of heart failure hospitalization over 326 ± 216 days of follow-up.101 Multivariate analysis showed that in addition to OptiVol level, a higher percentage of days with low activity, low HRV, and increased nighttime heart rate were independent predictions of hospitalization. In 62 patients with OptiVol algorithm, prospective observational measurements of NT-pro-BNP and clinical heart failure status were collected over 27 ± 2 weeks.102 There was a significant but weak relationship in all pooled change in impedance and change in BNP level over all the visits (r = 0.30; P < .001). However, BNP level increased significantly when an OptiVol alert was associated with

50 100 0

20

30

40

50

60 80

PCWP in cardiac care unit (mm Hg) 100 r = 86, p <.001

90

60

40

80 20 70 0 0

60

1

2

3

4

5

False positives per patient-year 50 –10

C

10

Sensitivity (%)

Impedance upon entry to cardiac care unit (W)

B

–8

–6

–4

–2

Total fluid I/O in cardiac care unit (L)

0

Figure 5-28  Algorithm performance on validation data set. Detector performance curve shows trade-off between sensitivity and falsepositive rate as threshold for detection changes. For validation data set, nominal threshold of 60 Ω/day resulted in sensitivity of 76.9% and falsepositive rate of 1.5 false-positive per patient-year of monitoring, as highlighted by circle. (From Yu CM, Wang L, Chau E, et al: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 112:841-848, 2005.)

5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring 70 60 50 40 30 20 10 0

n = 32

n = 12

n=8

< – 10%

B

>10%

NT-proBNP change (%) p <0.05

15 10 5 0 –5 –10 –15

< – 10%

0 + 10%

>10%

NT-proBNP change (%)

Figure 5-29  Increased brain natriuretic peptide (NT-proBNP) concentration and decreasing impedance suggest worsening heart failure status. A, Algorithm alerts and NT-proBNP changes in subcategories. Percentage of alerts associated with a decrease in NT-proBNP concentration (<−10%; n = 8), number of alerts with almost stable NT-proBNP concentration (0 ± 10%; n = 12), and number of alerts with an increase in NT-proBNP concentration (>10%; n = 32). B, Intrathoracic impedance change from the alert onset to patient evaluation in the three subgroups in A with a decreasing, stable, or increasing NT-proBNP concentration compared with the preceding visit. Upper and lower margins of the box represent the upper and lower quartiles; the line within, the median; and the whiskers, the data spread. (From Lüthje L, Vollmann D, Drescher T, et al: Intrathoracic impedance monitoring to detect chronic heart failure deterioration: relationship to changes in NT-proBNP. Eur J Heart Fail 9:716-722, 2007.)

clinical signs of ADHF (89 ±25% increase) versus an insignificant increase in those without signs (25% increase). In patients with an alert, BNP increased by more than 10% in most events. By the time of patient medical visit, impedance continued to fall, suggesting worsening heart failure status (Fig. 5-29). In 42% of cases, a device alert was not related to clinical signs of heart failure, although BNP overall increased by 25% in these patients. Furthermore, the number of days and the duration of time that OptiVol fluid level exceeds threshold are reported to have positive prediction of the subsequent frequency of ADHF102a (Fig. 5-30). The usefulness of OptiVol to prevent heart failure admissions was reported in a single-center case-control study of 27 patients with InSync Sentry compared with a clinically similar group of 27 patients with CRT-D without OptiVol.103 In patients with OptiVol monitoring, 12 of 27 had alerts resulting in intervention. Hospitalization occurred in only 1 of 27 over 1-year follow-up. In contrast, in the control patients, 7 of 27 had heart failure hospitalizations. When coupled with remote patient monitoring (Medtronic Carelink), 20 of 28 OptiVol alerts (71%) in 67 patients could be remotely managed.104 In one study, crossing the OptiVol threshold (>60 Ω/day) was related to a higher risk of atrial fibrillation.105 Atrial tachycardia occurred in 43% of patients before and in 29% after OptiVol level crossing. This relationship was not observed in another study, which did show a higher prevalence of ventricular tachycardia and ventricular fibrillation (VT/VF) at a lower level of OptiVol (15-45 Ω/day), suggesting VT/VF occurred at a time of volume overload.106

ADHF hospitalization rate (yr–1)

Impedance change (Ω) (alert onset → alert evaluation)

A

0 + 10%

167

The threshold for OptiVol alert was also tested in 115 patients implanted with the Medtronic InSync Sentry CRT-D.107 During follow-up of 9 ± 5 months, 45 OptiVol alerts occurred in 30 patients; 15 alerts (33%) were correlated with clinical signs and symptoms of heart failure, and the authors suggested an increase of threshold to 90 Ω/day may increase the specificity to 73%. They found no cause for falsepositive alerts, but heart failure patients had significantly higher OptiVol level versus those without. On the other hand, in the European InSync Sentry Observational Study on 373 subjects,108 the level of 60 Ω/day was associated with a 60% sensitivity and 60% positive prediction of ADHF. Nine of 53 events (17%) were not associated with an OptiVol alert, and in an additional 11 events, an increase in OptiVol level occurred but did not exceed the programmed detection threshold. When compared to daily body weight measurement, OptiVol crossing has a higher sensitivity (76% vs 23%), a lower rate of unexplained detection (1.9 vs 4.3/ patient-year), suggesting that impedance is a useful and better marker to weight change for heart failure monitoring.108a These studies confirm the usefulness of intrathoracic impedance to monitor ADHF but emphasize the need for fine-tuning the detection algorithm and individual programming of OptiVol detection level.

p = 0.001

1.4

0.7

0.0 0

>3

p = 0.005

1.0

0.5

0.0 0

B

1–3

Intrathoracic impedance fluid index threshold crossings (yr–1)

A ADHF hospitalization rate (yr–1)

Alerts (%)



1–3

>3

Days with intrathoracic impedance fluid index above threshold (yr–1)

Figure 5-30  Comparison (Poisson regression) of acute decompensated heart failure (ADHF) hospitalization rates between groups of subjects. A, Subjects with no intrathoracic impedance fluid index threshold crossing events (TCEs; n = 197), subjects with one to three TCEs (n = 79), and subjects with more than three TCEs (n = 28). B, Subjects with 0 (n = 1910), subjects with 1 to 30 (n = 31), and subjects with more than 30 (n = 82) intrathoracic impedance fluid index threshold crossing days per year. Error bars indicate 95% confidence intervals. (From Small RS, Wickemeyer W, Germany R, et al: Changes in intrathoracic impedance are associated with subsequent risk of hospitalizations for acute decompensated heart failure: clinical utility of implanted device monitoring without a patient alert. J Card Fail 15:475-481, 2009.)

168

SECTION 1  Basic Principles of Device Therapy

Advantages and Limitations

TABLE

Intrathoracic impedance is one of the most extensively used sensors for monitoring heart failure. Its advantages include the relative ease of instrumentation, requiring no additional leads or complex implantation. The battery energy expenditure is low. Intrathoracic impedance has been relatively well characterized in acute setting and for long-term monitoring. Although sensitive, its specificity may be limited because impedance in the vector used may be affected by clinical events that do not indicate pulmonary congestion, such as pleural effusion109 (Table 5-8). INTRACARDIAC IMPEDANCE Impedance signals derived from fully intracardiac electrodes better reflect cardiac volume changes than transthoracic impedance. Indeed, Salo et al.110 reported the use of a tripolar RV lead to measure RV volume changes during the cardiac cycle, from which RV volume and contractility can be derived for rate-adaptive pacing. With the addition of an LV lead in CRT, more accurate measurement of LV volume is now possible for heart failure monitoring. Unipolar Impedance from Right Ventricle Unipolar impedance from the RV apex to the CIED casing samples a small region in the cardiac apex. This results in a signal recorded by the closed-loop stimulation (CLS) sensor (see earlier). Because most current is lost over a distance of about 1 cm from the apex, the signal reflects regional contractility of the ventricle rather than a change in stroke volume. While during acute induction of ventricular fibrillation, the fall in unipolar RV impedance reflects the fall in arterial pressure, the sensitivity is insufficient to discriminate between hemodynamically stable ventricular tachycardia and supraventricular tachycardia.111 These results suggest that unipolar impedance reflects LV contractility only when the changes are significant, and it may not be able to detect small changes in cardiac contractility, as in heart failure monitoring. Multipolar Impedance Several groups and manufacturers have investigated the optimal electrode arrangement for detecting ventricular volumes. With currents flowing between intracardiac electrodes (RV, LV, and RA) and to the CIED casing, enlargement in ventricular volumes will decrease impedance as more of the heart is encompassed. Examining four intrathoracic and two intracardiac vectors in 16 dogs and five sheep, Panescu et al.112 monitored cardiac function with biweekly cardiac catheterization and echocardiography and LA pressure with an implantable

5-8 

Mechanism Blood viscosity Extrapulmonary changes Right-sided heart failure Pulmonary changes

35

–30

LV-Can LAP LV-RV

–25

LV-RA

–20

RV-Can RVcolCan

30 25

–15 –10

20 15 10

–5

RA-Can

0 –7 –6

3 4 5 6 7 8 9 10 11 12 13 14 15 16 Days

5

LAP (mm Hg)

Start of RV pacing

–35

Examples Anemia Pneumothoracic Pleural effusion Peripheral edema not detected Pneumonia

pressure sensor. After several weeks of high-rate pacing to induce heart failure, LVEF decreased significantly (52% to 34%), with increases in LV end-diastolic volume (65 to 97 mL), LV end-diastolic pressure (7 to 16 mm Hg), and LA pressure (7 to 26 mm Hg). Impedance value measured by all vectors decreased with the onset of heart failure (Fig. 5-31). The maximum decrease occurred with LV-can and LV-RV vectors. Importantly, LV-can impedance changes more with heart failure than vectors involving the right-sided heart electrodes (RA-can, RV-can, and RV coil-can), and RV-LV and LV-RA changes were intermediate. LA pressure correlated best with LV-can impedance (r2 = 0.73) than RV-can (r2 = 0.43) and RV coil-can (r2 = 0.52). Circadian variation in impedance also decreased in heart failure (5% ± 2% to 2% ± 1%). Thus, in these animal models, incorporation of an LV vector significantly improved the detection of LV volume increase in heart failure. Biventricular impedance has been measured using a quadripolar electrode arrangement.113,114 In nine mini-pigs with pacing-induced heart failure, biphasic pulses (15 µsec pulse width, 600 µA constant current amplitude) were injected between the RV ring and tip electrode, and impedance was sourced using the LV ring and tip electrode.114 The impedance signal (measured as voltage divided by 600 µA current) was recorded using 8-bite resolution, and the mean impedance was calculated over the entire cardiac cycle. “Stroke impedance” was calculated by the difference between impedance values during systole and diastole. “Systolic impedance” was defined as the highest impedance 50 to 500 msec after the R wave, whereas diastolic impedance was measured by a 20-msec window within the R wave. After 20 days of heart failure induction by rapid pacing in these animals, the increase in LV end-diastolic pressure was found to be significantly correlated with the end-diastolic impedance, which decreased by 30% (r = −0.81; P < .001). End-diastolic volume also trended in the same direction as the impedance value, which decreased by 20%. The corresponding measured intrathoracic impedance decreased by 8%, which had a poorer correlation with the end-diastolic pressure. The less striking change of intrathoracic impedance versus BiV-measured impedance might be attributed to the countering effect of lead/device

–40

Change in impedance (%)

Possible Causes of Increased OptiVol Fluid Index in Absence of Pulmonary Congestion

Figure 5-31  Impedance value measured by all vectors. Animal model shows left ventricular (LV) vector significantly improves detection of LV volume increase in heart failure. The changes in intracardiac impedance trend inversely with left atrial pressure (LAP). (From Panescu D, Naware M, Siou J, et al: Usefulness of monitoring congestive heart failure by multiple impedance vectors. Proc IEEE Eng Med Biol Soc 2008:5668-5670, 2008.)



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

TABLE

5-9 

Intrathoracic vs. Intracardiac (Biventricular) Impedance

Norm (ITZ)

1.05 Heart failure parameters Electrode arrangement

1

Lead/casing maturation Influence of lung disease Influence of lead location Circadian and postural effect Sensitivity and specificity

0.95

00:00 AM 04:00 AM 08:00 AM 12:00 PM 04:00 PM 08:00 PM Time of day Figure 5-32  Variation in intrathoracic impedance depends on time of day. In this animal model (pig #12), circles depict the 4-hour-averaged impedances as recorded by the pacemaker, normalized to the daily mean. Squares depict the means of summarized 4-hour averages. The line estimates diurnal variation by spline interpolation of the means. (From Stahl C, Beierlein W, Walker T, et al: Intracardiac impedance monitors hemodynamic deterioration in a chronic heart failure pig model. J Cardiovasc Electrophysiol 18:985-990, 2007.)

casing maturation, which did not occur with BiV impedance, and pulmonary fluid collection being relatively less in the porcine model of mild heart failure studied (Fig. 5-32). These animal experiments suggest that biventricular impedance can be used to monitor the LV size and pressure changes that occur with heart failure. The theoretical advantages over transthoracic impedance are no significant time lag for lead/pocket maturation and no influence of changes in pulmonary condition on impedance values (e.g., pleural effusion, pneumonia). Because LV end-diastolic pressure increases before pulmonary edema occurs, this sensor can be used to detect deterioration of early heart failure that has not resulted in significant pulmonary fluid accumulation, and to monitor LV function. The limitations include the need for an LV lead (which restricts its use to a CRT device), dependence on the relative position of RV-LV leads (only relative changes rather than absolute value can be detected), and significant diurnal (and possibly postural) changes that must be considered in an implantable system (see Fig. 5-32). Clinical Studies

AortaP (mm Hg) Z (ohm)

Figure 5-33  Biventricular (BiV) impedance in study of 14 heart failure patients. Example of raw data recording: ECG, surface electrocardiogram; AortaP, aortic blood pressure; Z, intracardiac impedance; vertical lines 100 msec in front of QRS complex. The respiratory influence is clearly visible in the pressure and impedance tracings. (From Bocchiardo M, Meyer zu Vilsendorf D, Militello C, et al: Intracardiac impedance monitors stroke volume in resynchronization therapy patients. Europace 12:702-707, 2010.)

ECG (mV)

An acute study of BiV impedance in 14 heart failure patients during implantation of a CRT device also tested the effect of different LV lead locations on BiV impedance measurements; changes in stroke

169

Applicability Clinical evaluations

Intrathoracic Impedance Pulmonary edema RV lead or coil to casing (tripolar) Takes about 1 month Yes Less Yes About 70% (depends on threshold) Pacemakers and ICD Relatively extensive

Biventricular Impedance LV volume RV-LV bipoles (quadripolar) Less Less Likely significant Yes N/A CRT-P or CRT-D Limited

CRT, cardiac resynchronization therapy; D, defibrillation ; ICD, implantable cardioverterdefibrillator; LV, Left ventricular; N/A, not available; P, pacing; RV, right ventricular.

volume were induced with overdrive pacing115 (Fig. 5-33). Data from 20 overdrive pacing episodes and six lead locations showed good correlation between measured stroke impedance and stroke volume (r = 0.82 ± 0.10) and pulse pressure (r = 0.81 ± 0.16). The authors reported no significant effect of LV lead positions on the efficacy of impedance measurement, although accuracy and signal size tended to be better in the midventricular region than in either the basal or the apical region. Lack of lead fixation was suggested for the one outlier in the study. At present, limited data are available on long-term outcome of these devices. Table 5-9 summarizes the relative merits and limitations of intrathoracic and biventricular (intracardiac) impedance. In patients with a suitable device (i.e., LV lead), combined transthoracic and BiV impedance likely can be used. MINUTE VENTILATION Because heart failure leads to compensatory hyperventilation (especially in the resting state), an expert system has been tested that combines activity and MV to predict heart failure.116 The algorithm includes (1) mean daily resting MV and MV during activity and (2) mean daily activity level. A stable MV and activity level will suggest stable clinical heart failure, whereas an increase in MV, especially at rest and combined with decrease in activity, suggests deteriorating heart failure. Conversely, a stable MV level with increase in activity indicates recovery from heart failure. A total of 19 patients with no heart failure history who had received a Talent DDDR (Sorin-ELA) were compared with 48 heart failure patients with a Talent CRT pacemaker. While mean activity was similar, the resting and activity MV levels were

1 0.5 0 –0.5 120 100 80 60 0.8 0.6 0.4 0.2 0 580

585

590

595 Time (s)

600

605

170

SECTION 1  Basic Principles of Device Therapy

higher in the CRT group. Overall, the expert system resulted in a sensitivity of 88%, specificity of 94.7%, positive predictive value of 71%, and negative predictive value of 98.2% for heart failure detection. ST-SEGMENT SHIFT An ST-segment deviation either heralds ischemia or myocardial injury. Myocardial ischemia requires medical therapy or revascularization, especially in symptomatic individuals. Myocardial injury, on the other hand, calls for medical emergency reperfusion. Prompt treatment of a myocardial infarction (MI) will significantly reduce mortality. Delay in patient recognition of MI-induced chest pain (or “silent” MI) contributes significantly to delayed MI presentation.117 Because long-term external ambulatory electrocardiographic recording is unlikely to be practical, electrograms have been proposed to reflect infarct and ischemia in an animal model.118 Incorporation into a CIED with patient alert and remote monitoring allows ST-segment monitoring. The Angel Med Guardian (now under St. Jude Medical) is a singlechamber device with an RV apical lead. An intracardiac electrogram (EGM) was derived from RV apex to the device casing. The device records 10 seconds of EGM data once every 90 seconds for normal sinus beat within 50 to 90 bpm. Data are amplified with a gain of 62.5 to 625 times and band-passed between 0.25 to 45 Hz, followed by A/D conversion at 200 Hz. ST-segment level is compared to the corresponding PQ-segment level, and a baseline ST level is calculated as a rolling 24-hour average, acquired hourly. The extent of the deviation is normalized by the average R-wave voltage. The “normalcy” of ST-segment deviation at different heart rates is further tested during an exercise test, because some ST shifts tend to occur at different heart rates in the absence of ischemia. A rate-adjusted spontaneous ST deviation then will be considered an ischemic event and an alert triggered. A limited number of Guardian devices have been implanted in humans.119 During angioplasty with temporary coronary artery occlusion, ST-segment deviations occurred, with a negative shift during left anterior descending artery occlusion and a positive shift in other arteries (Fig. 5-34). Ten abnormal alerts occurred in six patients, leading to coronary artery interventions. During stress testing, the EGM showed a much cleaner signal and greater shift than the corresponding surface ECG. Typically, a 40% ST depression in the EGM corresponds to −0.8

mV on the surface ECG. Because the EGM is recorded at the RV apex close to left anterior descending artery territory, ischemia in this artery leads to ST depression, whereas ischemia in other territories results in a reciprocal ST elevation. Further work is required to explore the ST-segment sensor’s ability to detect the problem artery. PEAK ENDOCARDIAL ACCELERATION The PEA sensor has been used for rate adaptation. The PEA signal measures the closure sound of the mitral valve and reflects cardiac contractility. A minimal PEA signal occurs during optimal A-V interval in DDD devices120 and reflects the optimal A-V interval in most patients. A new CRT-P (New Living CHF, Sorin) is now available to monitor heart function and to program A-V interval in CRT device. Both contractility and LV filling contribute to PEA, and an index known as “PEA area” is derived from the PEA values at different A-V and V-V intervals. The maximum PEA area will define the optimal V-V and A-V interval for the patient. In 15 patients implanted with CRT with PEA sensor, cardiac catheterization with LV dP/dt was measured with PEA area determined.35 A-V interval was scanned between 60 and 220 msec. The authors found a responder rate to CRT (defined as 10% increase in dP/dt) in 75% of patients. Concordance of PEA area versus dP/dt methods occurred in 8 of 12 patients. These data are interesting, although the role of PEA for A-V interval programming in the long term is uncertain, and the ability of the sensor to monitor LV function remains to be tested.

Combined Heart Failure Diagnostics The Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure (PARTNERS HF) is an observational study on the use of diagnostics to predict heart failure.121 A total of 100 U.S. sites prospectively recruited 694 CRT-D patients and followed them for 11.7 ± 2 months. Table 5-10 shows the diagnostic data considered important in an algorithm to predict ADHF. A positive algorithm was defined as the occurrence of 22 events in eight variables during a 1-month period, including long duration of atrial fibrillation (AF), rapid AF rate, increased OptiVol fluid index,

Baseline LAD

*

Inflation

Baseline LCX Inflation

Baseline RCA Inflation

0

5 Time in seconds

10

Figure 5-34  Guardian device recordings. Before (baseline) and 2 to 3 minutes after (inflation) balloon inflation, which occurred during angioplasty. Data are shown from three patients who underwent balloon occlusions of the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), resulting in ST-interval shifts of −42%, 34%, and 18%, respectively. In the LAD occlusion recording, the arrow points to the time at which the balloon was deflated. The negative ST shift begins to shift positive, toward the shape it demonstrated during the preocclusion baseline recording, within 2 beats. (From Hopenfeld B, John MS, Fischell DR, et al: The Guardian: an implantable system for chronic ambulatory monitoring of acute myocardial infarction. J Electrocardiol 42:481-486, 2009.)



171

5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring

TABLE

Eight Cardiac Compass Heart Failure Device Diagnostic Parameters and Algorithms Used in PARTNERS Heart Failure Study

5-10 

Diagnostic Parameter Atrial fibrillation (AF) duration Ventricular rate during AF Fluid index (OptiVol) Patient activity Night heart rate Heart rate variability (HRV) Percentage of pacing CRT ICD shock for potentially lethal VT/VF

Algorithm AF ≥6 hours on at least 1 day in patients without persistent AF (7 consecutive days with ≥23 hours of AF) AF = 24 hours and average ventricular rate during AF ≥90 bpm on at least 1 day High fluid index on at least 1 day; thresholds included ≥60, ≥80, and ≥100 Ω/day Average patient activity <1 hour over 1 week (nonoverlapping weekly windows) Average night heart rate >85 bpm for 7 consecutive days (nonoverlapping weekly windows) HRV <60 msec every day for 1 week (minimum 5 measured days) (nonoverlapping weekly windows) Ventricular pacing ≤90% for 5 of 7 days (nonoverlapping weekly windows) ≥1 shocks during the evaluation period

Data from Whellan DJ, Ousdigian KT, Al-Khatib SM, et al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.) CRT, cardiac resynchronization therapy; HF, Heart failure; bpm, beats per minute; ICD, implantable cardioverter-defibrillator; VT/VF, ventricular tachycardia/ventricular fibrillation.

Conclusion Sensors have been introduced to optimize pacing rate in patients with chronotropic incompetence. Technology has now evolved such that sensor-driven rate-adaptive pacing is a programmable parameter of almost all CIEDs. With the increasing use of CIEDs to treat and monitor heart failure, sensors have now been added to optimize programming of CRT devices and to monitor heart failure progression.

>2 diagnostic criteria met % triggered evaluations (N = 1324)

6% P <0.0001 Hazard ratio = 5.5 (95% CI: 3.4–8.8)

5%

+ Diagnostic

4% 3% 2% 1%

– Diagnostic

% of evaluations when >2 diagnostic criteria met (N = 980)

Monthly evaluations with subsequent heart failure hospitalization (pulmonary)

low patient activity, abnormal autonomic tone, and device therapy. A very high OptiVol fluid level (>100 Ω/day) alone is considered positive diagnosis of ADHF. In PARTNERS heart failure, 90 patients had 141 adjudicated heart failure events, occurring 60 days after implantation. A positive combined diagnostic set predicts a 5.5-fold increased risk of hospitalization in the next month, even after adjusting for the clinical variables (Fig. 5-35). Figure 5-36 shows the main diagnostic parameters are OptiVol level of 60 Ω/day or greater, low activity, and heart rate variability (HRV). Additional OptiVol (≥100 Ω/day; 28% of patients) is also predictive of ADHF. Further subgroup analysis suggests that the specificity of ADHF improves with a higher fluid index and using more nonfluid-related indices at the expense of lower specificity. Interestingly, in patients with a prior heart failure history, diagnostic parameters are no longer predictive. The reason for this post-hoc analysis is uncertain. Diagnostic accuracy improves if sampling is performed every 15 days versus less often (Fig. 5-37).

10

20

30

Days after diagnostic evaluation Figure 5-35  Kaplan-Meier estimates of heart failure risk. Percentage of monthly evaluations with a subsequent heart failure hospitalization caused by signs or symptoms of pulmonary congestion. Patients with a positive combined heart failure device diagnostic algorithm had a 5.5-fold increased risk of a subsequent heart failure event within 30 days. CI, Confidence interval. (From Whellan DJ, Ousdigian KT, Al-Khatib SM, et  al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS Heart Failure (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.)

29%

28%

N = 980 evaluations 80

67%

60

62% 43%

40 20

21% 7%

14%

18% 5%

0 AF

0 0

43%

OptiVol >100 met

AF

AF OptiVol Low High Low Low ICD + >60 activity night HRV pacing shock(s) heart % RVR rate Fluid Activity Autonomics Device Therapy

Figure 5-36  Combined heart failure device diagnostics triggered. Venn diagram shows that 72% of evaluations had two or more (≥2) heart failure device diagnostics triggered, with the remaining 28% triggered by OptiVol fluid index of ≥100 Ω/day. OptiVol fluid index, low activity, and low heart rate variability (HRV) were the most common reasons for triggers. AF, Atrial fibrillation; ICD, implantable cardioverter-defibrillator; RVR, rapid ventricular response. (From Whellan DJ, Ousdigian KT, Al-Khatib SM, et al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS Heart Failure (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.)

172

SECTION 1  Basic Principles of Device Therapy

Algorithms

P-value 2.7

Fluid index >60

<0.0001

3.3

Fluid index >80

<0.0001

3.9

Fluid index >100

<0.0001

3.2

1 criterion (excluding fluid)

<0.0001 6.4

>2 criterion (excluding fluid)

<0.0001

5.5

Combined algorithm 0.25

0.5

1.0

A

2.0

4.0

<0.0001 8.0

16.0

Hazard ratio

Prior HF event?

P-value 0.9

Yes

0.848

5.4

No 0.25

0.5

1.0

B

2.0

<0.0001

4.0

8.0

16.0

Hazard ratio

Evaluation frequency

P-value

6.9

15 days (semi-monthly)

<0.0001

5.5

30 days (monthly)

<0.0001

3.1

90 days (quarterly) 0.25

0.5

1.0

C

2.0

4.0

<0.0001 8.0

16.0

Hazard ratio

Figure 5-37  Risk stratification for different algorithms, heart failure event history, and evaluation frequencies. A, Various algorithms. An increasingly higher fluid index threshold identifies patients at higher risk, as does combined heart failure device diagnostic algorithms.  B, History of heart failure event. In patients without a previous heart failure event, the combined heart failure device diagnostic did not identify patients at high risk of a subsequent event; however, in patients with a previous event, the combined heart failure device diagnostic algorithm identified patients at a 5.4-fold increased risk of a subsequent heart failure event within 30 days. C, Evaluation frequency. Increasing the frequency of reviewing the heart failure device diagnostics from quarterly to monthly  will substantially increase the ability to identify patients at higher risk, whereas changing from monthly to semimonthly provides a less notable increase. Reproduced with permission. (From Whellan DJ, Ousdigian KT, Al-Khatib SM, et al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.)

REFERENCES 1. Karlof I: Haemodynamic effect of atrial triggered versus fixed rate pacing at rest and during exercise in complete heart block. Acta Med Scand 197:195-206, 1975. 2. Fananapazir L, Bennett DH, Monks P: Atrial synchronized ventricular pacing: contribution of the chronotropic response to improved exercise performance. Pacing Clin Electrophysiol 6: 601-608, 1983. 3. Lau CP, Camm AJ: Role of left ventricular function and Doppler derived variables in predicting hemodynamic benefits of rateresponsive pacing. Am J Cardiol 62:906-911, 1988. 4. Tse HF, Siu CW, Lee KLF, et al: The incremental benefit of rateadaptive pacing on exercise performance during cardiac resynchronization therapy. J Am Coll Cardiol 46:2292-2297, 2005. 5. Rickards AF, Norman J: Relation between QT interval and heart rate: new design of physiologically adaptive cardiac pacemaker. Br Heart J 45:56-61, 1981. 6. Wirtzfeld AL, Goedel-Meinen L, Bock T, et al: Central venous oxygen saturation for the control of automatic rate responsive pacing [abstract]. Circulation 64(Suppl IV):299, 1981. 7. Cammilli L: Initial use of a pH triggered pacemaker. Pacing Clin Electrophysiol 12:1000-1007, 1989. 8. Benditt DG, Mianulli M, Fetter J, et al: Single-chamber cardiac pacing with activity-initiated chronotropic response: evaluation by cardiopulmonary exercise testing. Circulation 75:184-191, 1987. 9. Menozzi C, Brignole M, Moracchini PV, et al: Intrapatient comparison between chronic VVIR and DDD pacing in patients affected by high degree AV block without heart failure. Pacing Clin Electrophysiol 13:1816-1822, 1990. 10. Oldroyd KG, Ray AP, Carter R, et al: Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block. Br Heart J 65:188-193, 1991. 11. Schuster P, Faerestrand S, Ohm OJ, et al: Proportionality of rate response to metabolic workload provided by a rate adaptive pacemaker with automatic rate profile optimization. Europace 7:54-59, 2005 12. Duru F, Bloch KE, Weilenmann D, et al: Clinical evaluation of a pacemaker algorithm that adjusts the pacing rate during sleep

using activity variance. Pacing Clin Electrophysiol 23:1509-1515, 2000. 13. Matula M, Alt E, Fotuhi P, et al: Rate adaptation of activity pacemakers under various types of means of locomotion. Eur J Cardiac Pacing Electrophysiol 2:49, 1992. 14. Lau CP, Mehta D, Toff WD, et al: Limitations of rate response of an activity-sensing rate–responsive pacemaker to different forms of activity. Pacing Clin Electrophysiol 11:141-150, 1988. 15. Lau CP, Ward DE, Camm AJ: Single-chamber cardiac pacing with two forms of respiration-controlled rate-responsive pacemaker. Chest 95:352-358,1989. 16. Duru F, Radicke D, Wilkoff BL, et al: Influence of posture, breathing pattern, and type of exercise on minute ventilation estimation by a pacemaker transthoracic impedance sensor. Pacing Clin Electrophysiol 23:1767-1771, 2000. 17. Cole CR, Jensen DN, Cho Y, et al: Correlation of impedance minute ventilation with measured minute ventilation in a rate responsive pacemaker. Pacing Clin Electrophysiol 24:989-993, 2001. 18. Simon R, Ni Q, Willems R, et al: Comparison of impedance minute ventilation and direct measured minute ventilation in a rate adaptive pacemaker. Pacing Clin Electrophysiol 26:21272133, 2003. 19. Bonnet JL, Geroux L, Cazeau S: Evaluation of a dual-sensor rate-responsive pacing system based on a new concept. French Talent Dr Pacemaker Investigators. Pacing Clin Electrophysiol 25:2198-2203, 1998. 20. Mond HG, Kertes PJ: Rate-responsive pacing using a minute ventilation sensor. Pacing Clin Electrophysiol 11:1866-1874, 1988. 21. Lau CP, Antoniou A, Ward DE, et al: Initial clinical experience with a minute ventilation sensing rate modulated pacemaker: improvements in exercise capacity and symptomatology. Pacing Clin Electrophysiol 11:1815-1822, 1988. 22. Schaldach M, Hutten H: Intracardiac impedance to determine sympathetic activity in rate responsive pacing. Pacing Clin Electrophysiol 15:1778-1786, 1992. 23. Pichlmaier AM, Braile D, Ebner E, et al: Autonomic nervous system controlled closed loop cardiac pacing. Pacing Clin Electrophysiol 15:1787-1791, 1992.

24. Witte J, Reibis R, Pichlmaier AM, et al: ANS-controlled rateadaptive pacing: clinical evaluation. Eur J Card Pacing Electrophysiol 6:53-59, 1996. 25. Wiegand U, Nuernberg M, Maier SK, et al: The COGNITION study rationale and design: influence of closed loop stimulation on cognitive performance in pacemaker patients. Pacing Clin Electrophysiol 31:709-713, 2008. 26. Occhetta E, Bortnik M, Audoglio R, et al: Closed loop stimulation in prevention of vasovagal syncope. Inotropy Controlled Pacing in Vasovagal Syncope (INVASY): a multicenter randomised, single-blind, controlled study. Europace 6:538-547, 2004. 27. Coenen M, Malinowski K, Spitzer W, et al: Closed loop stimulation and accelerometer-based rate adaptation: results of the PROVIDE study. Europace 10:327-333, 2008. 28. Clementy J: Dual-chamber rate-responsive pacing system driven by contractility: final assessment after 1-year follow-up. The European PEA Clinical Investigation Group. Pacing Clin Electrophysiol 21:2192-2197, 1998. 29. Gras D, Kubler L, Ritter P, et al: Recording of peak endocardial acceleration in the atrium. Pacing Clin Electrophysiol 32(Suppl 1):S240-S246, 2009. 30. Plicchi G, Marcelli E, Parlapiano M, et al: PEA-I and PEA-II based implantable haemodynamic monitor: preclinical studies in sheep. Europace 4:49-54, 2002. 31. Langenfeld H, Krein A, Kirstein M, et al: Peak endocardial acceleration–based clinical testing of the “BEST” DDDR pacemaker. European PEA Clinical Investigation Group. Pacing Clin Electrophysiol 21:2187-2191, 1998. 32. Bordachar P, Garrigue S, Reuter S, et al: Hemodynamic assessment of right, left and biventricular pacing by peak endocardial acceleration and echocardiography in patients with end-stage heart failure. Pacing Clin Electrophysiol 23:1726-1730, 2000. 33. Leung SK, Lau CP, Lau CT: Automatic optimization of resting a peak endocardial acceleration sensor: validation with Doppler echocardiography and direct cardiac output measurements. Pacing Clin Electrophysiol 23:1762-1766, 2000. 34. Deharo JC, Brunetto A, et al: DDDR pacing driven by con­ tractility versus DDI pacing in vasovagal syncope: a multicenter,



5  Implantable Sensors for Rate Adaptation and Hemodynamic Monitoring randomized study. Pacing Clin Electrophysiol 26:447-450, 2003. 35. Delnoy PP, Marcelli E, Oudeluttikhuis H, et al: Validation of a peak endocardial acceleration–based algorithm to optimize cardiac resynchronization: early clinical results. Europace 10: 801-808, 2008. 36. Lau CP, Leung SK, Guerola M, et al: Efficacy of automatically optimized rate adaptive dual sensor to stimulate sinus rhythm: evaluation by continuous recording of sinus and sensor rates during exercise testing and daily activities. Pacing Clin Electrophysiol 19:1672-1677, 1996. 37. Leung SK, Lau CP, Tang MO, et al: New integrated sensor pacemaker: comparison of the rate responses between an integrated minute ventilation and activity sensor and single sensor modes during exercise and daily activities and non-physiological interference. Pacing Clin Electrophysiol 19:1664-1671, 1996. 38. Leung SK, Lau CP, Tang MO: Cardiac output is a sensitive indicator of difference in exercise performance between single and dual sensor pacemakers. Pacing Clin Electrophysiol 21:35-41, 1998. 39. Kay GN, Ashar MS, Bubien R, et al: Relationship between heart rate and oxygen kinetics during constant workload exercise. Pacing Clin Electrophysiol 18:1853-1860, 1995. 40. Leung SK, Lau CP, Wu CW, et al: Quantitative comparison of rate response and oxygen uptake kinetics between different sensor modes in multisensory rate adaptive pacing. Pacing Clin Electrophysiol 17:1920-1927, 1994. 41. Leung SK, Lau CP, Tang MO, et al: An integrated dual sensor system automaticity optimized by target rate histogram. Pacing Clin Electrophysiol 21:1559-1566, 1998. 42. Pieragnoli P, Colella A, Moro E, et al: Blended dual sensor does not give additional benefits to single sensor in DDDR PM patients: results from the DUSISLOG study. Heart Rhythm 2:S40-S41, 2005. 43. Coman J, Freedman R, Koplan BA, et al: A blended sensor restores chronotropic response more favorably than an accelerometer alone in pacemaker patients: the LIFE study results. Pacing Clin Electrophysiol 31:1433-1442, 2008. 44. Gilliam FR 3rd, Giudici M, Benn A, et al: Design and rationale of the assessment of proper physiologic response with rate adaptive pacing driven by minute ventilation or accelerometer (APPROPRIATE) trial. J Cardiovasc Transl Res 4:21-26, 2011. 45. Lauer MS, Okin PM, Larson MG, et al: Impaired heart rate response to graded exercise: prognostic implications of chronotropic incompetence in the Framingham heart study. Circulation 93:1520-1526, 1996. 46. Azarbal B, Hayes SW, Lewin HC, et al: The incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: superiority over 85% of maximal age-predicted heart rate. J Am Coll Cardiol 44:423-430, 2004. 47. Lukl J, Doupal V, Sovova E, Lubena L: Incidence and significance of chronotropic incompetence in patients with indications for primary pacemaker implantation or pacemaker replacement. Pacing Clin Electrophysiol 22:1284-1291, 1999. 48. Protor EE, Leman RB, Mann DL, et al: Single versus dual chamber sensor-driven pacing: comparison of cardiac outputs. Am Heart J 122:728-732, 1991. 49. Wilkoff BL, Corey J, Blackburn G: A mathematical model of the cardiac chronotropic response to exercise. J Electrophysiology 3:176-180, 1989. 50. Kindermann M, Schwaab B, Finkler N, et al: Defining the optimum upper heart rate limit during exercise: a study in pacemaker patients with heart failure. Eur Heart J 23:1301-1308, 2002. 51. Vollmann D, Luthje L, Schott P, et al: Biventricular pacing improves the blunted force-frequency relation present during univentricular pacing in patients with heart failure and conduction delay. Circulation 113: 953-956, 2006. 52. Lau CP: Comparative hemodynamic studies between different pacing modes. In Lau CP, editor: Rate adaptive cardiac pacing, New York, 1993, Futura, p 55. 53. Lau CP, Rushby J, Leigh-Jones M, et al: Symptomatology and quality of life in patient with rate responsive pacemaker a double blind crossover study. Clin Cardiol 12:505-512, 1999. 54. Mabo P, Pouillot C, Kermarrec A, et al: Lack of physiological adaptation of the atrioventricular interval to heart rate in patients chronically paced in the AAIR mode. Pacing Clin Electrophysiol 14:2133-2142, 1991. 55. Lau CP, Tai YT, Leung WH, et al: Rate-adaptive pacing in sick sinus syndrome: effects of pacing modes and intrinsic conduction on physiological responses, arrhythmias, symptomatology and quality of life. Eur Heart J 15:1445-1455, 1994. 56. Passman R, Banthia S, Galvez D, et al: The effects of rate-adaptive atrial pacing versus ventricular backup pacing on exercise capacity in patients with left ventricular dysfunction. Pacing Clin Electrophysiol 32:1-6, 2009. 57. Van Hamel NM, Holwerda KJ, Slegers PC, et al: The contribution of rate-adaptive pacing with single or dual sensors to healthrelated quality of life. Europace 9:233-238, 2007. 58. Lamas GA, Knight JD, Sweeney MO et al: Impact of ratemodulated pacing on quality of life and exercise capacity: evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT). Heart Rhythm 4:1125-1132, 2007. 59. Tse HF, Wong KK, Siu CW, et al: Upgrading pacemaker patients with right ventricular apical pacing to right ventricular septal

pacing improves left ventricular performance and functional capacity. J Cardiovasc Electrophysiol 20:901-905, 2009. 60. Fonarow GC, Heywood JT, Heidenreich PA, et al; ADHERE Scientific Advisory Committee and Investigators: Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 153:1021-1028, 2007. 61. Ramani GV, Uber PA, Mehra MR: Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc 85:180195, 2010. 62. Krumholz HM, Parent EM, Tu N, et al: Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Arch Intern Med 157:99-104, 1997. 63. Adamson PB, Magalski A, Braunschweig F, et al: Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system. J Am Coll Cardiol 41:565-571, 2003. 64. Yu CM, Wang L, Chau E, et al: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 112:841-848, 2005. 65. Stevenson LW, Perloff JK: The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA 261:884-888, 1989. 66. McGee SR: Physical examination of venous pressure: a critical review. Am Heart J 136:10-18, 1998. 67. Chandhry SI, Wang Y, Concato J, et al: Patterns of weight change preceding hospitalization for heart failure. Circulation 116:15491554, 2007. 68. Pfisterer M, Buser P, Rickli H, et al: BNP-guided vs. symptomguided heart failure therapy. The Trial of Intensified vs. Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-CHF) randomized trial. JAMA 301:383-392, 2009. 69. Klersy C, De Silvestri A, Gabutti G, et al: A meta-analysis of remote monitoring of heart failure patients. J Am Coll Cardiol 54:1683-1694, 2009. 69a.  Inglis SC, Clark RA, McAlister FA, et al: Structured telephone support or telemonitoring programmes for patients with chronic heart failure. Cochrane Database Syst Rev CD007228, 2010. 69b.  Ferrante D, Varini S, Macchia A, et al: Long-term results after a telephone intervention in chronic heart failure: DIAL (Randomized Trial of Phone Intervention in Chronic Heart Failure) follow-up. J Am Coll Cardiol 56:372-378, 2010. 69c.  Koehler F, Winkler S, Schieber M, et al: Impact of remote telemedical management on mortality and hospitalizations in ambulatory patients with chronic heart failure: the telemedical interventional monitoring in heart failure study. Circulation 123:1873-1880, 2011. 69d.  Chaudhry SI, Mattera JA, Curtis JP, et al: Telemonitoring in patients with heart failure. N Engl J Med 363:2301-2309, 2010. 70. Zrenner B, Ndrepepa G, Müssig D, et al: The recording of monophasic action potentials with fractal-coated iridium electrodes in humans. Pacing Clin Electrophysiol 23:54-62, 2000. 71. Wilensky RL, Yudelman P, Cohen AI, et al: Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy. Am J Cardiol 62:276-283, 1988. 72. Callaghan F, Vollmann W, Livingston A, et al: The ventricular depolarization gradient: effects of exercise, pacing rate, epinephrine, and intrinsic heart rate control on the right ventricular evoked response. Pacing Clin Electrophysiol 12:1115-1130, 1989. 73. Cohn J, Levine TB, Olivari MT, et al: Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311:819-823, 1984. 74. Kadhiresan VA, Pastore J, Auricchio A, et al: Pacing therapies in congestive heart failure: a novel method—the activity log index—for monitoring physical activity of patients with heart failure. PATH-CHF Study Group. Am J Cardiol 89:1435-1437, 2002. 75. Braunschweig F, Mortensen PT, Gras D, et al: Monitoring of physical activity and heart rate variability in patients with chronic heart failure using cardiac resynchronization devices. InSync III Study Investigators. Am J Cardiol 95:1104-1107, 2005. 76. Bonaduce D, Petretta M, Marciano F, et al: Independent and incremental prognostic value of heart rate variability in patients with chronic heart failure. Am Heart J 138:273-284, 1999. 77. La Rovere MT, Pinna GD, Maestri R, et al: Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 107:565-570, 2003. 78. Fantoni C, Raffa S, Regoli F, et al: Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure. J Am Coll Cardiol 46:1875-1882, 2005. 79. Carbson G, Girouard S, Schlegl M, Butter C: Three-dimensional heart rate variability diagnostic for monitoring heart failure through an implantable device. J Cardiovasc Electrophysiol 15: 506, 2004. 80. Roosevelt G, Singh JP, Mullin CM, et al: Prognostic value of heart rate variability footprint and standard deviation of average 5-minute intrinsic R-R intervals for mortality in cardiac resynchronization therapy patients. J Electrocardiol 40:336-342, 2007. 81. Singh JP, Rosenthal LS, Hranitzky PM, et al: Device diagnostics and long-term clinical outcome in patients receiving cardiac resynchronization therapy. Europace 11:1647-1653, 2009.

173

82. Adamson PB, Smith AL, Abraham WT, et al: Continuous autonomic assessment in patients with symptomatic heart failure: prognostic value of heart rate variability measured by an implanted cardiac resynchronization device. InSync III Model 8042 and Attain OTW Lead Model 4193 Clinical Trial Investigators. Circulation 110:2389-2394, 2004. 82a.  Koplan BA, Kaplan AJ, Weiner S, et al: Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J Am Coll Cardiol 27:53:355-360, 2009. 83. Kamath GS, Cotiga D, Koneru JN, et al: The utility of 12-lead Holter monitoring in patients with permanent atrial fibrillation for the identification of nonresponders after cardiac resynchronization therapy. J Am Coll Cardiol 53:1050-1055, 2009. 84. Steimle AE, Stevenson LW, Chelimsky-Fallick C, et al: Sustained hemodynamic efficacy of therapy tailored to reduce filling pressures in survivors with advanced heart failure. Circulation 96:1165-1172, 1997. 85. Gibbs JS, Keegan J, Wright C, et al: Pulmonary artery pressure changes during exercise and daily activities in chronic heart failure. J Am Coll Cardiol 15:52-61, 1990. 86. Nathan AW, Perry SG, Cochrane T, et al: Ambulatory monitoring of pulmonary artery pressure: a preliminary clinical evaluation. Br Heart J 49:33-37, 1983. 87. Lau CP, Butrous GS, Ward DE, Camm AJ: Comparison of exercise performance of six rate-adaptive right ventricular cardiac pacemakers. Am J Cardiol 63:833-838, 1989. 88. Ohlsson A, Nordlander R, Bennett T, et al: Continuous ambulatory haemodynamic monitoring with an implantable system: the feasibility of a new technique. Eur Heart J 19:174-184, 1998. 89. Steinhaus DM, Lemery R, Bresnahan DR, Jr, et al: Initial experience with an implantable hemodynamic monitor. Circulation 93:745-752, 1996. 90. Reynolds DW, Bartelt N, Taepke R, Bennett TD: Measurement of pulmonary artery diastolic pressure from the right ventricle. J Am Coll Cardiol 25:1176-1182, 1995. 91. Magalski A, Adamson P, Gadler F, et al: Continuous ambulatory right heart pressure measurements with an implantable hemodynamic monitor: a multicenter, 12-month follow-up study of patients with chronic heart failure. J Card Fail 8:63-70, 2002. 92. Zile MR, Bourge RC, Bennett TD, et al: Application of implantable hemodynamic monitoring in the management of patients with diastolic heart failure: a subgroup analysis of the COMPASS-HF trial. J Card Fail 14:816-823, 2008. 93. Bourge RC, Abraham WT, Adamson PB, et al: Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 51:1073-1079, 2008. 94. Zile MR, Bennett TD, St John Sutton M, et al: Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation 118:1433-1441, 2008. 94a.  Adamson PB, Conti JB, Smith AL, et al: Reducing events in patients with chronic heart failure (REDUCEhf) study design: continuous hemodynamic monitoring with an implantable defibrillator. Clin Cardiol 30:567-575, 2007. 95. Ritzema J, Melton IC, Richards AM, et al: Direct left atrial pressure monitoring in ambulatory heart failure patients: initial experience with a new permanent implantable device. Circulation 116:2952-2959, 2007. 96. Ritzema J, Troughton R, Melton I, et al: Physician-directed patient self-management of left atrial pressure in advanced chronic heart failure. Hemodynamically Guided Home SelfTherapy in Severe Heart Failure Patients (HOMEOSTASIS) Study Group. Circulation 121:1086-1095, 2010. 97. Verdejo HE, Castro PF, Concepción R, et al: Comparison of a radiofrequency-based wireless pressure sensor to Swan-Ganz catheter and echocardiography for ambulatory assessment of pulmonary artery pressure in heart failure. J Am Coll Cardiol 50:2375-2382, 2007. 97a.  Adamson PB, Abraham WT, Aaron M, et al: CHAMPION trial rationale and design: the long-term safety and clinical efficacy of a wireless pulmonary artery pressure monitoring system. J Card Fail 17:3-10, 2011. 97b.  Abraham WT, Adamson PB, Bourge RC, et al: Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet 377:658-666, 2011. 97c.  Hoppe UC, Vanderheyden M, Sievert H, et al: Chronic monitoring of pulmonary artery pressure in patients with severe heart failure: multicentre experience of the monitoring Pulmonary Artery Pressure by Implantable device Responding to Ultrasonic Signal (PAPIRUS) II study. Heart 95:1091-1097, 2009. 98. Wang L, Lahtinen S, Lentz L, et al: Feasibility of using an implantable system to measure thoracic congestion in an ambulatory chronic heart failure canine model. Pacing Clin Electrophysiol 28:404-411, 2005. 99. Catanzariti D, Lunati M, Landolina M, et al: Monitoring intrathoracic impedance with an implantable defibrillator reduces hospitalizations in patients with heart failure. Italian Clinical Service OptiVol-CRT Group. Pacing Clin Electrophysiol 32:363370, 2009. 100. Maines M, Landolina M, Lunati M, et al: Intrathoracic and ventricular impedances are associated with changes in ventricular volume in patients receiving defibrillators for CRT. Italian Clinical Service OptiVol-CRT Group. Pacing Clin Electrophysiol 33:64-73, 2010.

174

SECTION 1  Basic Principles of Device Therapy

101. Perego GB, Landolina M, Vergara G, et al: Implantable CRT device diagnostics identify patients with increased risk for heart failure hospitalization. OptiVol-CRT Clinical Service Observational Group. J Interv Card Electrophysiol 23:235-242, 2008. 102. Lüthje L, Vollmann D, Drescher T, et al: Intrathoracic impedance monitoring to detect chronic heart failure deterioration: relationship to changes in NT-proBNP. Eur J Heart Fail 9:716-722, 2007. 102a.  Small RS, Wickemeyer W, Germany R, et al: Changes in intrathoracic impedance are associated with subsequent risk of hospitalizations for acute decompensated heart failure: clinical utility of implanted device monitoring without a patient alert. J Card Fail 15:475-481, 2009. 103. Maines M, Catanzariti D, Cemin C, et al: Usefulness of intrathoracic fluids accumulation monitoring with an implantable biventricular defibrillator in reducing hospitalizations in patients with heart failure: a case-control study. J Interv Card Electrophysiol 19:201-207, 2007. 104. Santini M, Ricci RP, Lunati M, et al: Remote monitoring of patients with biventricular defibrillators through the CareLink system improves clinical management of arrhythmias and heart failure episodes. J Interv Card Electrophysiol 24:53-61, 2009. 105. Jhanjee R, Templeton GA, Sattiraju S, et al: Relationship of paroxysmal atrial tachyarrhythmias to volume overload: assessment by implanted transpulmonary impedance monitoring. Circ Arrhythm Electrophysiol 2:488-494, 2009. 106. Ip JE, Cheung JW, Park D, et al: Temporal associations between thoracic volume overload and malignant ventricular arrhythmias: a study of intrathoracic impedance. J Cardiovasc Electrophysiol 22:293-299, 2011. 107. Ypenburg C, Bax JJ, van der Wall EE, et al: Intrathoracic impedance monitoring to predict decompensated heart failure. Am J Cardiol 99:554-557, 2007.

108. Vollmann D, Nägele H, Schauerte P, et al: Clinical utility of intrathoracic impedance monitoring to alert patients with an implanted device of deteriorating chronic heart failure. European InSync Sentry Observational Study Investigators. Eur Heart J 28:1835-1840, 2007. 108a.  Abraham WT, Compton S, Haas G, et al: Intrathoracic impedance vs daily weight monitoring for predicting worsening heart failure events: results of the Fluid Accumulation Status Trial (FAST). Congest Heart Fail 17:51-55, 2011. 109. Timperley J, Mitchell AR, Brown P, Betts TR: Changes in intrathoracic impedance from a pneumothorax: insights from an implanted monitoring system. Pacing Clin Electrophysiol 28:1109-1111, 2005. 110. Salo RW, Pederson BD, Olive AL, et al: Continuous ventricular volume assessment for diagnosis and pacemaker control. Pacing Clin Electrophysiol 7:1267-1272, 1984. 111. Kaye G, Arthur W, Edgar D, et al: The use of unipolar intracardiac impedance for discrimination of haemodynamically stable and unstable arrhythmias in man. Europace 8:988-993. 2006. 112. Panescu D, Naware M, Siou J, et al: Usefulness of monitoring congestive heart failure by multiple impedance vectors. Proc IEEE Eng Med Biol Soc 2008:5668-5670, 2008. 113. Zima E, Lippert M, Czygan G, Merkely B: Determination of left ventricular volume changes by intracardiac conductance using a biventricular electrode configuration. Europace 8:537-544, 2006. 114. Stahl C, Beierlein W, Walker T, et al: Intracardiac impedance monitors hemodynamic deterioration in a chronic heart failure pig model. J Cardiovasc Electrophysiol 18:985-990, 2007. 115. Bocchiardo M, Meyer zu Vilsendorf D, Militello C, et al: Intracardiac impedance monitors stroke volume in resynchronization therapy patients. Europace 12:702-707, 2010.

116. Page E, Cazeau S, Ritter P, et al: Physiological approach to monitor patients in congestive heart failure: application of a new implantable device-based system to monitor daily life activity and ventilation. Europace 9:687-693, 2007. 117. Faxon D, Lenfant C: Timing is everything: motivating patients to call 9-1-1 at onset of acute myocardial infarction. Circulation 104:1210-1211, 2001. 118. Fischell TA, Fischell DR, Fischell RE, et al: Real-time detection and alerting for acute ST-segment elevation myocardial ischemia using an implantable, high-fidelity, intracardiac electrogram monitoring system with long-range telemetry in an ambulatory porcine model. J Am Coll Cardiol 48:2306-2314, 2006. 119. Hopenfeld B, John MS, Fischell DR, et al: The Guardian: an implantable system for chronic ambulatory monitoring of acute myocardial infarction. J Electrocardiol 42:481-486, 2009. 120. Leung SK, Lau CP, Lam CT, et al: Automatic optimization of resting and exercise atrioventricular interval using a peak endocardial acceleration sensor: validation with Doppler echocardiography and direct cardiac output measurements. Pacing Clin Electrophysiol 23:1762-1766, 2000. 121. Whellan DJ, Ousdigian KT, Al-Khatib SM, et al; PARTNERS Study Investigators: Combined heart failure device diagnostics identify patients at higher risk of subsequent heart failure hospitalizations: results from PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients with Heart Failure) study. J Am Coll Cardiol 55:1803-1810, 2010.

6 

Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators DARREL F. UNTEREKER  |  ANN M. CRESPI  |  ANTHONY RORVICK  |  CRAIG L. SCHMIDT  |  PAUL M. SKARSTAD

This chapter discusses batteries and capacitors used to power pace-

makers, defibrillators, and similar implantable devices. Batteries are active components that convert chemical energy into electrical energy. Capacitors are passive and temporarily store energy, often to increase the available power (rate of energy delivery) in an electric circuit. This chapter provides practical information to help physicians manage patients who have implanted medical devices that require electrical power. The battery is conceptually different from the other components of an implantable medical device. In principle, the other components are designed to last indefinitely. However, for current cardiac devices such as pacemakers and defibrillators, the available chemical energy of the battery is consumed during its use. Eventually, the output of the battery becomes insufficient to operate the electronics and must be replaced. At present, batteries for implantable cardiac devices are part of the device, and the entire pulse generator must be replaced to renew the battery. However, this is not true of all implantable pulse generators. Many neurologic stimulators now use rechargeable batteries. In the future, more implantable devices may also use rechargeable batteries so that the energy powering the device can be renewed. While batteries transform chemical energy into electrical energy, capacitors act as energy storage devices. Capacitors that intermittently boost the power capability of electronic circuits are of principal interest here. The large capacitors in an implantable cardioverterdefibrillator (ICD) allow the device to deliver a therapeutic, highvoltage, high-energy shock to the heart over a few milliseconds, which the battery itself could not do. Understanding the properties and limitations of the components used to power implantable devices will help physicians not only better understand the devices, but also deliver the best care to their patients.

Batteries BASIC FUNCTION AND ELECTROCHEMISTRY Energy Storage A battery converts chemical energy into electrical energy. The source of this energy is the electrochemical reactions that occur within the battery. The type and amount of the materials participating in these reactions determine the deliverable energy of a battery. Chemical Reactions During a spontaneous chemical reaction, substances react to form reaction products. For example, in combustion, a fuel combines with oxygen (O2) from air to form water (H2O), carbon dioxide (CO2), and other species. The fuel is oxidized (loses electrons) during this process. Oxygen from air is reduced (gains electrons). The exact amounts of each that react are determined by the stoichiometry of the reaction. Equations 6-1 to 6-4 are examples of different types of reactions in which oxidation and reduction occur, called “redox” reactions, because electrons are transferred from one reactant to another.

2H2 + O2 → 2H2O (formation of water)



(6-1)

CH4 + 2O2 → CO2 + 2H2O (combustion of methane) (6-2)



4Fe + 3O2 → 2Fe2O3 (rusting of iron)

(6-3)

2Li + I2 → 2LiI (discharge of lithium/iodine pacemaker battery) (6-4) Such chemical reactions occur spontaneously because the products are in a lower energy state than the reactants. The difference in energy appears as heat in the case of combustion, or rusting. A battery or galvanic cell is designed to convert much of this energy difference into electrical energy rather than heat. A battery operates because the electrons transferred during a redox reaction are channeled from one terminal of the battery through the external circuit and back to the battery through its other terminal. The maximum work these electrons can do outside the battery is related to the difference in a thermodynamic quantity called the free energy of the reaction. MAJOR COMPONENTS OF BATTERIES Figure 6-1 shows a simple battery; the major parts are the anode, cathode, and electrolyte. The anode and cathode must be physically separated, and both must be in contact with the electrolyte. Anode and Cathode The two battery components involved in the electrochemical reaction during discharge are the anode and the cathode. The anode, lithium (Li) in most medical batteries, furnishes electrons to the external circuit, while the cathode, usually an oxide or halogen-rich compound, receives the electrons. The anode is defined as the electrode at which electrochemical oxidation occurs, and the cathode is the electrode at which electrochemical reduction occurs. Oxidation is a process in which electrons are removed or lost, and reduction is a process in which electrons are gained. This is true in all electrochemical cells. In a spontaneous galvanic cell such as a battery, the anode is electrically negative and the cathode electrically positive. This creates a seeming inconsistency. In nonspontaneous electrochemical reactions, such as those that occur at pacing electrodes, electrochemical reactions are driven by an externally applied voltage. In this case, oxidation (loss of electrons) will occur at the positive electrode and reduction (gain of electrons) at the negative electrode. Thus, for pacing electrodes, the anode is positive and the cathode is negative. The polarities are reversed, but the underlying electrochemical processes defining anode and cathode—oxidation and reduction, respectively—are the same. The terminology is entirely consistent. Electrolyte The anode and the cathode must be separated so that they cannot directly react with each other, but they also need to be connected by an ionically conducting medium called the electrolyte. As the battery discharges, it furnishes electrons at one terminal, pushes them through an external circuit, and receives them back at a second terminal. The

175

176

SECTION 1  Basic Principles of Device Therapy

of the battery for a test gas, usually helium, is less than 1 × 10−7 cm3/ sec at 1-atm pressure difference between the inside and outside of the battery.

e− External load

CLASSIFICATION OF BATTERIES A+ + C− e−

−

A+

C−

e−

+

AC

Batteries may be classified in many ways. For example, application, functional characteristics, chemistry, or the physical state of some component are often used to categorize batteries. One fundamental distinction is between primary and secondary batteries. Primary Batteries

Anode

Anode current collector

Electrolyte

Cathode current collector

Cathode

Figure 6-1  Schematic representation of sealed battery. The anode material is on the left, the cathode material on the right, and the electrolyte in the middle of the cell. The discharge reaction is A + C → AC. In this example, both A+ and C− are mobile ions, and the discharge product, AC, is insoluble and precipitates in the electrolyte solution.  In this figure, connections to the interior of the cell are made via feedthroughs.

electrolyte allows electric charge, as ions, to flow within the battery, completing the circuit. The electrolyte must conduct ions but not electrons. If the electrolyte conducted electrons, the battery would be shorted internally just as if the terminals were connected by a metal wire. Batteries with lithium anodes, such as those used to power pacemakers and ICDs, must use nonaqueous electrolytes because water readily reacts with lithium. Most Li-based batteries employ a mixture of organic ethers and esters as solvents for the electrolyte. A dissolved Li salt is used to make the electrolyte conductive. For example, lithium/ manganese dioxide batteries, widely used to power automatic cameras, often use electrolytes containing a lithium salt dissolved in dimethoxyethane ether and propylene carbonate ester. Separator The separator is a structural member of the battery that keeps the anode and cathode materials physically apart, thus preventing shorting of the battery. In batteries with liquid electrolytes, the separator is usually a porous polymer film that is immersed in and permeated by the electrolyte. In the case of lithium/iodine (Li/I2) batteries, traditionally used for pacemakers, the separator and electrolyte are the same (i.e., growing layer of solid, ionically conductive LiI discharge product). Current Collector The current collector makes the connection between the positive or negative terminal of the battery and its respective active electrode material inside the cell. A current collector is usually a wire connected to a screen, or grid, which is embedded in the anode or cathode material. The current collector may also serve as a structural member of the battery to provide physical integrity and strength to that electrode. Some medical batteries use the case of the cell as the current collector for one of the electrodes. Batteries are termed “case negative” if the anode is in contact with the case and “case positive” if the cathode is in contact with the case. SEALING OF BATTERIES Batteries used to power implantable pacemakers and ICDs are hermetically sealed, most often in welded containers with glass electrical feedthroughs to make electrical connections between the inside and the outside of the battery. This is necessary to prevent slow interchanges of materials between the battery and its surroundings. Medical batteries are typically considered hermetically sealed if the leak rate out

Primary batteries can only be used once. They are not designed to be recharged; in fact, it is dangerous to attempt to recharge them. A familiar example of a primary battery is the alkaline zinc/manganese dioxide flashlight battery. Most batteries used to power modern implantable medical devices are primary batteries that use lithium anodes because such batteries have very high energy densities. Secondary Batteries Secondary batteries are designed to be repetitively discharged and recharged. Familiar examples include the lead-acid batteries used in automobiles and lithium-ion batteries, widely used in portable electronic devices, home appliances, power tools, and electric vehicles. Lithium-ion batteries are also the most relevant secondary medical battery, used as supplemental power sources in some left ventricular assist devices and widely used to power implantable neurologic stimulators for control of chronic pain. Although not currently in development for pacemakers and ICDs, features such as more frequent telemetry could lead manufacturers to reconsider lithium-ion battery use in cardiac applications in the future. FUNCTIONAL CHARACTERISTICS OF BATTERIES Capacity The fundamental unit of battery capacity is the coulomb (C), or ampere-second (A-sec). This is the amount of charge delivered by one ampere (1 A) of current in 1 second. In the context of implantable devices, it is customary to express battery capacity in terms of amperehours (A-hr), which represents the charge carried by a current of 1 A flowing for 1 hour; 1 A-hr = 3600 C. A battery for an implantable medical device usually has a capacity rating of 1 2 to 2 A-hr. The methods for determining and specifying the capacity of a medical battery produce numbers ranging from upper-limit theoretical values that can never be achieved in the field to realistic values based on detailed models or accelerated testing.1-3 More sophisticated methods account for limited availability of the components within the battery, kinetic limitations on the chemical reaction, and losses to side-reactions over time. Estimating the deliverable capacity of implantable medical batteries is especially difficult because of their long service life. The time frame for the operation of most implantable medical devices is so long (5-10 years) that real-time measurements of capacity are not practical. Therefore, accelerated tests and models are typically used to estimate the amount of deliverable capacity in these batteries. Technology in this area is now highly developed, and it is possible to make highly accurate projections of deliverable battery capacity under a range of usage conditions.4-6 Energy and Energy Density The fundamental unit of energy is the joule (J). This is the energy given to one coulomb (1 C) of charge that is accelerated by a difference in potential of one volt (1 V). One joule is also the energy transferred by one watt (1 W) of power in 1 second. Just as battery capacity is often measured in ampere-hours, battery energy is often expressed in watthours (W-hr) instead of joules; 1 W-hr = 3600 J. An important battery parameter in the design of an implantable device is energy density, a quantity that can be expressed on either a

177

6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

mass or a volume basis. For medical applications, volume is usually more important than mass, so ratings based on volumetric energy density are most often used. The time integral of the product of voltage and current divided by the total volume of the battery is its deliverable energy density. Modern batteries for implantable devices have energy densities as high as 1 W-hr/cm3, including the case. Stoichiometry and Cell Balance The specific amount of anode and cathode materials that will react is determined by the stoichiometry of the battery reaction. A cell that contains exactly the required ratio of anode and cathode materials is said to be a “balanced” cell. However, most medical batteries are not designed with exactly the stoichiometric ratio of the active cathode and anode to provide predictable end-of-service characteristics. In many cases the anode (lithium) is in excess so that the voltage decrease near the end-of-service life is not too abrupt. The open-circuit voltage of a battery can be calculated from the thermodynamic free energy for the discharge reaction. This is the voltage that will be measured when there are no kinetic limitations, a condition that occurs only when an insignificant amount of current is being drawn from the battery. With the onset of current flow, the voltage at the battery terminals will be smaller than the open-circuit value. Both chemistry and battery design determine the relationship between voltage and current drawn from the battery. For example, a lead-acid battery for automotive use is constructed of very conductive materials and is designed with large-surface-area electrodes so that extremely high currents can be drawn from it to run an engine’s starter motor. On the other hand, a transistor radio battery is designed with small electrodes because relatively low currents are typically needed to power small portable electronic devices. Figure 6-2 shows a typical currentvoltage relationship in which the load voltage approaches the opencircuit voltage (OCV) as the current approaches zero. At the other extreme, the maximum (short-circuit) current is observed when the load voltage approaches zero. Internal Resistance and Impedance Electrical impedance and resistance are important battery properties that play a significant role in the clinical performance of many implantable devices. The terms impedance and resistance are often used interchangeably but are not the same. Both are terms for the change in voltage per unit change in current in an electric circuit, but they are measured under different conditions. Impedance is the more general term, encompassing effects of resistance, capacitance, inductance, and

OCV

Voltage

Increasing current density

2.5 2 A

1.5

B

C

D

1 0.5 0

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Discharged capacity (ampere-hours)

Cell Voltage and Current

Load voltage

3

V load (V)



Polarization

Current drain

Short-circuit current

Figure 6-2  Typical load voltage versus current drain plot for a battery. The load voltage is always less than the open-circuit voltage (OCV). Current drain increases toward the right. The maximum cell voltage is obtained at zero current, and the maximum current drain occurs at zero load voltage. The exact shape of the plot depends on the chemistry and design of the battery.

Figure 6-3  Load voltage versus capacity plot. For a lithium/iodine battery discharged at four magnitudes of constant current. Curve A = 40 µA/cm2, curve B = 20 µA/cm2, curve C = 10 µA/cm2, and curve D = 2 µA/cm2. The deliverable capacity decreases with increasing current in this current range because of increasing effects of polarization.

other circuit elements on the relationship between voltage and current. The resistive component of impedance is measured using directcurrent methods. Alternating-current and transient methods are used to measure the additional components of impedance besides resistance. For simple, resistive electric circuit elements, Ohm’s law, V = IR, accurately describes a linear relationship between voltage drop, V, and the corresponding change in current, I, with resistance, R, as the proportionality constant. However, a battery is a complex electrochemical device with several nonlinear processes operating in series/parallel combinations. Different processes may dominate at different current levels, depths of discharge, and time. Consequently, the relationship between current and voltage for a battery is, in general, nonlinear, even at very low currents. Although this relationship is sometimes characterized by a quantity called RDC, Ohm’s law should only be applied to batteries with caution. Non-Ideal Battery Behavior In addition to the principles and the nomenclature of battery operation, it is also important to understand factors that limit a battery’s ability to power an implantable device. Polarization.  Polarization is any process that causes the voltage at the terminals of a battery to drop below its open-circuit value when it is providing current. The internal resistance of the battery is one important cause. This is well illustrated in Figure 6-3 for the lithium/iodine battery, but the same is true for all batteries to some degree. The differences in the curves for discharge voltage versus capacity at four rates of constant current discharge are mainly caused by the voltage drop associated with internal resistance of the battery. Other contributing elements of voltage loss when a battery provides current are concentration polarization, which is associated with concentration gradients that may develop in the electrolyte or the active electrode materials, and activation polarization, which is associated with the kinetics of the electron-transfer reactions at the electrode/electrolyte interfaces. When current is drawn from a battery, all these processes occur to some extent. The net effect of these kinetic limitations is always observed as a decrease in the voltage at the terminals of the battery. In general, neither concentration polarization nor electron-transfer polarization conforms to Ohm’s law. Self-Discharge.  Self-discharge is the spontaneous discharge of a cell or battery by an internal chemical reaction rather than through useful electrochemical discharge. We have all seen the effects of self-discharge,

178

SECTION 1  Basic Principles of Device Therapy

such as the flashlight that does not work when needed after prolonged storage. One mechanism of self-discharge involves a slow, direct reaction between the anode and cathode; for example, if one or both of the active electrode materials are slightly soluble in the electrolyte. Other self-discharge processes may involve reactions between anode or cathode and another substance in the battery, such as the solvent in the electrolyte; for example, the typical reaction between the anode and the electrolyte solvent to form a passive film on the lithium anode or a gas that pressurizes the battery case. These parasitic reactions are usually very slow, but because medical batteries are expected to operate for many years, their accumulated effects can be appreciable. Although it is difficult to measure the very slow rate of self-discharge reactions, techniques such as microcalorimetry can detect the small amounts of heat involved.7,8 The heat generated can be used to calculate the rate of self-discharge by applying thermodynamic principles. Accurate assessment of self-discharge is an important element in predictive models of battery performance used in both device design and longevity estimation. BATTERIES IN IMPLANTABLE CARDIAC RHYTHM MANAGEMENT DEVICES Battery Design Requirements Implantable medical devices must be viewed as a system. The main requirement in battery selection for implantable devices is high reliability. Other factors include the desired longevity of the device (directly related to battery energy density, circuit design, and overall size) and an appropriate indication of impending battery depletion (end-of-service warning). The basic considerations when designing a battery for an implantable medical device include the current variations that will be imposed by the circuit as the device provides its service for the individual patient. Once the span of these application requirements is formulated, the current, voltage, and capacity requirements of the battery can be determined. An important limitation is the physical space, both volume and shape, within the device that can be allotted to the battery. Once this is determined, the required energy density can be calculated, and various battery systems and designs can be considered and evaluated. To put these decisions in perspective, one needs to realize that the battery occupies about a third of the volume of an ICD. The circuitry occupies another third, and the capacitors fill the remaining volume. In a pacemaker the battery and circuitry each occupy about half the volume. Power Requirements An important parameter for a device is the peak power requirement. For example, the rate of energy consumption differs greatly for pacemakers and defibrillators. Pacemakers use very small amounts of energy when they stimulate the heart, on the order of 15 µJ. Defibrillators, on the other hand, deliver as much 40 J for a defibrillation shock. A battery optimized for a pacemaker could never come close to supplying energy at the rate required to power a defibrillator. Likewise, a defibrillator battery is not an optimum choice to power a pacemaker, although it could easily supply the current needed. The high-power design of a defibrillator battery has a significantly lower energy density than that of a pacemaker battery, by a factor of as much as two. Thus, if a defibrillator battery was used primarily for pacing, and everything else were equal, it would need to be twice as large as an optimized pacemaker battery to obtain the same longevity. Optimizing a battery for longevity and power becomes more complicated when a device performs multiple functions, such as both bradycardia pacing and defibrillation. For example, up to now, the lithium/ iodine battery has been the dominant power source for implantable cardiac pacemakers, which typically have peak power demands of 100 to 200 µW. Under these conditions, the lithium/iodine battery, which is still used in many pacemakers, can maintain an adequate voltage, even when its internal resistance reaches several thousand ohms. On the other hand, an implantable cardiac defibrillator may have peak

power requirements approximately 10,000 times greater than those of a pacemaker. Under such a high power demand, the voltage of an Li/I2 battery would drop to almost zero, and the power delivered to the device would be almost nil. In recent years the distinction between a need for high-rate and low-rate batteries has become more blurred because features such as distance (“wireless”) telemetry and multisite pacing need both more current and more capacity to operate. The result is that battery designers have been challenged to develop medium-rate batteries that can deliver more power than pacemaker batteries of the past while still having a high energy density. Average vs. Instantaneous Current Drain Implantable medical devices are often characterized by their average current drain, although events such as therapy delivery and telemetry may require temporary current excursions that can differ greatly from the average value. The effect of the instantaneous current demand can be mitigated by using a capacitor that buffers the battery to allow short bursts of power that may be more than two orders of magnitude higher than it could deliver directly. This allows the use of battery designs with reduced anode and cathode surface areas and improved volumetric efficiency. The same principle involving a battery plus a capacitor is used to deliver the defibrillation therapy to the heart from an ICD, even though the magnitude of the current and voltage is much greater. Shape, Size, and Mass Constraints All device requirements (e.g., longevity, end-of-service indication, peak power) must be balanced against device volume, shape, and mass. Volume and thickness are particularly important for safe implantation in children and for esthetic reasons in many adults. The ratio of volume to surface area in the battery is an important parameter. The performance of a battery of fixed volume will vary substantially depending on its electrode surface area/volume ratios. The operating current and longevity demanded of the battery determine both the minimum areas and the amounts of anode and cathode needed. Increasing the electrode area/volume ratio increases current capability, but this ratio must not be too large, or the battery will be too costly and will have a diminished energy density and most likely greater complexity, raising reliability concerns. Size, Energy Density, and Current Drain The relationship between battery size and average current is not one of direct proportionality. For example, decreasing the average current by 50% will not permit a 50% reduction in battery size without compromising longevity because of the inactive materials in a battery (e.g., case, electrolyte, current collectors). Likewise, the usable energy density is also a function of the current demand on the cell. As the current from the cell is increased, the resulting voltage drops significantly (see Fig. 6-3), which reduces the time during which the cell can provide current at or above the minimum voltage necessary to operate the electronic circuits. Thus, usable energy density, which is directly proportional to the area under the discharge (voltage vs. capacity) curve, is also reduced. For very-high-rate batteries such as those used to power ICDs, this is not such an issue because their internal resistance is extremely low. THE BATTERY AND LONGEVITY OF PULSE GENERATOR Longevity is typically defined as the interval between device implantation and detection of the end-of-service indicator. Because therapy can vary substantially from patient to patient, the longevity requirement is typically linked to a specified set of nominal conditions and programmed parameters. The minimum battery capacity required to achieve the specified longevity can be calculated from the average current needed for this nominal set of conditions. The following equation relates the longevity of the pulse generator, L, to the deliverable capacity of the battery, Qdel, and the average pacing current, I:



6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators L = Qdel /8766 I



(6-5)

The unit of L is years, Qdel is in milliampere-hours (mA-hr), and I in milliamperes (mA). The conversion factor 8766 (365.25 days/yr × 24 hours/day) is needed because longevity is expressed in years, not hours. The actual capacity that is built into the battery must be larger than Qdel, because additional capacity is needed to account for self-discharge and other parasitic losses of capacity (Qsd). More capacity must also be included to allow for an interval between the end-of-service indicator and the time when the battery can no longer power the device (QEOL). The total capacity (QTotal) is defined as follows: Q Total = Qdel + Qsd + Q EOL



(6-6)

The average current drain in Equation 6-5 depends on the characteristic of the pulse generator circuitry and the requirements for therapy. It has two main components: the static current drain, which powers the electronic components even when no therapy is delivered, and the therapeutic current. The trend throughout the evolution of implantable devices has been that current demands decrease as technology is improved, which leads to smaller batteries and pulse generators while maintaining relatively constant longevity. Some expect that this trend will continue, but the path to lower current often has a sawtooth profile because new features and therapeutic modalities temporarily increase the required current. For ICDs, the situation is more complicated because of the unpredictable mixture of bradycardia and tachyarrhythmia therapy delivery and the constant need to have a very high power capability in any device that may be required to deliver a defibrillation shock quickly. Effect of Pulse Width on Pacing Current Increasing the pacing rate, pulse width, or pulse amplitude increases the average pacing current. The average pacing current, excluding static current, is directly proportional to the pacing rate. Recall that the pacing pulse results from the discharge of a capacitor through the electrode-heart interface. This capacitor produces a pulse in which the current decays exponentially with time, as shown for two different pulse widths in Figure 6-4. Thus, the time-dependent behavior of the current during the pacing pulse is given by the following equation: I = (VA /R H ) e − t/R HC



(6-7)

where VA is the amplitude at the beginning of the pacing pulse, RH is the impedance of the lead plus the heart (discussed later), C is the value of the capacitor that delivers the pacing pulse, and t is the time since the beginning of the pacing pulse. In Figure 6-4, A and B, the pulse width is tw and tw/2, respectively. The area under each current-time curve gives the total charge delivered during the pulse. Although the width of the pulse in B is half that of the pulse in A, the charge delivered by this pulse is considerably more than half that of the longer pulse. The exact ratio of the charge delivered in the two cases depends on the

179

values of RH and C. Nevertheless, reducing the pulse width by a given fraction will always reduce the average pacing current by a substantially smaller fraction because of the exponentially decaying shape of the pacing stimulus current curve. Effect of Pulse Amplitude on Pacing Current The definition of pacing pulse amplitude may vary somewhat between manufacturers of implantable pulse generators. For our purposes, pulse amplitude is defined as the voltage delivered to the heart at the beginning of the pacing pulse (“leading edge” voltage). As stated earlier, the area under the current-time curve gives the charge delivered per pulse. Thus, doubling the amplitude doubles the current and the total charge delivered to the heart. Also, because the charge per pulse is doubled, it might seem that the average pacing current drawn from the battery would also be doubled. However, the impact on the pacing current is much larger than that, as seen from the following argument. The energy per pacing pulse is defined as follows:

E = VA × I A × t w

(6-8)

In Equation 6-8, VA is the average pacing stimulus output voltage of the pulse generator, IA is the average pacing current delivered to the heart, and tw is the pulse width. If we consider the lead-electrode-heart interface to be mainly resistive, Ohm’s law, I = V/R, can be substituted in Equation 6-8, which becomes the following:

E = (VA 2 /R H ) × t w

(6-9)

In Equation 6-9, RH is the effective ohmic load of the heart and lead. From this equation it is readily apparent that energy consumption increases with the square of the output voltage. The effect of this energy increase on the current drawn from the battery may not be intuitive. Because the battery supplies all the energy delivered to the heart at a relatively constant voltage, any increase in energy is accompanied by a proportional increase in current drawn from the battery. Thus the average pacing current is increased by a factor of four if VA is doubled. In fact, this is the best situation; additional energy losses occur when the stimulus voltage is programmed to a higher level because the electronic circuit for increasing the stimulus voltage is not 100% efficient. EFFECT OF LEAD IMPEDANCE ON PACING CURRENT It is also important to consider the effect of RH on the average pacing current. RH is sometimes called “lead impedance,” but this is a misnomer. The impedance of the lead, itself, is mainly a resistance and it is relatively small (50-100 ohms). Most of the “lead” impedance actually arises at the electrode-tissue interface (500-1000 ohms or more). The factors affecting the impedance of this interface are discussed in Chapter 1. In general, the average pacing current is approximately inversely proportional to the sum of the actual lead and tissue interface impedances. Thus, there is a substantial interest in technologies that can increase RH at the electrode-tissue interface (without increasing the lead conductor resistance), thereby decreasing the pacing current while maintaining a constant or even reduced pacing threshold voltage.

Current

Current

Programming Effects on Longevity of Bradycardia Pulse Generators

tw/2

tw

A

Time

B

Time

Figure 6-4  Comparison of charge delivered to heart as pacing pulse width is shortened. The two cases (A and B) assume a discharge into the same patient. The pulse width, tw, is typically between 0.2 and 1.5 msec, and the maximum current is between 2 and 15 mA, depending on the pulse generator output voltage and the lead-heart interface resistance.

In summary, the wide range of available pacing parameters can have a dramatic effect on the current drain from the battery in an implanted pulse generator. For example, in the same patient, a bradycardia pulse generator with 6 years of longevity under nominal pacing parameters may reach its replacement time in 2 years at one extreme or more than 10 years at the other extreme. Therefore, it is important for clinicians to optimize parameters for the individual patient and to consider each device’s settings when predicting remaining device longevity for a specific patient. Considerations for Longevity of ICDs Most of the arguments concerning bradycardia pacemakers also apply to ICDs. However, ICDs are much more complicated than typical

SECTION 1  Basic Principles of Device Therapy

BATTERY END-OF-SERVICE INDICATION End-of-service requirements result from the need to indicate impending battery depletion in both pacemakers and defibrillators in a manner that allows adequate time to replace the device. In general, this requires a battery to have some measurable characteristic, such as voltage or impedance, which can be related to its state of discharge. The pulse generator end-of-service indication must occur well before the battery loses so much voltage that it cannot sustain cardiac pacing or perform defibrillation. Because longevity is a strong function of device settings, the longevity requirement is typically linked to a specific set of nominal pacing or defibrillation parameters. A detailed knowledge of the variations in battery performance, the changes in load current with pulse generator settings, and the accuracy of the end-of-service measurement circuitry is necessary to ensure that these requirements will be met. Elective Replacement Indicator All modern implantable pulse generators have an elective replacement indicator (ERI) that alerts the clinician to impending battery depletion and allows adequate time for replacement of the device. Typically, the ERI is designed to alert at least 3 months before the battery voltage drops to a level at which erratic pacing, loss of capture results, or loss of other critical features occur. Future devices will conform to CENELEC standards (European Committee for Electrotechnical Standardization). For pacemakers, the standard requires a recommended replacement time (RRT) such that at least 95% of the devices will have a prolonged service period (PSP) of at least 180 days. For ICD and CRT devices, the requirement is that at least 95% of the devices have a PSP of at least 90 days. Device manufacturers may choose to retain the ERI nomenclature and may set ERI to be coincident with RRT or between RRT and end of service. Methods for Monitoring State of Battery Discharge Battery Voltage.  The most common method to indicate impending battery depletion is to measure the battery voltage. Most modern devices incorporate a voltage measurement circuit in the form of an analog-to-digital converter. The digitized battery voltage can be compared with a value stored in a nonvolatile memory to trigger the ERI, or it can be telemetered to the programmer where the comparison is made. For lithium/iodine batteries, the battery voltage remains relatively constant throughout most of its discharge under low load conditions, as shown in the voltage versus capacity curve in Figure 6-5. This figure also shows the resistance of this battery as it discharges. Note that the resistance changes from a modest value at the beginning of service to a quite large value when it is almost depleted. Because the battery voltage is relatively constant for much of the pulse generator’s useful life, the telemetered voltage of this battery may not be particularly useful for estimating remaining service. Voltage characteristics during discharge differ for different battery chemistries, so clinicians should not assume familiarity with one model or that one type of battery can be applied to another. For example, the lithium/ iodine battery has a fairly flat discharge curve throughout most of its life at pacing currents. However, other battery chemistries have voltage characteristics much different than Li/I2. The lithium/silver vanadium oxide (Li/SVO) battery used in many ICDs has two distinct voltage regions before the typical ERI voltage. The region following the second plateau is sloped. The switch to the sloped discharge region can be used as the ERI trigger for this battery chemistry. This voltage is much less sensitive to current variances than the voltage chosen for an Li/I2

3

10 8

2.5

8

Voltage

7

2

6 5

1.5

4

1

3

Resistance

2

0.5 0

Resistance (kohms)

pacemakers, so it is not nearly as easy to generalize about the effect of different factors on their longevity. In general, the two main factors to consider are the expected frequency of tachyarrhythmia therapies and the percentage of time spent pacing the heart. The longevity may vary by a factor of two to three because of these issues alone, as discussed later.

V load (V)

180

1 0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

0

Discharged capacity (ampere-hours) Figure 6-5  Relationships among voltage, resistance, and delivered capacity. Voltage remains reasonably constant through the service life of lithium/iodine battery, whereas the resistance steadily builds up with discharge. Note the rapid falloff in voltage as the resistance rapidly increases near the end of service life.

battery because the internal resistance of the Li/SVO battery is much lower than the Li/I2, so for the Li/SVO system, voltage is a good indicator of remaining service life. Battery Impedance.  Battery impedance is another parameter used to signal the elective replacement point. Battery impedance is generally much less dependent on current than battery voltage and may convey more information about the battery’s state of discharge. For example, although the voltage of an Li/I2 battery remains relatively constant through most of its discharge, its impedance increases continuously, and especially rapidly as the battery approaches depletion (see Fig. 6-5). At depletion, battery impedance is not only useful for signaling the elective replacement point but may also provide an estimate of remaining service life. This feature has been incorporated into some pacemaker designs. Battery impedance is usually determined from the open-circuit and load-circuit voltages (or two different load-circuit voltages) of the battery by measuring the voltage drop across a known resistor within the pulse generator, then assuming Ohm’s law can be applied. Consumed Charge.  A final method used to indicate remaining battery life has been to measure the cumulative sum of the charge removed from the battery. This is accomplished by monitoring the current drawn from the battery or the current and voltage (i.e., energy) drawn from the battery. This method requires an accurate knowledge of the original deliverable capacity of the battery because the technique actually measures the capacity already used, and the amount left must be calculated by subtracting this from the initial value. False Triggering Any large increase in average battery current, even if temporary, in pulse generators that utilize battery voltage to indicate the elective replacement point may drop the battery voltage below the ERI trigger value before the true ERI point is reached; this occurs particularly with the Li/I2 battery because of its high resistance. For example, changes in current can result from electrophysiologic studies with noninvasively programmed stimulation (NIPS) in which the pacemaker is used to interrupt an episode of tachycardia by delivering short bursts of veryhigh-rate pacing, or from high pacing rates or telemetry sessions. Because ERI is usually latched (stored) when it is triggered, these temporary increases in current can cause a false, premature appearance of the ERI. In most cases, devices are designed to allow an ERI prematurely triggered to be reset. In some devices, ERI is inhibited during temporary high-current events to prevent false triggers.



6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

In ICDs, ERI is usually based on the battery voltage or the time required to charge the capacitor. The battery voltage is usually measured during normal sensing/pacing operation and not during a defibrillation therapy, when the battery voltage is depressed. Because of the very low internal resistance of ICD batteries, pacing parameters have a much smaller effect on triggering ERI in these devices, so false triggering is less of a problem. Alternatively, some ICDs base ERI determination on the time required to charge the output capacitor. This approach is possible because most battery designs have a reduced power capability as the battery approaches depletion. This method does not usually cause false ERI triggering.

181

Negative terminal Welded seal

Fill port Lithium anode P2VP film Cathode material

CLINICAL INDICATORS OF BATTERY REPLACEMENT TIME The clinical indicators of battery depletion vary widely among manufacturers of pulse generators. In fact, a single manufacturer may provide significant variations between various models. Of the following common indicators, the first three mainly pertain to older pacemakers that may still be implanted in some patients: 1. Stepwise change in pacing rate. Elective replacement time is indicated by a change in the pacing rate to a predetermined fixed rate (e.g., 65 bpm) or a fractional change in rate (e.g., 10% decrease from programmed rate). 2. Stepwise change in magnet rate. The magnet-pacing rate decreases in a stepwise fashion related to remaining battery life. 3. Pacing mode change. DDD and DDDR pulse generators may automatically revert to another mode such as VVI or VOO to reduce current drain and extend battery life. 4. Telemetered battery voltage or impedance. In modern pacemakers the battery voltage or the battery impedance can be telemetered to the programming device. This information is used in estimating remaining battery service life or in indicating an imminent ERI by algorithms performed outside the pulse generator. All manufacturers provide technical manuals containing tables or graphs that indicate the relationship between battery voltage or impedance and the estimated remaining service life of the device. BATTERY CHEMISTRIES USED IN PACEMAKERS Lithium/Iodine Battery The lithium/iodine battery is probably the most well known implantable battery because it has been used in the vast majority of cardiac pacemakers. The first implant of a pacemaker powered by an Li/I2 occurred in 1972.5,6,9 At least 13 million Li/I2-powered pacemakers have now been implanted. Many factors favor the use of this battery system. When the current demand is low, it is difficult to improve on the performance of Li/I2 batteries; their high energy density and low rate of self-discharge result in good longevity and small size. The inherently high impedance of the Li/I2 battery has not been a major disadvantage up to now because the current required by modern pacemaker circuits is low, typically about 10 µA. Note that the much larger current delivered during a (short duration) pacing pulse is drawn from a capacitor, which can charge between pacing pulses. The voltage and impedance characteristics of the Li/I2 cell also allow the clinician to monitor the approaching end-of-service indication. This battery system is simple, elegant in concept and is inherently resistant to many common modes of failure, as will be discussed below. As a result, Li/I2 batteries have attained a record of reliability unsurpassed among electrochemical power sources. Cell Structure.  Figure 6-6 shows a cutaway view of a typical Li/I2 battery. In general, Li/I2 batteries have a single, central lithium anode that is surrounded by cathode material, which is at least 96% iodine and has been thermally reacted with a polymer material to render a conductive mixture. The central anode is seen with an embedded current collector wire, and the iodine cathode fills much of the volume

Cathode P2VP film Anode Figure 6-6  Cutaway view of typical lithium/iodine battery. Easily identifiable interior parts include the anode feedthrough, anode current collector (wire), cathode, poly-2-vinylpyridine (P2VP) film on the anode, and port where the cathode material is poured into the cell. The connection to the cathode is through the battery case.

inside the battery. Figure 6-6 also shows several other important structures, including the electrical feedthrough that connects the anode to the outside of the cell. The case serves as the site of the electrical connection to the cathode, which is in direct contact with the inside of the container. Another visible feature is the fill port, the means by which the cathode mixture is introduced into the cell, after which the fill port is hermetically sealed. Discharge Curve.  Figure 6-5 shows the characteristic shapes of the voltage and resistance curves as a function of discharge for a typical Li/I2 battery. During most of the battery life, the voltage is stable near 2.8 V, and the resistance change is gradual and dominated by the growing electrolyte (LiI) thickness. Near the end of battery life, the cathode resistance rapidly dominates the resistance of the cell, as the cathode becomes lower in iodine content and less conductive. The region of discharge dominated by cathode resistance and declining cell voltage is used to signal the approaching “end of service” for most pacemakers powered by Li/I2 batteries.10 Effects of Current Drain on Deliverable Capacity.  Unfortunately, the high energy density of the Li/I2 battery may be negated if the application requires frequent periods of high current drain. This is caused by the high internal resistance of the battery, which results in voltage losses due to polarization (see Figs. 6-2 and 6-3). The Li/I2 battery system provided small, simple, highly reliable power sources with power characteristics almost ideally suited to the requirements of cardiac pacing for more than 3 decades. In the late 1990s, however, several device features that required higher power began to emerge. In many cases, these peak power requirements are beyond the capability of Li/I2 batteries. These new features include increased use of addressable memory to capture and store information about the electrical activity of the heart, the need for faster and longer-range telemetry to transmit this information outside the body, new physiologic sensors, and new therapies with higher power requirements, such as cardiac resynchronization and treatment of atrial fibrillation. These higherpower features are now being supported by new battery chemistries with similar energy density to lithium/iodine, but a much higher power capability. Lithium/Carbon Monofluoride Battery Lithium/carbon monofluoride (Li/CFx) batteries were introduced in commercial coin-type batteries in 1976. Carbon monofluoride (also

182

SECTION 1  Basic Principles of Device Therapy

known as CFx) is a cathode material with very high capacity and moderate power capability. The CFx material is a powder that is mixed with carbon as a conductivity enhancer plus a polymer binder and then pressed into a porous pellet. The battery comprises of a lithium anode, porous polymer separator material, and porous pressed-powder cathode pellet that are inserted into a case and hermetically sealed, similar to an Li/I2 battery. In contrast to the Li/I2 battery, however, the Li/CFx battery uses a liquid electrolyte composed of a lithium salt dissolved in an organic solvent (or solvent mixture). The energy density of this battery is similar to that of the Li/I2 battery, but it delivers significantly higher power. A typical discharge curve is shown in Figure 6-7, A. One feature of the Li/CFx system is that the voltage decline near end of battery life tends to be fairly abrupt, making it challenging for device manufacturers to engineer means of maintaining adequate replacement-time warning.

3.2 3.0 2.8 2.6 2.4 2.2 2.0 0%

20%

A

40%

60%

80%

100%

80%

100%

80%

100%

Cathode utilization

Lithium/Hybrid Cathode Battery New lithium battery chemistry with a cathode consisting of silver vanadium oxide (SVO) plus CFx has been developed to meet the needs of implantable devices with higher rate therapies and features.11,12 SVO has high power capability and is the same cathode material used to power ICDs. As previously described, CFx has modest power capability and more abrupt end-of-service characteristics, but a very high capacity. The blend of the two cathode materials, called a hybrid cathode, yields a primary battery that has an energy density equal to that of a lithium/iodine battery with approximately 100 times more power capability. It can support the new device features and also has good end-of-service detection because of the SVO. Hybrid cathode batteries have been used in implantable cardiac devices since 1999. Cumulative implants through 2009 total about 300,000. Plots of voltage versus percent of discharged capacity for SVO and CFx batteries are shown in Figure 6-7, A and B. The voltage curve of hybrid cathode behaves like a superposition of the two in proportion to the starting composition of the mixture (Fig. 6-7, C). The composition of the hybrid can be chosen based on the application, enhancing the capacity with a greater proportion of CFx or enhancing the power capability and end-of-service characteristics with more SVO. For low- and medium-rate applications, the composition can be chosen such that 85% to 90% of the battery capacity comes from CFx. In this composition range, efficiently designed medium-rate hybrid cathode batteries can match lithium/iodine in energy density at about 1 W-hr/cm3. Two basic hybrid cathode battery designs have been used in implantable pacemakers. Both types use lithium anodes, a porous polymer separator, a porous pressed-powder cathode pellet, and a liquid electrolyte of lithium salt dissolved in an organic solvent blend. The differences in the two designs are related to the construction of the cathode pellet, either a mixture of the SVO and CFx active materials or the CFx and SVO in separate layers, with the SVO layer adjacent to the lithium anode. In both cases the cathodes also contain a polymer binder and carbon as a conductivity enhancer. Although the methods of construction are different, the discharge behavior of either design is similar to that in Figure 6-7, C. BATTERY CHEMISTRIES USED IN DEFIBRILLATORS

3.2 3.0 2.8 2.6 2.4 2.2 2.0 0%

20%

B

40%

60%

Cathode utilization

3.2 3.0 2.8

Primarily CFx capacity

2.6 2.4

Primarily SVO capacity

2.2 2.0 0%

C

20%

40%

60%

Cathode utilization

Figure 6-7  Voltage versus percent discharged capacity. A, Typical discharge curve of a lithium/carbon monofluoride (Li/CFx) battery. B, Typical discharge of a lithium/silver vanadium oxide (Li/SVO) battery. C, Typical discharge curve of a CFx-SVO hybrid cathode battery.

Comparison of Pacemaker and Defibrillator Batteries Implantable defibrillators deliver up to 40 J of energy to the heart within a few milliseconds. By contrast, the energy required to stimulate the heart in bradycardia pacing is 1 to 10 µJ over 1 msec or less. Clearly, the demands placed on the battery that powers an implantable defibrillator are much different from those of a battery that powers a bradycardia pacemaker. Implantable defibrillators are designed to deliver a shock within about 10 seconds after the fibrillation or tachycardia is detected. When the ICD determines that a shock may be required, it begins to charge a high-voltage capacitor (discussed later). The time needed to charge the capacitors before the shock is delivered depends

on the ability of the battery to sustain a very high current during this period. Thus the implantable defibrillator requires a battery with high peak power, where power is the product of current and voltage (P = I × V). The high power required of defibrillator batteries dictates a different design than used for pacemaker batteries. Figure 6-6 shows a cutaway view of a typical battery used to power a pacemaker, with small and rather thick electrodes. Contrast this with Figure 6-8, which shows an analogous cutaway for a typical defibrillator battery, with very different construction. The long, thin anode and cathode, with two layers of



6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators Positive terminal

Fill port Anode connection to case Electrolyte Case liner Separator Cathode

Separator Separator Anode Figure 6-8  Cutaway view of typical high-rate defibrillator battery. In wound construction a sandwich of anode, separator, and cathode is rolled, flattened, and fitted inside the battery case. This battery uses a liquid electrolyte to ensure high internal conductivity. In this battery the anode is connected to the case and the cathode is connected to the feedthrough. Note the multiple connections to the cathode to ensure low internal resistance.

183

rapidly the battery is depleted. When the battery is depleted over a longer period, its internal impedance is higher in the latter half of the discharge curve. Figure 6-11 illustrates this phenomenon, with background voltage and internal impedance of Li/SVO batteries discharged over 3, 5, and 7 years. The internal impedance is unaffected by the discharge rate until midway through discharge. After that point the internal impedance always increases, but to a larger degree for slower discharge rates (i.e., longer discharge times). The higher internal resistance results in longer charge times, especially for the longest discharge periods. Charge Time–Optimized Li/SVO ICD Batteries.  One manufacturer has addressed the problem of the time-dependent increase in charge time by changing the ratio of anode to cathode material in the battery. The first Li/SVO batteries were made with an excess of lithium anode material so that the voltage only dropped slowly at the end of service life. “Cathode limitation” is the most efficient battery design if the goal is to optimize energy density. However, if the goal is to maintain a low charge time, it makes sense to use only part of the cathode capacity, ending the discharge partway onto the 2.6-V plateau where the charge time starts to increase. This is accomplished by reducing the amount of anode and increasing the amount of SVO cathode. As a result, the battery always remains in the region where internal impedance is low and charge times are short. 3.4

TYPES OF BATTERIES USED IN ICDS Three different types of battery chemistries are in use currently in ICDs: lithium/silver vanadium oxide, lithium/manganese dioxide, and lithium/layered SVO-CFx (also called “dual cathode”). The shapes of the discharge curves, resistance of the battery, and effects of time since implant vary among battery types. Regardless of the battery chemistry, all ICD batteries are used in much the same way. Most of the time the battery delivers a low current drain as required for sensing and pacing, which has negligible effect on the battery voltage. When it is necessary to charge the high-voltage capacitors, whether for capacitor formation (see Capacitors) or to deliver a therapeutic shock, the voltage drops quickly by about 1 V, then, after the capacitors are charged, recovers quickly to near the previous value (Fig. 6-9). Lithium/Silver Vanadium Oxide The first ICD battery chemistry put into widespread use was Li/SVO.11-17 These batteries have a distinctive discharge curve, with a slightly sloping voltage at about 3 V in the first third of discharge, followed by a decline in voltage to a flat region with about 2.6 V, and ending in a short region of declining voltage, as seen in Figure 6-10. The uppermost curve represents the battery voltage during normal sensing and bradycardia pacing operations (also called the “background” voltage). It is this background voltage that is typically monitored by the ICD and reported via telemetry. The “load” voltage is the voltage measured during charging of the defibrillation capacitors, and it is typically much lower than the background voltage. After many years of laboratory testing and experience in the field, it is apparent that the performance of Li/SVO batteries depends on how

Detection of arrhythmia

3.2

separator film in between, are rolled into a flattened coil. Alternatively, either or both of the electrodes of ICD batteries can be individual flatplate electrodes electrically connected to each other. Either method provides the high-power electrode area necessary for ICD batteries. The electrolyte in the defibrillator battery is a highly conductive solution of a lithium salt in organic solvents. The design with large, thin electrodes and liquid electrolyte gives the defibrillator battery the high power needed for quickly charging the high-voltage capacitors in the defibrillator. As mentioned, however, these same characteristics also reduce the energy density of the battery.

3 Voltage recovery

2.8 2.6

Shock delivered

2.4

Charge time

2.2 –5

2

0

5

10

15

20

Time (seconds) Figure 6-9  Typical voltage-time curve showing defibrillator battery voltage during delivery of a defibrillator shock. Left, Voltage before and during detection; middle, during charging of high-voltage capacitor; and right, voltage recovery after delivery of defibrillation shock.

3.4

20

Background voltage

3.2

18

Charge time

3.0

16

Load voltage

2.8

14

2.6

12

2.4

10

2.2

8

2.0

6

1.8

4

1.6

2

1.4

0 900

0

100

200

300

400

500

600

700

800

Capacity (ampere-hours) Figure 6-10  Typical plot of discharge characteristics of the lithium/ silver vanadium oxide ICD battery.

SECTION 1  Basic Principles of Device Therapy

Background voltage (V)

3.5 3.0

Background voltage

70

40

60

35

2.5

50

2.0

40

1.5 1.0

Area-normalized resistance

0.5 0.0 0%

30

7 years 5 years 3 years Zero-time

50%

20 10 100%

Area-normalized resistance (ohm cm2)

184

0

Percent depth of discharge Figure 6-11  Comparison of area-normalized resistance of lithium/ silver vanadium oxide battery for various battery longevities. The areanormalized resistance is the internal impedance of the battery, calculated from the drop in voltage during the pulse, the current, and  the area of the cathode. The area-normalized resistance = Acathode • (Vbackground − Vpulse)/Ipulse.

Lithium/Manganese Dioxide Another ICD manufacturer uses manganese dioxide batteries for use in ICDs. Lithium/manganese dioxide (Li/MnO2) batteries have been used in consumer and military batteries since the 1980s. For example, high-power Li/MnO2 batteries used for photoflash applications have similar electrical characteristics to those used in ICDs. Figure 6-13 provides a graph of Li/MnO2 battery performance. During the first half of battery life, the voltage remains almost constant at 3.1 V. In the second half of battery life, the voltage gradually slopes downward. This characteristic of the battery voltage, along with charge time and the amount of battery energy consumed, allows the clinician to judge how much longer the battery may last. The internal resistance and thus the charge time of Li/MnO2 batteries remain relatively constant until battery replacement is indicated by the ICD.19 Lithium/Layered Silver Vanadium Oxide–Carbon Monofluoride Another manufacturer of ICD batteries has combined the properties of two cathode materials, silver vanadium oxide and carbon monofluoride, to create a novel ICD battery that exploits the best features of those two materials. SVO provides high power while CFx contributes high capacity per unit volume. The construction of the cathode portion of the battery is rather complex, with a central CFx cathode sandwiched between two metallic current collectors, with SVO electrodes on each side. This arrangement of electrodes allows the SVO, which can discharge at very high rates, to be preferentially discharged when high current is needed to charge the capacitors. Over time the extra lithium ions that accumulate in the SVO part of the electrode equalize with the CFx part, so that the lithium ions become distributed equally within both parts of the cathode. The voltage curve starts at about 3.2 V, stays almost flat from about 20% to 50%, and then gradually declines. Figure 6-14 shows a typical discharge curve.20

3.00 2.75

25

2.50

20

2.25

15

2.00

Conventional SVO charge time

10

0

0

1

2

3

A

4

5

6

7

8

1.50 9

1.25

Longevity (yr)

40

3.25

Charge time– optimized battery voltage

35 30

1.75

Charge time– optimized charge time

5

25

Figure 6-12 compares the voltage and charge time of conventional SVO ICD batteries with charge time–optimized batteries that occupy the same volume in an ICD. For example, when discharged over 7 years, the charge time is considerably lower starting after 4 years for the charge time–optimized battery than the conventionally balanced battery (Fig. 6-12, A). The charge time–optimized battery maintains a much lower charge time in the latter half of ICD life, without substantially sacrificing longevity.18 The difference in charge time is much less when the battery is depleted over a shorter time, such as 3 years (Fig. 6-12, B).

Conventional battery voltage

30

3.25

Charge time– optimized battery voltage

3.00 2.75

Conventional battery voltage

2.50

20

2.25 Conventional SVO charge time

15 10

2.00

1.75 Charge time–optimized charge time 1.50

5 0 0.0

0.5

1.0

B

1.5

2.0

2.5

3.0

3.5

4.0

1.25

Longevity (yr)

Figure 6-12  Comparison of the performance of charge time– optimized batteries with conventionally balanced silver vanadium oxide (SVO) batteries as a function of time for battery longevity of 7 years (A) and 3 years (B). Both batteries occupy the same volume in the ICD.

SAFETY Most ICD batteries are designed to provide the power needed to deliver a therapeutic shock within 5 to 10 seconds after an arrhythmia is detected. With efficiency losses, this corresponds to a power capability of approximately 10-20 W. This is in marked contrast to that of 3.2

8

2.8

6 Battery voltage Internal resistance

2.4

4

2

2.0

1.6 0%

20%

40%

60%

80%

100%

0 120%

Extent of battery depletion Figure 6-13  Voltage and internal resistance with extent of discharge for a lithium/manganese dioxide ICD battery. Charge times remain fast and relatively steady as the internal resistance remains low until near the end of battery life. (Courtesy Boston Scientific.)



6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators 3500

Voltage (mV)

3000 2500 2000 1500 1000 500 0

0

10

20

30

40

50

60

70

80

90 100

% DOD Figure 6-14  Discharge curve for lithium/layered silver vanadium oxide–carbon monofluoride battery as a function of percent depth of discharge (DOD). This test lasted 6 months. A 3.15-A pulse was applied about every 15 days. Upper curve, Battery voltage on a low current drain. Lower curve, Battery voltage at the end of the 3.15-A pulse. Batteries of two different sizes were compared, 6.5 cm3 (blue) and 9.0 cm2 (orange), with minimal differences. (Courtesy Dr. Esther Takeuchi, State University of New York, Buffalo.)

most pacemaker batteries, which have power capability of less than 0.001 W. Typical ICD batteries have power capability comparable to AA Li/ MnO2 batteries widely used in consumer applications, and far less power capability than many other batteries used in familiar consumer products. Nevertheless, higher power by itself carries an increased risk of overheating in the event of a short circuit. To avoid this, ICD batteries are carefully designed and rigorously manufactured to prevent short circuits. Moreover, special separator materials are used that limit currents to safe levels in the event of a short circuit. Finally, all ICD battery designs are extensively tested under rigorous abuse conditions to verify the safety of the design.

Emerging Power Sources

185

6. Long calendar life. The best lithium-ion batteries will maintain more than 80% of initial capacity after 10 years of use. The only effect of capacity loss to the patient is reduced time between required recharges. It is not yet clear what future applications will emerge for rechargeable batteries in the cardiac rhythm management arena, but some applications are likely, and substantial patent activity is already occurring. In fact, neurologic spinal cord stimulators powered by rechargeable lithium-ion batteries have been developed by three different device manufacturers and make up the majority of current implants. Lithiumion batteries are also used to provide temporary power for some left ventricular assist devices (e.g., while patient is bathing). In many applications the time between recharges could be as long as weeks or months. Possible modes of lithium-ion battery application include the following: 1. Supporting relatively high-power, non–life-support features of a device (e.g., long-distance telemetry, physiologic sensors). In this case a primary battery would still be used to provide life-sustaining therapy. 2. Using a high-power rechargeable battery to charge the capacitor of an ICD while incorporating a low-power, high–energy density primary battery to provide the recharge energy. In some cases, this may be accomplished by placing the two cells in parallel. 3. Providing excellent longevity (up to 20 years or more) with small devices. In this case the rechargeable lithium-ion battery would serve as the sole power source. Presumably, such devices would be limited to patients who are physically and mentally capable of managing the recharge requirements. Principles of Operation The defining feature of a lithium-ion battery is that it contains no metallic lithium. Instead, lithium ions (Li+) are shuttled back and forth between the positive and negative electrodes during charge and discharge, as shown in Figure 6-15. The most common electrode materials are lithium cobalt oxide (LiCoO2) for the positive cathode material and a graphitic carbon to contain the intercalated lithium for the negative anode material. Many alternative materials are being developed and introduced in commercial batteries and will eventually migrate to batteries for implantable medical devices. The general cell construction is

RECHARGEABLE LITHIUM-ION BATTERIES Rechargeable lithium-ion cells were introduced to the consumer market by the Sony Corporation in 1992. Since that time, lithium-ion technology has been the major focus of research and development investment by many leading battery manufacturers. Lithium-ion batteries exhibit several characteristics that make them highly suitable for implantable medical applications, as follows: 1. High energy density. Although lithium-ion batteries have only about half the energy density of a typical ICD battery, they have double the energy density of older rechargeable batteries (e.g., NiCad). For applications that have a high average power requirement, lithium-ion batteries can provide both small size and excellent longevity. 2. No “memory effect.” Lithium-ion batteries can be partially charged or discharged with no deleterious effects. Thus the patient is free to develop a recharge schedule that is convenient. 3. High voltage. Lithium-ion batteries typically operate in the range of 3 to 4 V and are generally compatible with electronics for implantable devices that have historically used 3-V primary lithium batteries. 4. Low self-discharge. Lithium-ion batteries can be designed to have self-discharge rates of less than 1% per month. Furthermore, the self-discharged capacity is almost fully recoverable on subsequent recharge. 5. High cycle life. Several thousand charge/discharge cycles can be completed with much more than 50% capacity retention. This greatly exceeds the demands of most anticipated implantable applications.

e

e V

Charge

Li+

Discharge

Li+ discharge

Li+

Li+

Li+

Negative electrode (typically LixC)

Li+

Li+

Li+ charge

(Electrolyte)

Li+

Li+

Positive electrode (typically Li(1-x)CoO2)

Figure 6-15  Schematic diagram of a lithium-ion (Li+) battery showing lithium ions shuttling between the positive and negative electrodes as the battery is charged and discharged.

186

SECTION 1  Basic Principles of Device Therapy

4.2

similar to that shown for the Li/SVO battery. However, lithium-ion batteries are manufactured in their discharged state (e.g., using LiCoO2 and graphite) and then charged (or “formed”) after the cell is fully assembled.

4 3.8

Method of Recharge Cell voltage

To date, all of the implantable applications for rechargeable batteries involve recharge by transcutaneous electromagnetic induction. The implanted device incorporates a wound-wire coil that acts as the secondary to an externally located primary coil that is placed adjacent to the implanted device. Typical lithium-ion batteries are capable of accepting a full charge in 2 hours or less. Recharge times in future batteries with improved chemistries could become as short as 10 to 30 minutes. In addition to battery capacity, actual recharge time in ICDs depends on the relative positions of the primary and secondary coils, the depth of the implant, and the maximum power that can be transmitted while limiting heating of the primary coil or the implanted device.

3.4 3.2 3 2.8 2.6 0%

End of Service Life

20%

40%

60%

80%

100%

Depth of discharge

Lithium-ion batteries typically exhibit a gradually declining voltage during discharge that can be used as a “gas gauge” to indicate the state of discharge at a given time (Fig. 6-16). Information about the voltage can be telemetered to a patient controller or a monitor to alert the patient of the need to recharge the battery. However, the end of service for a device powered by a lithium-ion battery is not as readily apparent as for one powered by a primary battery. Because the lithium-ion battery slowly loses capacity as a function of both time and the total number of charge/discharge cycles, the patient may eventually experience a reduced interval between recharge sessions becomes too short to be acceptable to the patient. However, because rechargeable batteries can, in principle, provide unlimited energy, the eventual end of service may be determined by the lifetime of some other component of the implanted device. CAPACITORS The ICDs defibrillate the heart by delivering one or more high-energy, high-voltage shocks. The power capability and voltage of the battery alone are not sufficient to accomplish this. High-voltage capacitors are necessary to store and deliver the energy required for these shocks. The use of capacitors has important clinical implications, including delivered energy, device size, charge time, and longevity. Capacitance In its simplest form, a capacitor consists of two conductors, separated in space and electrically insulated from each other. When the conductors are charged, each stores an equal and opposite amount of charge. In an ideal capacitor, the amount of charge (Q) on each conductor is proportional to the difference in voltage (V) between the two conductors. The proportionality constant, C, is called the capacitance. Q=C×V



(6-10)

Figure 6-16  Monotonic discharge curve of the lithium-ion battery shows how it could be used as a “gas gauge” for determining the remaining capacity in a battery.

The simplest model of a capacitor is shown in Figure 6-17, A, in which the plates are separated in a vacuum. The conductors (or electrodes) consist of two parallel plates of area (A) separated by a distance (d). The capacitance, or ability to store charge as a function of voltage, is equal to A/d multiplied by a fundamental constant, ε0, the permittivity of free space, which is related to the energy required to separate charge in a vacuum. The value of the capacitance can be increased by inserting insulating materials, known as dielectrics, between the electrodes. The factor by which these materials increase the capacitance is called the dielectric constant, k, which is the ratio of the permittivity of the material to the permittivity of free space, ε/ε0. A simple capacitor containing a dielectric material is shown in Figure 6-17, B. Various materials are used as dielectrics the properties of which largely determine the properties of the capacitor. Energy Storage In an ICD, several capacitors are required to deliver a high-voltage, high-energy electric shock through the lead system to the heart. Capacitors are passive devices and therefore must store energy before it can be delivered. The process of storing energy in a capacitor is called “charging.” For a capacitor to be charged, both terminals must be connected to a charging circuit that includes a transformer and to a voltage source such as a battery. The transformer converts the low-voltage energy supplied by the battery into the high-voltage energy stored by the capacitor. The amount of energy stored on the capacitor is proportional to the square of the voltage on the capacitor, as follows: E = 12 C × V2 (6-11)

Parallel-plate capacitor

Parallel-plate capacitor with dielectric

d

d

A = Area

A

3.6

Dielectric constant = κ = ε/εo

A = Area C0 = Capacitance =

Charge Q ε A = = o Voltage V d

B

C = Capacitance =

Charge Q κεoA = = Voltage V d

Figure 6-17  Schematic representation of a parallel-plate capacitor with A, a vacuum, and B, a dielectric, between the capacitor plates. The capacitance is directly proportional to the area of the plates (A), and inversely proportional to the distance between the plates (d). The insertion of a dielectric material between the plates increases the capacitance by a factor of k, the dielectric constant, which is a characteristic of the particular insulating material.



6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators 800

Voltage (volts)

700 600 500 400

Voltage at time = one time constant = 750 (1 – 0.63) = 278 V

300 200

One time constant = RC = 5 ms

100 0

0

5

10

15

20

Time (milliseconds) Figure 6-18  Waveform for the discharge of an ideal 100-microfarad capacitor, charged to 750 V, into a 50-ohm load. These parameters approximate those for an implantable defibrillator in use.

Energy Delivery During defibrillation, the energy stored in the capacitor is delivered to the heart using an electrical path between the opposing electrodes of the capacitor. This connection allows the separated charge to recombine by traveling through the heart. When an ideal capacitor is discharged through a constant resistance, R, the voltage decays with time in an exponential manner, as seen in Figure 6-18. For an ideal capacitor discharged to 0 volts, the delivered energy would equal the stored energy. In ICDs the amount of energy delivered from the capacitor is less than the amount stored. One reason is that the therapy delivery is truncated before the capacitor is completely discharged, and the remaining energy is discarded. A truncated waveform is used because it defibrillates the heart more effectively than a waveform that is allowed to decay to 0 V, despite less energy being delivered to the heart. Other inefficiencies associated with the capacitor, device circuit, and delivery system also reduce the amount of stored energy delivered to the heart, as discussed later. Energy Density Energy density is an important parameter for capacitors as well as batteries. Capacitor energy density is typically expressed in terms of volume and has units of joules per cubic centimeter (J/cm3). The most energy-dense modern defibrillation capacitors deliver energies in excess of 5 J/cm3. As previously discussed, the highest energy density seen for implantable batteries is about 1 W-hr/cm3, which is the same as 3600 J/cm3, or more than 500 times as high as the best defibrillation capacitor. Why, then, use capacitors at all? The reasons are voltage and power. Defibrillation therapy requires the energy to be delivered rapidly at about 1000 W of power and starting at a voltage of 650 to 850 V. ICD batteries are designed to deliver the energy to the circuit at about 10 W of power with voltage between 2.5 and 3.0 V. Consequently, the ICD is designed with the battery as a large energy reservoir, analogous to the gas tank of an automobile, and the capacitor as the fuel injector to the engine. Nevertheless, it is important for the capacitors to have the highest practicable energy density in order to minimize the overall volume of the ICD.

187

to make the metal particles bond to one another (called sintering) while still remaining porous. For either material, an oxide film is electrochemically grown (called forming) on the exposed surfaces of the metal electrode. The oxide serves as the capacitor dielectric. Aluminum anodes are typically formed to support charging to about 400 V. Two capacitors are connected in series in the ICD to provide sufficient voltage for defibrillation. Tantalum anodes are typically formed to support charging to 175 to 250 V with three or four capacitors connected in series. The high capacitance, high voltage, and relatively low resistance of aluminum and tantalum electrolytic capacitors provide their high energy density (3-5 J/cc) and quick, efficient energy delivery that make them the capacitors of choice for ICDs. ICD Capacitor Construction Early ICD devices used commercially produced, cylindrically wound, aluminum electrolytic capacitors developed for flash photography applications. The need for smaller, thinner capacitors and specialized shapes led ICD manufacturers to develop stacked-plate aluminum electrolytic capacitors and custom tantalum electrolytic capacitors.21,22 Aluminum Electrolytic Capacitor Components.  All aluminum electrolytic capacitors are produced using the same basic materials of construction. Cylindrical and stacked-plate designs both incorporate an anode, a cathode, an electrolyte, and a separator material placed between the anode and cathode. The anode and cathode are aluminum foils that have been etched and formed, as previously described. Cylindrical Aluminum Electrolytic Construction.  Most commercially produced aluminum electrolytic capacitors employ wound electrodes in a cylindrical shape. Strips of anode and cathode foil, spaced apart by a paper separator, are wound into a coil. Figure 6-20 shows a cutaway view of an aluminum electrolytic photoflash capacitor of the type typically used in the first few generations of ICDs. Stacked-plate Aluminum Electrolytic Construction.  ICD manufacturers have developed stacked-plate aluminum electrolytic capacitor technology to improve the energy density, minimize the thickness, and allow a variety of shapes compared with cylindrically wound capacitors. The details of construction vary among manufacturers, but several design themes are common. Foils and separators are cut to a specific geometry and layered such that multiple anode plates are

ICD Capacitor Types The defibrillation capacitors used in past and current ICDs are called electrolytic capacitors, most often based on aluminum or tantalum electrode materials. The metal electrode materials are processed so they have a very large surface area, which allows for a high capacitance. For aluminum electrolytic capacitors, the positive electrode (anode in a capacitor) starts as a thin foil that has been etched to create a large number of tunnels. Figure 6-19 shows a scanning electron micrograph of a cross section of a highly etched anode foil. For tantalum electrolytic capacitors, the anode is made from tantalum metal powder pressed into a porous pellet and heated to a high enough temperature

Figure 6-19  Photomicrograph of a replica made from the etched anode foil used in aluminum electrolytic capacitors. The long, linear structures are tunnels etched into the aluminum foil. In this example some of the tunnels are etched completely through the foil to provide an electrical connection between the two sides. Magnification is about 800×.

188

SECTION 1  Basic Principles of Device Therapy

Terminals Crimp seal

Wound stack

Separator Anode Anode Separator Cathode Figure 6-20  Cutaway view of wound aluminum electrolytic capacitor used in early implantable defibrillators. The anode and cathode connections are brought out of the capacitor using feedthroughs. The capacitor is closed with a crimp seal. Notice that two layers of anode material are used for each layer of cathode material. The entire wound capacitor coil is saturated with electrolyte (not shown).

Deformation.  The non-ideal process that is most apparent is called deformation. As previously explained, the dielectric material in electrolytic capacitors is created by “forming,” immediately after which the dielectric is almost free of defects. Over time, the chemical environment within the capacitor or relaxation of residual stress will cause microscopic imperfections in the oxide film on the anode. When the capacitor is charged to a high voltage after a long period of disuse, additional energy is required to regrow oxide in these areas to heal the defects.23 This process is known as re-formation. The additional energy needed to re-form the dielectric results in longer charge times in ICDs. In a typical aluminum capacitor, 25% or more additional energy (and time) may be required to charge the capacitor if it has been many months since the last charge. The amount of additional energy drops to about 15% for capacitors not charged for about a month. Tantalum capacitors perform similarly, although the rate of deformation may be somewhat slower. Figure 6-23 shows capacitor deformation in typical aluminum capacitors for various charging intervals. To minimize the clinical effect of deformation, current ICDs incorporate a programmable maintenance routine that automatically charges the capacitor to high voltage to heal the dielectric at intervals of 1 month, 3 months, or 6 months. Leakage Current.  Leakage current is another non-ideal process that occurs in all capacitors to some extent. After a capacitor is charged, some of the energy “leaks” off the capacitor, and the voltage decreases with time. This happens quickly enough to affect how ICDs are designed; leakage current is the major reason why ICDs are only charged just before a shock is to be delivered. Internal Resistance.  The final important non-ideality is internal resistance. All capacitor types have some level of internal resistance, as do batteries. Electrolytic capacitors used in ICDs typically have a

Connector

sandwiched between cathodes and layers of porous separator paper. The geometry of the plates is selected so that the finished capacitor fits efficiently in the ICD. The energy density of stacked-plate capacitors can approach 4 J/cc versus the 2.5 J/cc typical of the coiled configuration. Figure 6-21 shows a cutaway view of a stacked-plate aluminum electrolytic capacitor similar to those used in current ICDs. Tantalum Electrolytic Capacitor Construction.  Tantalum electrolytic capacitors have the same basic elements as aluminum electrolytic capacitors. In tantalum capacitors the anode is made using pressed, sintered, and formed tantalum pellet. The cathode in a tantalum capacitor is typically deposited directly on the inside of the capacitor case, making it the negative terminal of the capacitor. Tantalum capacitors have similar benefits to stacked-plate aluminum capacitors but provide higher energy and simpler construction than aluminum capacitors. Rather than layered anode foils, tantalum capacitors have a single anode pellet. The simple and efficient construction minimizes the volume of materials that do not contribute to energy storage (cathode, separator, encasement), thus maximizing energy density. Tantalum capacitors used in current ICDs have an energy density of 5 J/cc or more. The primary drawback of tantalum capacitors is their mass. Because tantalum is very dense, tantalum capacitors are approximately 50% heavier than aluminum capacitors with equivalent energy. Figure 6-22 shows a cutaway view of a tantalum electrolytic capacitor similar to those used in some current ICDs. Non-Ideal Behavior in Capacitors Although the electrolytic capacitors used in ICDs have performance characteristics well suited to the ICD application, their performance does deviate from ideal in ways that can be clinically significant.

Feedthroughs

Anode/cathode stack

Cathodes

Paper wrap

Papers Anodes

Fill port Figure 6-21  Cutaway view of stacked-plate aluminum electrolytic capacitor used in current implantable defibrillators. Anode and cathode layers are cut to a specific geometry and are stacked upon one another. Anode and cathode terminals exit the welded capacitor housing through feedthroughs. The capacitor encasement is laser welded. Note that four layers of anode material are used for each layer of cathode material (some designs use up to five layers). The entire capacitor stack is saturated with electrolyte (not shown).



6  Power Systems for Implantable Pacemakers, Cardioverters, and Defibrillators

189

Capacitor Failure Modes

Encasement Cathode

Capacitor failure modes depend greatly on the specific conditions of device use. The failure modes most relevant to the ICD application are discussed here.

Separator

Short Circuit.  Short circuit occurs when the electrodes at opposite polarity come into direct electrical contact. In electrolytic capacitors, a short circuit occurs when the anode and cathode touch, such as when the separator is punctured, torn, or improperly aligned. Short circuit may result in the total failure of the capacitor or only partial loss of function. If the capacitor short-circuits while it is charged, its energy can quickly be discharged, which can irreversibly harm the device. If the short circuit occurs when the capacitor is uncharged, it will not be able to be charged, and the full energy of the therapy will not be delivered.

Encasement Cathode

Anode

Dielectric Oxide Degradation.  As previously discussed, capacitor deformation is an important ICD capacitor performance characteristic. The increases in charge time resulting from deformation are minimized by charging the device periodically to repair the microscopic oxide defects that form over time. In rare cases where the oxide is not properly formed or contains contaminants, normal oxide degradation can be accelerated. Depending on the severity of the issue, periodic maintenance charging may not be sufficient to keep device charge time at specified levels, and in extreme cases the device may fail to charge. Manufacturers thoroughly test incoming materials and assemble products in clean environments to ensure robust and predictable performance. Future Developments

Figure 6-22  Cutaway view of a tantalum electrolytic capacitor used in current implantable defibrillators. Design incorporates a single tantalum anode pellet pressed from tantalum powder. A tantalum lead wire exits the welded housing by a feedthrough. Highcapacitance cathode material is deposited directly on the case. The entire electrode assembly is saturated with electrolyte (not shown).

Electrolytic capacitors are expected to remain the technology of choice for many future generations of ICD. Research continues on materials and processing methods to continue to improve energy density and performance. There is no clear path to integration of alternate capacitor technologies, such as ceramic, polymer, or double layer, but new materials and processes are being investigated that might provide smaller size and improved performance characteristics.

resistance of about 2 to 4 ohms, which results in about 5% energy loss when a capacitor is discharged into a typical 50-ohm therapeutic load. Resistance is accounted for in the design of the capacitor and ICD so that the desired energy is actually delivered during a defibrillation therapy.

Effects of Batteries and Capacitors on Defibrillation Performance

60% Photoflash capacitor performance

Percent deformation

50% 40% 30% 20%

Stacked-plate capacitor performance

10% 0%

0

2

4

6

8

Time since last charge (months) Figure 6-23  Percent deformation. For typical photoflash capacitor used in early ICDs and typical stacked-plate performance. Percent deformation is percentage of additional energy required to charge a capacitor after some period at open-circuit voltage.

ENERGY LOSSES IN DEFIBRILLATORS The processes of charging the capacitors and discharging the energy through the leads of a cardiac defibrillator have numerous inefficiencies, which result in a substantial disparity between the chemical energy consumed in the battery and the electrical energy delivered to the heart. Besides capacitor deformation, leakage current, and capacitor resistance, as previously discussed, other losses are inherent in the design of the device-charging circuit and leads. The most significant loss of energy is associated with the battery. Batteries in ICDs are designed to be as small as possible, which means that they tend to be operated near their maximum power capability. An ideal power source operates at maximum power when the load placed on the power source matches the internal resistance of the power source. This well-known concept is often referred to as “impedance matching.” In terms of energy efficiency, it means that when a power source is operating at maximum power, only half of the total energy consumed is delivered to the external load. The remainder of the energy is dissipated as heat inside the ICD. Considering all these contributions, the overall efficiency of the battery/charging-circuit/ capacitor/lead system for current ICDs is less than 50%. To put this energy consumption in clinical perspective, the energy content of a typical ICD battery is on the order of 15,000 J. A system operating at 50% efficiency would consume 70 J from the battery, or about 0.5% of the total energy. This equates to about 10 to 15 days of longevity reduction for each 35-J shock delivered.

190

SECTION 1  Basic Principles of Device Therapy

CLINICAL IMPLICATIONS OF DESIGN When comparing the performance of ICDs, many principal parameters are interrelated, and optimizing one may degrade another. The clinician should be aware of these issues to develop realistic expectations for device performance. Four principal characteristics of an ICD interact, primarily because of the battery and the defibrillation capacitors: size, longevity, charge time, and defibrillation energy. Smaller ICDs may be desirable, but all else being equal, small size trades off longevity, charge time, and maximum shock energy. Higher maximum shock energy will extend charge time and reduce longevity. The ICD manufacturer must strike an appropriate balance between ICD volume and clinically important parameters such as longevity, charge time, and maximum shock energy. The clinician should also be aware that charge times are generally specified assuming formed capacitors. Since deformed capacitors

consume additional energy in charging, charge times for devices that have not been recently charged can be up to 25% longer for the first defibrillation therapy delivered. Specific device use conditions also have a significant impact on observed device performance. As discussed earlier, the energy removed from the battery during each charge of the output capacitor represents a significant fraction of its total energy, on the order of 0.5% to 1.0%. Thus the longevity of a defibrillator depends greatly on the frequency of the shock therapy. This is further complicated by single-, dual-, or triple-chamber pacing conditions. For example, a device used only as a defibrillator that delivers few therapeutic shocks may last more than 13 years, whereas the same device may only last 3 to 5 years if implanted in a patient who requires significant triplechamber pacing or if many shocks are delivered. Longevity differences can be a factor of three or greater depending on how the device is used.

REFERENCES 1. Brennen KR, Fester KE, Owens BB, Untereker DF: Pacemaker battery capacity: a consideration of the manufacturer’s problem. Proceedings of the VIth World Symposium on Cardiac Pacing, Montreal, 1979, Pacesymp. 2. Brennen KR, Fester KE, Owens, BB, Untereker DF: A capacity rating system for cardiac pacemaker batteries. J Power Sources 5:25, 1980. 3. Broadhead J: Electrochemical principles and reactions. In Linden D, editor: Handbook of batteries and fuel cells, ed 2, New York, 1994, McGraw-Hill. 4. Holmes CF: An approach to the reliability of implantable lithium batteries. J Power Sources 26:185, 1989. 5. Schmidt CL, Skarstad PM: Impedance behavior in lithium iodine batteries. In Abraham KM, Solomon M, editors: Proceedings of the Symposium on Primary and Secondary Lithium Batteries, PV91 3, 1991, Electrochemical Society, pp 75-85. 6. Schmidt CL, Skarstad PM: Development of a physically based model for the lithium iodine battery. In Keily T, Baxter BW, editors: Power sources 13, Leatherhead, England, 1991, International Power Sources Committee, pp 347-361. 7. Untereker DF, Owens BB: Microcalorimetry: a tool for the assessment of self-discharge processes in batteries. Reliability Technology for Cardiac Pacemakers II, Gaithersburg, Md, 1977, National Bureau of Standards Workshop.

8. Untereker DF: The use of a microcalorimeter for analysis of load dependent processes occurring in a primary battery. J Electrochem Soc 125:1907, 1978. 9. Owens BB, editor: Batteries for implantable biomedical devices. New York, 1986, Plenum. 10. Antonioli G, Baggioni F, Consiglio F, et al: Stimulatore cardiaco implantible con nuova battaria a sato solido al litio. Minerva Med 64:2298, 1973. 11. Weiss DJ, Cretzmeyer JW, Crespi AM, et al: Electrochemical cells with end-of-service indicator. US Patent 5:180, 642, 1993. 12. Schmidt CL, Skarstad PM: The future of lithium and lithium-ion batteries in implantable medical devices. J Power Sources 97/98:742-746, 2001. 13. Takeuchi ES, Quattrini JP: Batteries for implantable defibrillators. Med Electronics 119:114-117, 1989. 14. Liang CC, Bolster E, Murphy RM: Metal oxide cathode material for high energy density batteries. US Patents 4:310, 609_1982 and 4,391,729_1983. 15. Holmes CF, Keister P, Takeuchi E: High rate lithium solid cathode battery for implantable medical devices. Prog Batteries Solar Cells 6:64, 1987. 16. Crespi AM: Silver vanadium oxide cathode material and method of preparation. US Patent 5:221, 453, 1993.

17. Crespi A, Schmidt C, Norton J, et al: Modeling and characteristics of the resistance of lithium/SVO batteries for implantable cardioverter defibrillators. J Electrochem Soc. 148:A30-A37, 2001. 18. Medtronic. Tachyarrhythmia technical concept paper. Vol V, No 1. Marquis ICD Battery Technology. 19. Root MJ: Lithium-manganese dioxide cells for implantable defibrillator devices: discharge voltage models. J Power Sources 2008. doi:10.1016/j.jpowsour.12:083, 2009. 20. Gan H, Rubino RS, Takeuchi ES: Dual-chemistry cathode system for high-rate pulse applications. J Power Sources 146:101-106, 2005. 21. Strange TF, Graham TV: Beyond photoflash; development of a polyanode capacitor. In Proceedings of the 20th Capacitor and Resistor Technology Symposium, CARTS 2000, Huntington Beach, Calif, 2000, pp 16-21. 22. Breyen MD, Rorvick AW, Skarstad PM: Efficiently packaged aluminum electrolytic capacitors for implantable cardioverterdefibrillators. In Proceedings of the 22nd Capacitor and Resistor Technology Symposium, CARTS 2002, New Orleans, 2002, pp 197-202. 23. Norton J, Anderson C: Energy management in aluminum electrolytic capacitors: In Proceedings of the 23rd Capacitor and Resistor Technology Symposium, CARTS 2003, Scottsdale, Ariz, 2003, pp 269-277.

7 

The Biologic Pacemaker J. KEVIN DONAHUE

In October 1958, the first fully internalized pacemaker was implanted

at the Karolinska Institute in Sweden. Within hours, the unit ceased to function, or as Senning wrote in a retrospective account, “At 2 am the pacemaker became silent.”1 In a Medline search with the keywords “implantable pacemaker,” the first five citations (starting in 1960) are case reports of various implants, and the sixth (1962) is entitled “Complications of an implantable cardiac pacemaker.”2 Since that initial implant, millions of pacemakers have been implanted, saving lives and reducing or even eliminating symptoms. Along with these benefits of electronic pacemakers, however, complications occur in 5% to 10% of patients undergoing implant procedures.3,4 Acute complications range from minor hematomas to more severe infections, pneumothoraces, and cardiac perforations. Long-term management of pacemaker patients is complicated by device and lead failures and a requirement to change out the device when the battery fails. These limitations of device therapy have motivated the search for alternatives. One widely publicized approach over the last few years is to create a “biologic pacemaker” by either gene transfer or cell transplantation methods (Table 7-1). This chapter reviews the literature on this approach.

Gene Therapy Approaches BETA-2 ADRENERGIC RECEPTOR GENE TRANSFER In the first attempt at genetic modulation of heart rate, Edelberg et al.5 injected plasmids containing the beta-2 adrenergic receptor (β2-AR) into mouse right atria. They found expression of the vector in 81% of myocytes at the injection site and a heart rate of 550 beats per minute (bpm) for the active-treatment group, significantly higher than the 370 bpm rate in controls. In a subsequent pig study, these investigators did not quantify gene transfer but reported a heart rate of 163 bpm for the β2-AR–receiving pigs relative to 127 bpm for controls.6 These studies showed promising results but also raised questions. The investigators did not report the time course of heart rate increase for the mice, but in the pigs they found a statistically significant increase in heart rate only on the second day after injection. The usual experience with plasmid-mediated gene transfer is that the effect persists for several weeks or even months after gene transfer.7-9 The transient effect for the β2-AR experiments suggests that some toxic effect from expression of this gene may be a limiting factor. Additional concerns involve possible mechanisms for the increase in heart rate. The mouse study did not target the specialized conducting system, and under ordinary circumstances, atrial myocytes should not display automaticity. A potential mechanism for the heart rate increase from β2-AR expression in atrial myocytes is Gs-mediated activation of adenylate cyclase, causing an intracellular cascade that ultimately results in phosphorylation of the type 1 calcium channel and the ryanodine receptor. Increased activity of these calcium-handling proteins could cause automaticity by the calcium clock mechanism, but sustained increase in intracellular calcium would likely be toxic. The porcine study did target sinus node by injecting in the area electrically mapped as the earliest site of activation during sinus rhythm, but the extremely transient functional change in pigs suggests that toxicity may be a concern even in sinus nodal tissues. An additional concern from the figures demonstrating gene expression is that the green from the green fluorescent protein in controls and the red from β2-AR immunostaining in the active-treatment group

are apparently extracellular. These concerns should probably be addressed before considering translation of the β2-AR findings. IK1 KNOCKOUT In the next illustration of heart rate modulation, investigators used a dominant negative mutation of the gene encoding the IK1 channel (KCNJ2 GYG144-146AAA) to create automaticity.10 IK1 (also called the inward rectifier current) is the principal current responsible for maintaining the cardiac myocyte’s resting membrane potential. The logic behind this strategy was that differences in IK1 between atrial and sinus nodal myocytes account for the relative instability of sinus nodal membrane potential, so that a deficit of IK1 would increase the probability of phase 4 depolarization and automaticity. The investigators admitted that their primary interest was in the electrophysiologic effects of IK1 on the action potential, and that they did not intentionally create pacemaking nodes. Their delivery method essentially scattered the transgene around the ventricular myocardium. Nonetheless, they found evidence of ventricular automaticity in 40% of animals expressing the KCNJ2-AAA mutation. Further investigation found that at least 80% of endogenous IK1 needed to be eliminated for automaticity to occur.11 There have been no subsequent reports applying this strategy to other models. No attempt was made to quantify rate or stability of the idioventricular rhythm in this report.10 Other concerns rising from the KCNJ2AAA strategy include the repolarization delaying effects of gene expression and the possibility of atrioventricular (AV) nodal suppressing effects. The investigators reported some level of action potential prolongation and increased QT interval at all expression levels of the transgene, as opposed to the pacing phenotype that was only visible with 80% suppression of IK1. Inspection of the limited reported data also shows no apparent AV nodal conduction, even in areas where the atrial beat is timed far enough away from the proceeding ventricular beat that AV nodal conduction should reasonably be expected. This finding is extrapolated from extremely limited data and should be assessed with more care if IK1 knockout becomes part of a biopacing strategy. Overall, the findings with IK1 knockout suggest that this may be a component of an overall biopacing strategy (with the previous caveats), but that the limited rate in pigs suggests that it might need to be applied with other interventions to increase automaticity. IF MANIPULATIONS Since the early attempts at pacemaker induction, almost all subsequent gene transfer approaches have involved manipulation of If, the putative pacemaker (funny) current. The first attempts consisted of intramyocardial injections of adenovirus vectors encoding wild-type HCN2. The initial report targeted the left atrium,12 and a subsequent report showed gene transfer to the left bundle branch (LBB).13 In both reports, transgene function was not apparent during normal sinus rhythm. During vagal stimulation–induced sinus arrest, the transgene-expressing animals had a significantly higher escape rhythm than controls, and this rhythm mapped to the target area. Overall, the escape rate was inadequate to be a viable pacemaker replacement, and the transgene-driven rhythm could not be seen outside of vagal stimulation, so the investigators could not comment on stability of this rhythm over time. An additional report with the HCN4 isoform suggested that automaticity was not limited to HCN2. Cai et al.14 injected adenoviruses

191

192

TABLE

7-1 

SECTION 1  Basic Principles of Device Therapy

Results of Molecular Therapy Experiments to Induce Cardiac Automaticity

Gene Therapy Transgene [Reference] β2-Adrenergic receptor [6]

Vector Plasmid

Target Right atrium

Results 50% increase in HR

KCNJ2 GYG144-146AAA [10] HCN1 EVY235-237ΔΔΔ [16]

Adenovirus

Whole heart

Adenovirus

Left atrium

Observed ventricular automaticity Average HR 64 bpm in sick sinus syndrome model

HCN2 wild type [12]

Adenovirus

Left atrium

[13, 15]

Adenovirus

LV left bundle branch

HCN2 E324A [15]

Adenovirus

HCN212 [17]

Adenovirus

HCN4 wild type [14]

Adenovirus

LV left bundle branch LV left bundle branch Right ventricle

Cell Therapy Cell Type [Reference] Fetal atrial myocytes [18]

Manipulation None

Human embryonic stem cells [19] Human mesenchymal stem cells [20, 21] Guinea pig lung fibroblasts [22]

Problems Effect only seen for 1 day; rhythm not mapped to gene transfer site QT prolongation, no attempt to quantify rate or stability Only 2 animals per group; competing electronic pacemaker DDD 60 bpm limits analysis of biopacing rhythm; limited data Long pause before onset of escape rhythm; no visible phenotype during sinus rhythm; no data on durability Long pause before onset of escape rhythm; no visible phenotype during sinus rhythm (visible with AV block); required backup pacing 26% of the time Required VVI 45 bpm pacing 36% of the time

Escape rhythm during vagal arrest mapped to target area 54 bpm LV escape rhythm during vagal arrest, average HR 57 bpm after AV node ablation Average HR 53 bpm after AV node ablation All animals developed VT

All animals developed VT

Average HR 69 bpm after AV node ablation

No data on rate stability; animals only followed for 24 hours

Target Left ventricle

Results Average HR 70 bpm after AV node ablation

CM derivation and isolation of beating cells HCN2 gene transfer

Left ventricle

Average HR 59 bpm after AV node ablation

Problems Only 2 animals per group; long pause before stable biopacing; no long-term rhythm stability data; questionable feasibility for translation Stable rhythm seen in only half of study animals; no long-term rhythm stability data

Left ventricle

Average HR 52-61 bpm after AV node ablation

HCN1 gene transfer, co-infusion with PEG5000 for cell fusion

Left ventricle

Observed ventricular escape beats during methacholineinduced sinus arrest

Long pause before stable biopacing; after AV node ablation, animals still had 25% of beats from VVI 35 electronic pacemaker No stable biopacing

AV, Atrioventricular; HR, heart rate; LV, left ventricular; VT, ventricular tachycardia.

encoding either wild-type HCN4 with green fluorescent protein (GFP) or GFP alone into porcine ventricles.14 They performed AV nodal ablation 3 to 4 days after gene transfer and measured the residual ventricular rate. The HCN4-expressing animals had a ventricular escape rate of 69 bpm, whereas the rate was only 41 bpm in the GFP controls. Pace mapping of the rhythm in the HCN4-expressing animals showed that the rhythm originated from the target region. The heart rate measurement was essentially an acute study, so no data on rate stability were provided. Bucchi et al.15 tested the hypothesis that mutations of the HCN channel could improve automaticity. They compared wild-type HCN2 to HCN2-E324A. This mutation was chosen because biophysical analysis suggested it would increase channel activation. The mutation alters the voltage dependence of activation so that the channel becomes active at less negative membrane potential, thus increasing the rate of channel opening during cellular repolarization. The authors hypothesized that this increase in If would lead to faster phase 4 depolarization and thus a faster heart rate. Events did not proceed as planned. The investigators injected adenoviruses encoding the wild-type HCN2, the HCN2-E324A mutant, or GFP into the LBB of dogs. They implanted electronic pacemakers, ablated the AV node, and watched. They saw no significant increase in heart rate when comparing the wild-type and mutant channels (both were better than GFP control), and they noted a greater need for the electronic pacemaker backup in animals expressing the HCN2 mutant than the wildtype HCN2. To investigate this discrepancy with expectations, the investigators found that the mutant channel did, indeed, have the predicted kinetics, but it also had a decrease in peak current caused by a decrease in expression compared with the wild-type channel. The investigators did not define the cause for the decreased expression, but presumably it was cellular toxicity to the mutant channel because the virus vector and DNA control elements were the same for the wild-type and mutant HCN2 genes.

In addition to finding that behavior of mutant channels involves factors other than the predicted biophysical profile, the AV node ablation allowed Bucchi et al.15 to comment on the long-term behavior of the biopacing node. Two important findings were the inadequacy of both pacing rate and rhythm stability after gene transfer. As noted, the average rate of animals receiving wild-type HCN2 was only 57 bpm, which is considerably lower than the normal canine heart rate. Even with this average heart rate of 57 bpm, the wild-type HCN2–expressing animals had frequent episodes when biopacemaking activity was lost, requiring the backup electronic pacemaker 26% of the time. The electronic pacemaker was programmed VVI 45 bpm, so drop-out of the biopacemaker was not caused by overdrive suppression from the electronic pacemaker. The cause was certainly failure of the biopacing node, but the exact mechanism was not reported; loss of automaticity and exit block were likely possibilities. Tse et al.16 reported another strategy to improve pacing rate with a mutation of the HCN1 isoform. HCN1-EVY235-237ΔΔΔ was a deletion mutation that shortened the S3-4 linker of the channel, with a predicted biophysical effect of increased probability of channel opening. Using a porcine model, the investigators ablated enough of the sinus node to cause sick sinus syndrome, implanted an electronic dual-chamber pacemaker programmed to DDD mode with a lower rate limit of 60 bpm, and then injected either an adenovirus vector encoding the HCN1 mutant or saline into the left atrial appendage. There were only two animals in each group. After gene transfer, the active-treatment group had a spontaneous rate of 64 bpm but still required the electronic pacemaker 14% of the time, which is difficult to interpret given the programmed lower rate limit of 60 bpm and the observed average spontaneous rate of 64 bpm. There is little room for movement below the average rate, although the only 14% use of electronic pacing suggests that the heart rate could not have varied far from the average, or one would have expected a higher percentage of pacing. No rate or rhythm data from the two saline-injected animals were



7  The Biologic Pacemaker

provided. Given the limitations of this report, it is difficult to interpret it in the overall context of biopacing strategies. The danger of HCN mutation was illustrated by Plotnikov et al.,17 who reported ventricular tachycardia in dogs after injection of a chimeric HCN channel that had components of both HCN1 and HCN2 isoforms. One day after injection of adenoviruses encoding this chimeric channel into LBB, they noted ventricular tachycardia (VT) at rates in excess of 200 bpm in all animals. They further connected the arrhythmia with the gene transfer by showing VT elimination after exposure to ivabradine, an If-blocker with relative HCN1 specificity. Overall, gene transfer with HCN-family genes suggests that automaticity is achievable, but concerns about baseline rate, stability of heart rate over time, and most importantly, assessment for proarrhythmia need to be addressed before this strategy becomes viable.

Cell Therapy Strategies The first report of cell transplantation for cardiac pacing used a strategy of first isolating canine fetal atrial myocytes, “including sinus node,” and then injecting these cells into the ventricles of adult dogs.18 The investigators did not attempt to identify or isolate a spontaneously beating subpopulation, choosing instead to inject the mixed population from cell isolation. Two dogs received the cardiomyocytes, and two control dogs received fibroblast injections. Three weeks after cell injections, the investigators performed AV node ablation and observed the ventricular rate. Initially after ablation, all animals had a nodal escape of approximately 35 bpm. After 5 to 30 minutes, the two dogs receiving atrial myocytes developed a ventricular escape rhythm at 70 bpm that mapped to the cell injection site. The two control animals had no alteration in rhythm beyond the initial 35-bpm nodal escape. Further study showed that the ventricular rhythm had an escape recovery time of 710 msec after 150-bpm burst pacing, which suggested some level of stability for the rhythm. As with many of the original gene therapy pacing studies, this phenotyping study was acute, and long-term rhythm stability was not assessed. Several practical problems limit translation of these findings, primarily the need to isolate cells from third-trimester fetuses and the need for information on long-term stability of the cells and the rhythm. Immunologic reaction to the cell transplant is another consideration. Overall, however, this report established the feasibility of cell transplant pacemakers. Similar work showed viability of embryonic stem cell (ESC)–derived cardiomyocytes for pacing. Kehat et al.19 used methods frequently reported in the field to cultivate spontaneously beating cardiomyocytes from undifferentiated ESCs. They first allowed the human cells to grow with specialized culture medium overlying a “feeder layer” of neonatal mouse fibroblasts. The resulting cell population developed into “embryoid bodies,” with suspension culture again using specialized medium. Spontaneously beating cells were mechanically dissected away from the embryoid bodies and injected into pigs after AV node ablation. The 13 pigs that received cell therapy had backup electronic pacemakers in this uncontrolled study. Shortly after AV node ablation, the animals had only a nodal escape rhythm. At electrophysiologic study 1 to 3 weeks after cell injection/ablation, two of the animals still only had a nodal rhythm, five had isolated monomorphic premature ventricular contractions (PVCs) or short runs of ventricular rhythm, and six had sustained ventricular rhythm that mapped to the cell injection site. The average rate of the ventricular rhythm (59 bpm) was competitive with the nodal escape rhythm (61 bpm), so the investigators were unable to comment on rhythm stability or long-term viability of this approach. These issues are relevant when contemplating translation of the ESC results, in addition to ethical concerns voiced by some about the use of human ESCs, and the need for extensive manipulation of the cells, which would not be readily scalable. Potapova et al.20 reported a novel hybrid cell and gene therapy approach. They transduced human mesenchymal stem cells (MSCs) with the HCN2 gene, then transplanted these cells into canine left ventricle. Their hypothesis was that the HCN2-expressing cell would couple with nearby ventricular myocytes and essentially act as a driver

193

for phase 4 depolarization in the myocytes. With sufficient connectivity, the myocyte would transmit its membrane potential to the MSC during repolarization; this would activate If in the MSC, and that current would be transmitted across the gap junctions to the ventricular myocyte, causing phase 4 depolarization and thus automaticity in the two-cell unit. The investigators were motivated to use the cell therapy approach by concerns about dangers in long-term expression gene transfer vectors that would be needed to transduce the ventricular myocytes directly in vivo, although they admitted that these concerns had not yet been demonstrated in animal or human studies using adeno-associated virus. Potapova et al.20 compared four control animals to six animals receiving the HCN2-transduced MSCs. As in their initial HCN2 gene transfer studies, they saw no spontaneous rhythms, so they used strong vagal stimulation to induce sinus arrest. All animals had nodal or ventricular escape rhythms during the sinus arrest period. Of the four control animals, two had right ventricular (RV) escape rhythms and 2 had left ventricular (LV) escape rhythms. The average escape rate for the controls was 45 bpm. Five of the six HCN2-MSC animals had LV escape rhythms, and the average rate of 61 bpm was significantly higher than in the controls. The investigators mapped the escape to the target site in the HCN2-MSC animals. In a subsequent study, Plotnikov et al.21 tested the dose-response for HCN2-transduced MSC injections.21 They evaluated animals receiving 155,000 to 850,000 cells. In this study the researchers performed AV nodal ablation with electronic pacemaker implantation (VVI 35 bpm) for long-term follow-up of the escape rhythm. In all animals, spontaneous rhythms became apparent after 2 to 3 days, but this rhythm remained unstable for at least 2 weeks. For animals receiving less than 600,000 cells, the rhythm never stabilized, and the average rate was 43 bpm. After 2 weeks the animals receiving 600,000 to 850,000 cells had a relatively stable rhythm at an average rate of 52 bpm for the 42-day duration of the study. With linear regression analysis, the investigators showed a correlation between rate and number of injected cells for the higher-dose animals. Even with this level of biopacing, however, 25% of observed beats originated from the VVI 35 bpm electronic pacemaker. A further concern was that only 70% of the ventricular beats pace-mapped to the injection site in the high-dose group, although this was an improvement over the 10% mapped to the target site in the low-dose group. Cho et al.22 reported a variation on the HCN-transduced cell transplant approach. They transduced fibroblasts with the HCN1 isoform and then used polyethylene glycol 5000 (PEG5000) to induce fusion of the HCN1-expressing fibroblasts with ventricular myocytes. This largely in vitro study showed viability of the cell fusion concept and automaticity of the resulting fibroblast-myocyte complex. Very limited in vivo data in guinea pigs injected with the PEG5000/transduced fibroblast mixture showed occasional ventricular escape beats coming from the target region after methacholine-induced sinus arrest. The investigators hypothesized that an additional factor beyond the HCN1 expression was the increased cell surface area of the fibroblast/myocyte complex that diluted IK1 from the myocyte by approximately 20%. An important in vitro investigation by Fahrenbach et al.23 showed improved pacing with suppression of connexin 43 (Cx43) expression. These investigators used ESCs isolated from Cx43 knockout transgenic mice. The cells still expressed connexins 40 and 45, so some cellular connectivity was possible, but the overall level of connectivity was reduced. The investigators cultured spontaneously beating ESCderived cardiomyocytes from either wild type of Cx43−/− mice with HL-1 cells (an immortalized mouse atrial tumor cell line). The Cx43 knockout cells required a longer time to connect to the underlying HL-1 cells, but once connectivity was established, the Cx43−/− cells had a much higher probability of becoming the dominant pacing node for the culture dish. These results are consistent with the observations of reduced cell connectivity in histologic studies of sinus node tissues. The concept from sinus node studies is that limited cellular connectivity allows the rhythm to arise gradually in an isolated node, without suppression from the strong polarizing influence of the surrounding myocytes.

194

SECTION 1  Basic Principles of Device Therapy

Based on the Fahrenbach et al.23 results, some rhythm stability problems in the previously noted gene and cell therapy examples could be caused by too much connectivity between the automatic cells, and the surrounding myocytes could be suppressing phase 4 depolarization in the biopacing node.

Conclusion Given the overwhelming success of electronic pacemakers, the efficacy and safety of biologic pacemakers will need to be well established before

translation to clinical practice is contemplated. Currently, both gene transfer and cell transplantation strategies indicate that automaticity can be induced after a variety of manipulations. Problems common to all investigated strategies (where data are available to evaluate) include drop-off of automaticity resulting in either asystole or activation of a backup electronic pacemaker, inadequacy of baseline rate, and demonstration of long-term rhythm stability. Still, these are very early studies; the challenges are there, but none of the identified problems is insurmountable. Over the next several years, we can anticipate continued research in this field and likely solutions to these problems.

REFERENCES 1. Senning A: Cardiac pacing in retrospect. Am J Surg 145: 733-739, 1983. 2. Appelbaum I, Parsonnet V, Sonnet V, et al: Complications of an implantable cardiac pacemaker. J Newark Beth Isr Hosp 13:166174, 1962. 3. Pakarinen S, Oikarinen L, Toivonen L: Short-term implantationrelated complications of cardiac rhythm management device therapy: a retrospective single-centre 1-year survey. Europace 12:103-108, 2010. 4. Parsonnet V, Bernstein A, Lindsay B: Pacemaker-implantation complication rates: an analysis of some contributing factors. J Am Coll Cardiol 13:917-921, 1989. 5. Edelberg J, Aird W, Rosenberg R: Enhancement of murine cardiac chronotropy by the molecular transfer of the human beta-2 adrenergic receptor cDNA. J Clin Invest 101:337-343, 1998. 6. Edelberg J, Huang D, Josephson M, et al: Molecular enhancement of porcine cardiac chronotropy. Heart 86(5):559-562, 2001. 7. Perales JC, Ferkol T, Beegen H, et al: Gene transfer in vivo: sustained expression and regulation of genes introduced into the liver by receptor-targeted uptake. Proc Natl Acad Sci USA 91:40864090, 1994. 8. Muramatsu T, Arakawa S, Fukazawa K, et al: In vivo gene electroporation in skeletal muscle with special reference to the duration of gene expression. Int J Mol Med 7:37-42, 2001.

9. Ziady AG, Kim J, Colla J, et al: Defining strategies to extend duration of gene expression from targeted compacted DNA vectors. Gene Ther 11:1378-1390, 2004. 10. Miake J, Marban E, Nuss H: Biological pacemaker created by gene transfer. Nature 419:132-133, 2002. 11. Miake J, Marban E, Nuss H: Functional role of inward rectifier current in heart probed by Kir2.1 overexpression and dominantnegative suppression. J Clin Invest 111:1529-1536, 2003. 12. Qu J, Plotnikov A, Danilo PJ, et al: Expression and function of a biological pacemaker in canine heart. Circulation 107: 1106-1109, 2003. 13. Plotnikov A, Sosunov E, Qu J, et al: Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates. Circulation 109:r31-r37, 2004. 14. Cai J, Yi FF, Li YH, et al: Adenoviral gene transfer of HCN4 creates a genetic pacemaker in pigs with complete atrioventricular block. Life Sci 80:1746-1753, 2007. 15. Bucchi A, Plotnikov A, Shlapakova I, et al: Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker. Circulation 114:992-999, 2006. 16. Tse H, Xue T, Lau C, et al: Bioartificial sinus node constructed via in vivo gene transfer of an engineered pacemaker HCN channel reduces the dependence on electronic pacemaker in a sick-sinus syndrome model. Circulation 114:1000-1011, 2006.

17. Plotnikov AN, Bucchi A, Shlapakova I, et al: HCN212-channel biological pacemakers manifesting ventricular tachyarrhythmias are responsive to treatment with I(f) blockade. Heart Rhythm 5:282-288, 2008. 18. Ruhparwar A, Tebbenjohanns J, Niehaus M, et al: Transplanted fetal cardiomyocytes as cardiac pacemaker. Eur J Cardiothorac Surg 21:853-857, 2002. 19. Kehat I, Khimovich L, Caspi O, et al: Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22:1282-1289, 2004. 20. Potapova I, Plotnikov A, Lu Z, et al: Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res 94:952-959, 2004. 21. Plotnikov AN, Shlapakova I, Szabolcs MJ, et al: Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 116:706-713, 2007. 22. Cho HC, Kashiwakura Y, Marban E: Creation of a biological pacemaker by cell fusion. Circ Res 100:1112-1115, 2007. 23. Fahrenbach JP, Ai X, Banach K: Decreased intercellular coupling improves the function of cardiac pacemakers derived from mouse embryonic stem cells. J Mol Cell Cardiol 45:642-649, 2008.

8 

Pacemaker, Defibrillator, and Lead Codes and Headers ROBERT ANDREW PICKETT  |  GEORGE H. CROSSLEY III

In the continuing pursuit of therapy for the arrhythmia patient,

tremendous strides have been made in pacing and defibrillation platforms. Along with these advances, much standardization has been introduced to limit differences and disparities among device types and to allow for compatibility. In the 1960s, pacemakers served to stimulate one chamber at a fixed rate. By the 1980s, implantable cardioverter-defibrillators (ICDs) offered lifesaving therapy by way of shock only, without supportive pacing for bradycardia. However, many patients require both antibradycardia and antitachycardia therapies. Later, cardiac resynchronization therapy (CRT) for congestive heart failure was developed and has become the standard of care for these patients. With each of these advances in device therapy, the traditional means of describing device function have become inadequate, requiring new standardized terminology. Devices are used for more indications in the treatment of patients with bradyarrhythmias, tachyarrhythmias, and congestive heart failure, and more algorithms are developed either to stimulate multiple chambers (cardiac resynchronization) or to minimize unnecessary pacing when possible.1,2 It is noteworthy that, unlike some therapies, the generic pacemaker codes have withstood the test of time.

Pacemaker Codes THREE-POSITION ICHD CODE (1974) In 1974 the Inter-Society Commission for Heart Disease Resources (ICHD) proposed a three-position code to allow a uniform system to describe the functionality of a pacemaker platform.3 The goal was to create a generic code that would work among all platforms; it would also allow for concise description of what was becoming a more complex issue. The first letter of the code was to distinguish the chamber(s) being paced. The second letter was to determine the chamber(s) that were sensed for intrinsic electrical depolarizations and to start the timer for determining the next paced beat delivery. The third letter of the code was to describe how the pacing was to be affected by a sensed event (i.e., inhibiting pacing or triggering pacing in response to sensing). Position one can be the atrium (A), the ventricle (V), or both atrium and ventricle (D) for location of pacing. Position two again represents atrium (A), the ventricle (V), or both (D), meaning sensing can occur for spontaneous electrical depolarizations in either chamber. The third position describes whether sensing leads to inhibition of pacing (I), triggering the delivery of a pacing stimulus (T), or both inhibition and triggering (D). Tables 8-1 and 8-2 outline the options and different pacing configurations. The outstanding feature of this code is its utility in describing pacemaker function despite all the therapeutic advances since its introduction. Changes have been proposed, but this code endures with the addition of a letter to indicate rate-responsive pacing. FIVE-POSITION ICHD CODE (1981) In 1981, in response to changes in the technology of pacing, two more positions were added. The first three positions remained unchanged, and position four was developed to convey the ability to program the pacemaker. With advancements in pacing, it became important to determine if a pulse generator could be programmed. As the ability to

reprogram the pacing rate, pacing output, and mode were introduced into pacemakers, the fourth position could be listed as programmable (P), which generally implied one feature, or multiprogrammable (M), which implied multiple parameters, or none (O). A fifth letter was included to determine if the device had the capability of antitachycardia pacing. Interestingly, this fifth letter was used in the pacing platform and was not for ICD platforms, which were not available at the time this code was developed. A second modification of the ICHD nomenclature occurred in 1983 to distinguish, in the fourth letter, if a device had the ability to internally store data such as battery voltage, serial numbers, or electrograms. This was designated communicating (C). Table 8-3 shows the different options for all five positions, but as one would surmise, it is now assumed all devices can store information and can be programmed, thus obviating the need for that nomenclature. Currently, pacing platforms that provide antitachycardia pacing are typically identified based on the specifics of the device platform rather than an additional letter in the code (e.g., Medtronic EnRhythm pacing platform allows atrial antitachycardia pacing therapy). Using this convention, a single-chamber pacing system today would be described as VVIM to designate multiprogrammability or VVIC to designate the presence of telemetry (communication). In reality, this fourth letter is implied due to the presence of telemetry and multiprogrammability in all of our current platforms. Table 8-4 provides examples of the many different ways to describe pacemaker function that are highly descriptive of the available features on pacing systems, but not readily used in day-to-day management of pacemakers. NASPE/BPEG GENERIC (NBG) PACEMAKER CODE The Mode Code Committee of the North American Society of Pacing and Electrophysiology (NASPE), now known as the Heart Rhythm Society, in cooperation with the British Pacing and Electrophysiology Group (BPEG), developed a code in 1987 (Table 8-5).4 The one change still used today is the letter R in the fourth position to represent ratemodulated pacing to treat chronotropic incompetence. The R in the fourth position was developed in response to the many sensors available to help the pacemaker mimic sinus nodal function in response to external or internal stimuli. The other development in the nomenclature is the use of the letter S for shock delivery for tachyarrhythmias with the fifth position in the code. The NASPE/BPEG Generic (NBG) Pacemaker Code retains all the characteristics of the 1974 ICHD Code and some of those of the later five-position codes. To deal with the increasing complexity of later devices, however, it was considered necessary to clarify several features and to define more explicitly how the code was to be used. Positions I, II, and III were still used exclusively for antibradycardia pacing, but position IV had the option of describing either programmability or rate-responsive pacing. With establishment of programmability in almost all devices, position IV evolved to denote the presence or absence of rate-response pacing. Position V is for describing the ability to deliver antitachycardia therapy, as either antitachycardia pacing or a shock. As of 1987, shocks were described as either low-energy cardioversions or high-energy defibrillation. No distinction was made between low-energy and high-energy shocks in the nomenclature. The original code of 1981 allowed for different letters to describe different

195

196

TABLE

8-1 

SECTION 1  Basic Principles of Device Therapy

The 1974 Three-Position ICHD Code or Three-Letter Identification Code*

First Letter Chambers paced

Second Letter Chambers sensed

Third Letter Mode of response

*Letters used: A, atrium; D, double-chamber; I, inhibited; O, not applicable; T, triggered; V, ventricle. Adapted from Parsonnet V, Furman S, Smyth NPD: Implantable cardiac pacemakers: Status report and resource guideline. Pacemaker Study Group, Inter-Society Commission for Heart Disease Resources (ICHD). Circulation 50:A-21, 1974. Copyright 1974 American Heart Association.

forms of pacing trains used in tachycardia termination, such as burst (B), scanning (S), or external (E). The update of 1987 simplified the descriptors to pacing (P), shock (S), or pacing and shocks (D).4,5 REVISED NBG CODE In light of evolving pacemaker technology and increasing interest in multisite pacing, the 1987 NBG Code was modified by a multinational task force under the chairmanship of David Hayes, MD. Three major changes were made that simplified the code. It was assumed that all pacemakers were communicative and programmable, eliminating the need for those codes. Further, this revised code established a system to describe the function of ICDs. The structure of the revised NBG Code is summarized in Table 8-6, with examples of its use in Table 8-7.6 Note that with each modification, the first three positions continue to describe antibradycardia pacing, but in this update, no mention of antitachycardia pacing is made.7 Positions I, II, and III indicate the chambers in which pacing and sensing occur and the effect of sensing on the triggering or inhibition of subsequent pacing stimuli. In this context, “sensing” refers specifically to the detection of spontaneous cardiac depolarizations (or spurious interference signals interpreted as spontaneous cardiac depolarizations) outside the refractory periods of the pulse generator. Position IV is now used only to indicate the presence (R) or absence (O) of an adaptive-rate mechanism (rate modulation). This position is also used to denote that changes can occur in pacing parameters, such as changes in the atrioventricular (AV) delay in response to increased heart rates. Position V indicates whether multisite pacing, as described earlier, is present in none of the cardiac chambers (O); in one or both of the atria (A), with stimulation sites in each atrium or more than one stimulation site in either atrium; in one or both of the ventricles (V), with stimulation sites in both ventricles or more than one stimulation site in either ventricle; or in dual chambers (D), in one or both of the atria and in one or both of the ventricles. Resynchronization pacing is often used to treat congestive heart failure in patients with a wide QRS, but the device is rarely described using a fifth letter to denote ventricle (V) as the site of pacing in both ventricles. In reality, a biventricular pacemaker with rate-responsive pacing “on” would be categorized as DDDRV pacing in both atrium and ventricle, sensing in atrium and ventricle, inhibition or triggered activity dependent on intrinsic activation rates, with rate-responsive pacing and the presence of pacing leads in the right and left ventricle. TABLE

8-3 

TABLE

8-2 

Mode VOO AOO DOO VVI VVT AAI AAT VAT DVI

Pacing Modes Described by the Three-Position ICHD Code Description Asynchronous ventricular pacing; no sensing function Asynchronous atrial pacing; no sensing function Dual-chamber (AV-sequential) asynchronous pacing; no sensing function Ventricular pacing inhibited by ventricular sensing Ventricular pacing triggered instantaneously by ventricular sensing Atrial pacing inhibited by atrial sensing Atrial pacing triggered instantaneously by atrial sensing Ventricular pacing triggered after a delay by atrial sensing Dual-chamber (AV-sequential) pacing inhibited by ventricular sensing

Modified from Parsonnet V, Furman S, Smyth NPD: Implantable cardiac pacemakers: status report and resource guidelines. Pacemaker Study Group, Inter-Society Commission for Heart Disease Resources (ICHD). Circulation 50:A21, 1974. Copyright 1974 American Heart Association. AV, Atrioventricular.

As multisite pacing and physiologic pacing with leads in specific positions (e.g., Bachman bundle) are further investigated, use of the fifth letter may become more prevalent.8,9

Defibrillator Codes NASPE/BPEG DEFIBRILLATOR (NBD) CODE On January 23, 1993, the NASPE (now Heart Rhythm Society) Board of Trustees approved the adoption of the NASPE/BPEG Defibrillator (NBD) Code (Table 8-8).10 It was developed by the NASPE Mode Code Committee, composed of members of NASPE and BPEG, and was intended for describing cardiac-defibrillator capabilities and operation. The resultant code for ICDs is similar in form to the longestablished pacing code. Although the pacing code described antibradycardia pacing in detail and then acknowledged the presence of antitachycardia therapy, the ICD code describes the antitachycardia therapy in detail and then acknowledges the presence of antibradycardia pacing. No indication is made to distinguish between low-energy cardioversion and high-energy defibrillation. Position (potential) I denotes the chamber where the shock is delivered; position II indicates antitachycardia pacing function; position III reports how the tachycardia is detected, i.e. based on electrograms or hemodynamic changes, and position IV reports the presence of antibradycardia pacing. In current practice, given the lack of a selective atrial defibrillator, the first letter will always be V for ventricle as the location of the shock and the third letter will always be E for electrogram because all ICDs are using electrograms for determination of arrhythmia. The second position will be rarely used because antitachycardia pacing is so widely prevalent on ICDs, and with so many combinations of therapies, a single letter cannot reliably describe them. Given the state of current practice, an ICD is still described most often using the same four letters (including rate-responsive pacing) as in the pacing realm.

The 1981 Five-Position ICHD Code

Position I (Chambers Paced)

Position II (Chambers Sensed)

Position III (Modes of Response)

V = ventricle A = atrium D = double

V = ventricle A = atrium D = double O = none

S = single chamber†

S = single chamber†

T = triggered I = inhibited D = double* O = none R = reverse Comma optional here†

Position IV (Programmable Functions) P = programmable (rate and/or output) N = normal-rate competition M = multiprogrammable C = communicating O = none

Modified from Parsonnet V, Furman S, Smyth NPD. Revised code for pacemaker identification. PACE 4:400, 1981. *Triggered and inhibited response. †Manufacturer’s designation only.

Position V (Special Antitachyarrhythmia Functions) B = bursts S = scanning E = external



8  Pacemaker, Defibrillator, and Lead Codes and Headers

TABLE

8-4 

Pacing Modes Described by the Five-Position ICHD Code

Mode VDD,M (VDDM)

DDD,M (DDDM)

VVI,MB (VVIMB)

AAR,ON (AARON) AOO,OE (AOOOE)

Description Ventricular antibradycardia pacing inhibited by ventricular sensing, triggered after delay by atrial sensing; multiprogrammable device; no antitachyarrhythmia (antitachycardia) function. Dual-chamber (AV-sequential) antibradycardia pacing inhibited by sensing in either chamber, with ventricular pacing triggered after delay by sensing in atrium after ventricular event; multiprogrammable device; no antitachycardia function. Ventricular antibradycardia pacing inhibited by ventricular sensing; multiprogrammable device; pacing bursts for ventricular tachycardia, means of activation unspecified. No antibradycardia function; nonprogrammable device; normal-rate competition for termination of atrial tachycardia, activated by atrial sensing. Asynchronous atrial antibradycardia pacing; nonprogrammable device; externally activated atrial antitachycardia pacing, nature unspecified.

Modified from Parsonnet V, Furman S, Smyth NPD: Revised code for pacemaker identification. PACE 4:400, 1981. AV, Atrioventricular.

NBD CODE, SHORT FORM As an additional means of concisely distinguishing among devices limited to cardioversion or defibrillation and those that incorporate antitachycardia and antibradycardia pacing, a short-form code was defined (Table 8-9). It is intended for use only in conversation and again rarely used given the widespread prevalence of both antitachycardia pacing and shocking across platforms and manufacturers.

Lead Code NASPE/BPEG PACEMAKER-LEAD (NBL) CODE In 1996 the NASPE Board of Trustees voted to adopt a generic code for pacemaker leads, to be known as the NASPE/BPEG PacemakerLead (NBL) Code. The code was approved subsequently by BPEG, and its definition and usage conventions were published as a NASPE Policy TABLE

8-5 

197

Statement. The NBL Code is a four-position generic code intended for use in conversation, record keeping, writing, and labeling. All four positions (potentials), as defined in Table 8-10, are used in every circumstance, unlike the NBG Code, for which only three or four of the five positions are often used. Table 8-11 provides examples of the use of the simple NBL Code.11 The NBL Code is designed so that it cannot be confused with the NBG or NBD Codes. As with those earlier codes, the characteristics were chosen in terms of clinical priority to describe characteristics with significant influence on the behavior of the device under consideration. For this reason, the NBL Code does not address such features as connector design and electrode location. Moreover, until there was emergence of clearer patterns in the electrode configurations used for cardioversion and defibrillation, with or without the pulse generator housing serving as part of the electrode system, it was believed that attempts to design a practical code encompassing leads used for cardioversion and defibrillation as well as pacing would be premature.12

Headers In the early history of pacing systems, differences among lead sizes, pacing configurations and polarity, and manufacturer variability led to a wide variety of pacemaker/ICD headers (connections of the lead[s] to the generator). With the proliferation of international standards (IS-1) technology, many of the connection issues of the past have disappeared. IS-1 lead technology and defibrillation connections (DF-1) header standards have resolved many of the differences in compatibility between manufacturers and platforms. Physicians now have a wider array of generators and systems from which to choose depending on patient need. The new international standard connections for leads and defibrillation leads (IS-4 and DF-4) will likely replace the bulkier IS-1/DF-1 technology (Figs. 8-1 and 8-2). This will further streamline connections and decrease the complexity and frequency of connections that could be a failure point in the system function. This should reduce the size of the junction for connecting the lead(s) to the generators, commonly referred to as headers (Figs. 8-3 and 8-4). With IS-4/DF-4 technology, rather than making three separate connections between ICD pace/sense, right ventricular (RV) defibrillation coil, and superior vena cava (SVC) coil with the

The NASPE/BPEG Generic (NBG) Pacemaker Code*

Position I (Chambers Paced)

Position II (Chambers Sensed)

Position III (Response to Sensing)

Position IV (Programmability, Rate Modulation)

Position V (Antitachyarrhythmia Functions)

O = none A = atrium V = ventricle D = dual (A + V)

O = none A = atrium V = ventricle D = dual (A + V)

O = none T = triggered I = inhibited D = dual (T + I)

O = none P = simple programmable M = multiprogrammable C = communicating R = rate modulation

O = none P = pacing (antitachyarrhythmia)

S = single (A or V)†

S = single (A or V)†

S = shock D = dual (P + S)

Modified from Bernstein AD, Camm AJ, Fletcher RD, et al: The NASPE/BPEG Generic Pacemaker Code for antibradyarrhythmia and adaptive-rate pacing and antitachyarrhythmia devices. PACE 10:794, 1987. *Positions I to III are used exclusively for antibradyarrhythmia (antibradycardia) function. †Manufacturer’s designation only

TABLE

8-6 

Revised NASPE/BPEG Generic Code for Antibradycardia Pacing

Position I (Chambers Paced)

Position II (Chambers Sensed)

Position III (Response to Sensing)

Position IV (Rate Modulation)

Position V (Multisite Pacing)

O = none A = atrium V = ventricle D = dual (A + V) S = single (A or V)*

O = none A = atrium V = ventricle D = dual (A + V) S = single (A or V)*

O = none T = triggered I = inhibited D = dual (T + I)

O = none R = rate modulation

O = none A = atrium V = ventricle D = dual (A + V)

Modified from Bernstein AD, Daubert JC, Fletcher RD, et al. The Revised NASPE/BPEG Generic Code for antibradycardia, adaptive-rate, and multisite pacing. PACE 25:260-264, 2000. *Manufacturer’s designation only.

198

TABLE

8-7 

SECTION 1  Basic Principles of Device Therapy

TABLE

Examples of Revised NBG Code

Code VOO, VOOO, or VOOOO VVIRV

AAI, AAIO, or AAIOO AAT, AATO, or AATOO

AATOA

DDD, DDDO, or DDDOO

DDI, DDIO, or DDIOO DDDR or DDDRO DDDRA DDDOV DDDRD

8-9 

Meaning Asynchronous ventricular pacing; no sensing, rate modulation, or multisite pacing. Ventricular inhibitory pacing with rate modulation and multisite ventricular pacing (i.e., biventricular pacing or more than one pacing site in one ventricle). This mode is often used in patients with heart failure, chronic atrial fibrillation, and intraventricular conduction delay; assessed by atrial fibrillation group in MUSTIC study.* Atrial pacing inhibited by sensed spontaneous atrial depolarizations; no rate modulation or multisite pacing. Atrial pacing with atrial outputs elicited without delay on atrial sensing during alert period outside pulse generator’s refractory period (used primarily as diagnostic mode to determine exactly when atrial depolarizations are sensed); no rate modulation or multisite pacing. Atrial pacing with atrial outputs elicited without delay on atrial sensing during alert period outside pulse generator’s refractory period, without rate modulation but with multisite atrial pacing (i.e., biatrial pacing or more than one pacing site in one atrium).† Dual-chamber pacing (normally inhibited by atrial or ventricular sensing during alert portion of VA interval or by ventricular sensing during alert portion of AV interval, and with ventricular pacing triggered after programmed PV interval by atrial sensing during alert portion of VA interval); no rate modulation or multisite pacing. Dual-chamber pacing without atrium-synchronous ventricular pacing (atrial sensing merely cancels pending atrial output without affecting escape timing); no rate modulation or multisite pacing. Dual-chamber, adaptive-rate pacing; no multisite pacing. Dual-chamber, adaptive-rate pacing with multisite atrial pacing (i.e., biatrial pacing or more than one pacing site in one atrium); assessed in multicenter DAPPAF study.‡ Dual-chamber pacing without rate modulation but with multisite pacing (i.e., biventricular pacing or more than one pacing site in one ventricle).§ Dual-chamber pacing with rate modulation and multisite pacing both in the atrium (i.e., biatrial pacing or pacing in more than one site in one atrium) and in the ventricle (i.e., biventricular pacing or pacing in more than one site in one ventricle).

Modified from Bernstein AD, Daubert J-C, Fletcher RD, et al. The Revised NASPE/ BPEG Generic Code for antibradycardia, adaptive-rate, and multisite pacing. PACE 25:260264, 2000. *Leclerq C, Walker S, Linde C, et al. Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J 23:1780-1787, 2002. †Revault d’Allonnes G, Pavin D, Leclerq C, et al. Long-term effects of biatrial synchronous pacing to prevent drug-refractory atrial tachyarrhythmias: a nine-year experience. J Cardiovasc Electrophysiol 11:1081-1091, 2000. ‡Fitts SM, Hill MR, Meral R, et al. Design and implementation of the Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) clinical trial. J Interv Card Electrophysiol 2:139-144, 1998. §Cazeau S, Leclerq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873880, 2001. MUSTIC, Multisite Stimulation in Cardiomyopathy.

TABLE

8-8 

The NASPE/BPEG Defibrillator Code, Short Form

Code ICD-S ICD-B ICD-T

Meaning ICD with shock capability only ICD with bradycardia pacing as well as shock ICD with tachycardia (and bradycardia) pacing as well as shock

Modified from Bernstein AD, Camm AJ, Fisher JD, et al. The NASPE/BPEG Defibrillator Code. PACE 16:1776, 1993. ICD, Implantable cardioverter-defibrillator.

TABLE

8-10 

The NASPE/BPEG Pacemaker-Lead (NBL) Code

Potential I (Electrode Configuration)

Potential II (Fixation Mechanism)

Potential III (Insulation Material)

Potential IV (Drug Elution)

U = unipolar B = bipolar M = multipolar

A = active P = passive O = none

P = polyurethane S = silicone rubber D = dual (P + S)

S = steroid N = nonsteroid O = none

Modified from Bernstein AD, Parsonnet V. The NASPE/BPEG Pacemaker-Lead Code. PACE 19:1535, 1996.

TABLE

8-11  Code UPSO BAPS

Examples of the NBL Code Meaning Unipolar passive-fixation lead with silicone-rubber insulation but without elution of an anti-inflammatory agent Bipolar active-fixation lead with polyurethane insulation and steroid elution

Modified from Bernstein AD, Parsonnet V. The NASPE/BPEG Pacemaker-Lead Code. PACE 19:1535, 1996.

header, an IS-4 lead will have one connection with a DF-4 header, minimizing the risk of poor contact between header set screw and lead pin.

Conclusion The practice of electrophysiology has benefited greatly from the standardization of lead-header connections and the use of standard tools of communication regarding the configuration of pacemakers, ICDs, and defibrillators.

The NASPE/BPEG Defibrillator (NBD) Code

Potential I (Shock Chamber)

Potential II (AntitachycardiaPacing Chamber)

Potential III (Tachycardia Detection)

Potential IV (AntibradycardiaPacing Chamber)

O = none A = atrium

O = none A = atrium V = ventricle D = dual (A + V)

E = electrogram H = hemodynamic V = ventricle D = dual (A + V)

O = none A = atrium V = ventricle D = dual (A + V)

Modified from Bernstein AD, Camm AJ, Fisher JD, et al. The NASPE/BPEG Defibrillator Code. PACE 16:1776, 1993.

Figure 8-1  Standard dual-coil DF4 ICD lead. (Courtesy Medtronic, Minneapolis.)



8  Pacemaker, Defibrillator, and Lead Codes and Headers

199

Figure 8-2  Standard dual-coil DF1/IS1 ICD lead. (Courtesy Medtronic, Minneapolis.)

Figure 8-3  Standard IS-1/DF-1 dual-coil ICD header. (Courtesy Medtronic, Minneapolis.)

Figure 8-4  DF-4 dual-coil ICD header. (Courtesy Medtronic, Minneapolis.)

REFERENCES 1. Bristow MR, Saxon LA, Boehmer J, et al: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350(21):2140-2150, 2004. 2. Mirowski M: The automatic implantable cardioverterdefibrillator: an overview. J Am Coll Cardiol 6:461-466, 1985. 3. Parsonnet V, Furman S, Smyth NPD: Implantable cardiac pacemakers: status report and resource guidelines. Pacemaker Study Group, Inter-Society Commission for Heart Disease Resources (ICHD). Circulation 50:A21, 1974. 4. Bernstein AD, Camm AJ, Fletcher RD, et al: The NASPE/BPEG Generic Pacemaker Code for antibradyarrhythmia and adaptiverate pacing and antitachyarrhythmia devices. Pacing Clin Electrophysiol 10(4 Pt 1):794-799, 1987. 5. Bernstein AD, Brownlee RR, Fletcher RD, et al: Report of the NASPE Mode Code Committee. PACE 7:395, 1984.

6. Bernstein AD, Daubert JC, Fletcher RD, et al: The Revised NASPE/ BPEG Generic Code for antibradycardia, adaptive-rate, and multisite pacing. PACE 25:260-264, 2000. 7. Bernstein AD, Camm AJ, Furman S, Parsonnet V: The NASPE/ BPEG codes: use misuse, and evolution. PACE 24:787-788, 2001. 8. Epstein AE, Dimarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: executive summary. Heart Rhythm 5(6):934-955, 2008. 9. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and

Antiarrhythmia Devices), with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51:e1-e62, 2008. 10. Bernstein AD, Camm AJ, Fisher JD, et al: The NASPE/BPEG Defibrillator Code. PACE 16:1776, 1993. 11. Bernstein AD, Parsonnet V: The NASPE/BPEG Pacemaker-Lead Code. PACE 19:1535, 1996. 12. Gregoratos G, Cheitlin MD, Conill A, et al: ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). J Am Coll Cardiol 31:1175-1209, 1998.

9 

Basic Physiology and Hemodynamics of Cardiac Pacing FRITS W. PRINZEN  |  MARC STRIK  |  FRANÇOIS REGOLI  |  ANGELO AURICCHIO

C

ardiac pacing has significantly improved the survival and quality of life in patients with bradycardia. When first introduced, pacemakers were simply lifesaving devices that provided a fixed pacing rate during bradycardia. With advances in technology and understanding of cardiac physiology during artificial pacing, devices have been developed that mimic the normal cardiac automaticity and atrioventricular (AV) activation sequence. Accordingly, pacemakers are capable of raising the pacing rate with exercise without the need to rely on sinus activity, so-called rate-adaptive pacing. Moreover, a novel target of pacing was introduced to improve electromechanical synchrony rather than cardiac rhythm: cardiac resynchronization therapy (CRT). The use of CRT to treat patients with heart failure has given new impetus to evaluation of the hemodynamic effect of spontaneously occurring or pacing-induced ventricular conduction delay, as well as abnormal AV timing. In addition, inappropriate right ventricular pacing not only may have deleterious effects on ventricular mechanics, but ultimately may increase morbidity and mortality. It is now clear that a truly physiologic pacemaker maintains the normal sequence and timing of atrial and ventricular activation over a wide range of heart rates, varies the heart rate in response to metabolic demands, and preserves the normal, rapid, synchronous sequence of ventricular activation when required.

Physiology of Electrical and Mechanical Activation ELECTRICAL ACTIVATION DURING SINUS RHYTHM The cardiac action potential originates from the sinus node, located high in the right atrium (Fig. 9-1). Its cells depolarize spontaneously and initiate the spontaneous depolarization of action potentials at a regular rate from the sinus node. This rate depends on various conditions, such as atrial stretch and sympathetic activation, but is usually between 60 and 100 beats per minute (bpm) at rest. Myocytes are electrically coupled to each other through gap junctions. These structures consist of connexin molecules and allow direct intercellular communication.1 Gap junctions do not have a preferential direction of conduction, but because the action potential starts in the sinus node, it spreads from there through the atria. Evidence suggests specialized conduction pathways in the atrium, but their (patho) physiologic relevance is still disputed. In the human heart, spreading of the action potential through the atria takes approximately 100 msec, after which the impulse reaches the AV node (see Fig. 9-1). In the normal heart the AV node is the only electrical connection between the atria and ventricles, because a fibrous ring (anulus fibrosus) is present between the remaining parts of the atria and ventricles. The AV nodal tissue conducts the electrical impulses very slowly; indeed, it takes approximately 80 msec for these impulses to travel from the atrial side to the ventricular side of the AV node. This delay between atrial activation and ventricular activation has functional importance because it allows optimal ventricular filling. Its slow conduction renders the AV node sensitive to impaired conduction and even complete conduction block, an important indication for ventricular pacing. As with other locations in the heart, conduction in

the AV node has no preferential direction. Consequently, impulses can also be conducted retrogradely through the AV node, a condition that can occur when the ventricles are electrically stimulated. From the AV node, the electrical impulse reaches the His bundle, the first part of the specialized conduction system of the ventricles called the Purkinje system. Within this system the electrical impulse is conducted approximately four times faster (3-4 m/sec) than in the working myocardium (0.3-1 m/sec). This difference results because Purkinje cells are longer and have a higher content of gap junctions.1-5 The intraventricular conduction system can be regarded as a trifascicular conduction system consisting of the right bundle branch (RBB) and two divisions of the left bundle branch (LBB). The RBB proceeds subendocardially along the right side of the interventricular septum until it terminates in the Purkinje plexuses of the right ventricle; the LBB also has a short subendocardial route. It seems that the bifascicular vision of structure of the LBB is oversimplified.6 The general picture that now emerges is that the left ventricular Purkinje network is composed of three main, widely interconnected parts, depending on the anterior subdivision, the posterior subdivision, and a centroseptal subdivision of the left main bundle. This third medial or centroseptal division supplies the midseptal area of the left ventricle and arises from the LBB, from its anterior or posterior subdivision, or both. The fascicles continue in a network of subendocardially located Purkinje fibers. In the left ventricle, Purkinje fibers form a network in the lower third of the septum and free wall, which also covers the papillary muscles.4,7 In humans the bundles are present only underneath the endocardium, whereas other species (e.g., ox, sheep, goat) have networks of Purkinje fibers across the entire ventricular wall.8,9 It is important to note that the His bundle as well as the right and left bundle branches and their major tributaries are electrically isolated from the adjacent myocardium. The only sites where the Purkinje system and the normal working myocardium are electrically coupled are the Purkinje-myocardial junctions. The exits of the Purkinje system are located in the subendocardium of the anterolateral wall of the right ventricular (RV) and the inferolateral left ventricular (LV) wall4,10 (see Fig. 9-1). This area of exit corresponds with the area of the ventricular muscle that is activated earliest.2-5,11,12 The distribution of the Purkinjemyocardial junctions is spatially inhomogeneous, and the junctions themselves have varying degrees of electrical coupling.13 Endocardial activation of the right ventricle starts near the insertion of the anterior papillary muscle 10 msec after onset of LV activation11 (Fig. 9-2). After activation of the more apical regions, the activation of the ventricular working myocardium occurs predominantly from apex to base, both in the septum and in the LV and RV free wall. Further depolarization occurs centrifugally from endocardium to epicardium as well as tangentially.11,12 The earliest epicardial breakthrough occurs in the pretrabecular area in the right ventricle, from which there is an overall radial spread toward the apex and base. The last part of the right ventricle that becomes activated is the AV sulcus and pulmonary conus. Overall, the posterobasal area of the left ventricle (or an area more lateral) is the last part of the heart to be depolarized (see Fig. 9-2). The time between arrival of the impulse in the His bundle and the first ventricular muscle activation is approximately 20 msec,4 whereas

203

204

SECTION 2  Clinical Concepts

AV node His bundle (4)

Sinus node 1

3

2

8

9 Purkinjemyocardial junctions (7)

Bundle branch (5)

Purkinje fibers (6) Figure 9-1  Conduction of the impulse in the heart. The impulse originates in the sinus node (1), continues in the atrial wall (2), and is delayed in the atrioventricular (AV) node (3). Conduction within the ventricles is initially rapid within the rapid conduction system: His bundle (4), right and left bundle branches (5), and Purkinje fibers (6). The impulse is transferred from the rapid conduction system to the working myocardium in the Purkinje-myocardial junctions (7), which are located in the endocardium. Within the slowly conducting working myocardium, the impulse is conducted from endocardium to epicardium.

5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100

Figure 9-2  Three-dimensional isochronic representation of the electrical activation in an isolated human heart. Shaded scale indicates activation time in milliseconds. (Modified from Durrer D, van Dam RT, Freud GE, et al: Total excitation of the isolated human heart. Circulation 41:899-912, 1970.)

(Ca2+-induced Ca2+ release). These processes increase intracellular Ca2+ from approximately 10−7 M to 2 × 10−6 M. This high calcium concentration catalyzes the interaction between myosin and actin filaments, leading to contraction. After repolarization, relaxation occurs as Ca2+ dissociates from the contractile apparatus and is taken up again by the sarcoplasmic reticulum through the action of sarcoplasmic reticular Ca2+–adenosine triphosphatase (SERCA). Intracellular Ca2+ homeostasis is also maintained through action of the sodium-calcium (Na+/ Ca2+) exchanger (NCX). Normally, this exchanger removes Ca2+ from the cell (forward mode). Figure 9-3 also shows that the intracellular Ca2+ concentration rises rapidly after the upstroke of the action potential, but that there is some delay between the Ca2+ increase and the development of force. This delay is the main determinant of the delay between electrical and mechanical activation. The electromechanical delay, that is, the delay between the depolarization and the onset of force development, amounts to approximately 30 msec.15,16 On a global basis, this delay can be observed as the delay between the R wave of the electrocardiogram (ECG) and the rise in LV pressure (Fig. 9-4). Electromechanical coupling in failing hearts is

total ventricular activation lasts 60 to 80 msec, corresponding to a QRS duration of 70 to 80 msec.11 These numbers illustrate the important role of the Purkinje fiber system in the synchronization of myocardial activity. This role results from the system’s unique propagation properties and its geometrically widespread distribution. During normal orthodromic excitation, fast propagation over long fibers, together with wide distribution of Purkinje-myocardial junctions, induces a high degree of coordination between distant regions of the myocardium. MECHANICAL ACTIVATION DURING SINUS RHYTHM As in many other muscle cells, electrical activation leads to contraction in cardiac myocytes, a process referred to as excitation-contraction (E-C) coupling. In cardiac E-C coupling, the calcium ion (Ca2+) plays a central role14 (Fig. 9-3). The contraction-relaxation cycle starts when depolarization leads to entry of Ca2+ into the cell through voltagedependent L-type Ca2+ channels. This Ca2+ entry triggers a much larger amount of Ca2+ to be released from the sarcoplasmic reticulum K

Ca2

Na NCX Ca2

Na a

Na

1 2

Ca2 b c

A

NCX f

Sarcoplasmic reticulum

Ca2

0

Ca2

d

Ca2

e

3 4

SERCA

Action potential Ca2 transient

B

200 ms

Force

Figure 9-3  Excitation-contraction (E-C) coupling in myocardium. A, Schematic representation of the major pathways involved in calcium ion (Ca2+) homeostasis in the cardiomyocyte. a, Ca2+entry via L-type Ca2+ channel; b, Ca2+-induced Ca2+ release from the sarcoplasmic reticulum; c, Ca2+induced contraction; d, dissociation of Ca2+ from the contractile apparatus; e, reuptake of Ca2+ via sarcoplasmic reticular Ca2+–adenosine triphosphatase (SERCA); f, Ca2+ efflux via the Na+/Ca2+ exchanger (NCX). B, Schematic tracing of a Ca2+ transient, an action potential, and contractile force. The numbers indicate the different phases of the action potential: 0, upstroke; 1, fast early depolarization; 2, plateau phase; 3, repolarization phase; 4, resting membrane potential.

9  Basic Physiology and Hemodynamics of Cardiac Pacing

Electrical events



R

R T

P Q

S Ventricular systole

P Q Ventricular diastole

S

AV closure AV opening

Pressure

Aortic pressure

Left ventricular pressure

MV closure

MV opening

Ventricular volume

Left atrial pressure

IC Ejection Systole

IR RVF Diastasis AC Diastole

Figure 9-4  Events of the cardiac cycle. Left atrial, aortic, and left ventricular pressures are correlated with electrical events and left ventricular volume. AC, Atrial contraction; AV, aortic valve; IC, isovolumic contraction; IR, isovolumic relaxation; MV, mitral valve; RVF, rapid ventricular filling. See text for description.

different from that in normal hearts. A prominent feature of heart failure is that the relation between SERCA and the NCX changes. Often, SERCA is downregulated17 and NCX upregulated in the heart failure state.18 On the one hand, the reduced SERCA activity leads to less Ca2+ loading of the sarcoplasmic reticulum, resulting in less Ca2+ release during the subsequent activation, and thus a weaker contraction (systolic dysfunction). On the other hand, during diastole, Ca2+ removal from the cytosol is slower and incomplete, leading to a slower relaxation and greater diastolic stiffness (diastolic dysfunction). The upregulation of the NCX and the elevated intracellular Na+ concentrations in failing myocardium19 may compensate for the SERCA downregulation.20,21 The high Na+ concentration facilitates the NCX to work in the “reverse mode,” that is, to remove intracellular Na+ and exchange it for extracellular Ca2+. This additional Ca2+ enhances systolic function at least to some extent. Because the SERCA pump is much faster in pumping calcium than the NCX, insufficiency in contraction and relaxation in failing hearts is most pronounced at higher heart rates. These changes result in decreasing contractile force with increasing heart rate, a negative force-frequency relation.17 The changes in the failing myocardium lead to the altered expression of other proteins involved in E-C coupling, as well as shifts in isoforms of various contractile proteins.22 Because of the tight coupling between excitation and contraction, atrial activation is followed by atrial contraction, and ventricular activation by ventricular contraction. Consequently, atrial contraction precedes ventricular contraction, as illustrated in Figure 9-4. Because of this timing, the atrial contraction adds about 20% to the volume of the ventricles. This “atrial kick” increases the length of ventricular muscle cells and their sarcomeres. The sarcomere length is an

205

important determinant of myocardial contractile force. Over the entire physiologic range of sarcomere lengths (1.6-2.4 µm), the longer the sarcomeres, the greater is the contractile force. This effect, known as the Frank-Starling relation (Starling curve; Starling law of the heart), is only partly related to the overlap of actin and myosin, as generally mentioned in textbooks. More important to the Frank-Starling relation is the growing affinity of troponin C for calcium at increasing sarcomere length,23 although the cause of this greater sensitivity is not completely understood. Ventricular contraction starts after ventricular depolarization. After a short isovolumic contraction phase, the aortic valve opens, starting the ejection phase. The velocity of emptying of the ventricle is highest in the first half of the ejection phase because of a higher pressure gradient between the left ventricle and the aorta. In the second half of the ejection phase, LV pressure actually falls below aortic pressure, but the aortic valve stays open because of the inertia of the flowing blood. With increasingly negative LV-aortic pressure gradients, the aortic valve closes and the isovolumic relaxation phase starts, ending with the opening of the mitral valve. Because of the filling of the atrium during ventricular systole, atrial pressure is relatively high. This event, in combination with the rapid fall in LV pressure, causes a positive AV pressure gradient during the early filling phase. Thus, rapid acceleration of blood occurs, contributing to most of the LV filling in the early diastolic phase. This event is also reflected by the large Ei wave on mitral valve Doppler recordings in healthy hearts (Fig. 9-5). Atrial contraction, after the P wave on the ECG, produces a surge of blood into the ventricle at the end of diastole, causing the final and optimal filling of the ventricle. Reversal of the pressure gradient across the mitral valve, caused by atrial relaxation and ventricular contraction, pulls the valve cusps in apposition, facilitating closure of the valve. Therefore, coupling and proper timing of atrial and ventricular contractions are important determinants of ventricular pump function. The loss of atrial systole diminishes effective LV stroke volume by 25% at low heart rates and by almost 50% at higher heart rates. How different modes of pacing influence the atrial contribution to pump function and how this contribution affects pump function in different categories of patients are discussed later. Although both Frank-Starling and force-frequency relations are properties of the myocardium itself, which can regulate cardiac function to an important extent, extrinsic factors also modulate cardiac performance. Many of these factors are related to the autonomic nervous and hormonal systems. The afferent parts of these systems can be divided into low-pressure and high-pressure domains. Low-pressure

1 m/s -

.5 m/s Ei

Ai ¹⁄³ DFT

DFT

Time (ms) Figure 9-5  Pulsed Doppler recording of transmitral flow, illustrating the technique used to measure various segments of the timed velocity integral and diastolic filling period (ms, milliseconds; m/s, meters per second). The relationship between early diastolic filling and filling associated with atrial systole can be quantitated. Possible measurements include early and atrial velocities, the ratio of early to atrial velocities, the early (Ei) and atrial (Ai) flow-velocity integral (area under flow-velocity curve), the ratio of early to atrial flow-velocity integrals, and the amount of diastolic filling occurring in the first third of diastole ( 1 3 DFT [diastolic filling time]). (From Pearson AC, Janosik DL, Redd RM, et al: Doppler echocardiographic assessment of the effect of varying atrioventricular delay and pacemaker mode on left ventricular filling. Am Heart J 115:611, 1988.)

206

SECTION 2  Clinical Concepts

sensors are present in the atria and pulmonary circulation. Stimulation, from increased pressures and stretch, leads to parasympathetic stimulation and sympathetic withdrawal. Moreover, atrial stretch induces release of atrial natriuretic factor (ANF). This 28–amino acid polypeptide is a potent arterial and venous vasodilator that increases urine production. The low-pressure sensors monitor the filling status of the circulation. However, erroneous readings may occur during inadequate AV synchronization, leading to elevated atrial pressures (cannon A waves). Stimulation of the reflexes and ANF production are involved in the so-called pacemaker syndrome (see later). The high-pressure sensors consist predominantly of the baroreceptors in the arterial system. These sensors feed back to the brainstem through afferent neurons in the vagal and glossopharyngeal nerves. Stimulation of these receptors through a decrease in blood pressure induces sympathetic stimulation and parasympathetic withdrawal. Although reduced parasympathetic activation is the most important factor leading to the increase in heart rate during hypotension, the greater sympathetic stimulation induces arterial and venous vasoconstriction and increases myocardial contractility. Other pressure sensors are found in the juxtaglomerular apparatus in the kidneys. Their stimulation leads to greater production of renin, angiotensin, and aldosterone, resulting in vasoconstriction as well as water and salt retention. These systems are effective in maintaining equilibrium in blood pressure and cardiac output during short-term variations. However, sustained neurohumoral stimulation is an important factor in the long-term development of hypertrophy and the rise in filling pressure. ABNORMAL ACTIVATION SEQUENCE DURING LEFT BUNDLE BRANCH BLOCK AND RIGHT VENTRICULAR PACING The normal, physiologic, and almost synchronous sequence of electrical activation is lost in diseases affecting the ventricular conduction system, such as block of the left or right bundle branch24 and the presence of an accessory pathway bypassing the AV node, as in the WolffParkinson-White syndrome.25 Additionally, ectopic impulse generation, occurring during ventricular pacing and extrasystoles,26,27 leads to abnormal impulse conduction. Under all these circumstances, the impulse is conducted primarily through the slowly conducting working myocardium rather than rapidly through the specialized conduction system. As a consequence, under conditions of abnormal activation, the time required for activation of the entire ventricular muscle, expressed as QRS duration, is at least twice as long as that during normal sinus rhythm. The extent of asynchrony (dyssynchrony) and the sequence of activation during abnormal conduction are determined by at least four myocardial properties, as follows: 1. Conduction through the myocardium is up to four times slower than conduction through the Purkinje system.4 2. Conduction is approximately two times faster along the muscle fibers than perpendicular to them.28 Therefore, in a particular layer, the wavefront around a pacing site has an elliptical shape, especially in the epicardial and midmyocardial layers.29 3. Impulses originating from the working myocardium rarely reenter into parts of the rapid conduction system. Early researchers had believed that such reentry was ubiquitous and that the amount of reentry was the main determinant of the total asynchrony of ventricular activation.30 However, later studies indicated that, although parts of the intact rapid conduction system are often present, ectopically generated impulses appear to couple poorly to the rapidly conducting specialized conduction system.12 Myerburg et al.4 elegantly showed that impulses coming from the normal myocardium can enter the Purkinje system only at the apical part of this system (presumably the Purkinje-myocardial junctions; see Fig. 9-1). This finding implies that the impulse often has traveled already for some time before reaching Purkinje-myocardial junctions. Also, to reach remote zones, the impulse must travel retrogradely through one

branch of the system all the way to the proximal part and then descend to another part. Therefore, in most cases, the sequence of activation during ventricular pacing is governed by slow conduction through the normal myocardium, away from the pacing site.16,26,27,31 4. Most endocardial fibers, even though not part of the Purkinje system, conduct impulses faster than the fibers in the rest of the LV wall.32 Moreover, the endocardial circumference is smaller than its epicardial counterpart. Therefore, total time required for electrical activation is shorter for LV endocardial pacing than for LV epicardial pacing.29,33 Detailed studies on the three-dimensional spread of activation during ventricular pacing in canine hearts have been conducted since the 1960s.12,26 The sequence of electrical activation in LBB block (LBBB) is similar to that during RV apex pacing. This sequence can be derived from the QRS configuration of the surface ECG27,34,35 and from endocardial activation maps in experimental LBBB and RV pacing.36 The similarity has lead to the use of AV sequential RV apex pacing as a model for “experimental LBBB.”34,37,38 Until recently, information on impulse conduction in patients with LBBB was limited to the data reported by Vassallo et al.24,27 These investigators mapped LV endocardial activation during RV apex pacing and in LBBB at a limited number of endocardial sites, showing that activation starts at the RV endocardium in both conditions. The first noticeable activation at the LV endocardium after right-to-left conduction of the impulse occurs at a single breakthrough site, which in almost all patients is the LV breakthrough time, 50 to 70 msec after the earliest RV activation. The impulse is conducted from the septum toward the distal free wall in a gradual manner, the site of latest activation generally being the inferoposterior wall.11 More recently, this finding has been confirmed using high-resolution mapping system39-42 (Fig. 9-6). These studies also showed that activation patterns differ among patients largely because of differences in the origin of LBBB: either a proximal conduction block43,44 or a uniform but slow conduction through the LBB.45 In approximately one third of patients with heart failure and typical LBBB QRS morphology, transseptal activation time (i.e., time between earliest RV and LV septal breakthrough point) is bimodally distributed and has a large range in both groups of patients, with transseptal conduction time of 40 msec or less and longer than 40 msec.46 This indicates great heterogeneity in the RV-to-LV activation time. Furthermore, in patients with LBBB, the total LV endocardial activation time ranges from 60 to 160 msec. Etiology does not seem to have a major impact on the total endocardial activation time. Of note, the sum of transseptal and total endocardial activation times does not account for the maximum QRS duration, which is 20 to 60 msec longer, probably because of LV endocardial-toepicardial conduction time (Fig. 9-7). These data also show that QRS duration provides a reasonable although imperfect estimate of total electrical asynchrony. Patients with LBBB show a peculiar spread of ventricular activation.40,42 Indeed, in two thirds of patients with LBBB, a functional line of block is present, resulting in a U-shaped electrical activation wavefront. The presence and location of the line of block have been also recently observed in canine model of LBBB using the same noncontact mapping system.46a The activation front propagates first around the inferior wall and then spreads onto the lateral and basal walls. The location and length of the line of block vary greatly and are related to the site and time of LV breakthrough. In patients with significant prolongation of the QRS duration (>150 msec), the line of block is consistently located in an anterior position. In contrast, in patients with QRS duration of 120 to 150 msec, the line of block is usually shorter and is located anteriorly, laterally, or posteriorly40 (Movie 9-1). ABNORMAL CONTRACTION PATTERNS DURING LEFT BUNDLE BRANCH BLOCK AND RIGHT VENTRICULAR PACING Given the tight relationship between excitation and contraction in the myocardium, it is not surprising that asynchronous electrical



9  Basic Physiology and Hemodynamics of Cardiac Pacing

207

Noncontact mapping

Contact mapping

Figure 9-6  Contact and noncontact mapping in patient with left bundle branch block and heart failure. The unipolar isopotential activation sequence (upper panel) shows a U-shaped activation front that rotated around the apex and activated the lateral wall late, whereas the bipolar propagation map (lower panel) shows a longer activation time in the anterior region. ANT, Anterior; LAT, lateral. (Modified from Auricchio A, Fantoni C, Regoli F, et al: Characterization of left ventricular activation in patients with heart failure and left bundle-branch block. Circulation 109:1133-1139, 2004.)

activation also leads to asynchronous contraction. Regions where the impulse arrives first also start to contract first.47 During LBBB or ventricular pacing, local contraction patterns differ not only in the onset of contraction, but also, and more importantly, in the pattern of contraction. These contraction patterns imply that opposing regions of the ventricular wall are out of phase and that energy generated by one region is dissipated in opposite regions. In patients with LBBB or RV pacing, the early-contracting region is most often the septum. The earliest-contracting fibers can shorten rapidly by up to 10% just during the isovolumic contraction phase, because the remaining muscle fibers are still in a relaxed state (Movie 9-2). This rapid, early shortening is followed by an additional but modest systolic shortening, eventually followed by systolic stretch (from delayed mechanical contraction of other regions, in lateral wall), and premature relaxation (Fig. 9-8). In late-activated regions, in contrast, the fibers are stretched in the early systolic phase (up to 15%) from contraction of the early-activated region. Doubling of net systolic shortening and delayed relaxation occur in late-activated regions.31,48 The discoordination between earlyand late-activated regions leads to lower output and reduced efficiency of the heart as a pump. The regional differences in contraction pattern most likely results from the local differences in myocardial fiber length during the early systolic phase. This is supported by studies using two isolated papillary muscles in series in which asynchronous stimulation caused a downward shift in the force-velocity relation in the earlier-activated muscle and an upward shift in the later-activated one.49 Furthermore, during ventricular pacing, regional systolic fiber shortening increases with greater isovolumic stretch.50 Similarly, a close correlation exists between the time of local electrical activation and the extent of systolic fiber shortening.51 Therefore, the regional differences in contraction pattern during ventricular pacing are most likely caused by regional differences in effective preload and local differences in the contraction force triggered by the Frank-Starling relation. On M-mode echocardiography, abnormal contraction patterns during RV pacing and LBBB appear as paradoxical septal motion.52

However, this motion is not actually paradoxical, because it is really the net result of different forces. The motion is caused by the asynchrony between RV and LV, which produces dynamic alterations in transseptal pressure differences,52,53 and by presystolic shortening of septal muscle fibers.54 Abnormal septal motion results in a diminished contribution of the interventricular septum to LV ejection. This has been measured in experimental LBBB using MRI tagging54 and in patients with LBBB QRS morphology using speckle tracking.55,56 The septal regions, even in absence of detectable scar, showed the lowest amount of systolic strain within LV; in contrast, the lateral wall shows the highest regional strain.55 This finding demonstrates that LBBB determines a unique and unequal LV strain distribution that may be corrected by CRT.55-57 Effect of Left Bundle Branch Block and Right Ventricular Pacing on Local Energetic Efficiency The local differences in wall motion and deformation mentioned previously reflect regional differences in myocardial work.48,58 This relationship was demonstrated by construction of local fiber stress–fiber strain diagrams and calculation of local external and total mechanical work. In regions close to the pacing site (or septum in patients with LBBB), shortening occurs at low pressure, whereas these areas are transiently being stretched at higher ventricular pressures. As a consequence, the stress-strain loops have a figure-8-like shape with a low net area, indicating the absence of external work. In regions remote from the pacing site (or lateral wall in patients with LBBB), the loops are wide, and external work can be up to twice that during synchronous ventricular activation (Fig. 9-9). Total myocardial work (sum of external work and potential energy) in LBBB and with RV pacing is reduced by 50% in early-activated regions and is increased by 50% in lateactivated regions in comparison with atrial pacing.48,54,59 Several studies reported that ventricular pacing and LBBB are associated with regional differences in myocardial blood flow,31,35,38,54,58-60 glucose uptake,38,61 and oxygen consumption.58,62 During RV apex pacing and LBBB, low values are found in the septum, the

208

SECTION 2  Clinical Concepts

300

250

Time (msec)

200

150

100

50

0 Transseptal time

A

Total endocardial activation time (by Carto mapping)

Time to end of QRS complex (QRS max)

89 msec Y+

Mitral value –58 msec

His

Total ventricular activation: 101 msec LV transseptal time: 58 msec LV RV

B

Isochronal step: 10 msec

Apex 1.48 cm

Figure 9-7  A, Distribution of transseptal time, total endocardial activation time, and total QRS duration in 140 heart failure patients with a QRS duration of 120 msec or longer. Patients are ordered according to and transseptal time. B, Three-dimensional electroanatomic mapping of the right ventricle (RV) and left ventricle (LV). A color-coded activation sequence indicated the earliest (red) and the latest (blue) endocardial activation region. The earliest activated region is the anterolateral region of the RV, and the latest part is the posterobasal region of the LV.

early-activated part of the left ventricle. Compared with sinus rhythm, myocardial blood flow and oxygen consumption are 30% lower in early-activated regions and 30% higher in late-activated regions.31,58,59 Controversy surrounds the cause of the reduced septal blood flow and glucose uptake in LBBB and RV apex pacing. Various observations, such as close correlations among local myocardial oxygen consumption, work, and blood flow, suggest that the lower blood flow is a physiologic adaptation to the lower demand. However, at higher heart rates, the asynchronous contraction pattern may also impede myocardial perfusion.38,63 In patients with RV pacemakers, false-positive findings of perfusion defects may result from this redistribution.64

The nonuniform contraction patterns translate into a lower efficiency of conversion of metabolic energy into mechanical pump function. This was observed in isolated, isovolumically beating hearts,65 as well as in anesthetized open-chest,66,67 closed-chest,59 and conscious dogs.68 Mills et al.59 also showed that efficiency remained low after 4 months of RV pacing. In all these preparations, RV apex pacing reduced mechanical output, whereas myocardial oxygen consumption was unchanged or even increased compared with atrial pacing; thus efficiency decreased by 20% to 30% in these studies. The opposite change was found when ventricular activation in patients with preexisting dyssynchrony caused by LBBB-like activation was improved by biventricular (BiV) or LV pacing alone. In these patients, BiV pacing



9  Basic Physiology and Hemodynamics of Cardiac Pacing Midseptum

Anterior

Midlateral

Normal

RV apex pacing mJ/g 8

LV free wall pacing

*

0 Fiber stress Fiber length Apex 0

200

Time (msec)

Figure 9-8  Contraction patterns in 24 regions of the anterior septum and anterior left ventricular (LV) free wall during pacing at the LV lateral wall. Each graph in the array represents circumferential strain versus time in a specific region. The left ventricle is displayed as if cut down the septum and folding the surface out onto the page. For the sake of clarity, the posterior half of the left ventricle is not shown, but the distribution of strains in this part of the LV wall is a mirror image of that in the anterior wall. Rows represent different levels from base (top) to apex (bottom) of the left ventricle, and columns are circumferential positions from midseptum (far left) via the LV anterior wall to the LV lateral wall (far right). Tics at the vertical axis denote a strain of 0.1 (≈10% shortening); tics on the horizontal axis denote 100 msec. Note the early shortening near the pacing site (*) and the prestretch in regions remote from the pacing site. (Modified from Prinzen FW, Peschar M: Relation between the pacing induced sequence of activation and left ventricular pump function in animals. Pacing Clin Electrophysiol 25:484-498, 2002.)

Fiber length

and Tau, are strongly influenced by pacing.78-80 Parameters of auxotonic relaxation (rate of segment lengthening or LV volume increase) are also lower during ventricular pacing than during sinus rhythm, but the difference is less pronounced than for the isovolumic relaxation parameters.73,78 As a consequence of the slower contraction and relaxation, isovolumic contraction and relaxation phases last longer, thus leaving less time 3

Cardiac output: liters/minute

Both RV pacing and LBBB reduce systolic and diastolic function. These effects are independent of changes in preload and afterload. This conclusion is based on results from studies using preparations in which preload and afterload were controlled,65 as well as those in which preload- and afterload-independent indices of ventricular function were determined68,70-72 (Figs. 9-10 and 9-11). The negative mechanical effect of dyssynchronous activation has been observed under various loading conditions73 and during exercise.74 Ventricular pacing also causes a deterioration in pump function in patients with coronary artery disease,75 as well as those with already-impaired LV function76 (Fig. 9-12). Impaired regional and global cardiac pump function has been observed in patients and animals with LBBB, even if LBBB was not accompanied by other cardiovascular diseases.53,54 Therefore, it appears that under all circumstances, dyssynchrony is an important, independent determinant of cardiac pump function. Although LV dP/dtmax is a preload-dependent parameter, it is also sensitive to changes in ventricular activation sequence, as shown both in animal models and in humans34,76-78 (see Fig. 9-12). Thus, LV dP/ dtmax appears to be an appropriate marker of dyssynchrony-induced changes in LV global contractile function and its correction by any pacing technique. Additionally, the rate of ventricular relaxation is slower during ventricular pacing, with more pronounced detrimental effect on relaxation, in patients with impaired ventricular function76 (see Fig. 9-12). Isovolumic relaxation parameters, such as LV dP/dtmin

Fiber length

Figure 9-9  Upper panels, Maps of local external work during normal (right atrial), left ventricular (LV) free wall, and right ventricular (RV) apex pacing in a dog heart. External work values are presented in color II scale; for values, see scale bar; asterisk denotes pacing site. The LV wall is represented as a circle with the base located at the outer contour and the apex in the middle. Lower panels, Fiber length–fiber stress diagrams from three regions are displayed, indicating the shape of the diagram in normally activated (left), early-activated (middle), and late-activated (right) regions. (Modified from Prinzen FW, Hunter WC, Wyman BT, et al: Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol 33:1735-1742, 1999.)

improved the maximal rate of rise of LV pressure (LV dP/dtmax) without increasing myocardial oxygen consumption, indicating improved efficiency.69 Efficient conversion of metabolic energy to pumping energy is of particular interest in patients with compromised coronary circulation, because higher oxygen consumption over longer periods (as in β-agonist therapy) leads to higher mortality. Effect of Asynchronous Activation on Systolic and Diastolic Pump Function

Fiber stress

0 0.2

Fiber stress

Circumferential strain

S

Base

209

2

1

0

0

5

10

15

20

25

30

LAmean cm H2O Atrial pace

Ventricular pace

Figure 9-10  Relationship between cardiac output and mean left atrial pressure (LAmean) during atrial pacing (open circles) compared with ventricular pacing (solid circles) in an intact dog model. For any given mean LA pressure, the cardiac output is higher with atrial pacing than with ventricular pacing. (From Mitchell JH, Gilmore JP, Sarnoff SJ: The transport function of the atrium: factors influencing the relation between mean left atrial pressure and left ventricular end diastolic pressure. Am J Cardiol 9:237, 1962.)

210

SECTION 2  Clinical Concepts

40

SR

Pace

20

0

30

40

50

60

70

80

90

LV volume (mL) Figure 9-11  Pressure-volume (P-V) diagrams during sinus rhythm (SR) (purple lines) and left ventricular (LV) pacing (Pace) (blue lines) before and during caval vein occlusion. The end-systolic P-V relation (straight lines) shifts rightward during ventricular pacing. These data indicate that the left ventricle operates at a larger volume under all loading conditions, and that at a given LV volume, LV pressure development and stroke volume are reduced. (Modified from Van Oosterhout MFM, Prinzen FW, Arts T, et al: Asynchronous electrical activation induces inhomogeneous hypertrophy of the left ventricular wall. Circulation 98:588-595, 1998.)

for ventricular filling and ejection.53,65,81 Therefore, it is not surprising that cardiac output and systolic arterial and LV pressures are also affected by a dyssynchronous activation. In general, stroke volume is affected more than systolic LV pressure,72,77 presumably because baroreflex regulatory mechanisms partly compensate the decrease in blood pressure. This idea is supported by the finding of higher catecholamine levels82 and greater systemic vascular resistance74 during ventricular pacing. With regard to the changes in stroke volume, it is important to note that ventricular pacing, especially RV apex pacing, can induce mitral regurgitation, as has been demonstrated in animals83,84 and patients.85,86 In addition to reduced stroke volume at unchanged preload, ejection fraction is usually found to be depressed during ventricular pacing74,87 as well as in LBBB.88 Similarly, ventricular pacing can increase pulmonary wedge pressure.74 The negative inotropic effect of ventricular pacing under various loading conditions is clearly illustrated by a rightward shift of the LV function curve, that is, the relationship between cardiac output and mean atrial pressure71 (see Fig. 9-10). Later studies showed a rightward shift of the end-systolic pressure-volume (P-V) relation (see Fig. 9-11), thus suggesting that for each end-systolic pressure, the LV must operate at a larger LV volume.70,72,89 Cause of Reduced Pump Function An obvious cause of reduced pump function during abnormal electrical activation is the asynchronous contraction of the different parts of the ventricular muscle. Using a mathematical simulation, Suga et al.90 divided the LV wall into two elements with similar contractile properties. Contractility of the whole left ventricle decreased considerably when the asynchrony exceeded 100 msec. This concept is supported by experimental observations in dogs with LBBB. In studies using combinations of pacing sites, minimal intra-LV asynchrony, assessed by endocardial electrical activation mapping, consistently led to the highest LV dP/dtmax.36 In addition to intraventricular asynchrony, interventricular asynchrony may affect ventricular pump function. An extensive overview of studies on RV and LV pacing showed that RV pacing consistently reduces LV function more than LV pacing.91 Even at similar levels of intraventricular asynchrony, LV dP/dtmax is lower during RV pacing than during LV pacing.36 This suggests important roles for interventricular asynchrony and associated interventricular

Electrical and Structural Remodeling Asynchronous electrical activation not only has acute mechanical consequences, but also influences cardiac structure and function over time. A particular adaptation of the heart to ventricular pacing occurs when the abnormal activation created by pacing is stopped but repolarization remains abnormal, a phenomenon called cardiac memory.98 Several investigators found evidence that, as in the nervous system, short-term cardiac memory (<1 hour) involves changes in ion channels and phosphorylation of target proteins,99 and that long-term cardiac memory (≈3 weeks of pacing) involves altered gene programming and protein expression.98,100 Interestingly, in humans, cardiac memory appears to reach a steady state within 1 week,101 which appears to be quicker than in dogs.98 Costard-Jäckle and Franz102 have demonstrated opposite changes in repolarization in regions remote from and close to a pacing site starting within 1 hour of ventricular pacing. The repolarization abnormalities related to cardiac memory also have a mechanical counterpart. During sinus rhythm immediately after a period of ventricular pacing, relaxation is disturbed.103 Moreover, systolic function deteriorates between 2 hours and 1 week after ventricular pacing has been stopped (Fig. 9-13). After ventricular pacing is stopped for 1 week, it takes 1 1 2 days for ejection fraction to 2000 *p  .0005 1500

*

*

*

*

1000 500 0

90 80 70 60 50 40 30 20 10 0

T (msec)

60

dP/dt dP/dt (mm Hg/sec)

LV pressure (mm Hg)

80

mechanical interaction. This ventricular interaction is also expressed by abnormal septal motion in asynchronous ventricles.52 Also, the pathway of activation may be a determinant of ventricular function. The sequence of activation from apex to base appears to be important. As already mentioned, the ventricular myocardium is activated from apex to base during normal sinus rhythm. Among all LV pacing sites, the LV apex appears to keep LV pump function closest to that seen during atrial pacing.26,59,92-94 The observation that the addition of pacing sites during LV apex pacing does not improve and sometimes even reduces LV function emphasizes the importance of a ventricular activation directed from apex to base.94 An additional cause of the reduction in pump function during asynchronous activation is mitral valve insufficiency.83,85 This diminishes LV pump function directly by reducing the volume ejected into the aorta and indirectly by reducing LV cavity volume. The immediate cause of mitral valve regurgitation during RV apex pacing is papillary muscle desynchronization.95 In addition, papillary muscle tethering forces may be increased,96 and the transmitral pressure gradient may be decreased.97

Normal Impaired Normal Impaired Normal Impaired LV LV LV LV LV LV dP/dt Atrial pacing

dP/dt

Isovolumic relaxation time (T)

AV sequential pacing

Figure 9-12  Hemodynamic effects of atrial and atrioventricular (AV) sequential pacing in patients with normal and impaired left ventricular systolic function. Note that +dP/dt (maximal rate of rise in LV pressure) is significantly lower in both groups of patients with AV sequential pacing than in patients with atrial pacing. However, only in patients with impaired LV systolic function −dP/dt (maximal rate of decline in LV pressure) is significantly lower, and the isovolumic relaxation time significantly longer, during AV sequential pacing than during atrial pacing. (Modified from Bedotto JB, Grayburn PA, Black WH, et al: Alterations in left ventricular relaxation during atrioventricular pacing in humans. J Am Coll Cardiol 15:658, 1990.)



9  Basic Physiology and Hemodynamics of Cardiac Pacing

Ejection fraction (%)

75 70 65 60 55 50 45 40 1 wk atrial pacing

1 wk ventricular pacing 50

100

150

Atrial pacing 200

250

Time (hours)

Figure 9-13  Left ventricular (LV) ejection fraction before pacing, during short-term and midterm (1 week) ventricular pacing, and during the first days after restoration of normal sinus rhythm. During the entire experimental period, the heart rate was kept at 80 bpm with the use of fixed-rate pacing at the right atrium and, during the week of ventricular pacing, dual-chamber pacing with an AV interval of 100 msec. (Data derived from Nahlawi M, Waligora M, Spies SM, et al: Left ventricular function during and after right ventricular pacing. J Am Coll Cardiol 44:1883-1888, 2004.)

return to its prepacing value.104 It seems likely that changes in the function of an ion channel, such as the L-type calcium channel,99 underlie the reduction in ejection fraction during the first week of ventricular pacing. Therefore, electrical and contractile remodeling appears to occur soon after the onset of asynchronous activation. In addition to the long-term effect on cardiac memory, longerlasting (>1 month) ventricular pacing and LBBB lead to major structural changes, such as ventricular dilatation and asymmetrical hypertrophy.54,70,105 The ventricular dilatation appears related to the LV operating at a larger volume. Global hypertrophy may be induced by this global dilatation, as well as by the greater sympathetic stimulation82 (Fig. 9-14). The asymmetry of hypertrophy appears to be more prominent during LV pacing than during RV pacing and LBBB.54,70,106 However, regardless of pacing site and underlying conduction disturbance, the asymmetry of hypertrophy is characterized by a more pronounced growth of the late-activated myocardium, that is, the same region that shows enhanced contractile performance because of early systolic prestretch. It has been observed in juvenile canine hearts that ventricular pacing leads to fiber disarray,107 which may also be the result of the regionally different and abnormal distribution of mechanical work.31,48,58,59,108 In ventricles undergoing long-term pacing,70 myocyte diameter is increased in late-activated regions, but the number of capillaries per myocyte is unchanged (van Oosterhout and Prinzen, unpublished data). Therefore, the diffusion distance for oxygen increases, potentially leading to compromised oxygenation, which is known to render hypertrophic myocardium susceptible to ischemia. Resynchronization has been shown to result in improved coronary reserve, suggesting that the structural remodeling at the microvascular level may also be reversible.109 An alternative explanation is that CRT could be simply decreasing the oxygen demand in the late-activated regions. In conditions such as infarction and hypertension, ventricular remodeling appears, at least initially, to be meant to compensate for the loss of function and the increased load, respectively. However, dilatation and hypertrophy do not reduce the asynchronous activation induced by pacing or LBBB; if any, they increase it.54,70 The reasons are the longer path length of impulse conduction (dilatation) and the larger muscle mass to be activated (hypertrophy). Moreover, chronic asynchronous activation also reduces expression of gap-junction channels110 and induces lateralization of these channels.111 Akar et al.112 have related the reduced expression in nonfailing and failing asynchronous hearts to slower impulse conduction, especially in the late-activated regions. Moreover, they showed that action potential duration increases

211

in the late-activated myocardium. These molecular changes may render the myocardium not only more asynchronous, but also more susceptible to arrhythmias. Even more complicated molecular changes occur in animal models with combined asynchronous activation and heart failure, such as that caused by rapid ventricular pacing. Under these conditions, betaadrenergic receptors are downregulated,113 as are many ion channels, such as most potassium and calcium channels, whereas other channels display a regional difference in expression, such as the L-type calcium channel.114 Moreover, in both patients with LBBB115 and animal models of dyssynchrony,113 several proteins related to or facilitating the apoptotic process show unique regional distribution, further confirming the hypothesis that abnormal electrical activitation sequence may contribute to remodeling in heart failure patients. All these processes may lead to a vicious circle in which dilatation and hypertrophy further reduce LV pump function, either directly or by increasing asynchrony of activation (see Fig. 9-14). As is the case after myocardial infarction, initial compensatory hypertrophy may result in heart failure many years later. Clinical evidence for such an important role of asynchronous activation in the development of heart failure is discussed later.

Physiologic Effects of Heart Rate and Atrioventricular Synchrony CORRECTION OF BRADYCARDIA BY PACING Cardiac pacing is the only effective treatment for symptomatic bradycardia. Permanent pacemakers have been implanted since the early 1960s to prevent death or syncope caused by ventricular asystole. Although asystole is clearly to be prevented, bradycardia does not always immediately lead to pump failure. This fact can be derived from studies on young patients with congenital AV block. As a compensation for the bradycardia, these patients have enlarged hearts and an increased ejection fraction.116,117 In a 10-year follow-up study, 9 of 149 patients demonstrated dilated cardiomyopathy.117 At the onset of acquired complete heart block, cardiac output is smaller than with normal heart rate.118 As a result, compensatory increases in sympathetic tone and end-diastolic ventricular volume occur, leading to higher atrial rates, enhanced ventricular contractility, and augmented stroke volume. Over the short term, the canine heart adapts to bradycardia by increasing diastolic volume and neurohumoral activation, which results in BiV hypertrophy118-120 (Table 9-1). Asynchronous electrical activation Dyscoordinate contraction Reduced pump function Longer Increased conduction Rightward shift Neurowall stress path length P-V relation humoral Molecular/ activation cellular Ventricular dilatation Regional changes mechanical differences Hypertrophy Asymmetrical hypertrophy Reduced efficiency

Reduced coronary reserve

Susceptibility ischemia

Figure 9-14  Possible relationships among the various consequences of asynchronous activation of the ventricles, resulting from ventricular pacing or conduction disturbances, and the deterioration of pump function over time. P-V, Pressure-volume. For details, see text.

212

SECTION 2  Clinical Concepts

9

Hemodynamic Effects of Ventricular Pacing in Complete Heart Block (CHB)

9-1 

Hemodynamic Parameter Ventricular rate Cardiac index Stroke volume Sympathetic tone Ventricular contractility Systemic vascular resistance Atrial rate

CHB with Slow Ventricular Response

8

Ventricular Pacing in CHB

↓ ↓ ↑ ↑ ↑ ↑ ↑

↑ ↑ ↓ ↓ ↓ ↓ ↓

Relative change (%)

LV cavity volume

50 25 QTc-time

0

2

4

6

8

10

12

14

5 4 3 1

75

0

6

2

Although these adaptations initially manage to return cardiac output to the level before the onset of AV block, this compensatory effect usually fades after 2 months of heart block. After 4 months, contractility is back to baseline, but LV cavity volume and corrected QT interval (QTc) continue to increase118 (Fig. 9-15); the latter increase is associated with an enhanced susceptibility to arrhythmias.119 If complete AV block persists for more than 4 months, congestive heart failure (CHF) ensues.120 Development of CHF may originate from the ventricular dilatation and hypertrophy initiated early after the start of heart block. The importance of the duration of overload is confirmed by the observation that the frequency of CHF symptoms in patients with complete heart block correlates with the duration of heart block. CHF has been described during chronic complete heart block even in patients with normal ventricular function. Brockman and Stoney121 reported that in two thirds of their patients with complete heart block and CHF, symptoms were relieved by ventricular pacing alone, and no additional medical therapy was required. Breur et al.122 showed that, in patients with congenital heart block, implantation of a pacemaker resulted in less LV dilatation than in the untreated control group, in which the LV cavity gradually dilated. Similarly, in dogs with AV block, LV dilatation gradually progresses over time (see Fig. 9-15), whereas ventricular pacing readily reverses the LV dilatation and hypertrophy caused by AV block.93 However, longer-lasting ventricular pacing in hearts with AV block may lead to LV dilatation and hypertrophy secondary to the effect of asynchronous activation. Two studies on young adults who received pacing for approximately 10 years showed a high preponderance of CHF and LV dilatation.123,124 These data strongly suggest that in the patient with AV block, the short-term and long-term effects of RV pacing are different. Therefore, the decision whether or not to start pacemaker treatment using RV pacing or the choice of the pacing site should be made carefully (see later).

LV contractility

7 No. of patients

TABLE

16

Time (weeks) Figure 9-15  Effect of atrioventricular (AV) block on left ventricular (LV) cavity volume (structural remodeling), LV contractility (contractile remodeling), and corrected QT interval (QTc-time) (electrical remodeling) in canine hearts, relative to their values before onset of AV block. Note the gradual and continuing increase in LV cavity volume over time, the early-onset and maintained electrical remodeling, and the biphasic contractile remodeling. (Modified from Peschar M, Vernooy K, Cornelussen RN, et al: Structural, electrical and mechanical remodeling of the canine heart in AV-block and LBBB. Eur Heart J 25 Suppl D:6165, 2004.)

0 51–55 56–60 61–65 66–70 71–75 76–80 81–85 86–90 Optimal ventricular rates at rest Figure 9-16  Histogram of optimal ventricular pacing rates at rest as defined by cardiac outputs determined by dye dilution in patients with complete heart block. (From Sowton E. Hemodynamic studies in patients with artificial pacemakers. Br Heart J 26:737, 1964.)

Early studies suggested that the maximal increase in cardiac output during ventricular pacing at rest occurs at rates between 70 and 90 bpm125-127 (Fig. 9-16). Further rises in rates result in either no additional increase or a decrease in cardiac output accompanied by greater peripheral vascular resistance. In contrast, there is growing evidence that lower heart rates may be particularly beneficial. Indeed, in animal models it appears that bradycardia promotes angiogenesis.128,129 Moreover, Lei et al.130 demonstrated that reducing normal heart rates by 20% to 30% through the continuous infusion of alinidine in a post– myocardial infarction (post-MI) rat model increased basic fibroblast growth factor, its receptor, and expression of related proteins. Bradycardia in this model also increased capillary length density in the border zone of the infarct by 40% and in the remote zone by 14%. Bradycardia also increased arteriolar density in the septum by 62%. These changes translated to a 23% greater coronary reserve, a smaller increase in post-MI left LV volume, and a greater preservation of ejection fraction in the bradycardic animals. Although the relationship between optimal resting ventricular pacing rate and ventricular dysfunction has not been systematically evaluated, it is likely that different resting ventricular rates are required in patients with systolic and diastolic dysfunction. For example, Ishibashi et al.131 reported that in elderly hypertrophic patients, even 25% increases in heart rate, as induced by atrial pacing, significantly reduced cardiac mechanical efficiency. The investigators went as far as to suggest that coronary perfusion itself in elderly hypertensive hypertrophic patients is negatively affected by an increase in heart rate (Fig. 9-17). They recommended that in the treatment of elderly hypertensive patients, the control of the heart rate in addition to the control of blood pressure might be helpful in minimizing the occurrence of myocardial ischemia and might slow down the subsequent progression to heart failure. Since then, their recommended treatment has become common practice with the use of β-blocker therapy to prevent MI and heart failure. In addition to maintaining resting heart rate in the physiologic range, pacemaker therapy preferably allows the heart rate to rise during exercise. A rise in heart rate with greater workload improves exercise capacity. Over the years a number of sensors have been incorporated into VVIR pacemakers. Many investigators have compared the exercise hemodynamics between sensor-driven VVIR pacing and VVI pacing. The percentage improvements of heart rate and exercise duration during symptoms-limited exercise in the VVIR and VVI pacing modes from a number of larger series for currently available rate-adaptive systems showed variable but consistent increases of 69% in rate and 32% in exercise tolerance when patients received VVIR pacing. Notably, most of the early comparative series of patients given VVI and VVIR pacing are rather small and have mixed patient populations in terms of symptoms of heart failure and degree of ventricular dysfunction.



9  Basic Physiology and Hemodynamics of Cardiac Pacing

External mechanical efficiency (%)

50

40

30

20

10

(r  0.56, p  0.02) 0 40

60

80

100

120

Beats/min Figure 9-17  The relationship between heart rate and external mechanical efficiency of the heart (measured as left ventricular work divided by myocardial oxygen consumption expressed as energy using a conversion factor of 2.06), for basal condition (closed circles) and different atrial pacing rates (open circles, 25% above basal heart rate; triangles, 50% above basal heart rate) in elderly hypertensive patients.

The use of an atrial sensing electrode to synchronize ventricular stimulation with intrinsic sinus node discharge (atrial synchronous ventricular pacing–VAT) allowed the implementation of a more physiologic form of pacing. The addition of ventricular sensing capability to this pacing mode resulted in the development of the VDD mode as a combination of VAT plus VVI. Both VVI and VDD modes of pacing prevent syncope due to bradycardia, but conventional VVI units are unable to respond to exertion by raising the pacing rate to meet the demand for a greater cardiac output. The importance of increasing heart rate to augment cardiac output with exercise has been clearly documented in several studies.132-134 Because the improvement in exercise performance is caused predominantly by an increase in heart rate, it is expected that favorable hemodynamic results will be obtained by rate-adaptive systems. Consequently, the modern approach to the management of complete symptomatic heart block involves the use of pacemaker units that provide not only basic ventricular pacing support, but also adaptation of the pacing rate to physiologic needs. A major concern, especially in compromised hearts, is that heart rate should not increase too much, because shortened diastolic filling time, reduced LV compliance at higher rates of ventricular pacing, and increased systemic vascular resistance may limit cardiac output.116,126 Rowe et al.135 found other reasons not to increase pacing rate too greatly. They examined cardiac output and coronary blood flow at low (47 bpm), intermediate (77 bpm), and high (117 bpm) ventricular pacing rates in patients with complete heart block. Cardiac output rose with an increase from low to intermediate pacing but diminished at the high rate. However, coronary blood flow and cardiac oxygen consumption rose progressively with increasing heart rates, thus indicating lower pumping efficiency at the high rate. OPTIMAL ATRIOVENTRICULAR INTERVAL Importance of Atrioventricular Synchronization Basically, the role of the atrial contraction is to help maintain a laminar flow of blood from the venous system to the ventricles; this role is

213

tightly integrated with the movement of the ventricles to create a smooth motion of blood across the system. To perform its role, the atrium changes its function from that of a conduit during early filling to that of a booster pump during atrial systole, to that of a reservoir during ventricular systole. These changes are closely related to longitudinal displacement of the anulus of the mitral and tricuspid valves along the long axis of the heart. Indeed, the anulus is displaced toward the apex of the ventricles during systole and toward the atria during diastole, thus significantly contributing to the smooth movement of blood from the atria to the ventricles. This displacement keeps the overall volume of the heart almost constant during systole and diastole.136 An optimally timed atrial contraction (before isovolumic contraction phase) maximizes LV filling and thereby its output by virtue of the Frank-Starling relation. Too early atrial contraction (as in long PQ times and dual-chamber pacing with long AV intervals) causes a loss of the booster pump function of the atrium. Moreover, early atrial contraction may initiate early mitral valve closure, thereby limiting ventricular diastolic filling time. This observation can be explained by the importance of three factors collaborating to achieve optimal closure of the AV valves. First, the ending of transvalvular flow at the end of the atrial contraction makes the valvular leaflets approach one another. Second, at the beginning of ventricular contraction, the anulus of the AV valves contracts, as do the papillary muscles that hold the leaflets. Simultaneously, at the start of ventricular contraction, ventricular pressure rises above atrial pressure, and the valves close. When these factors are misaligned, an opportunity for diastolic and systolic mitral regurgitation is created. In the early years of pacing, the electrical stimulus was selectively applied to the ventricle (ventricular single-chamber pacing, or V pacing). With V pacing, the contraction of atria and ventricles is uncoupled, leading to an atrial contribution to LV filling that varies from beat to beat. This also results in large beat-to-beat variations in stroke volume, systolic pressure, and other hemodynamic variables.137 The introduction of sequential AV pacing resulted in more regular heart beats and improved hemodynamics in both animals78,138,139 and patients.140 With advances in pacemaker technology, appreciation of the importance of maintaining AV synchrony has improved, and programming of optimal AV intervals in patients with dual-chamber pacemakers is of great importance.141 Figure 9-18 summarizes the main consequences of an optimal AV timing. Because filling time is limited, especially at high heart rates, the atrial contribution to stroke volume is more prominent at high than at low heart rates.142 Patients with Normal Left Ventricular Function The AV interval that maximizes resting cardiac output during dualchamber pacing varies widely among patients, usually reported as 125 to 200 msec. In patients with pacemakers, cardiac output increased by 4% to 20% when the AV interval was lengthened from 0 to between 100 and 130 msec.140,143-145 Optimal AV interval can be determined in most patients during dual-chamber pacing by means of various invasive and noninvasive measurements. Most often, optimal AV interval is assessed by LV outflow recording with Doppler echocardiography (Fig. 9-19). Doppler-derived cardiac outputs at varying AV intervals can be used to fine-tune the AV interval. In patients with preserved ventricular function, this method is highly reliable, is sensitive to small output changes, and has a low interobserver variability. The optimal AV interval determined with Doppler echocardiography correlates well with the optimal AV interval determined with radionuclide ventriculography. Factors that may influence the optimal AV interval in different patients are summarized in Table 9-2. In addition to interpatient variability, other factors may influence determination of optimal AV interval in the same patient, such as heart rate, paced or sensed atrial event, posture, and drugs.146-150 Moreover, in a specific patient’s lifetime, there may be situations in which the optimal AV interval is different from the AV interval considered to be physiologic. For example, AV

214

SECTION 2  Clinical Concepts

Acute and chronic effects of an optimal atrioventricular delay

• Maintains a laminar flow • Optimizes pumping action • Helps close auriculoventricular valves • Preempts diastolic regurgitation

• Minimizes atrial pressures • Maximizes efficiency of the pump • Optimizes filling time • Minimizes mean ventricular pressure required for optimum preload Chronic effects

Acute effects

• Minimizes ventricular diastolic pressures • Minimizes use of neurohormonal compensatory mechanisms • Minimizes ventricular preloads • Minimizes risk of compensatory remodeling • May decrease risk of stroke

• Increases preload and ventricular diastolic pressures • Increases stroke volume and cardiac output • Increases venous return • Prevents circulatory reflexes • Increases ventricular contractility through Starling effect

Figure 9-18  Hemodynamic effects of programming optimal atrioventricular (AV) delay.

sequential pacing for complete heart block complicating an acute MI or after cardiac surgery yields optimal hemodynamics at AV intervals in the range of 80 to 120 msec. This may be related to a surge of intrinsic catecholamine levels or to administered inotropic drugs and reduced LV compliance in these acutely stressful situations. The programmed AV interval regulates the timing of right atrial (RA) and RV conduction, which in a normal heart without significant atrial electrical disease usually coincides with that of left atrial (LA) and LV conduction. From a hemodynamic point of view, LA and LV conduction is most important, followed by the left-sided AV interval. The physiologic left-sided AV interval depends on several parameters, including the programmed AV interval, latency in atrial capture and sensing, interatrial conduction time, latency in ventricular capture, and interventricular conduction time.151 Because of the complex AVDI  50 ms FVI  14.9 cm

AVDI  175 ms FVI  19.0 cm

AVDI  300 ms FVI  15.3 cm

relationship among these intervals (see Fig. 9-19), significantly different right-sided and left-sided AV intervals in the same patient and in different patients can be recorded. Among these times, the one that most influences the optimal left-sided AV interval is the interatrial conduction time, measured as the time from the atrial pacing spike to the atrial depolarization on the esophageal electrogram or to the A wave on Doppler echocardiography. Patients with near-normal interatrial conduction time (≤90 msec) derive the greatest hemodynamic benefit from programmable AV intervals of about 150 msec; in contrast, in those patients presenting with prolonged interatrial conduction time, the AV interval should be set at 200 msec or longer to maximize cardiac output. Of particular note, programming a short AV interval in patients with prolonged interatrial conduction delay may result in depolarization of the LA after LV mechanical activation. This may produce hemodynamic values equivalent to or worse than those seen in patients with VVI pacing alone. Pacemaker syndrome may also occur under these circumstances. Latency in atrial capture and sensing may lead to different optimal AV intervals for sensed P waves and paced P waves (Fig. 9-20). The magnitude of atrial capture and sensing latencies varies among patients and may be affected by the lead and pacemaker circuitry characteristics, electrode position, tissue interface, amplitude and rate of stimulation, P-wave morphology, myocardial disease, electrolytes and other metabolic factors, and drugs. The optimal AV interval for a sensed P wave is about 30 to 40 msec shorter than the optimal AV interval for TABLE

9-2 

Possible Factors Influencing Optimal Atrioventricular Intervals

Type Interpatient

Figure 9-19  Left ventricular outflow recording at atrioventricular delay interval (AVDI; also AV interval) of 50, 175, and 300 msec during AV sequential pacing at identical heart rates in the same patient. The largest flow velocity integral (FVI) reflecting ventricular stroke volume occurs at AVDI 175 msec. Significant decreases are noted in stroke volume at AVDIs 50 and 300 msec. (From Janosik DL, Pearson AC, Buckingham TA, et al: The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing. J Am Coll Cardiol 14:499, 1989. Reprinted with permission of the American College of Cardiology.)

Intrapatient

Variables Atrial capture latency Atrial sensing latency Intra-atrial conduction delay Ventricular capture latency Intraventricular conduction delay Underlying myocardial disease Heart rate Catecholamine levels Heart rate Paced or sensed atrial event Catecholamine levels Drugs



9  Basic Physiology and Hemodynamics of Cardiac Pacing Paced P wave AVDI

Programmed AVDI  200 ms Effective PQ 1 60 ms

PQ

Sensed P wave-fixed AV delay AVDI

Programmed AVDI  200 ms Effective PQ  240 ms

PQ

Figure 9-20  Programmed atrioventricular delay interval (AVDI) and effect of PQ interval. Top, When a paced P wave occurs, the effective PQ interval is shorter than the programmed AV delay because of latency in atrial capture. Bottom, When a sensed P wave occurs, the effective PQ interval is longer than the programmed AVDI because of latency in atrial sensing. (From Janosik DL, Pearson AC, Buckingham TA, et al: The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing. J Am Coll Cardiol 14:499, 1989. Reprinted with permission of the American College of Cardiology.)

a paced P wave followed by a paced QRS at a similar heart rate (Fig. 9-21). However, differences between optimal AV intervals for a paced P wave and a sensed P wave may be as great as 100 msec in some individuals. New dual-chamber pacemakers incorporate programmable features designed to adjust the AV interval automatically in response to paced versus sensed P waves and in response to the atrial rate. It is important to recognize that the physiologic AV interval is never equivalent to the programmed AV interval for either a paced or a sensed atrial DVI II

A 150 V

event. The physiologic PQ interval begins with the onset of the P wave; however, with a sensed P wave, the programmed AV interval begins when the native P wave is sensed (so with a delay compared with onset of atrial activation), and with a paced P wave, the programmed AV interval begins with the atrial pacing spike, which is followed by further atrial depolarization. The importance of variation in AV interval during exercise in patients given physiologic pacing who have normal ventricular function is still controversial. Because the major determinant of augmentation of cardiac output during exercise is heart rate, the contribution of atrial systole and relative timing of the atrial and ventricular contraction may diminish in significance. Studies analyzing the effects of variation in AV interval during exercise have yielded conflicting results.152-156 There are two major limitations to these studies: the relatively small sample size of most and the use of a fixed AV interval during each exercise test, but a different AV interval between exercise efforts. There is evidence that a rate-adaptive AV interval, which is automatically decremented in response to an increased atrial rate, is beneficial to cardiopulmonary performance during exercise.157 In patients with chronotropic incompetence and high-level AV block, Sulke et al.158 performed randomized double-blind crossover assessments of rate-adaptive and different fixed AV interval settings during 2 weeks of normal activity and performance on an exercise treadmill in patients undergoing DDDR pacing. There was a subjective improvement in quality of life with rate-adaptive AV intervals compared with fixed AV intervals, and patients preferred the rate-adaptive settings (Fig. 9-22). Notably, the longest AV interval (250 msec) was least preferred and was associated with the highest symptom prevalence. Moreover, exercise duration was not significantly different in any setting in DDDR mode but was significantly reduced in DDD mode.158 Patients with Depressed Left Ventricular Function In general, relaxation is slower in failing hearts than in normal hearts. Consequently, less blood enters the ventricles during the rapid filling phase, as can be observed from lower E waves on Doppler echocardiograms. Therefore, failing hearts are more dependent on properly timed atrial contraction than normal hearts. This has been demonstrated in comparisons of patients with decompensated heart failure and compensated nonvalvular heart disease.125 This knowledge clarifies why

LA LA V 35

A pace M

V pace

VDD II

A 150 V LA

Esoph lead

LA V 110

A sense M V pace

100

LA V 35

LA V 110

Left A-V extension in VDD 75 (110-35)

Figure 9-21  Interatrial conduction and change in the timing of left atrial (LA) depolarization with pacing mode change from DDD to VDD. The time delay between right atrial pacing artifact and LA depolarization is 115 msec (top), resulting in an LA-to-ventricular sequence of only 35 msec. With mode change to VDD (bottom), the LA-to-ventricular sequence extends by 75 msec, resulting in an LA-to-ventricular sequence of 110 msec. (From Wish M, Fletcher RD, Gottdiener JS, Cohen AI: Importance of left atrial timing in the programming of dual-chamber pacemakers. Am J Cardiol 60:566, 1987.)

Visual analog scale score (%)

Esoph lead

215

90

*

80

70

*

60

50 125 ms

175 ms

250 ms

RR AVD

AV delay setting in DDDR mode Figure 9-22  Exercise capacity ( ) and patient’s perception of general well-being ( ) during everyday activity at fixed AV delay settings of 125, 175, and 250 msec and rate-responsive AV delay (RR AVD) settings in DDDR mode. , P < .05; m, P < .03; *, P < .01. (Modified from Sulke AN, Chambers JB, Sowton E. The effect of atrioventricular delay programming in patients with DDDR pacemakers. Eur Heart J 13:464, 1992.)

216

SECTION 2  Clinical Concepts

ATRIAL PACE

AV PACE 60

AV PACE 180

.2 m/s 150

CO 5.2 l/m

CO 2.4 l/m

CO 3.0–1/m

0

A

B

C

Figure 9-23  Mitral flow-velocity curve and simultaneous left atrial (LA) and left ventricular (LV) pressure curves in a patient with severe LV dysfunction and long PR interval. A, Atrial pacing with antegrade native conduction and long atrioventricular (AV) delay interval (also AV interval). There is an increase in LV pressure above LA pressure during atrial relaxation and middiastole (arrowhead), resulting in a shortening of diastolic filling time and the onset of diastolic mitral regurgitation (m/s, meter per second). The baseline cardiac output (CO) is 3 L/min (l/m). B, AV pacing at short AV delay interval of 60 msec. Diastolic filling occurs throughout all of diastole. Atrial contraction occurs simultaneously with LV contraction, resulting in a reduction in cardiac output and an increase in mean LA pressure compared with A. C, Atrioventrucular (AV) pacing at the optimal AV delay interval of 180 msec. There is now an optimal relationship between the mechanical LA and LV contractions, so that diastolic filling period is maximized and the mean LA pressure is maintained at a low level, resulting in a rise in LV diastolic pressure and improvement in CO to 5.2 L/min. (From Nishimura RA, Hayes DL, Holmes DR: Mechanism of hemodynamic improvement by dual chamber pacing for severe left ventricular dysfunction: An acute Doppler and catheterization hemodynamic study. J Am Coll Cardiol 25:281, 1995.)

optimal timing of atrial and ventricular stimulation in patients with pacemakers is of special interest in patients with heart failure. Some investigators have shown that pacemakers can actually improve the coupling between atria and ventricles over that without pacing. This issue applies to patients with excessively long PQ times. In two studies of subjects with these findings, hemodynamic benefit was achieved with AV sequential pacing at a physiologic AV interval159,160 (Fig. 9-23). Reducing the prolonged AV interval increased diastolic filling time and reduced diastolic mitral regurgitation (Fig. 9-24). These beneficial effects are striking, because these studies were performed before the era of resynchronization, and the RV apex was used as a ventricular pacing site, presumably the least preferable site from a hemodynamic point of view (see later). The actual role of the atrial contraction in patients with dilated ventricles and low ejection fraction varies among individuals. The booster pump action of the LA is noticeable as a “shoulder” in the LV pressure tracing, and the LV does not start contracting immediately after atrial contraction (Fig. 9-25). If this plateau lasts too long, diastolic mitral regurgitation could occur. About 20% of the patients in

I AEG VEG 20

PCW

PCW 0 AV pace

V pace

Figure 9-24  Surface electrocardiographic lead I, atrial electrogram (AEG), ventricular electrogram (VEG), and pulmonary capillary wedge pressure (PCW) recordings from a single patient during atrioventricular (AV) pacing (AV pace) and ventricular pacing (V pace) at 80 bpm with an AV interval of 150 msec. The cannon A wave is noted (arrow) on the PCW tracings. (From Reynolds DW: Hemodynamics of cardiac pacing. In Ellenbogen KA [ed]. Clinical cardiac pacing, pp 120-161. Cambridge, Blackwell Scientific, 1992. Reprinted by permission of Blackwell Scientific Publications.)

heart failure studies for whom complete hemodynamic data are available show this type of diastolic LV pressure waveform.161-163 Figure 9-25 shows that using an optimized AV interval, in this case with BiV pacing, results in coincidence of the peak of the booster action of the atrial contraction and LV pressure development. Auricchio et al.164 demonstrated that the maximum improvement in aortic pulse pressure, independent of the site being paced, occurs when this coincidence is achieved. Examination and calculation of cardiac output with Doppler echocardiography, as frequently performed in patients with dual-chamber pacemakers, is more problematic in patients with depressed ejection fraction in whom the value of the effect of pacing may be near the rate of uncertainty in the method.165 Thus, the number of repetitions required to obtain a clinically meaningful and reproducible approximation of the optimal AV interval makes this method, as single assessment, almost impractical for patients with depressed ejection fraction. The most utilized echocardiographic parameters for optimizing AV interval in patients with heart failure include echocardiography-based inflow or preload evaluations (e.g., velocity-time integral of transmitral flow or EA duration)166 and measures of systolic function using time-velocity integral at the LV outflow tract.167,168 Comparison of these different methods with invasive LV dP/dtmax to optimize AV interval in patients with CRT showed that mitral inflow velocity-time integral proved most accurate. The formerly used Ritter method, based on calculating the optimal AV timing by analyzing filling patterns obtained during only two AV intervals, has been found to be accurate to optimize AV interval in CRT patients.169 Indeed, this method was created for patients with high-degree block, and some caution is advised in patients with intact AV conduction.170 In these patients the electromechanical delay is not constant and varies as a function of the extent of collision between the intrinsically conducted depolarization wavefront and the wavefront generated by the artificial pacing spike. Therefore, in patients with an intact conduction system, the extent of collision between these two wavefronts will be different at the long and short AV delay intervals tested in the Ritter method, making the assumption required by the method completely invalid—that is, the electromechanical delay is unchanged at any tested AV delay. Another consideration is important when deciding whether to use an inflow-based method for optimization of the AV interval. In patients with ventricular conduction delay who have CRT devices, the echocardiographic inflow-based method of optimizing AV delay interval



9  Basic Physiology and Hemodynamics of Cardiac Pacing

217

Atrial electrogram Ventricular electrogram

232 ms Figure 9-25  The atrial electrogram, right ventricular electrogram, left ventricular (LV) pressure, and aortic pressure tracings of a patient with New York Heart Association (NYHA) Class III heart failure from the Pacing Therapies for Congestive Heart Failure (PATH-CHF-II) trial.149 Note the effect of programming an AV interval of 128 msec in the biventricular device. With this AV interval, the ventricular pressure starts right at the peak of the pressure increase created by the booster action of the left atrium. This AV interval provides the maximum preload at the minimal mean LV diastolic pressure while maximizing the time available for diastole, thus enabling higher heart rate increases without compromising filling time.

128 ms

Aortic pressure

LV pressure Atrial booster pump effect

neither optimizes the synchrony of the ventricular contraction nor accounts for how much preexcitation of the late-activated region is required to restore intraventricular synchrony (see later). ROLE OF VENTRICULAR SYNCHRONY Abnormal asynchronous activation causes abnormal contraction patterns, inefficient and depressed pump function, and ventricular remodeling. Wiggers30 recognized the importance of normal electrical activation of the ventricle for optimal pump function in 1925 (Fig. 9-26). However, it took about 70 years for the concept to gain broad interest. Two teams of investigators regarded the abnormal activation as being of little importance, because AV sequential pacing allowed for significantly better cardiac pump function than V pacing.137,138 Nevertheless, one group showed better pump function during LV apex pacing than during pacing at RV sites.138 In the 1960s, Kosowsky et al.139 compared RV apex pacing with His bundle pacing, the latter maintaining the normal activation but allowing variation of the AV interval. They concluded that AV synchrony and proper sequence of activation are equally important, as confirmed by later animal and human studies.76,77,144 Clinical Consequences of Asynchronous Activation The combination of acute adverse hemodynamic effects and long-term ventricular remodeling (see Fig. 9-14) may explain why abnormal

Figure 9-26  Original recording made by Wiggers, showing that in a paced beat (the second; note the widened QRS complex), left ventricular and aortic pressures are lower than in the preceding and sequential beats. (Modified from Wiggers CJ: The muscular reactions of the mammalian ventricles to artificial surface stimuli. Am J Physiol 73:346378, 1925.)

Ventricular pressure raise starts at peak of atrial booster pump effect

electrical activation and asynchronous electrical activation have major implications for a patient’s clinical status. Studies have shown that morbidity and mortality are higher in patients with long-term RV apex pacing than with atrial pacing.145,171-173 In patients with sinus node disease and good ventricular function, the risk of heart failure was significantly high after more than 7 years in a comparison of atrial pacing and RV pacing.173 In a similar population the risk of hospitalization for heart failure within 3 years increased with percentage of time patients underwent pacing at the RV apex.174 Interestingly, development of heart failure and atrial fibrillation was more sensitive to percentage of pacing than to pacing mode (single- or dual-chamber pacing). In patients who received an ICD, the incidence of heart failure was higher within a year in those with pacing at VVI 70 bpm rather than in the backup mode.175 Although pacing and, even more, heart failure started at a later age in the previous studies, RV pacing in children can also induce impaired pump function. Tantengco et al.123 observed such adverse effects after approximately 10 years of pacing. The dramatic effects of ventricular pacing in otherwise healthy myocardium may be explained by the pronounced structural changes in juvenile hearts.107,176 The deleterious effect of ventricular pacing is relatively easy to discover when start of pacing is exactly known, although spontaneous evolution in a dilated cardiomyopathy cannot be excluded. Whether adverse effects of asynchronous activation are also applicable to LBBB has been less clear, because LBBB is a silent event that is often accompanied by considerable comorbidity.177-179 Longitudinal studies determining cardiovascular mortality and morbidity show that the presence of LBBB always carries a poor prognosis. In a 29-year follow-up study of 3983 pilots, the morbidity and cardiovascular mortality rate among those showing signs of LBBB was 17.2%, and the most common clinical event observed was sudden death without any previous symptoms (17%). These percentages are 10 times higher than those in subjects without LBBB.180 In the Framingham Study, cumulative cardiovascular mortality over 10 years was approximately five times higher in patients with LBBB than in those without LBBB.181 In a population of 110,000, the risk for development of cardiovascular diseases was 21% in the 112 patients with LBBB, compared with 11% in age- and gender-matched controls. Moreover, cardiac mortality was strongly increased in the patients with LBBB. The first direct evidence for an effect of LBBB on pump function came from studies in patients with intermittent LBBB.182,183 Further proof of the negative effect of LBBB on hemodynamics has come from later studies in an animal model of LBBB, created by ablation of the proximal part of the LBB.54,184,185 After ablation, duration of the QRS complex, asynchrony of RV-LV contraction, and asynchrony of

218

SECTION 2  Clinical Concepts

electrical activation within the LV all increase significantly; also, relative to normal conduction values in the same species, these increases are similar in degree to the increases seen in patients with LBBB.24,186 This finding suggests that, although the LBBB in patients may not be caused exclusively by proximal lesions, this model closely resembles the LBBB in patients. All studies on this animal model of LBBB show that LBBB reduces systolic and diastolic LV function and induces paradoxical septal wall motion.54,184,185 Therefore, both RV apex pacing and LBBB seem to be conditions that increase the risk of heart failure and cardiac death, especially in patients with already-compromised function. For this reason, efforts to prevent RV apex pacing or correct LBBB are increasing. With current knowledge of electrical impulse conduction, the best solution may depend on whether the heart has normal or disturbed intrinsic conduction within the ventricles. In the following discussion, various possible strategies are described, with current and possible future applications. Strategies to maintain synchrony of activation are distinguished from those to restore synchrony. Strategies to Maintain Ventricular Synchrony Approaches to achieve or maintain ventricular synchrony include atrial pacing and pacing from alternative ventricular sites, including the His bundle. More recently, LV pacing and BiV pacing have been specifically indicated in patients with ventricular conduction disturbance. Both methods are commonly referred as “cardiac resynchronization therapy” and are discussed separately later. Atrial Pacing.  Atrial pacing maintains normal ventricular activation, although limited to patients with intact AV nodal conduction. In a comparison of atrial pacing with RV apex pacing in patients with sinus node disease (e.g., VVI vs. AAI), Andersen et al.173 reported less development of all-cause mortality and cardiovascular death, better maintenance of ventricular function and perfusion,187 absence of atrial dilatation,188 and a lower incidence of atrial fibrillation.173,189 Although earlier studies compared atrial pacing with single-chamber pacing, later studies in patients with sick sinus syndrome showed a similar disadvantage of ventricular pacing in the dual-chamber mode compared with atrial pacing. Because the risk of AV block in this patient category (0.6%-1.7%/yr)190,191 is considerably lower than that for development of heart failure (as high as 12%),174 atrial pacing is an immediately applicable, easy, and effective way to avoid abnormal ventricular activation. Alternative-Site Ventricular Pacing.  Patients with disturbed AV conduction are pacemaker dependent and require ventricular pacing. His bundle pacing is the way to maintain physiologic ventricular impulse conduction. Animal studies showed that QRS duration was shorter with pacing in the high ventricular septum than with RV apex pacing.77,176,192 In the 1960s, Scherlag’s group showed that His bundle pacing results in the same QRS duration and pressure development as sinus rhythm and atrial pacing and in better hemodynamics than RV apex pacing.139,193 In 2000, Deshmukh et al.194 first reported successful His bundle pacing in patients on a permanent basis. Using improved implant tools, Zanon et al.195 showed that His bundle pacing preserves normal distribution of myocardial blood flow and mechanics. Nevertheless, because of the relatively difficult positioning of the pacing lead into the His bundle, pacing in the vicinity of His bundle is more often used. The literature refers to this position as “high RV septal” or “RV outflow tract” (RVOT), but in some studies, “RVOT” appears to imply pacing at the high RV free wall. Pacing in this region leads to abnormal QRS configuration compared with atrial pacing. Comparative studies of the acute hemodynamic effects of high septal pacing and RV apex pacing showed a moderate beneficial effect of septal pacing on LV pump function, although several studies found no significant difference between high septal and RV apex pacing.196 Combined RV apex and RVOT pacing in patients resulted in shorter QRS duration than RVOT pacing alone but did not lead to further improvement of cardiac output.197

Longer-term studies appear to show a more consistent beneficial effect of high septal pacing. Tse et al.198 randomly assigned 24 patients to either RV apex or high septal pacing. After 18 months of pacing, perfusion defects and regional wall motion abnormalities were less common and ejection fractions were higher in the high septal pacing group. The reports explicitly mentioned that the “RVOT” lead was positioned in the interventricular septum. Unfortunately, however, the exact best site at the RV septum is not well known. One animal study showed that the RV site for best hemodynamic function differs for individual hearts.94 Also, RV midseptal pacing performed similar to RV apical pacing.59 In contrast, single-site LV pacing often results in better cardiac pump function than RV pacing.91,199 Turner et al.200 showed that LV pacing may also lead to more synchronous activation if pacing is performed at longer AV intervals during maintained AV conduction in patients with a relatively narrow QRS complex. Because electrical asynchrony and mechanical asynchrony within the LV wall are similar in RV pacing and LV pacing201 (Fig. 9-27), the less detrimental hemodynamic effect of LV pacing may be explained by better interventricular coupling. This mechanism may also partially account for the beneficial hemodynamic effects of LV pacing in patients with heart failure and AV node ablation.202 In these patients, no fusion can occur between the impulse wavefronts from endogenous conduction and LV stimulation. However, long-term comparative data in some subgroups of patients are still missing, so no definitive conclusions can be drawn. Animal studies have shown that within the left ventricle, the septum and apex may be ideal pacing sites; pacing in these sites was associated with LV pump function close to that during normal sinus rhythm, even

Late diastole

Early systole

Mid systole

End systole

Midseptum RA

RVa LV

RVa

LV

Figure 9-27  Three-dimensional reconstruction of left ventricular wall with myocardial strain represented in color. Data were obtained using magnetic resonance imaging (MRI) tagging in a normal dog heart. Blue indicates contraction (negative circumferential strain), red indicates the reference state (end diastole), and yellow indicates stretch (positive circumferential strain). Data are shown for late diastole and early systole, midsystole, and late systole for right atrial (RA), biventricular (RVa+LV), RV apex (RVa), and left ventricular (LV) pacing. White arrow points to the midseptum. Note the considerable strain differences during both RVa and LV pacing in early systole and midsystole. RVa + LV pacing reduces these differences, but differences are still more pronounced than during RA pacing. (Modified from Wyman BT, Hunter WC, Prinzen FW, et al: Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction. Am J Physiol 282:H372H379, 2002.)



9  Basic Physiology and Hemodynamics of Cardiac Pacing

TABLE

9-3 

Hemodynamic Parameters during VDD Pacing at Various Ventricular Sites in Dogs* Ventricular Site

Parameter Heart rate Stroke volume Stroke work LV dP/dtpos LV dP/dtneg Tau ESLVP EDLVP QRS duration

RV Apex 1.048† 0.930†‡ 0.789†‡ 0.931†‡ 0.799†‡ 1.1† 0.952† 1.137† 1.862†‡

LV Lat 1.03 0.991‡ 0.980‡ 0.926†‡ 0.840† 1.189†‡ 0.978 1.231† 1.997†

LV Post 1.02 0.873†‡ 0.869‡ 0.927†‡ 0.849† 1.199†‡ 0.983 1.215 1.820†‡

LV Apex 1.03 1.05 1.08 0.99 0.94 1.06 0.96 1.3 1.940‡

LV Septum 1.01 1.03 1.00 1.00 0.93 1.04 0.99 1.22 1.670†

Data from Peschar M, de Swart H, Michels KJ, et al: Left ventricular septal and apex pacing for optimal pump function in canine hearts. J Am Coll Cardiol 41:1218-1226, 2003. *All values are expressed relative to the corresponding value during sinus rhythm. For all parameters, values during left ventricular (LV) apex and LV septum pacing were not significantly different from those in sinus rhythm, except QRS duration. Right ventricular (RV) apex pacing leads to the most dramatic reduction in LV systolic and diastolic function. †P < .5 compared with SR apex pacing. ‡P < .05 compared with LV apex pacing. ESLVP/EDLVP, End-systolic/end-diastolic left ventricular pressure; LV Lat, lateral left ventricle; LV Post, posterior left ventricle.

with pacing at short AV intervals94,203 (Table 9-3). Studies in children now support the superior performance of LV apex pacing over RV pacing with respect to hemodynamic function93 and echocardiographic indices of dyssynchrony204 and reverse remodeling.205 LV septal pacing is not yet clinically feasible, because positioning a lead in the LV cavity carries a risk of embolization and stroke.206 In an animal study, Mills et al.59 advanced a lead from the right ventricle through the interventricular septum to reach the LV septal endocardium. Even after 4 months of pacing, LV septal pacing provided cardiac pump function and efficiency similar to that during natural conduction. The degree of asynchrony induced by single-site ventricular pacing can be reduced by pacing at two or more sites simultaneously, preferably opposite to each other. This “multisite” pacing, however, reduces QRS duration by no more than 20% compared with single-site pacing.50 Animal studies showed that BiV pacing does lead to better LV pump function than RV pacing.50,94,207 Also, in patients with atrial fibrillation and AV node ablation, hemodynamic performance was better during BiV pacing than during single-site LV or RV pacing.208 It is important to note that in patients with normal ventricular conduction, such novel pacing sites (LV apex, RVOT, His bundle, multisite) at best prevented a reduction of pump function compared with atrial pacing or sinus rhythm, but never improved pump function. Also, left intraventricular mechanical asynchrony is only partially normalized, even with BiV pacing.209 Multisite pacing cannot outmatch the quick impulse conduction and its extensive spread through the network of Purkinje fibers. Therefore, avoiding any ventricular pacing would be preferable in hearts with normal ventricular conduction. Minimizing Ventricular Pacing One approach to avoiding any type of ventricular pacing has been to program fixed, long AV intervals; however, this approach resulted in occasional retrograde AV conduction and higher risk of arrhythmias in one third of a select population.210 For many years, some pacemakers have incorporated an algorithm based on the programming of two AV delays: a short, physiologic AV delay and a longer AV delay. These devices start pacing with the longer AV delay and continue at this setting if they find intrinsically conducted ventricular beats. If the intrinsic conduction is not present or fails to occur, the devices automatically switch to the shorter and more physiologic AV delay. When functioning at the shorter AV delay, these devices periodically extend the AV delay to test for intrinsic conduction at programmable intervals. This type of algorithm is called AV search hysteresis.211

219

Rather than prolonging the AV delay, an algorithm called managed ventricular pacing (MVP) has been implemented in two studies.212,213 With this algorithm, when intrinsic activity is present, only the atrium is paced; the ventricle is monitored on a beat-to-beat basis to verify intact AV conduction. Only in cases of transient and persistent loss of AV conduction does the MVP algorithm pacemaker switch to the DDDR mode. The mode intermittently tests for return of normal AV conduction. During atrial fibrillation, the device operates in the DDIR mode. With this approach, the cumulative percentage of ventricular pacing was reduced from a mean of 74% to 4%, with 80% of the patients being paced on the ventricle for less than 1% of the time. In a study with 1065 patients, MVP reduced the risk of developing persistent atrial fibrillation from 12.7% to 7.9% over a mean follow-up of 1.7 years.214 Because many patients undergo pacing for sinus node disease, algorithms such as AV search hysteresis and MVP are promising for maintenance of ventricular synchrony in patients with predominantly intact AV and intraventricular conduction (Fig. 9-28). However, a recent study indicates that conservative programming of lower rate and rate response is advisable to minimize risk of AV decoupling and uncoupling as well as ventriculoatrial (VA) coupling.215

Strategies to Restore Synchrony: Cardiac Resynchronization Therapy Biventricular pacing devices, first implanted in March 1993,216 were approved by the U.S. Food and Drug Administration (FDA) in 2001. The beneficial hemodynamic effects of BiV pacing during that smallscale study have been reproduced many times.161,217-220 The consistency of the results of small but prospective randomized trials, such as Pacing Therapies for Congestive Heart Failure (PATH-CHF),161,162 Multisite Stimulation in Cardiomyopathy (MUSTIC),221 Cardiac Resynchronisation in Heart Failure (CARE-HF),222 and Multicenter InSync Randomized Chronic Evaluation (MIRACLE),223 have removed any doubt

Ventricular conduction

Normal

Abnormal

AV conduction

Yes

No

Atrial MVP

His bundle LV (apex) RV septal BiV (especially if RVA pacing)

Discontinue RVA pacing if present

BiV LV

(Check mechanical asynchrony) Figure 9-28  Flow diagram showing most physiologic mode and/or site of pacing. Potential adverse effects of ventricular pacing and conduction disturbance, such as left bundle branch block (LBBB), on cardiac pump function. Ventricular pacing can induce nonphysiologic atrioventricular (AV) as well as interventricular (biventricular, BiV) and intraventricular asynchrony. Assuming normal PQ times, LBBB causes only abnormal interventricular and intraventricular asynchrony. Effects of AV asynchrony are explained in text; LV, left ventricular; MVP, managed ventricular pacing; RVA, right ventricular apex.

220

SECTION 2  Clinical Concepts

LAO 60°

Y

111 msec

Y

137 msec

52 msec

46 msec

2

X

Total Ventricular Activation Time: 157 msec RV Activation Time: 57 msec LV Activation Time: 105 msec

Y

2

X

Total Ventricular Activation Time: 189 msec RV Activation Time: 85 msec LV Activation Time: 137 msec

95 msec

110 msec

2

Total Ventricular Activation Time: 205 msec RV Activation Time: 130 msec LV Activation Time: 145 msec

Figure 9-29  Color-coded electroanatomic isochronal maps of right ventricular (RV) and left ventricular (LV) activation in three patients with heart failure and left bundle branch block. The earliest ventricular activation site is recorded at the RV anterolateral region (red spot) in all three cases. After almost 40 to 60 msec, a single LV septal breakthrough site is noted (not shown). The latest-activated region is the LV posterolateral wall (blue to purple isochronal lines). The total activation endocardial time and endocardial RV and LV activation times are shown for each patient.

about the feasibility and clinical efficacy of CRT in highly symptomatic patients with heart failure. Large, multicenter, randomized controlled clinical trials (RCTs) have consistently demonstrated significant reductions in mortality and hospitalization rates with CRT in patients who had moderate to advanced heart failure despite optimal pharmacologic therapy and who presented with ventricular conduction delay, sinus rhythm, and depressed LV ejection fraction.222 PHYSIOLOGY OF CARDIAC RESYNCHRONIZATION THERAPY With the introduction of CRT, the use of cardiac pacemakers has been transformed from “just” artificial maintenance of the heart rhythm to restoration of pump function. Although the primary objective of BiV pacing may be to reduce intra-LV asynchrony, it can also be used to establish optimal interventricular coupling as well as AV coupling. The latter especially applies to left-sided AV coupling, because in LBBB the atrio-LV delay is usually prolonged. Parsai et al.224 showed that patients respond to CRT if at least one of the mechanisms of CRT is active.224 The predominant intraventricular conduction abnormality in about one third of patients with heart failure is LBBB, where activation spreads from the RBB to the RV wall and, after transseptal conduction, within the LV from the septum to the LV lateral wall (Fig. 9-29). Thus, pacing at the LV lateral wall is used to create an activation wavefront, which moves in the opposite direction from a spontaneously occurring activation wavefront.16,26,201 Consequently, during BiV pacing, two activation wavefronts are generated and merge approximately in the middle.36,209 A similar effect is obtained by single-site LV pacing using an AV interval that allows merging of the intrinsic activation originating from the RBB with the wavefront derived from the LV pacing lead. This merging wavefront leads to less electrical asynchrony in comparison with LBBB.36 Because of the tight E-C coupling in the heart, CRT also improves coordination of contractions between the cardiac chambers and within the LV wall, as shown with different imaging techniques55,225 (see Fig. 9-27). More specifically, CRT uniformly prolongs the time to maximum contraction55 and thus restores a more coordi-

nated contraction pattern, resulting in a more homogeneous distribution of regional loading conditions.56 The improved synchrony leads to improvement of cardiac pump function, as determined by LV dP/dtmax, pulse pressure, cardiac output, and ejection fraction.* Such improved systolic pump function is achieved at unchanged or even lower filling pressures, denoting a true improvement of ventricular contractility through better coordination of contraction. Moreover, Nelson et al.69 showed that better coordination of contraction improves mechanical pump function while slightly decreasing myocardial energy consumption, suggesting that CRT improves the efficiency of the cardiac pump. Further improvement in pump function may be mediated by a reduction in mitral regurgitation225 and prolongation of diastolic filling time. These beneficial effects occur almost immediately after the start of resynchronization.36,161 Another possible mechanism for the improvement in LV pump function by BiV and LV pacing is that it improves ventricular interaction and relieves external constraint,228,229 a mechanism that could work even in patients with a narrow QRS complex.229 The idea is that early LV contraction also allows early LV filling. In hearts with high central venous pressures, where presumably the RV occupies much of the pericardial space, the early LV activation may allow the LV to fill first, and thereby better, thus recruiting more of its Frank-Starling mechanism.228 A variety of cardiac and extracardiac processes triggered by CRT are responsible for its long-term beneficial effect. First, the improved pump function reduces neurohumoral activation, an effect evidenced by an increase in heart rate variability and a reduction in plasma brain natriuretic peptide (BNP) levels.230 Furthermore, the improved contractility and pump efficiency at a smaller end-diastolic volume reduce mechanical ventricular stretch. This latter reduction and the probably associated reduction in neurohumoral activation may well explain the beneficial reverse-remodeling effect of CRT.225,231 As elegantly demonstrated by Yu et al.,225 such reverse remodeling points to structural *References 36, 161, 219, 220, 226, 227.



9  Basic Physiology and Hemodynamics of Cardiac Pacing

Resynchronization

patients with only mild heart failure or impairment of LV function.233,234 These data indicate that resynchronization cures “dyssynchronopathy” independent of the severity of heart failure. Most CRT studies focus on the left ventricle, but a few indicate that RV function may also be improved by better synchronization of the electrical activation. This would especially apply to right bundle branch block (RBBB). Three-dimensional electroanatomic mapping data have provided the rationale for implementing CRT in these patients.235 However, rather than focusing on LV-based pacing, resynchronization of RBBB requires RV pacing. This also applies to children with repaired congenital defects such as tetralogy of Fallot, who present with rightsided heart failure.236,237

Desynchronization

1000

dP/dt (mm Hg/s)

900

*

800 † 700

†

DETERMINATION OF MECHANICAL ASYNCHRONY

600

†

500

Reverse remodeling

400 225 † Left ventricular volume (mL)

221

200

*

* *

175

*

150 †

*

125

CRT

100 Baseline 1wk

1mo

*

3mo

* * off- off-1wk off-4wk immed

Figure 9-30  Acute hemodynamic and long-term reverse-remodeling effects of cardiac resynchronization therapy (CRT). (Modified from Yu CM, Chau E, Sanderson JE, et al: Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 105:438-445, 2002.)

improvement in the myocardium. These investigators showed the increasing reverse-remodeling effect of resynchronization over time by measuring the time course of LV cavity volume and LV dP/dtmax during the first 3 months after the start of CRT and 1 month after CRT was temporarily stopped, when some beneficial effect of CRT was still noticeable, indicating tissue adaptation (Fig. 9-30). Study in canine LBBB hearts showed that isolated LBBB induces LV dilatation as well as hypertrophy and that these derangements are almost completely reversed by BiV pacing.54,57 Interestingly, BiV pacing reversed the hypertrophy in the LV wall, especially in the late-activated LV lateral wall.57 This reduction in hypertrophy is important because hypertrophy gives rise to various molecular changes,232 resulting in greater risk for contractile failure and arrhythmias. Indeed, in dogs with LBBB, where heart failure was induced by 6 weeks of rapid atrial pacing, calcium homeostasis was affected most in the LV lateral wall.114 Notably, both hemodynamic improvement36,185 and reverse remodeling57 have been observed to a similar extent in dogs with LBBB (with and without heart failure) and in patients with primary and secondary dilated cardiomyopathies. Although CRT was originally indicated for patients with severe heart failure (NYHA Class III and IV), several studies demonstrated that CRT can also induce reverse remodeling in

The primary goal of CRT is to restore atrioventricular, interventricular, and intraventricular synchrony. Because QRS duration is a poor predictor of the response to CRT,225,238,239 mechanical asynchrony was thought to be a better index for selection of CRT patients. Although studies have reported that measurement of mechanical asynchrony is a better predictor of the response to CRT than duration of the QRS complex, most were small and observational. Interventricular asynchrony can be determined from the time difference between pulmonary and aortic valve openings with conventional echocardiography186 or from the time to peak velocity in the RV and LV walls on tissue Doppler imaging (TDI). Other approaches are determination of the phase difference of RV and LV wall motion using nuclear imaging53 and use of the time or phase difference with increased RV and LV pressures.184,240 For practical reasons, the echocardiographic approach is most often used. Intraventricular asynchrony usually requires more sophisticated equipment. The most detailed mechanical activation maps have been obtained through mapping of myocardial shortening (strain) patterns with magnetic resonance imaging (MRI) tagging48,201,209,241 (see Fig. 9-8). These studies have shown that the pattern of deformation gradually changes with increasing distance from the site of earliest activation (asterisk in Fig. 9-8). With the less expensive noninvasive method of M-mode echocardiography, the timing difference of maximal inward motion at the septum and posterior wall, or the septal-posterior wall motion delay (SPWMD),238 can be calculated. The disadvantages of this simple technique are that peaks of septal wall motion may not be precisely defined, and M-mode sections perpendicular to the septum may be difficult to acquire. With color TDI and with pulsed-wave TDI, the time to peak systolic velocity can be measured in different regions of the myocardium.225,242,243 Local contraction can be derived only through subtraction of velocities in nearby regions. Such analysis on digitally stored color-coded tissue Doppler images yields myocardial strain and strain rate.97 Such information is equivalent to that obtained with MRI tagging, but with the great advantage that TDI can also be employed in the presence of a pacemaker. Strain measurements differentiate better than TDI between active systolic contraction and passive displacement. Likewise, Breithardt et al.97 demonstrated more consistent behavior of strain than of velocity signals. However, image acquisition and analysis are timeconsuming and operator dependent, and subtraction of two strain rate signals can create inaccuracies. Therefore, the clinical applicability of strain-rate imaging is limited. A more recent development is the measurement of two-dimensional strain using speckle tracking. This technique uses the same principle as MRI tagging: measurement of the deformation of the tissue by displacement of markers in the tissue. Rather than markers artificially applied, as in MRI tagging, speckle tracking uses the differences in gray level naturally occurring in cardiac tissue as markers. Depending on the echocardiographic section used, longitudinal, circumferential, or radial strains can be measured. Although this technique shows promise and may have less technical limitations than TDI, the various echocardiographic systems appear to handle the strain signals differently in terms of tracking and spatial and temporal filtering, and the

222

SECTION 2  Clinical Concepts

Strain

0

?

?

AVO

AVC

AVO

Time Time to peak shortening

AVC Time

ISF =

+

SRS =

equipment allows only minimal interference by the user. Also, only a few studies showed a true validation of the technique, and this was not in conditions comparable to LBBB or CRT. Nevertheless, speckle-tracking measurements have provided promising results. Mechanical dyssynchrony determined by this technique appeared to predict the response to CRT better than TDI,244 at least partly because strain measurement by speckle tracking is independent of the angle between ultrasound beam and the ventricular wall. TDI measures the velocity of displacement of the myocardial segments relative to the ultrasound transducer and in the direction of the ultrasound beam. Likewise, the longitudinal velocity, as usually determined in basal regions, is the sum of all velocities developed in all regions between the transducer and a particular area. Analysis of strain signals may also be less difficult to interpret than the frequently multiphasic velocity signals.245 TDI mechanical asynchrony is also observed in a considerable number of healthy volunteers. Mechanical Asynchrony or Discoordination? With mechanical asynchrony the focus over the last decade, the results of two randomized multicenter studies were unexpected. The PROSPECT and RethinQ studies showed poor predictive value for mechanical asynchrony as an index of CRT response in patients with wide and narrow QRS complex.246,247 These disappointing results can be explained only partly by technical limitations of the TDI technique. Even when using the “gold standard” technique in cardiac deformation measurements, MRI tagging, determination of mechanical asynchrony (i.e., timing difference in onset or peak shortening) did not predict CRT response.248,249 A better approach for achieving a mechanical predictor of CRT response may be to analyze discoordination of contraction. Whereas measurement of asynchrony requires determining the onset or peak of shortening in a certain region, discoordination is assessed by analyzing the strain curves over a large period of the cardiac cycle (e.g., systole or diastole). Reported indices include the CURE index,245 internal stretch fraction (ISF),249 and septal rebound stretch (SRS)55 (Fig. 9-31). All three parameters provided a good prediction of CRT response, and better than using mechanical asynchrony measures in two studies.55,249 THE SITE OF PACING From a theoretical point of view, the “optimal” sites of pacing are those that establish the greatest reduction in total activation time. This requires that the slowly propagating electrical wavefront originating from the RBB is replaced by or fused with one or more activation wavefronts originating elsewhere. In current practice, CRT is most often achieved by pacing the RV and the LV simultaneously or sequentially. The RV pacing site used is usually the RV apex, and recent trials failed to show improved CRT efficacy during RV septal versus RV apical pacing.250,251 The preferred LV pacing site is often the latest-activated region, which in LBBB is usually the basal part of the posterolateral wall.39,40

Figure 9-31  Schematic representation of the determination of mechanical asynchrony (left panel) and discoordination (right panel). Mechanical asynchrony is often calculated from the time between the time to peak shortening in the septum (green) and lateral wall (red). Discoordination can be assessed as internal stretch fraction (ISF) or septal rebound stretch (SRS). AVC, aortic valve closure; AVO, Aortic valve opening.

By using extensive epicardial mapping and MRI strain analysis, Helm et al.252 demonstrated that in dyssynchronous canine hearts, the area of late electrical and mechanical activation indeed closely matched the area that caused maximal LV dP/dtmax increase during pacing. This region spans about 40% of the LV free wall, especially the lateral wall. In similar studies, Rademakers et al.253 showed that in the presence of an infarction, the optimal site of LV pacing depends on the scar location. Gasparini et al.254 showed that placing the LV lead close to the ventricle’s basal portion conferred greater improvements in LV ejection fraction, quality of life, and distance walked in 6 minutes, similar to those reported for lateral lead placement. Their findings confirm previous observations by Butter et al.,218 who showed that both anterior and lateral wall pacing sites improve LV contractility and pump function. However, pacing from the lateral wall resulted in a significantly larger increase in LV contractility; moreover, in about one third of patients, pacing from the anterior wall significantly depressed LV function. It is important to note that Butter paced the LV from a “middle-apical” position. High-resolution mapping data help explain these apparently discrepant findings (see Fig. 9-29). In patients with LBBB, the basal region of the heart is always the last region to be activated, with minor differences between the superior part of the left ventricle (around aortic root) and posterior and posterobasal regions;40 the latter regions were the pacing sites selected by Gasparini.254 In contrast, the anterior middle-apical part of the left ventricle is usually early-activated, representing the LV breakthrough site, and activation of the middle-apical part of the lateral wall, one of the pacing sites tested by Butter et al.,218 is significantly delayed. Accounting for the differences in activation time in individual patients and using TDI to locate the region with the latest mechanical activation, Ansalone et al.255 investigated whether concordance of LV lead position and latest-activated region influences the outcome of CRT. Indeed, the greatest effect on functional parameters was seen when the LV lead was in the latest-activated region. Although optimization of the pacing site is often difficult when the transcoronary venous access is used, positioning the LV lead through limited thoracotomy may be helpful. During this procedure, LV pressure-volume analysis showed the importance of choosing the best position of the LV lead.226 During a coronary sinus approach, the left ventricle is paced at the epicardial surface, whereas under physiologic conditions, excitation of the LV initiates at the endocardium.11 In a canine LBBB model, endocardial LV pacing during CRT consistently reduced electrical asynchrony compared with conventional epicardial CRT (Fig. 9-32). In parallel with these electrophysiologic improvements, endocardial CRT also improved systolic LV pump function and decreased dispersion of repolarization compared with epicardial LV pacing at the same site.33 Additionally, the hemodynamic effects for endocardial sites were less dependent on location and AV delay than epicardial sites. LV endocardial pacing in patients can be established through a transatrial septal approach, shown to be technically feasible and effective during acute and midterm follow-up.206,256-259 However, its long-term effects



9  Basic Physiology and Hemodynamics of Cardiac Pacing LBBB

EPI-BiV pacing

223

ENDO-BiV pacing

Pace site 0

20

40

60

80

100

120 (ms)

Figure 9-32  Three-dimensional reconstruction of electrical activation times of the left and right ventricles during baseline LBBB (left) and biventricular (BiV) pacing with conventional epicardial (EPI) and novel endocardial (ENDO) left ventricular electrode position. Data from epicardial contact mapping and endocardial non-contact mapping in a canine heart with LBBB induced by radiofrequency ablation.59

compared to epicardial pacing and the development of systemic thromboembolic complications need to be investigated further. Given individual variations in etiology, severity, patterns of delayed ventricular activation, location of scar regions, and extent of mitral regurgitation in heart failure, it seems unlikely that one pacing site will “fit all.” This is further exemplified by studies in canine hearts with LBBB and with chronic myocardial infavetion, where the optimal site of LV pacing depended on the infarction site.253 Not surprisingly, pacing inside scar tissue, as in patients with a posterolateral scar, provides little benefit.260 Although stimulating the latest-activated regions makes sense, increasing evidence supports that pacing other areas may be at least as effective. In dogs, acute and chronic LV apical and LV septal pacing maintained regional cardiac mechanics, contractility, relaxation, and efficiency near native levels.59 Derval et al.259 investigated 11 LV pacing sites (10 endocardial, 1 CS) in 35 nonischemic, dilated cardiomyopathy patients but failed to reveal a single optimal pacing site. However, selecting the best location individually doubled LV dP/dtmax compared with conventional coronary sinus pacing. Given the electrical similarity of the spontaneously occurring LBBB and the LBBB induced by RV pacing, several centers have explored the feasibility of “upgrading” already-implanted RV pacemakers to BiV units or, in the case of a new implant, to use BiV pacing from the beginning. The results appear to depend on the clinical setting. In patients with already-implanted RV pacing leads, the upgrade leads to improvement in cardiac function and clinical outcome.261,262 However, the situation is less clear when RV and BiV pacing are compared in patients with atrial fibrillation immediately after AV nodal ablation.263,264 In these crossover studies, parameters such as quality of life, New York Heart Association (NYHA) diagnostic class, and 6-minute walking distance showed modest differences between RV pacing and BiV pacing. However, echocardiographic measures demonstrated moderate improvements with BiV over RV pacing.263 These findings are supported by experimental data showing that both RV pacing and BiV DDD pacing are able to completely reverse LV hypertrophy and dilatation induced by chronic AV nodal ablation in dogs.265 Together, these data suggest that the effects of ventricular pacing should be considered in light of the disease being treated. Another important, yet unresolved issue is whether LV pacing alone is sufficient for adequate CRT. In dogs and patients with LBBB, LV pacing improves LV pump function at least as much as BiV pacing.36,161,219,220 LV pacing also leads to clinical improvement at up to 1 year of follow-up.266,267 The promising effect of pacing at this single site can be explained by the fusion between the LV pacing–triggered wavefront and the wavefront created by intrinsic conduction through the RBB.36 The Device Evaluation of CONTAK RENEWAL 2 and

EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE HF) study was a large, prospective randomized trial comparing single-site LV pacing to simultaneous and sequential BiV pacing.268 The three groups (each >100 patients) showed similar echocardiographic reverse remodeling after 3 and 6 months. Compared to LV pacing, simultaneous BiV pacing trended toward greater improvement in LV size. Importantly, however, the same AV delays were programmed for all groups, at approximately half the intrinsic PQ time. Therefore, during single-site LV pacing, the heart was predominantly depolarized by the activation wavefront originating from the LV electrode. Without electrical fusion with an activation wavefront from the RBB, the optimal effect of single-site LV pacing may be missed.36 Even if LV pacing were sufficient for proper resynchronization, other factors would continue to warrant RV lead placement in many patients. In particular, current implantable defibrillator systems require an RV lead for tachyarrhythmia sensing and high-voltage therapies. Moreover, if a patient undergoing CRT also requires optimization of the AV interval because of prolonged PQ time or backup ventricular pacing, an RV lead would be important to allow pacing in case of dislodgement of the LV lead, which occurs in 5% to 10% of patients. ATRIAL PACING AND SENSING Given the rationale of CRT, continuous ventricular pacing should be provided to maximize pump function and cardiac efficiency. Many people equivocally equate a pacemaker with a resynchronizer, but even though they are remarkably similar in function and characteristics, the two devices fundamentally differ in one respect. The primary goal of a pacemaker is to restore the rhythm when absent; a secondary, less important, and even questionable goal (because of extreme difficulty in maintaining correct sequence of activation in ventricles during ventricular pacing) is to restore the proper AV timing in patients with first-degree AV block. In contrast, the primary goal of a resynchronizer is to resynchronize all the time, whether intrinsic activation is present or not. This difference creates opposite goals for the two devices in many situations. A minimum heart rate is required to maintain adequate heart function without triggering heart failure. A minimum heart rate is also required to enable the heart to generate enough cardiac output to sustain the body’s metabolic needs. Nevertheless, we now know that cardiac efficiency is higher at lower heart rate (see Fig. 9-17) and that lower heart rates favor angiogenesis. A first attempt to define an adequate heart rate could be taken by stating that given these two opposing driving forces, the optimal heart rate for a given patient would be the lowest rate that creates sufficient cardiac output to satisfy basic metabolic needs in that patient at a given point. For a patient with normal

224

SECTION 2  Clinical Concepts

RA Sensed events

LA RV PR150ms

100 ms

Right atrial pace

Tricuspid closure

LA

RV

100 ms

Septum

LV

110 ms Septum

RA contr Lateral

LA contr

AV delay for optimum ventricular resynchronization

RA

110 ms

RA contr Right atrial pace

LV

Lateral

LA contr

Mitral closure

BV pacing spike

AV90ms

AV90ms

100 ms

100 ms

RA contr Septum

RA contr Septum

Lateral

Lateral

Tricuspid and mitral closure Figure 9-33  Left atrial (LA) contraction (contr) after mitral valve closure. Top panel, Schematic illustration of a patient undergoing atrial pacing, in whom sensing in both ventricles has an interatrial conduction delay of 100 msec (ms) and, for the sake of simplicity, an equal mechanical delay. The patient’s intrinsic atrioventricular (AV) interval (marked as PR in the figure) is 150 msec. The figure illustrates how after a small electromechanical delay, the right and left atrial (RA and LA) contractions follow their electrical activations. This patient also has an intraventricular conduction defect, which makes the septum (marked as RV) activate 110 msec earlier than the lateral wall of the left ventricle (marked as LV). Similarly, both activations are followed after a small electromechanical delay by the septal and left lateral wall contractions. The mechanical asynchrony of the LV prevents the LA from contracting (contr) against a closed mitral valve. Bottom panel, Septum and left lateral wall are resynchronized with the optimum AV interval. Note clinically significant increase in filling time created by resynchronization. BV, Biventricular.

50 40

r20.63694

y12.175266.56701x

30 Change in mortality (%)

ventricular function and no heart failure, a more aggressive stance could be taken with respect to programming higher parameters for lower rate limit (LRL) and rate response in the presence of sinus bradycardia or chronotropic incompetence. In the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial, dual-chamber ICD pacing was programmed to an LRL of 70 bpm and short AV intervals; its results strongly suggest that these settings were worse than a simple setting of the ICD to VVI with an LRL of 40 bpm. Many now believe that most of the detrimental effects observed in the DDD arm of this trial resulted from RV pacing creating an asynchronous contraction.175 In the DAVID-II study, VVI backup pacing at 40 bpm was compared with atrial pacing at 70 bpm. The data showed no significant difference between these two settings with respect to clinical outcome and survival as backup pacing.269 Therefore, a heart rate of 70 bpm does not seem to have a detrimental effect in the failing heart, as long as the sequence of conduction is normal. To summarize, the data available strongly suggest caution in programming the pacemaker’s LRL to be higher than the sinus rate in patients with heart failure, whether or not they have sick sinus syndrome. This is especially important because RA pacing may cause interatrial conduction delays, leading to LA contraction against a closed mitral valve and thus lower cardiac output and elevated pulmonary pressure (Fig. 9-33). Moreover, higher-than-necessary heart rates worsen mechanical efficiency, decrease angiogenesis, exacerbate heart failure, and may even increase mortality (Fig. 9-34). In patients who receive an implant (CRT or CRT-D device) primarily for heart failure indications, a general rule is to program the LRL below the sinus rate, unless a clear clinical need to pace the atrium can be documented.

PROFILE

PROMISE FIRST

20 10 0

VHeFT (prazosin)

10 20 30

SOLVED

40

CONSENSUS

VHeFT(HDZ/ISDN)

50 60

Vesnarinone 70 6 5 4 3 2 1 0 1 2

3

4

5

6

7

8

9

Change in heart rate (bpm) Figure 9-34  Relationship between the chronic changes in heart rate obtained with several drug therapies and their effect on mortality rates in patients with heart failure. Curiously, there is a strong correlation between mortality benefit and the ability of a drug to achieve a reduction in the heart rate of the patients in the active therapy arm of the trial. HDZ/ISDN, Hydralazine/isosorbate dinitrate; VHeFT, veteran Affairs Vasodilator Heart Failure Trial.



9  Basic Physiology and Hemodynamics of Cardiac Pacing

ATRIOVENTRICULAR OPTIMIZATION As discussed earlier, the AV interval strongly influences ventricular preload and thereby stroke volume in patients with reduced ejection fraction. During CRT, however, the AV interval also affects ventricular pump function by modifying ventricular asynchrony. At long AV intervals, the impulse conducted through the AV node and RBB is allowed to spread into the right ventricle and from there toward the left ventricle, maintaining (part of) the LBBB activation sequence. At shorter AV intervals, however, complete capture occurs from the pacing site(s), allowing resynchronization. The largest improvements in dP/dtmax occur at this point of transition from noncapture to complete capture. The best LV pump function is obtained with a relatively short AV interval, which allows complete activation of the ventricles from the two pacing sites.161 This AV interval may be different from the one resulting in optimized preload164 (Fig. 9-35). In one half of patients, the AV interval for optimal preload is usually longer than that for optimal synchrony; thus it is no surprise that the mean difference between the two AV intervals is close to zero.161 To date, prospective controlled data are still scanty to help determine the relative importance of optimizing synchrony and optimizing preload. Considering that asynchrony is a major cause of depressed pump function in patients with intraventricular conduction abnormalities, and that resynchronization has both short-term and longterm beneficial effects, we postulate that the primary target should be resynchronizing the ventricles, and that optimizing the ventricular inflow is of secondary importance in the majority of patients. The importance of restoration of ventricular asynchrony is supported by studies on the beneficial effect of CRT in patients with permanent atrial fibrillation (AF). In these patients, no preload optimization can be performed, and any possible beneficial effect on preload through CRT is excluded. Nevertheless, CRT has been shown to be effective in patients with AF and wide QRS complexes, especially once the AV node is ablated, abolishing any interference of underlying irregular, higherrate AF spontaneous rhythm. The extent of improvement appears to be comparable to that seen in patients in sinus rhythm, in functional terms as well as long-term prognosis.270-272 To optimize AV delay, invasive and noninvasive determinations of cardiac contractility and stroke volume may be performed. Invasive

225

determination (e.g., using LV dP/dtmax)273 is probably more accurate but is cumbersome and expensive and may carry significant risk for the patient. Noninvasive measurements comprise diastolic inflow measurements (mitral valve E and A wave) and systolic outflow measurements (aortic velocity time integrals, finger arterial pulse pressure). The advantage of outflow measurements is accounting for possible influences of CRT on mitral regurgitation, but mitral inflow is usually easier to measure and more accurate.169 Although validated to optimize AV interval in these patients, these echocardiographic methods remain time-consuming, with unproven clinical effect on large patient cohorts in prospective RCTs. Recent data suggest that the finger plethysmography for assessing arterial pressure and stroke volume is accurate274 and correlates well with echocardiographic methods for AV optimization in these patients.275 Integrated device–based algorithms to optimize AV interval have distinct clinical advantages, and different algorithms have been developed. One algorithm is based on measuring peak endocardial acceleration (PEA), a surrogate of LV dP/dtmax, using a lead with a microaccelerometer at the tip. The tip sensor detects vibration amplitude of the first heart sound, and this value should correlate with LV dP/dt.276 Other AV optimization algorithms are based on a combination of automatic measurements by intracardiac electrograms (EGMs) and surface ECGs268 or through indirect measurement of mechanical timing using surface ECGs or intracardiac signals.277,278 Some studies have found excellent correlation between EGM-based algorithm and invasively derived dP/dtmax268,279 or conventional echocardiography,277 whereas a more recent report demonstrated the reduced accuracy of a device-based interval algorithm optimization compared to conventional echocardiographic methods.278 Particularly relevant in this regard are the results of the large multicenter randomized trial SMARTAV that prospectively compared different modalities of AV interval optimization in CRT recipients, namely empirical AV delay of 120 msec, device electrogram-based algorithm, and echocardiographically guided AV optimization. Neither device electrogram nor echocardiographically based AV optimization conferred greater reduction of left ventricular end-systolic volume during follow-up compared to the empiric approach.279a Other preliminary data were presented about the CLEAR and FREEDOM trials. The CLEAR trial investigated the effect of periodic AV and interventricular (VV) optimization using the PEA

AVL  0 p  0.001 Responders 100 (a) 75 % maximum PP change

(b)

AVL APLS AP RA

10 mm Hg LS

50 25 0 25

(c) 100 ms (d)

50 200 150 100 50

0

50

100 150 200

AVL (ms) Figure 9-35  Maximum preload is associated with maximum increase in pulse pressure. Left, Upstroke of intraventricular pressure waveform in a patient with NYHA Class III heart failure (PATH-CHF-I trial). (a), During pacing at an intermediate AV interval; (b), during intrinsic propagation through the AV node of the normal atrial depolarization; (c), the ventricular electrogram during intrinsic activation; (d), the atrial electrogram. AVL, Time from peak of intraventricular pressure increase created by booster pump action of left atrium (AP) and the start of the ventricular contraction (LS); RA, right atrial. Right, Relationship between percent increase in aortic pulse pressure (PP) versus baseline (no pacing) obtained during cardiac resynchronization therapy (CRT) at different atrioventricular (AV) intervals (y-axis) versus the time between AP and LS for all the patients in whom hemodynamics improved with CRT in the PATH-CHF-I trial.

226

SECTION 2  Clinical Concepts

sensor. The clinical composite score had increased in 86% of periodically optimized patients versus 62% in the control group (P < .0007).280 Moreover, the proportion of patients who died from any cause or were hospitalized with heart failure was significantly lower (9%) in the sensor-based optimization group than the control group (25%; P < .001). In contrast, the FREEDOM study, using regular optimization with the Quickopt algorithm, did not improve CRT response.281 Until now the evidence suggests that device-based algorithms for AV optimization may not be equivalent because each may lead to a different outcome. EFFECT OF INTERVENTRICULAR DELAY Most CRT devices now offer independent programming of AV and VV intervals. Studies on the effect of changing VV intervals during BiV pacing have reported conflicting results.208,227,282 Because of variability in the conduction disturbances, as well as ischemic or scarred regions, different timing of stimulation of the two ventricles may be optimal.283,284 In fact, more recent data from larger patient populations indicate the need for optimizing VV interval, with most patients requiring early LV offset. The largest prospective multicenter study evaluating the effectiveness of sequential pacing showed that sequential BiV pacing increased stroke volume and exercise capacity during follow-up to a greater extent than simultaneous BiV pacing for CRT.282 Also, as with Vanderheyden et al.,285 this study confirms that about 60% of patients require early LV offset to optimize CRT. In the Rhythm-II ICD trial, patients with optimal programming of AV and VV interval showed better acute hemodynamic improvements; however, this did not translate into a difference in echocardiographic response after 6 months.286 An optimal setting of the VV interval may have a positive influence. According to the current model of how CRT works, the best resynchronization would be achieved by maximizing the synchrony of the activation through manipulation of the three activation wavefronts originating from the RBB, RV, and LV pacing leads. However, this same reasoning also indicates that an optimal VV interval may depend on the AV interval. The previously cited studies have not tested all the possible variations. Therefore, differences in optimal VV intervals may be caused, for example, by the use of different AV intervals. In clinical practice, performing such elaborate optimization protocol may be impractical and time-consuming, unless a simple technique such as finger blood pressure measurement is used,275,284 with integrated optimization software that simultaneously elaborates and computes the noninvasive hemodynamic data. Optimal use of the extensive possibilities to vary timing of stimulation may be fully applicable only if medical equipment manufacturers provide adequate tools specifically designed and validated for the fine-tuning of AV and VV intervals to provide optimized CRT. It should be emphasized, however, that several prospectively designed studies evaluating the effect of VV timing optimization on symptoms and clinical outcome have failed to show a real

ECG lead II

Pacer rate 67

150 100 50

Arterial pressure

0

M.G.H. #153 79 43

Figure 9-36  Radial artery pressure from a patient with complete atrioventricular (AV) block during fixed-rate ventricular pacing. Peak systolic pressure is seen when the PR interval is 270 msec (arrow).

clinical benefit. This might indicate that in the CRT population, VV timing plays a secondary role in modulating response to CRT. It is also possible, however, that a visible individual benefit may be diluted in the general population, or that the biologic variability offsets the minor (yet relevant in the individual patient) effect.

Pacemaker Syndrome When first described, pacemaker syndrome was attributed to ventricular pacing and recognized primarily as a problem of single-chamber ventricular pacemakers. However, with the greater use of dual-chamber pacing modes, it has become apparent that pacemaker syndrome is not unique to single-chamber pacing and may occur in different pacing modalities.287-290 Pacemaker syndrome is an array of cardiovascular and neurologic signs and symptoms resulting from disruption of appropriate AV synchrony (AV dyssynchrony) caused by suboptimal pacing, inappropriate programming of pacing parameters, or upper-limit behavior of AV synchronous pacing systems. The pathogenesis of pacemaker syndrome is complex, involving atrial and vascular reflexes and the neurohumoral system as well as the direct hemodynamic consequences of the loss of atrial systole. Patients most prone to the development of pacemaker syndrome are those with 1 : 1 retrograde ventriculoatrial (VA) conduction (Figs. 9-36 and 9-37) and those with lower stroke volume during ventricular pacing than with sinus rhythm or dualchamber pacing. This syndrome may occur, however, with any mode of pacing that results in permanent or temporary disruption of atrial and ventricular synchronous contraction. Patients treated with CRT devices may also theoretically demonstrate a pacemaker syndrome caused by inappropriate LA and LV timing. Indeed, interatrial conduction time can be significantly prolonged in patients with dilated cardiomyopathy. During CRT, the contraction of the late-activated region (most often located in LV lateral

1.0 m/sec

1 Second

Figure 9-37  Doppler aortic flow-velocity integrals during ventricular pacing in a patient with complete heart block. The effect of fortuitously timed P waves (arrows) on aortic flow is demonstrated.



9  Basic Physiology and Hemodynamics of Cardiac Pacing

227

“Shortness of breath”

Figure 9-38  Continuous rhythm strips recorded with a transtelephonic cardiac monitor in a 65-year-old farmer with pacemaker syndrome. This patient’s underlying rhythm disorder was sick sinus syndrome with sinus bradycardia, and he had experienced multiple episodes of atrial fibrillation 1 year earlier. His sinus bradycardia was exacerbated by treatment with quinidine, verapamil, and digoxin. One month after implantation of a VVIR device, the patient returned to his physician complaining of fatigue, weakness, dizziness, malaise, and shortness of breath. After documentation of this rhythm by a cardiac event monitor, he underwent further testing. During VVI pacing, ventriculoatrial (VA) dissociation occurred. During VVI pacing at 90 bpm, the patient’s blood pressure dropped to 90 systolic/68 diastolic mm Hg; during AAI pacing, it was 160/90 mm Hg (at 90 bpm). During sinus rhythm at 58 to 64 bpm, the blood pressure measured 136/70 mm Hg. A DDDR pacemaker was implanted, and within 48 hours, the patient’s symptoms were abolished. He returned to his active, vigorous lifestyle and experienced no subsequent episodes of atrial fibrillation for 1 year. (From Ellenbogen KA, Wood MA, Strambler B: Pacemaker syndrome: Clinical, hemodynamic, and neurohumoral features. In Barold SS, Mujica J [eds]: New perspectives in cardiac pacing. Mt Kisco, NY, Futura, 1992.)

wall) is advanced to coincide with the start of the contraction of the early-activated region (most often in interventricular septum and RV free wall) to maximize mechanical synchrony and thus efficiency.55,69 In a heart where the LA mechanical contraction has been delayed(e.g., because of combined interatrial block and atrial pacing), LA contraction might occur against a closed mitral valve, especially during BiV pacing, in which LV contraction has been advanced with respect to atrial activation (Fig. 9-38). This phenomenon has been described for patients with pacemakers, in whom the issue is less likely, because RV pacing normally delays the mechanical contraction of the left ventricle, increasing the time available for the left atrium to contract before the mitral valve is finally closed by LV contraction and subsequent pressure increase.151 In NYHA functional classes III and IV heart failure, occurrence of the LA contraction after closure of the mitral valve may trigger sudden increases in pulmonary pressures, similar to cannon A waves seen in pacemaker syndrome (usually observable in jugular veins). These increases could lead to acute decompensation and pulmonary edema in a patient with heart failure. It is also important to realize that this situation could be triggered by atrial pacing because of the increased AV delay that this mode of pacing creates. Pacemaker syndrome can be treated with an upgrade of the implanted device or with reprogramming of the parameters to achieve the optimal synchrony of atrial and ventricular contraction. Symptoms associated with pacemaker syndrome are variable in severity and onset (Table 9-4). Although the exact incidence is unknown, moderate to severe symptoms of pacemaker syndrome occur in an estimated 5% to 7% of patients in whom the ventricle is mostly paced (Fig. 9-38). Up to 10% of patients undergoing VVI pacing present with mild symptoms. The pathophysiology of pacemaker syndrome is rather complex, involving hemodynamic, neurohumoral, and baroreceptor changes. In addition to direct hemodynamic effect of loss of AV synchrony or 1 : 1 retrograde VA conduction, atrial and vascular reflexes initiated by atrial distention or elevated atrial pressures may also play a role. Atrial receptors and cardiopulmonary reflexes have been the subject of several in-depth reviews.291,292 Ellenbogen et al.293,294 extensively investigated the role of baroreflex activity during pacemaker syndrome provoked by VA pacing, providing evidence that inadequate systemic sympathetic response plays a key role in the onset of pacemaker syndrome (Fig. 9-39). Indeed, when patients assume an upright position, blood

is pooled in the lower extremities, and the arterial baroreceptors are activated to compensate for the decrease in cardiac output and systolic blood pressure. In some patients, pacemaker syndrome results from the inability to compensate further for the upright posture and augmentation of autonomic tone. In other patients, pacemaker syndrome may result from modification of these vascular responses through the effects of drugs, such as vasodilators and diuretics. In still other patients, pacemaker syndrome may result from activation of inhibitory atrial and cardiopulmonary reflexes that counteract the protective vasoconstrictor reflex (see Fig. 9-39). These responses may be further modified by the production of catecholamines and ANF. Circulating levels of ANF are frequently elevated in patients with complete AV block and bradycardia, being reduced within minutes of programming.295,296 Pacemaker syndrome during AAI or AAIR pacing has been described and emphasizes the role of AV dyssynchrony in the pathogenesis. Patients originally undergoing pacing for sick sinus syndrome may later demonstrate AV conduction abnormalities, or AV nodal conduction may be impaired by drugs with AV node–blocking properties (e.g., digoxin, β-blockers, calcium channel blockers, antiarrhythmics), leading to prolonged and hemodynamically unfavorable atrial R-wave (AR) intervals. AV dyssynchrony may also occur in patients with

TABLE

9-4 

Degree Mild

Moderate

Severe

Symptoms of Pacemaker Syndrome Symptoms Pulsations in neck, abdomen Palpitations Fatigue, malaise, weakness Cough Apprehension Chest fullness or pain Headache, jaw pain Shortness of breath on exertion Dizziness, tiredness, vertigo Orthopnea, paroxysmal nocturnal dyspnea Choking sensation Confusion or alteration of mental state Presyncope Syncope Shortness of breath at rest, pulmonary edema

228

SECTION 2  Clinical Concepts

VVI pacing Sinoaortic baroreceptors

Retrograde VA conduction

↓ C.O. ↓ S.V. ↓ B.P.

↑ L.A.P. ↑ P.A.P.

()

() Vagal cardiopulmonary mechanoreceptors Afferent Input

()

()

()

()

()

()

()

Sympathetic outflow

Effector organs

↑ Epi

Parasympathetic outflow

Vasoconstriction

↑ Tachycardia contractility

Arterial Baroreflex

Bradycardia

Vasodilation

Vagal Cardiopulmonary Reflex

Figure 9-39  Multiple reflex pathways in pacemaker syndrome. Arterial baroreflexes detect a decrease in stroke volume when atrioventricular (AV) asynchrony occurs, leading to sympathetic activation and vasoconstriction. Conversely, AV asynchrony results in higher atrial wall tension and activation of reflex pathways, leading to vagally mediated vasodilatation as well as release of humoral substances (e.g., ANP) that further facilitate these reflexes (e.g., counteracting baroreflex-mediated vasoconstriction). BP, Blood pressure; CO, cardiac output; Epi, epinephrine; LAP, left atrial pressure; PAP, pulmonary artery pressure; SV, stroke volume; VA, ventriculoatrial.

dual–AV nodal pathway physiology during a shift in conduction from the fast pathway to the slow pathway with prolonged AV conduction time. Unfavorable sequencing of atrial and ventricular contractions may occur during AAIR pacing at high sensor-driven rates.288 This situation most often results when the slope determining the sensor-driven rate is programmed too aggressively and out of proportion to the exercise-induced increase in catecholamine levels. As the paced atrial rate progressively increases, the appropriate corresponding decrement in PR interval does not occur, and the interval may even lengthen, Name 25 mm/s 10 mm/mv

eventually resulting in a paced P wave occurring immediately after the preceding R wave (Fig. 9-40). This event most frequently occurs in the earlier stages of exercise and, in some patients, is corrected as the patient continues to exercise. The VDD pacing mode is similar to DDD mode but without the capability of atrial pacing. The VDD mode, previously out of favor, has been revived by the development of CRT.222,297 Atrioventricular dyssynchrony and pacemaker syndrome may also occur during dual-chamber pacing as a result of inappropriate

ID 20-MAY-93 14:38 10-100 Hz Pgm 004B

Name ID: 25 mm/s 10 mm/mv 16-100B

V1 II V5

aVR aVL

Figure 9-40  AAIR pacemaker recording. Patient was receiving β-blockers and experienced pacemaker syndrome while walking. His heart rate increased from 70 to 90 bpm, and his paced atria-sensed QRS (AR) interval increased from 180 msec to more than 500 msec, resulting in shortness of breath. Discontinuing β-blockers and reprogramming the pacemaker to a less “aggressive” slope resulted in a much shorter prolongation of the AR interval with exercise.



9  Basic Physiology and Hemodynamics of Cardiac Pacing

programming, prolonged atrial conduction time, or normal upper rate limit behavior.289,290,298 In AV sequential pacing modes, selection of an inappropriate AV interval may result in an adverse AV sequencing and hemodynamics. Differential AV intervals for paced and sensed atrial events and rate-adaptive AV intervals are useful in some patients for maintaining AV synchrony over a wide range of heart rates at rest and during exercise. The maximum atrial tracking rate is determined by the total atrial refractory period (TARP), which is composed of the AV interval and the postventricular atrial refractory period (PVARP). Long AV intervals or long PVARP intervals are sometimes programmed to avoid pacemaker-mediated tachycardia. When the TARP is too long, the maximal atrial tracking rate is low. Patients may experience symptoms of pacemaker syndrome during exercise when their atrial rate exceeds the maximal atrial tracking rate (MATR), resulting in 2 : 1 AV block and a sudden, marked decrease in cardiac output in patients with complete heart block, or in a lack of ventricular pacing in patients with normal AV conduction (crucial in CRT because therapy would stop). This situation may be improved with reprogramming of shorter AV intervals or PVARP intervals to allow 1 : 1 ventricular tracking at higher atrial rates.

Pacing in Hypertrophic Obstructive Cardiomyopathy In patients with hypertrophic obstructive cardiomyopathy (HOCM), systolic anterior motion of the mitral valve toward the intraventricular septum is associated with LV outflow tract obstruction, often with significant mitral regurgitation. Such patients are extremely sensitive to changes in preload and to conditions that diminish LV filling and result in decreased LV cavity size and increased intraventricular gradient. Thus, these patients may respond quite differently to ventricular pacing than patients with a normal heart. It has long been known that patients with HOCM who require pacing because of bradycardia experience significantly more benefit from pacing modes that preserve AV synchrony than from ventricular pacing.299,300 Moreover, the abnormal sequence of electrical activation following RV pacing may generate a beneficial effect on the septal wall motion in patients with HOCM.160,301,302 RV pacing causes the septum to move away from the free wall during systole, increasing the LV outflow tract diameter and reducing the intraventricular outflow gradient (Fig. 9-41). In addition to widening of the LV outflow gradient, apex pacing may also reduce the Venturi effect and diminish systolic anterior motion of the mitral valve.160 Because of the proposed mechanism of benefit resulting from the altered sequence of a paced ventricular contraction, AV sequential or atrial synchronous pacing must be

229

A

B Figure 9-41  Schematic representation of a monoplane ventriculography. Patient had severe hypertrophic obstructive cardiomyopathy during AAI pacing at a rate of 90 bpm (A) and during DDD pacing at a rate of 90 bpm and an atrioventricular (AV) delay interval of 50 msec  (B). Note that the alteration in ventricular contraction pattern produced by right apical pacing results in less left ventricular outflow tract obstruction during systole. (From Jeanrenaud X, Goy JJ, Kappenberger LK: Effects of dual-chamber pacing in hypertrophic obstructive cardiomyopathy. Lancet 339:1318, 1992.)

performed with a short AV interval to ensure ventricular preexcitation (see Fig. 9-41). Pacing may be especially indicated in patients with HOCM who have significant intraventricular gradients and symptoms despite medical therapy. In these patients, implantation of a sequential AV pacemaker significantly reduces ventricular outflow gradient, improves NYHA functional class and quality of life, and reduces symptoms, including syncope and presyncope. After initial enthusiasm about the role of pacemaker therapy in patients with HOCM, controversy arose later regarding its efficacy and long-term safety.303 Most randomized studies showed flaws in their design.304 Also, at the same time pacemaker therapy was introduced, transcatheter ablation was introduced for reduction of the outflow tract obstruction. The efficacy of the two therapies has not yet been compared. A recent study found promising effects of pacemaker therapy in patients with heart failure and HOCM, including progressive reduction of the outflow tract obstruction and in heart failure class.305 The few existing data suggest that pacing therapy is not beneficial in patients with nonobstructive hypertrophic cardiomyopathy or in those with minimal intraventricular gradients.306 This topic is discussed in more detail in Chapter 15.

REFERENCES 1. Saffitz JE, Davis LM, Darrow BJ, et al: The molecular basis of anisotropy: role of gap junctions. J Cardiovasc Electrophysiol 6:498-510, 1995. 2. Scher AM, Young AC, Malmgreen AL, Paton RR: Spread of electrical activity through the wall of the ventricle. Circ Res 1:539547, 1953. 3. Scher AM, Young AC, Malmgren AL, Erickson RV: Activation of the interventricular septum. Circ Res 3:56-64, 1955. 4. Myerburg RJ, Nilsson K, Gelband H: Physiology of canine intraventricular conduction and endocardial excitation. Circ Res 30:217-243, 1972. 5. Hoffman BF, Cranefield PF, Stuckley JH, et al: Direct measurement of conduction velocity in in situ specialized conduction system of mammalian heart. Proc Soc Exp Biol Med 102:55-57, 1959. 6. Kulbertus HE, Demoulin JC: The left hemiblocks: significance, prognosis and treatment. Schweiz Med Wochenschr 112:15791584, 1982. 7. Uhley HN, Rivkin L: Peripheral distribution of the canine A-V conduction system. Am J Cardiol 5:688-691, 1960. 8. Abramson DI, Margolin S: A Purkinje conduction network in the myocardium of the mammalian ventricles. J Anat 70:251259, 1936. 9. Truex RC, Copenhaver WM: Histology of the moderator band in man and other mammals with special reference to the conduction system. Am J Anat 80:173-200, 1947.

10. Berenfeld O, Jalife J: Purkinje-muscle reentry as a mechanism of polymorphic ventricular arrhythmias in 3-dimensional model of ventricles. Circ Res 82:1063-1077, 1998. 11. Durrer D, Dam v RT, Freud GE, et al: Total excitation of the isolated human heart. Circulation 41:899-912, 1970. 12. Spach MS, Barr RC: Ventricular intramural and epicardial potential distributions during ventricular activation and repolarization in the intact dog. Circ Res 37:243-257, 1975. 13. Rawling DA, Joyner RW, Overholt ED: Variations in the functional electrical coupling between the subendocardial Purkinje and ventricular layers of the canine left ventricle. Circ Res 57:252-261, 1985. 14. Bers DM: Cardiac excitation-contraction coupling. Nature 415:198-205, 2002. 15. Van Heuningen R, Rijnsburger WH, Ter Keurs HEDJ: Sarcomere length control in striated muscle. Am J Physiol 242:H411-H420, 1982. 16. Prinzen FW, Augustijn CH, Allessie MA, et al: The time sequence of electrical and mechanical activation during spontaneous beating and ectopic stimulation. Eur Heart J 13:535-543, 1992. 17. Hasenfuss G, Reinecke H, Studer R: Relation between myocardial function and expression of sarcoplasmic reticulum Ca2+ATPase in failing and nonfailing human myocardium. Circ Res 75:434-442, 1994. 18. Studer R, Reinecke H, Bilger J, et al: Gene expression of the cardiac Na+-Ca2+ exchanger in end-stage human heart failure. Circ Res 75:443-453, 1994.

19. Verdonck F, Volders PG, Vos MA, Sipido KR: Increased Na+ concentration and altered Na/K pump activity in hypertrophied canine ventricular cells. Cardiovasc Res 57:1035-1043, 2003. 20. O’Rourke B, Kass DA, Tomaselli GF, et al: Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure. Circ Res 84:562-570, 1999. 21. Pogwizd SM, Qi M, Yuan W, et al: Upregulation of Na+/Ca2+ exchanger expression and function in an arrhythmogenic rabbit model of heart failure. Circ Res 85:1009-1019, 1999. 22. Swynghedauw B: Molecular mechanisms of myocardial remodeling: review. Physiol Rev 79:215-262, 1999. 23. Cooper GI: Load and length regulation of cardiac energetics. Annu Rev Physiol 52:505-522, 1990. 24. Vassallo JA, Cassidy DM, Marchlinski FE, et al: Endocardial activation of left bundle branch block. Circulation 69:914-923, 1984. 25. Durrer D, Roos JP: Epicardial excitation of the ventricles in a patient with a Wolff-Parkinson-White syndrome (type B). Circulation 35:15, 1967. 26. Lister JW, Klotz DH, Jomain SL, et al: Effect of pacemaker site on cardiac output and ventricular activation in dogs with complete heart block. Am J Cardiol 14:494-503, 1964. 27. Vassallo JA, Cassidy DM, Miller JM, et al: Left ventricular endocardial activation during right ventricular pacing: effect of underlying heart disease. J Am Coll Cardiol 7:1228-1233, 1986. 28. Spach MS, Miller WT, Geselowitz DB, et al: The discontinuous nature of propagation in normal canine cardiac muscle:

230

SECTION 2  Clinical Concepts

evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res 48:39-54, 1981. 29. Frazier DW, Krassowska W, Chen PS, et al: Transmural activations and stimulus potentials in three-dimensional anisotropic canine myocardium. Circ Res 63:135-146, 1988. 30. Wiggers CJ: The muscular reactions of the mammalian ventricles to artificial surface stimuli. Am J Physiol 73:346-378, 1925. 31. Prinzen FW, Augustijn CH, Arts T, et al: Redistribution of myocardial fiber strain and blood flow by asynchronous activation. Am J Physiol 259:H300-H308, 1990. 32. Myerburg RJ, Gelband H, Nilsson K, et al: The role of canine superficial ventricular fibers in endocardial impulse conduction. Circ Res 42:27-35, 1978. 33. Van Deursen C, Van Geldorp IE, Rademakers LM, et al: Left ventricular endocardial pacing improves resynchronization therapy in canine left bundle-branch hearts. Circulation Arrhythm Electrophysiol 2:580-587, 2009. 34. Askenazi J, Alexander JH, Koenigsberg DI, et al: Alteration of left ventricular performance by left bundle branch block simulated with atrioventricular sequential pacing. Am J Cardiol 53:99-104, 1984. 35. Hirzel HO, Senn M, Nuesch K, et al: Thallium-201 scintigraphy in complete left bundle branch block. Am J Cardiol 53:764-769, 1984. 36. Verbeek X, Vernooy K, Peschar M, et al: Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block. J Am Coll Cardiol 42:558-567, 2003. 37. Ono S, Nohara R, Kambara H, et al: Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block. Circulation 85:1125-1131, 1992. 38. Rosenbush SW, Ruggie N, Turner DA, et al: Sequence and timing of ventricular wall motion in patients with bundle branch block. Circulation 66:113-119, 1982. 39. Rodriguez LM, Timmermans C, Nabar A, et al: Variable patterns of septal activation in patients with left bundle branch block and heart failure. J Cardiovasc Electrophysiol 14:135-141, 2003. 40. Auricchio A, Abraham WT: Cardiac resynchronization therapy: current state of the art, cost versus benefit. Circulation 109:300307, 2004. 41. Lambiase PD, Rinaldi A, Hauck J, et al: Non-contact left ventricular endocardial mapping in cardiac resynchronisation therapy. Heart 90:44-51, 2004. 42. Fung JW, Yu CM, Yip G, et al: Variable left ventricular activation pattern in patients with heart failure and left bundle branch block. Heart 90:17-19, 2004. 43. Sohi GS, Flowers NC, Horan LG, et al: Comparison of total body surface map depolarization patterns of left bundle branch block and normal axis with left bundle branch block and left-axis deviation. Circulation 67:660-664, 1983. 44. Narula OS: Longitudinal dissociation in the His bundle: bundle branch block due to asynchronous conduction within the His bundle in man. Circulation 56:996-1006, 1977. 45. Becker RA, Erickson RV, Scher AM: Ventricular excitation in experimental bundle-branch block. Circ Res 5:5-10, 1957. 46. Prinzen FW, Auricchio A: Is echocardiographic assessment of dyssynchrony useful to select candidates for cardiac resynchronization therapy? Echocardiography is not useful before cardiac resynchronization therapy if QRS duration is available. Circ Imaging 1:70-78, 2008. 46a.  Strik M, Ploux S, Vernooy K, Prinzen FW: Cardiac resynchronization therapy: Refocus on electrical substrate. Circ J 75:12971304, 2011. 47. Badke FR, Boinay P, Covell JW: Effect of ventricular pacing on regional left ventricular performance in the dog. Am J Physiol 238:H858-H867, 1980. 48. Prinzen FW, Hunter WC, Wyman BT, McVeigh ER: Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol 33:1735-1742, 1999. 49. Tyberg JV, Parmley WW, Sonnenblick EH: In vitro studies of myocardial asynchrony and regional hypoxia. Circ Res 25:569579, 1969. 50. Prinzen FW, van Oosterhout MFM, Vanagt WYR, et al: Optimization of ventricular function by improving the activation sequence during ventricular pacing. PACE 21:2256-2260, 1998. 51. Delhaas T, Arts T, Bovendeerd PHM, et al: Subepicardial fiber strain and stress as related to left ventricular pressure and volume. Am J Physiol 264:H1548-H1559, 1993. 52. Little WC, Reeves RC, Arciniegas J, et al: Mechanism of abnormal interventricular septal motion during delayed left ventricular activation. Circ Res 65:1486-1490, 1982. 53. Grines CL, Bashore TM, Boudoulas H, et al: Functional abnormalities in isolated left bundle branch block. Circulation 79:845853, 1989. 54. Vernooy K, Verbeek XA, Peschar M, et al: Left bundle branch block induces ventricular remodelling and functional septal hypoperfusion. Eur Heart J 26:91-98, 2005. 55. De Boeck BW, Teske AJ, Meine M, et al: Septal rebound stretch reflects the functional substrate to cardiac resynchronization therapy and predicts volumetric and neurohormonal response. Eur J Heart Fail 11:863-871, 2009. 56. Klimusina J, De Boeck BW, Faletra FF, et al: Redistribution and homogenization of left ventricular strain by cardiac resynchronization therapy in heart failure patients. Eur J Heart Fail 13:186194, 2001.

57. Vernooy K, Cornelussen RN, Verbeek XA, et al: Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts. Eur Heart J 28:2148-2155, 2007. 58. Delhaas T, Arts T, Prinzen FW, Reneman RS: Regional fibre stress–fibre strain area as estimate of regional oxygen demand in the canine heart. J Physiol (Lond) 477:481-496, 1994. 59. Mills RW, Cornelussen RN, Mulligan LJ, et al: Left ventricular septal and left ventricular apical pacing chronically maintain cardiac contractile coordination, pump function and efficiency. Circulation Arrhythm Electrophysiol 2:571-579, 2009. 60. Nielsen JC, Boetcher M, Toftegaard Nielsen T, et al: Regional myocardial blood flow in patients with sick sinus syndrome randomized to long-term single chamber atrial or dual chamber pacing: effect of pacing mode and rate. J Am Coll Cardiol 35:1453-1461, 2000. 61. Nowak B, Sinha AM, Schaefer WM, et al: Cardiac resynchronization therapy homogenizes myocardial glucose metabolism and perfusion in dilated cardiomyopathy and left bundle branch block. J Am Coll Cardiol 41:1523-1528, 2003. 62. Lindner O, Vogt J, Kammeier A, et al: Effect of cardiac resynchronization therapy on global and regional oxygen consumption and myocardial blood flow in patients with non-ischaemic and ischaemic cardiomyopathy. Eur Heart J 26:70-76, 2005. 63. Beppu S, Matsuda H, Shishido T, Miyatake K: Functional myocardial perfusion abnormality induced by left ventricular asynchronous contraction: experimental study using myocardial contrast echocardiography. J Am Coll Cardiol 29:1632-1638, 1997. 64. Ten Cate TJ, Visser FC, Panhuyzen-Goedkoop NM, et al: Pacemaker-related myocardial perfusion defects worsen during higher pacing rate and coronary flow augmentation. Heart Rhythm 2:1058-1063, 2005. 65. Boerth RC, Covell JW: Mechanical performance and efficiency of the left ventricle during ventricular stimulation. Am J Physiol 221:1686-1691, 1971. 66. Baller D, Wolpers HG, Zipfel J, et al: Unfavorable effects of ventricular pacing on myocardial energetics. Basic Res Cardiol 76:115-123, 1981. 67. Baller D, Wolpers H-G, Zipfel J, et al: Comparison of the effects of right atrial, right ventricular apex and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency: a laboratory investigation. PACE 11:394-403, 1988. 68. Owen CH, Esposito DJ, Davis JW, Glower DD: The effects of ventricular pacing on left ventricular geometry, function, myocardial oxygen consumption and efficiency of contraction in conscious dogs. PACE 21:1417-1429, 1998. 69. Nelson GS, Berger RD, Fetics BJ, et al: Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundlebranch block. Circulation 102:3053-3059, 2000. 70. Van Oosterhout MF, Prinzen FW, Arts T, et al: Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall. Circulation 98:588-595, 1998. 71. Gilmore JP, Sarnoff SJ, Mitchell JH, Linden RJ: Synchronicity of ventricular contraction: observations comparing hæmodynamic effects of atrial and ventricular pacing. Br Heart J 25:299-307, 1963. 72. Park RC, Little WC, O’Rourke RA: Effect of alteration of left ventricular activation sequence on the left ventricular endsystolic pressure-volume relation in closed-chest dogs. Circ Res 57:706-717, 1985. 73. Bahler RC, Martin P: Effects of loading conditions and inotropic state on rapid filling phase of left ventricle. Am J Physiol 248:H523-H533, 1985. 74. Leclercq C, Gras D, Le Helloco A, et al: Hemodynamic importance of preserving the normal sequence of ventricular activation in permanent cardiac pacing. Am Heart J 129:1133-1141, 1995. 75. Betocchi S, Piscione F, Villari B, et al: Effects of induced asynchrony on left ventricular diastolic function in patients with coronary artery disease. J Am Coll Cardiol 21:1124-1131, 1993. 76. Bedotto JB, Grayburn PA, Black WH, et al: Alterations in left ventricular relaxation during atrioventricular pacing in humans. J Am Coll Cardiol 15:658-664, 1990. 77. Rosenqvist M, Bergfeldt L, Haga Y, et al: The effect of ventricular activation sequence on cardiac performance during pacing. PACE 19:1279-1287, 1996. 78. Zile MR, Blaustein AS, Shimizu G, Gaasch WH: Right ventricular pacing reduces the rate of left ventricular relaxation and filling. J Am Coll Cardiol 10:702-709, 1987. 79. Blaustein AS, Gaasch WH: Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate. Am J Physiol 244, 1983. 80. Heyndrickx GR, Vantrimpont PJ, Rousseau MF, Pouleur H: Effects of asynchrony on myocardial relaxation at rest and during exercise in conscious dogs. Am J Physiol 254:H817-H822, 1988. 81. Zhou Q, Henein M, Coats A, Gibson D: Different effects of abnormal activation and myocardial disease on left ventricular ejection and filling times. Heart 84:272-276, 2000. 82. Lee MA, Dae MW, Langberg JJ, et al: Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology. J Am Coll Cardiol 24:225-232, 1994. 83. Maurer G, Torres MA, Corday E, et al: Two-dimensional echocardiographic contrast assessment of pacing-induced mitral

regurgitation: relation to altered regional left ventricular function. J Am Coll Cardiol 3:986-991, 1984. 84. Miyazawa K, Shirato K, Haneda T, et al: Effects of varying pacemaker sites on left ventricular performance. Tohoku J Exp Med 120:301-308, 1976. 85. Mark JB, Chetham PM: Ventricular pacing can induce hemodynamically significant mitral valve regurgitation. Anesthesiology 74:375-377, 1991. 86. Twidale N, Manda V, Holliday R, et al: Mitral regurgitation after atrioventricular node catheter ablation for atrial fibrillation and heart failure: acute hemodynamic features. Am Heart J 138:1166-1175, 1999. 87. Rosenqvist M, Isaaz K, Botvinick EH, et al: Relative importance of activation sequence compared to atrioventricular synchrony in left ventricular function. Am J Cardiol 67:148-156, 1991. 88. Bramlet DA, Morris KG, Coleman RE, et al: Effect of AA-adrenoceptor antagonists (phentolamine, nicergoline and prazosin) on reperfusion arrhythmias and noradrenaline release in perfused rat heart. Circulation 67:1059-1065, 1983. 89. Little WC, Park RC, Freeman GL: Effects of regional ischemia and ventricular pacing on LV dP/dTmax-end-diastolic volume relation. Am J Physiol 252:H933-H940, 1987. 90. Suga H, Goto Y, Yaku H, et al: Simulation of mechanoenergetics of asynchronously contracting ventricle. Am J Physiol 259: R1075-R1082, 1990. 91. Prinzen FW, Peschar M: Relation between the pacing induced sequence of activation and left ventricular pump function in animals. PACE 25:484-498, 2002. 92. Klotz DH, Lister JW, Jomain SL, et al: Implantation sites of pacemakers after right ventriculotomy and complete heart block. JAMA 186:929-931, 1963. 93. Vanagt WY, Verbeek XA, Delhaas T, et al: The left ventricular apex is the optimal site for pediatric pacing: correlation with animal experience. Pacing Clin Electrophysiol 27:837-843, 2004. 94. Peschar M, de Swart H, Michels KJ, et al: Left ventricular septal and apex pacing for optimal pump function in canine hearts. J Am Coll Cardiol 41:1218-1226, 2003. 95. Ypenburg C, Lancellotti P, Tops LF, et al: Acute effects of initiation and withdrawal of cardiac resynchronization therapy on papillary muscle dyssynchrony and mitral regurgitation. J Am Coll Cardiol 50:2071-2077, 2007. 96. Otsuji Y, Gilon D, Jiang L, et al: Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering. J Am Coll Cardiol 32:398404, 1998. 97. Breithardt OA, Stellbrink C, Herbots L, et al: Cardiac resynchronization therapy can reverse abnormal myocardial strain distribution in patients with heart failure and left bundle branch block. J Am Coll Cardiol 42:486-494, 2003. 98. Rosen MR: The heart remembers: clinical implications. Lancet 357:468-471, 2001. 99. Plotnikov AN, Yu H, Geller JC, et al: Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart. Circulation 107:2844-2849, 2003. 100. Patberg KW, Plotnikov AN, Quamina A, et al: Cardiac memory is associated with decreased levels of the transcriptional factor CREB modulated by angiotensin II and calcium. Circ Res 93:472478, 2003. 101. Wecke L, Rubulis A, Lundahl G, et al: Right ventricular pacing– induced electrophysiological remodeling in the human heart and its relationship to cardiac memory. Heart Rhythm 4:14771486, 2007. 102. Costard-Jäckle A, Franz MR: Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts: evidence for cardiac “memory”. Circulation 80:1412-1420, 1989. 103. Alessandrini RS, McPherson DD, Kadish AH, et al: Cardiac memory: a mechanical and electrical phenomenon. Am J Physiol 272:H1952-H1959, 1997. 104. Nahlawi M, Waligora M, Spies SM, et al: Left ventricular function during and after right ventricular pacing. J Am Coll Cardiol 44:1883-1888, 2004. 105. Prinzen FW, Cheriex EM, Delhaas T, et al: Asymmetric thickness of the left ventricular wall resulting from asynchronous electrical activation: a study in patients with left bundle branch block and in dogs with ventricular pacing. Am Heart J 130:1045-1053, 1995. 106. Van Oosterhout MFM, Arts T, Muijtjens AMM, et al: Remo­ deling by ventricular pacing in hypertrophying dog hearts. Cardiovasc Res 49:771-778, 2001. 107. Karpawich PP, Justice CD, Cavitt DL, Chang CH: Developmental sequelae of fixed-rate ventricular pacing in the immature canine heart: an electrophysiologic, hemodynamic and histopathologic evaluation. Am Heart J 119:1077-1083, 1990. 108. Waldman LK, Covell JW: Effects of ventricular pacing on finite deformation in canine left ventricles. Am J Physiol 252:H1023H1030, 1987. 109. Knaapen P, van Campen LM, de Cock CC, et al: Effects of cardiac resynchronization therapy on myocardial perfusion reserve. Circulation 110:646-651, 2004. 110. Patel PM, Plotnikov A, Kanagaratnam P, et al: Altering ventricular activation remodels gap junction distribution in canine heart. J Cardiovasc Electrophysiol 12:570-577, 2001. 111. Spragg DD, Akar FG, Helm RH, et al: Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts. Cardiovasc Res 67:77-86, 2005.



112. Akar FG, Spragg DD, Tunin RS, et al: Mechanisms underlying conduction slowing and arrhythmogenesis in nonischemic dilated cardiomyopathy. Circ Res 95:717-725, 2004. 113. Chakir K, Daya SK, Aiba T, et al: Mechanisms of enhanced betaadrenergic reserve from cardiac resynchronization therapy. Circulation 119:1231-1240, 2009. 114. Aiba T, Hesketh GG, Barth AS, et al: Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy. Circulation 119:1220-1230, 2009. 115. Vanderheyden M, Mullens W, Delrue L, et al: Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy responders versus nonresponders. J Am Coll Cardiol 51:129-136, 2008. 116. Kertesz NJ, Friedman RA, Colan SD, et al: Left ventricular mechanics and geometry in patients with congenital complete atrioventricular block. Circulation 96:3430-3435, 1997. 117. Udink ten Cate FE, Breur JM, Cohen MI, et al: Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children. J Am Coll Cardiol 37:11291134, 2001. 118. Peschar M, Vernooy K, Cornelussen RN, et al: Structural, electrical and mechanical remodeling of the canine heart in AV-block and LBBB. Eur Heart J 6(Suppl D):61-65, 2004. 119. Vos MA, De Groot SHM, Verduyn SC, et al: Enhanced susceptibility for aquired torsade de pointes arrrhythmias in the dog with chronic, complete AV block is related to cardiac hypertrophy and electrical remodeling. Circulation 98:1125-1135, 1998. 120. Brockman SK: Cardiodynamics of complete heart block. Am J Cardiol 16:72-83, 1965. 121. Brockman SK, Stoney WS: Congestive heart failure and cardiac output in heart block and during pacing. Ann NY Acad Sci 167:534-545, 1969. 122. Breur JM, Udink Ten Cate FE, Kapusta L, et al: Pacemaker therapy in isolated congenital complete atrioventricular block. Pacing Clin Electrophysiol 25:1685-1691, 2002. 123. Tantengco MV, Thomas RL, Karpawich PP: Left ventricular dysfunction after long-term tight ventricular apical pacing in the young. J Am Coll Cardiol 37:2093-2100, 2001. 124. Thambo JB, Bordachar P, Garrigue S, et al: Detrimental ventricular remodeling in patients with congenital complete heart block and chronic right ventricular apical pacing. Circulation 110:3766-3772, 2004. 125. Benchimol A, Ellis JC, Dimond EG: Hemodynamic consequences of atrial and ventricular pacing in patietins with normal and abnormal hearts. Am J Med 39:911-922, 1965. 126. Sowton E: Haemodynamic studies in patients with artificial pacemakers. Br Heart J 26:737-746, 1964. 127. Karlof I, Bevegard S, Ovenfors CO: Adaptation of the left ventricle to sudden changes in heart rate in patients with artificial pacemakers. Cardiovasc Res 7:322-330, 1973. 128. Wright AJ, Hudlicka O: Capillary growth and changes in heart performance induced by chronic bradycardial pacing in the rabbit. Circ Res 49:469-478, 1981. 129. Brown MD, Davies MK, Hudlicka O: The effect of long-term bradycardia on heart microvascular supply and performance. Cell Mol Biol Res 40:137-142, 1994. 130. Lei L, Zhou R, Zheng W, et al: Bradycardia induces angiogenesis increases coronary reserve, and preserves function of the postinfarcted heart. Circulation 110:796-802, 2004. 131. Ishibashi Y, Shimada T, Nosaka S, et al: Effects of heart rate on coronary circulation and external mechanical efficiency in elderly hypertensive patients with left ventricular hypertrophy. Clin Cardiol 19:620-630, 1996. 132. Kristensson B, Arnman K, Ryden L, et al: The haemodynamic importance of atrioventricular synchrony and rate increase at rest and during exercise. Eur Heart J 6:773-778, 1985. 133. Perhsson SK: Influence of heart rate and atrioventricular synchrony on maximal work tolerance in patients treated with artificial pacemakers. Acta Med Scand 214:311-315, 1983. 134. Fananapazir L, Bennett DH, Monks P: Atrial synchronized ventricular pacing: contribution of the chronotropic response to improved exercise performance. PACE 6:601-608, 1983. 135. Rowe GG, Stenlund RR, Thomsen JH, et al: Coronary and systemic hemodynamic effects of cardiac pacing in man with complete heart block. Circulation 40:839-845, 1969. 136. Bowman AW, Kovacs SJ: Left atrial conduit volume is generated by deviation from the constant-volume state of the left heart: a combined MRI-echocardiographic study. Am J Physiol Heart Circ Physiol 286:H2416-H2424, 2004. 137. Samet P, Castillo P, Bernstein WH: Hemodynamic consequences of sequential atrioventricular pacing. Am J Cardiol 21:207-212, 1968. 138. Daggett WM, Bianco JA, Powel WJ, Austen WG: Relative contribution of the atrial systole-ventricular systole interval and of patterns of ventricular activation to ventricular function during electrical pacing of the dog heart. Circ Res 27:69-79, 1970. 139. Kosowsky BD, Scherlag BJ, Damato AN: Re-evaluation of the atrial contribution to ventricular function. Am J Cardiol 21:518524, 1968. 140. Faerestrand S, Ohm OJ: A time-related study of the hemodynamic benefit of atrioventricular synchronous pacing evaluated by Doppler echocardiography. PACE 8:838-848, 1985. 141. Masuyama T, Kodama S, Nakatani S, Kitakabe A: Effects of atrioventricular interval on left ventricular diastolic filling assessed with pulsed Doppler echocardiography. Cardiovasc Res 23:10341042, 1989.

9  Basic Physiology and Hemodynamics of Cardiac Pacing 142. Mitchell JH, Gupta RC, Payne RM: Influence of atrial systole on effective ventricular stroke volume. Circ Res 17:11-18, 1965. 143. Mehta D, Gilmour S, Ward DE, Camm AJ: Optimal atrioventricular delay at rest and during exercise in patients with dual chamber pacemakers: a non-invasive assessment by continuous wave Doppler. Br Heart J 61:161-166, 1989. 144. Tanabe A, Mohri T, Ohga M, et al: The effects of pacing-induced left bundle branch block on left ventricular systolic and diastolic performances. Jpn Heart J 31:309-317, 1990. 145. Nielsen JC, Andersen HR, Thomsen PEB, et al: Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to singlechamber atrial or ventricular pacing. Circulation 97:987-995, 1998. 146. Wish M, Fletcher RD, Gottdiener JS, et al: Importance of left atrial timing in the programming of dual-chamber pacemakers. Am J Cardiol 60:566-571, 1987. 147. Janosik DL, Pearson AC, Buckingham TA, et al: The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing. J Am Coll Cardiol 14:499-507, 1989. 148. Catania SL, Maue-Dickson W: AV delay latency compensation. J Electrophysiol 3:242, 1987. 149. Sutton R: The atrioventricular interval: what considerations influence its programming? Eur J Cardiac Pacing Electrophysiol 3:192, 1992. 150. Alt EU, VonBirbra H, Blömer H: Different beneficial AV intervals with DDD pacing after sensed or paced atrial events. J Electrophysiol 1:250, 1987. 151. Chirife R, Ortega DF, Salazar AI: Nonphysiological left heart AV intervals as a result of DDD and AAI “physiological” pacing. Pacing Clin Electrophysiol 14:1752-1756, 1991. 152. Capucci A, Boriani G, Specchia S, et al: Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing. Pacing Clin Electrophysiol 15:1908-1913, 1992. 153. Daubert C, Richter P, Mabo P, et al: Physiological relationship between AV interval and heart rate in healthy subjects: applications to dual-chamber pacing. Pacing Clin Electrophysiol 9: 1032-1039, 1986. 154. Luceri RM, Brownstein SL, Vardeman L, et al: PR interval behaviour during exercise: implications for physiological pacemakers. Pacing Clin Electrophysiol 13:1719-1723, 1990. 155. Barbieri D, Percoco GF, Toselli T, et al: AV delay and exercise stress test: behaviour in normal subjects. Pacing Clin Electrophysiol 13:1724-1727, 1990. 156. Haskell RJ, French WJ: Physiological importance of different atrioventricular intervals to improved exercise performance in patients with dual-chamber pacemakers. Br Heart J 61:46-51, 1989. 157. Ritter PH, Vai F, Bonnet JL, et al: Rate-adaptive atrioventricular delay improves cardiopulmonary performance in patients implanted with a dual-chamber pacemaker for complete heart block. Eur J Cardiac Pacing Electrophysiol 1:31, 1991. 158. Sulke AN, Chambers JB, Sowton E: The effect of atrio-ventricular delay programming in patients with DDDR pacemakers. Eur Heart J 13:464-472, 1992. 159. Brecker SJ, Xiao HB, Sparrow J, Gibson DG: Effects of dualchamber pacing with short atrioventricular delay in dilated cardiomyopathy. Lancet 340:1308-1312, 1992. 160. Nishimura RA, Hayes DL, Holmes DRJ, Tajik AJ: Mechanism of hemodynamic improvement by dual-chamber pacing for severe left ventricular dysfunction: an acute Doppler and catheterization hemodynamic study. J Am Coll Cardiol 25:281-288, 1995. 161. Auricchio A, Stellbrink C, Block M, et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group. Circulation 99:29933001, 1999. 162. Auricchio A, Stellbrink C, Sack S, et al: Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol 39:2026-2033, 2002. 163. Auricchio A, Kloss M, Trautmann SI, et al: Exercise performance following cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Am J Cardiol 89:198-203, 2002. 164. Auricchio A, Ding J, Spinelli JC, et al: Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. J Am Coll Cardiol 39:1163-1169, 2002. 165. Dupont WD, Plummer WDJ: Power and sample size calculations for studies involving linear regression. Control Clin Trials 19:589-601, 1998. 166. Morales MA, Startari U, Panchetti L, et al: Atrioventricular delay optimization by Doppler-derived left ventricular dP/dt improves 6-month outcome of resynchronized patients. Pacing Clin Electrophysiol 29:564-568, 2006. 167. Sawhney NS, Waggoner AD, Garhwal S, et al: Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy. Heart Rhythm 1:562-567, 2004. 168. Hardt SE, Yazdi SH, Bauer A, et al: Immediate and chronic effects of AV-delay optimization in patients with cardiac resynchronization therapy. Int J Cardiol 115:318-325, 2007. 169. Jansen AH, Bracke FA, van Dantzig JM, et al: Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in

231

patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 97:552-557, 2006. 170. Kindermann M, Froehlig G, Doerr T, Schieffer H: Optimizing the AV delay in DDD pacemaker patients with high degree AV block: mitral valve Doppler versus impedance cardiography. PACE 20:2453-2462, 1997. 171. Santini M, Alexidou G, Ansalone G, et al: Relation of prognosis in sick sinus syndrome to age, conduction defects and modes of permanent cardiac pacing. Am J Cardiol 65:729-735, 1990. 172. Rosenqvist M, Brandt J, Schueller H: Atrial versus ventricular pacing in sinus node disease: a treatment comparison study. Am Heart J 111:292-297, 1986. 173. Andersen HR, Nielsen JC, Thomsen PEB, et al: Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick sinus syndrome. Lancet 350:12101216, 1997. 174. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 107:2932-2937, 2003. 175. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular back-up pacing in patients with an implantable defibrillator. JAMA 288:3115-3123, 2002. 176. Karpawich PP, Justice CD, Chang CH, et al: Septal ventricular pacing in the immature canine heart: a new perspective. Am Heart J 121:827-833, 1991. 177. Schneider JF, Thomas HE, Jr, Sorlie P, et al: Comparative features of newly acquired left and right bundle branch block in the general population: the Framingham Study. Am J Cardiol 47:931-940, 1981. 178. Freedman RA, Alderman EL, Sheffield LT, et al: Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance. J Am Coll Cardiol 10:73-80, 1987. 179. Eriksson P, Hansson PO, Eriksson H, Dellborg M: Bundlebranch block in a general male population: the study of men born 1913. Circulation 98:2494-2500, 1998. 180. Rabkin SW, Mathewson FAL, Tate RB: Natural history of left bundle-branch block. Br Heart J 43:164-169, 1980. 181. Schneider JF, Thomas HE, Jr, Kreger BE, et al: Newly acquired left bundle branch block: the Framingham Study. Ann Intern Med 90:303-310, 1979. 182. Takeshita A, Basta LL, Kioschos JM: Effect of intermittent left bundle branch block on left ventricular performance. Am J Med 56:251-255, 1974. 183. De Nardo D, Antolini M, Pitucco G, et al: Effects of left bundle branch block on left ventricular function in apparently normal subjects: study by equilibrium radionuclide angiocardiography at rest. Cardiology 75:365-371, 1988. 184. Verbeek X, Vernooy K, Peschar M, et al: Quantification of interventricular asynchrony during LBBB and ventricular pacing. Am J Physiol 283:H1370-H1378, 2002. 185. Liu L, Tockman B, Girouard S, et al: Left ventricular resynchronization therapy in a canine model of left bundle branch block. Am J Physiol 282:H2238-H2244, 2002. 186. Rouleau F, Merheb M, Geffroy S, et al: Echocardiographic assessment of the interventricular delay of activation and correlation to the QRS width in dilated cardiomyopathy. Pacing Clin Electrophysiol 24:1500-1506, 2001. 187. Nielsen JC, Boetcher M, Toftegaard Nielsen TT, Pedersen AK, Andersen HR: Regional myocardial blood flow in patients with sick sinus syndrome randomized to long-term single chamber atrial or dual chamber pacing—effect of pacing mode and rate. JACC 35:1453-1461, 2000. 188. Nielsen JC, Kristensen L, Andersen HR, et al: A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 42:614-623, 2003. 189. Kristensen L, Nielsen JC, Mortensen PT, et al: Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual-chamber pacing in 177 patients with sick sinus syndrome. Heart 90:661-666, 2004. 190. Andersen HR, Nielsen JC, Thomsen PE, et al: Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome. Circulation 98:1315-1321, 1998. 191. Kristensen L, Nielsen JC, Pedersen AK, et al: AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker. Pacing Clin Electrophysiol 24:358-365, 2001. 192. Karpawich PP, Gates J, Stokes KB: Septal His-Purkinje ventricular pacing in canines: a new endocardial electrode approach. PACE 15:2011-2015, 1992. 193. Scherlag BJ, Kosowsky BD, Damato AN: A technique for ventricular pacing from the His bundle of the intact heart. Am J Physiol 22:584-587, 1967. 194. Deshmukh P, Casavant DA, Romanyshyn M, Anderson K: Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation 101:869-877, 2000. 195. Zanon F, Bacchiega E, Rampin L, et al: Direct His bundle pacing preserves coronary perfusion compared with right ventricular apical pacing: a prospective, cross-over mid-term study. Europace 10:580-587, 2008. 196. De Cock CC, Giudici MC, Twisk JW: Comparison of the haemodynamic effects of right ventricular outflow-tract pacing

232

SECTION 2  Clinical Concepts

with right ventricular apex pacing: a quantitative review. Europace 5:275-278, 2003. 197. Buckingham TA, Candinas R, Schlapfer J, et al: Acute hemodynamic effects of atrioventricular pacing at different sites in the right ventricle individually and simultaneously. PACE 20:909915, 1997. 198. Tse HF, Yu C, Wong KK, et al: Functional abnormalities in patients with permanent right ventricular pacing: the effect of sites of electrical stimulation. J Am Coll Cardiol 40:1451-1458, 2002. 199. Puggioni E, Brignole M, Gammage M, et al: Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation. J Am Coll Cardiol 21:234-238, 2004. 200. Turner MS, Bleasdale RA, Vinereanu D, et al: Electrical and mechanical components of dyssynchrony in heart failure patients with normal QRS duration and left bundle branch block: impact of left and biventricular pacing. Circulation 109:2544-2549, 2004. 201. Wyman BT, Hunter WC, Prinzen FW, McVeigh ER: Mapping propagation of mechanical activation in the paced heart with MRI tagging. Am J Physiol 276:H881-H891, 1999. 202. Etienne Y, Mansourati J, Gilard M, et al: Evaluation of left ventricular based pacing in patients with congestive heart failure and atrial fibrillation. Am J Cardiol 83:1138-1140, 1999. 203. Tyers GFO: Comparison of the effect on cardiac function of single-site and simultaneous multiple site ventricular stimulation after A-V block. J Thorac Cardiovasc Surg 59:211-217, 1970. 204. Gebauer RA, Tomek V, Kubus P, et al: Differential effects of the site of permanent epicardial pacing on left ventricular synchrony and function in the young: implications for lead placement. Europace 11:1654-1659, 2009. 205. Vanagt WY, Prinzen FW, Delhaas T: Reversal of pacing-induced heart failure by left ventricular apical pacing. N Engl J Med 357:2637-2638, 2007. 206. Jais P, Takahashi A, Garrigue S, et al: Mid-term follow-up of endocardial biventricular pacing. Pacing Clin Electrophysiol 23:1744-1747, 2000. 207. Fei L, Wrobleski D, Groh W, et al: Effects of multisite ventricular pacing on cardiac function in normal dogs and dogs with heart failure. J Cardiovasc Electrophysiol 10:935-946, 1999. 208. Hay I, Melenovsky V, Fetics BJ, et al: Short-term effects of rightleft heart sequential cardiac resynchronization in patients with heart failure, chronic atrial fibrillation, and atrioventricular nodal block. Circulation 110:3404-3410, 2004. 209. Wyman BT, Hunter WC, Prinzen FW, et al: Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction. Am J Physiol Heart Circ Physiol 282:H372H379, 2002. 210. Nielsen JC, Pedersen AK, Mortensen PT, Andersen HR: Programming a fixed long atrioventricular delay is not effective in preventing ventricular pacing in patients with sick sinus syndrome. Europace 1:113-120, 1999. 211. Olshansky B, Day J, McGuire M, et al: Inhibition of unnecessary RV pacing with AV search hysteresis in ICDs (INTRINSIC RV): design and clinical protocol. Pacing Clin Electrophysiol 28:62-66, 2005. 212. Sweeney MO, Shea JB, Fox V, et al: Randomized pilot study of a new atrial-based minimal ventricular pacing mode (MVP) in dual-chamber implantable cardioverter-defibrillators. Heart Rhythm 1:160-167, 2004. 213. Sweeney MO, Ellenbogen KA, Casavant D et al: Multicenter, prospective, randomized safety and efficacy study of a new atrial-based managed ventricular pacing mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol 16:811-817, 2005. 214. Sweeney MO, Bank AJ, Nsah E, et al: Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 357:1000-1008, 2007. 215. Sweeney MO, Ellenbogen KA, Tang AS, et al: Severe atrioventricular decoupling, uncoupling, and ventriculoatrial coupling during enhanced atrial pacing: incidence, mechanisms, and implications for minimizing right ventricular pacing in ICD patients. J Cardiovasc Electrophysiol 19:1175-1180, 2008. 216. Bakker PF, Meijburg HW, de Vries JW, et al: Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function. J Interv Card Electrophysiol 4:395-404, 2000. 217. Cazeau S, Ritter P, Lazarus A, et al: Multisite pacing for end-stage heart failure: early experience. Pacing Clin Electrocardiol 19:1748-1757, 1996. 218. Butter C, Auricchio A, Stellbrink C, et al: Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation 104:3026-3029, 2001. 219. Blanc JJ, Etienne Y, Gilard M, et al: Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 96:3273-3277, 1997. 220. Kass DA, Chen C-H, Curry C, et al: Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 99:1567-1573, 1999. 221. Cazeau S, Leclercq C, Lavergne T, et al: Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873-880, 2001. 222. Cleland JG, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005.

223. Abraham WT, Fisher WG, Smith AL, et al: Cardiac resynchronization in chronic heart failure. N Engl J Med 346:1845-1853, 2002. 224. Parsai C, Bijnens B, Sutherland GR, et al: Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms. Eur Heart J 30:940-949, 2009. 225. Yu CM, Chau E, Sanderson JE, et al: Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 105: 438-445, 2002. 226. Dekker AL, Phelps B, Dijkman B, et al: Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops. J Thorac Cardiovasc Surg 127:1641-1647, 2004. 227. Van Gelder BM, Bracke FA, Meijer A, et al: Effect of optimizing the VV interval on left ventricular contractility in cardiac resynchronization therapy. Am J Cardiol 93:1500-1503, 2004. 228. Bleasdale RA, Turner MS, Mumford CE, et al: Left ventricular pacing minimizes diastolic ventricular interaction, allowing improved preload-dependent systolic performance. Circulation 110:2395-2400, 2004. 229. Williams LK, Ellery S, Patel K, et al: Short-term hemodynamic effects of cardiac resynchronization therapy in patients with heart failure, a narrow QRS duration, and no dyssynchrony. Circulation 120:1687-1694, 2009. 230. Adamson PB, Kleckner K, Van Hout WL, et al: Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. J Am Coll Cardiol 108:266-269, 2003. 231. St John Sutton MG, Plappert T, Abraham WT, et al: Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 107:1985-1990, 2003. 232. Spragg DD, Leclercq C, Loghmani M, et al: Regional alterations in protein expression in the dyssynchronous failing heart. Circulation 108:929-932, 2003. 233. St John Sutton M, Ghio S, Plappert T, et al: Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association Class I/II heart failure. Circulation 120:1858-1865, 2009. 234. Van Geldorp IE, Vernooy K, Delhaas T, et al: Beneficial effects of biventricular pacing in chronically right ventricular–paced patients without severe heart failure. Europace 12:223-229, 2010. 235. Dubin AM, Feinstein JA, Reddy VM, et al: Electrical resynchronization: a novel therapy for the failing right ventricle. Circulation. 107:2287-2289, 2003. 236. Thambo JB, Dos Santos P, De Guillebon M, et al: Biventricular stimulation improves right and left ventricular functions after tetralogy of Fallot repair: acute animal and clinical studies. Heart Rhythm 7:344-350, 2010. 237. Delhaas T, Prinzen FW: Right ventricular or biventricular pacing in repaired tetralogy of Fallot? Heart Rhythm 7:351-352, 2010. 238. Pitzalis MV, Iacoviello M, Romito R, et al: Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol 40:1615-1622, 2002. 239. Penicka M, Bartunek J, De Bruyne B, et al: Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography. Circulation 109:978-983, 2004. 240. Yu Y, Kramer A, Spinelli J, et al: Biventricular mechanical asynchrony predicts hemodynamic effect of uni- and biventricular pacing. Am J Physiol 285:H2788-H2796, 2003. 241. Zwanenburg JJ, Götte MJ, Marcus JT, et al: Propagation of onset and peak time of myocardial shortening in time of myocardial shortening in ischemic versus nonischemic cardiomyopathy: assessment by magnetic resonance imaging myocardial tagging. J Am Coll Cardiol 46:2215-2222, 2005. 242. Bax JJ, Molhoek SG, van Erven L, et al: Usefulness of myocardial tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy. Am J Cardiol 91:94-97, 2003. 243. Garrigue S, Jais P, Espil G, et al: Comparison of chronic biventricular pacing between epicardial and endocardial left ventricular stimulation using Doppler tissue imaging in patients with heart failure. Am J Cardiol 88:858-862, 2001. 244. De Boeck BWL, Meine M, Leenders GE, et al: Practical and conceptual limitations of tissue Doppler imaging to predict reverse remodelling in cardiac resynchronisation therapy. Eur J Heart Failure 10:281-290, 2008. 245. Bilchick KC, Dimaano V, Wu KC, et al: Cardiac magnetic resonance assessment of dyssynchrony and myocardial scar predicts function class improvement following cardiac resynchronization therapy. JACC Cardiovasc Imaging 1:561-568, 2008. 246. Chung ES, Leon AR, Tavazzi L, et al: Results of the predictors of response to CRT (PROSPECT) trial. Circulation 117:2608-2616, 2008. 247. Beshai JF, Grimm RA, Nagueh SF, et al: Cardiac resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 357:2461-2471, 2007. 248. Rüssel IK, Zwanenburg JJ, Germans T, et al: Mechanical dyssynchrony or myocardial shortening as MRI predictor of response to biventricular pacing? J Magn Reson Imaging 26:14521460, 2007.

249. Kirn B, Jansen A, Bracke F, et al: Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization. Am J Physiol 295:H640-H646, 2008. 250. Haghjoo M, Bonakdar HR, Jorat MV, et al: Effect of right ventricular lead location on response to cardiac resynchronization therapy in patients with end-stage heart failure. Europace 11:356-363, 2009. 251. Bulava A, Lukl J: Similar long-term benefits conferred by apical versus mid-septal implantation of the right ventricular lead in recipients of cardiac resynchronization therapy systems. Pacing Clin Electrophysiol 32(Suppl 1):32-37, 2009. 252. Helm RH, Byrne M, Helm PA, et al: Three-dimensional mapping of optimal left ventricular pacing site for cardiac resynchronization. Circulation 115:953-961, 2007. 253. Rademakers L, van Kerckhoven R, van Deursen CJM, et al: Myocardial infarction does not preclude electrical and hemodynamic benefits of CRT in dyssynchronous canine hearts. Circulation Arrhythm Electrophysiol 3:361-368, 2010. 254. Gasparini M, Mantica M, Galimberti P, et al: Is the left ventricular lateral wall the best lead implantation site for cardiac resynchronization therapy? Pacing Clin Electrophysiol 26:162-168, 2003. 255. Ansalone G, Giannantoni P, Ricci R, et al: Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing. J Am Coll Cardiol 39:489-499, 2002. 256. Jaïs P, Douard H, Shah DC, et al: Endocardial biventricular pacing. Pacing Clin Electrophysiol 21:2128-2131, 1998. 257. Van Gelder BM, Scheffer MG, Meijer A, Bracke FA: Transseptal endocardial left ventricular pacing: an alternative technique for coronary sinus lead placement in cardiac resynchronization therapy. Heart Rhythm 4:454-460, 2007. 258. Pasquié JL, Massin F, Macia JC, et al: Long-term follow-up of biventricular pacing using a totally endocardial approach in patients with end-stage cardiac failure. Pacing Clin Electrophysiol 30(Suppl 1):31-33, 2007. 259. Derval N, Steendijk P, Gula LJ, et al: Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. J Am Coll Cardiol 55:566-575, 2010. 260. Bleeker GB, Kaandorp TA, Lamb HJ, et al: Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation 113:969-976, 2006. 261. Leon AR, Greenberg JM, Kanuru N, et al: Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol 39:12581263, 2002. 262. Valls-Bertault V, Fatemi M, Gilard M, et al: Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation. Europace 6:438-443, 2004. 263. Brignole M, Gammage M, Puggioni E, et al: Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation. Eur Heart J 26:712-722, 2005. 264. Leclercq C, Walker S, Linde C, et al: Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J 23:1780-1787, 2002. 265. Peschar M, Vernooy K, Vanagt WYR, et al: Absence of reverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles. Cardiovasc Res 58:510-517, 2003. 266. Touiza A, Etienne Y, Gilard M, et al: Long-term left ventricular pacing: assessment and comparison with biventricular pacing in patients with severe congestive heart failure. J Am Coll Cardiol 38:1966-1970, 2001. 267. Blanc JJ, Bertault-Valls V, Fatemi M, et al: Midterm benefits of left univentricular pacing in patients with congestive heart failure. Circulation 109:1741-1744, 2003. 268. Rao RK, Kumar UN, Schafer J, et al: Reduced ventricular volumes and improved systolic function with cardiac resynchronization therapy: a randomized trial comparing simultaneous biventricular pacing, sequential biventricular pacing, and left ventricular pacing. Circulation 115:2136-2144, 2007. 269. Wilkoff BL, Kudenchuk PJ, Buxton AE, et al: The DAVID (Dual Chamber and VVI Implantable Defibrillator) II trial. J Am Coll Cardiol 53:872-880, 2009. 270. Delnoy PP, Ottervanger JP, Luttikhuis HO, et al: Comparison of usefulness of cardiac resynchronization therapy in patients with atrial fibrillation and heart failure versus patients with sinus rhythm and heart failure. Am J Cardiol 99:1252-1257, 2007. 271. Molhoek SG, Bax JJ, Bleeker GB, et al: Comparison of response to cardiac resynchronization therapy in patients with sinus rhythm versus chronic atrial fibrillation. Am J Cardiol 94:15061509, 2004. 272. Gasparini M, Auricchio A, Metra M, et al: Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrioventricular junction ablation in patients with permanent atrial fibrillation. Eur Heart J 29:16441652, 2008. 273. Van Gelder BM, Meijer A, Bracke FA: The optimized V-V interval determined by interventricular conduction times versus



invasive measurement by LVdP/dtmax. J Cardiovasc Electrophysiol 19:939-944, 2008. 274. Whinnett ZI, Davies JE, Willson K, et al: Determination of optimal atrioventricular delay for cardiac resynchronization therapy using acute non-invasive blood pressure. Europace 8:358-366, 2006. 275. Van Geldorp I, Delhaas T, Hermans B, et al: Comparison of a non-invasive arterial pulse contour technique and echo Doppler aorta velocity-time integral on stroke volume changes in optimization of cardiac resynchronization therapy. Europace 13:8795, 2011. 276. Tassin A, Kobeissi A, Vitali L, et al: Relationship between amplitude and timing of heart sounds and endocardial acceleration. Pacing Clin Electrophysiol 32(Suppl 1):101-104, 2009. 277. Baker JH, McKenzie Jr, Beau S, et al: Acute evaluation of programmer-guided AV/PV and VV delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dualchamber ICD implants. J Cardiovasc Electrophysiol 18:185-191, 2007. 278. Kamdar R, Frain E, Warburton F, et al: A prospective comparison of echocardiography and device algorithms for atrioventricular and interventricular interval optimization in cardiac resynchronization therapy. Europace 12:84-91, 2010. 279. Gold MR, Niazi I, Giudici M, et al: A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy. J Cardiovasc Electrophysiol 18:490-496, 2007. 279a.  Ellenbogen KA, Gold MR, Meyer TE, et al: Primary results from the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial. Circulation 122:2660-2668, 2010. 280. Delnoy PP, Lunati M, Nagele H, et al: Periodic VV and AV delays optimization in cardiac resynchronization therapy improves patients’ clinical outcome: results from the CLEAR study. Heart Rhythm 5:S55, 2010. 281. Abraham WT, Gras D, Yu CM, et al: Results from the FREDOM trial: assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy. Am Heart J 159:944-948, 2010. 282. León AR, Abraham WT, Brozena S, et al: Cardiac resynchronization with sequential biventricular pacing for the treatment of

9  Basic Physiology and Hemodynamics of Cardiac Pacing moderate-to-severe heart failure. J Am Coll Cardiol 46:22982304, 2005. 283. Sogaard P, Egeblad H, Kim WY, et al: Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 40:723-730, 2002. 284. Whinnett ZI, Davies JE, Willson K, et al: Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay. Heart 92:1628-1634, 2006. 285. Vanderheyden M, De Backer T, Rivero-Ayerza M, et al: Tailored echocardiographic interventricular delay programming further optimizes left ventricular performance after cardiac resynchronization therapy. Heart Rhythm 2:1066-1072, 2005. 286. Boriani G, Biffi M, Müller CP, et al: A prospective randomized evaluation of VV delay optimization in CRT-D recipients: echocardiographic observations from the RHYTHM II ICD study. Pacing Clin Electrophysiol 32(Suppl 1):120-125, 2009. 287. Levine PA, Seltzer JP, Pirzada FA: The “pacemaker syndrome” in a properly functioning physiologic pacing system. Pacing Clin Electrophysiol 6:279-282, 1983. 288. Den Dulk K, Lindemans FW, Brugada P, et al: Pacemaker syndrome with AAI rate variable pacing: importance of atrioventricular conduction properties, medication and pacemaker programmability. Pacing Clin Electrophysiol 11:1226-1233, 1988. 289. Torresani J, Ebagost A, Alland-Latour G: Pacemaker syndrome with DDD pacing. Pacing Clin Electrophysiol 7:1148-1151, 1984. 290. Pierantozzi A, Bocconcelli P: DDD pacemaker syndrome and atrial conduction time. Pacing Clin Electrophysiol 17:374-376, 1994. 291. Mary DASG: Electrophysiology of atrial receptors. In Hainsworth RMK, Mary DASG, editors: Cardiogenic reflexes, Oxford, 1987, Oxford Scientific, pp 3. 292. Hainsworth R: Reflexes from the heart. Physiol Rev 71:617-658, 1991. 293. Ellenbogen KA, Thames MD, Mohanty PK: Importance of regurgitant fraction for left ventricular end-systolic wall stress to end-systolic volume ratio in patients with chronic mitral regurgitation. Am J Cardiol 65:53-59, 1990.

233

294. Ellenbogen KA, Wood MA, Stambler B: Clinical, hemodynamic and neurohumoral features. In Barold SS, Mujica J, editors: New perspectives in cardiac pacing, NY, Futura, 1992, Mt Kisco. 295. Vardas PE, Travill CM, Williams TDM, et al: Effect of dualchamber pacing on raised plasma atrial natriuretic peptide concentrations in complete atrioventricular block. Br Med J 296:94, 1988. 296. Ellenbogen KA, Kapadia K, Walsh M, et al: Increase in plasma atrial natriuretic factor during ventriculoatrial pacing. Am J Cardiol 64:236-237, 1989. 297. Bristow MR, Saxon LA, Boehmer J, et al: Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004. 298. Pieterse MG, den Dulk K, van Gelder BM, et al: Programming a long pace atrioventricular interval may be risky in DDDR pacing. Pacing Clin Electrophysiol 17:252-257, 1994. 299. Shemin RJ, Scott WC, Kastl DG, et al: Hemodynamic effects of various modes of cardiac pacing after operation for idiopathic hypertrophic subaortic stenosis. Ann Thorac Surg 27:137, 1979. 300. Gross JN, Keltz TN, Cooper JA, et al: Profound “pacemaker syndrome” in hypertrophic cardiomyopathy. Am J Cardiol 70:1507-1511, 1992. 301. Jeanrenaud X, Goy JJ, Kappenberger L: Effects of dual-chamber pacing in hypertrophic obstructive cardiomyopathy. Lancet 339:1318-1823, 1992. 302. Nishimura RA, Trusty JM, Hayes DL, et al: Dual-chamber pacing for hypertrophic cardiomyopathy. J Am Coll Cardiol 29:435-441, 1997. 303. Maron BJ: Hypertrophic cardiomyopathy: a systematic review. JAMA 287:1308-1320, 2002. 304. Mohiddin SA, Page SP: Long-term benefits of pacing in obstructive hypertrophic cardiomyopathy. Heart 96:328-330, 2010. 305. Galve E, Sambola A, Saldaña G, et al: Late benefits of dualchamber pacing in obstructive hypertrophic cardiomyopathy: a 10-year follow-up study. Heart 96:352-356, 2010. 306. Cannon RO, Tripodi D, Dilsizian V, et al: Results of permanent dual-chamber pacing in symptomatic nonobstructive hypertrophic cardiomyopathy. Am J Cardiol 73:571-575, 1994.

234

SECTION 2  Clinical Concepts

10  10

Clinical Trials of Atrial and Ventricular Pacing Modes CARSTEN W. ISRAEL

History and Rationale for Different Pacing Modes Cardiac pacing has been developed to treat syncope caused by bradycardia and asystole, initially in patients with permanent third-degree atrioventricular (AV) block. For this purpose, a single lead implanted in the ventricle and pacing at a prespecified rate was sufficient. This simple method of pacing (later coded “VOO 70”) was able to demonstrate a mortality reduction in patients with AV block despite that pacemaker implantation required open-chest surgery at that time.1 Cardiac pacing in permanent third-degree AV block was found not only to prevent syncope, but also to improve symptoms, exercise capacity, and prognosis. It was therefore also used for other patients with bradycardia, such as from intermittent high-degree AV block and sinus node disease (SND). With technical advancement, the limitations of fixed-rate ventricular pacing were overcome by the development of sensors to provide rate-adaptive (R) ventricular pacing. Rate-adaptive pacing was used to improve the hemodynamic benefit of ventricular single-chamber pacing by providing ventricular rates that take into account the metabolic needs of the patient. In patients with SND, however, ventricular single-chamber pacing in VVI and VVI(R) modes did not reduce mortality2 and could even cause symptoms that were later termed pacemaker syndrome.3 To treat SND, atrial single-chamber pacing has been used, particularly in the Scandinavian countries,4 although many physicians remained skeptical about atrial pacing because it could not prevent asystole if AV block occurred.5 However, a number of advantages of atrial versus ventricular single-chamber pacing were observed, including the absence of pacemaker syndrome, better cardiac output and exercise capacity, resolution of mitral regurgitation that could be induced by ventricular pacing, and a lower incidence of atrial fibrillation. Therefore, alternative pacing modes were desired, particularly for patients with SND. The development of dual-chamber pacemakers created hope that DDD pacing would restore and maintain normal AV synchrony and thus provide “physiologic” pacing. It was anticipated that this closer approximation of normal physiology would reduce patient morbidity and mortality and improve quality of life (QOL). After the introduction of dual-chamber pacing, numerous case reports and small studies showed how dual-chamber (physiologic) pacing resolves mitral regurgitation, is associated with lower plasma epinephrine levels, improves exercise tolerance, resolves VVI pacing–associated heart failure, and has other beneficial effects. However, the theoretical advantages of dual-chamber pacing (maintenance of AV synchrony, preservation of sinus node control over heart rate in patients with AV block, maintenance of normal ventricular activation via His-Purkinje system in SND patients) required confirmation in prospective clinical studies given their higher cost, greater complexity, and potential for complications. This was the rationale for trials comparing pacing modes, as outlined in this chapter. Currently, recommendations in international guidelines require confirmation by large, randomized controlled trials (RCTs). However, most RCTs have yielded unexpected results, particularly because the theoretical advantages of dual-chamber pacing have never been clearly demonstrated. All these trials have some results that require further explanation. From these experiences, physicians should consider a

234

number of lessons in the daily practice of implanting and following pacemakers. This chapter presents only a selection of the most important or most representative studies comparing different pacing modes and modalities. COMPARISON STUDIES Ventricular Pacing with Versus Without Rate Response (VVI vs. VVIR) Crossover studies in the 1980s and early 1990s randomized small numbers of patients to fixed-rate ventricular single-chamber pacing (VVI) versus rate-adaptive ventricular pacing (VVIR) with the use of different sensors6-12 (Table 10-1). These studies unequivocally favor rate-adaptive pacing and showed an improvement in submaximal and maximal exercise in terms of objective data (e.g., exercise duration, maximal exercise capacity in watts or duration, VO2 at anaerobic threshold) or subjective data (e.g., pacing mode preference, symptom scores/questionnaires) compared with fixed-rate VVI pacing. This advantage was still present in studies that included patients with SND or retrograde AV conduction. The most striking advantage of VVIR over VVI pacing was observed in patients with AV node ablation for atrial fibrillation. However, these studies were small and not blinded. Therefore, a significant bias in favor of rate-adaptive pacing cannot be excluded. Many patients in these studies were younger than the average age of pacemaker patients. In elderly patients with a sedentary lifestyle and patients with severe heart disease that precludes any exercise above minimal levels (two large groups of pacemaker patients), there is likely no difference between VVI and VVIR pacing. In some patients, VVIR pacing resulted in an increase in angina pectoris. The improvement in exercise capacity in VVIR pacing is based on an increase in heart rate, which increases myocardial oxygen consumption with potentially disadvantageous consequences in ischemic heart disease. In addition, whenever a patient has an intrinsic ventricular rhythm at an adequate rate, this is preferred to avoid deleterious effects of ventricular desynchronization by right ventricular pacing (see later). Lastly, the use of rate-adaptive pacing requires conservative programming of parameters related to the pacing rate, because “overpacing” (i.e., pacing rate faster than needed) is more symptomatic than “underpacing.” Ventricular Pacing with Rate Response Versus Dual-Chamber Pacing (VVIR vs. VDD/DDD/DDDR) With the advent of dual-chamber pacing, a number of trials tested if rate-adaptive ventricular pacing (VVIR) with an artificial sensor driving the heart rate was comparable to dual-chamber pacing, in which the sinus node determines the heart rate. Investigators observed that sensors frequently reacted inappropriately and were therefore inferior to a chronotropically competent sinus node to increase the heart rate linearly according to metabolic needs during exercise.13 Most studies showed a superiority of dual-chamber pacing in terms of exercise capacity, symptoms, and hemodynamic parameters13-20 (Table 10-2). Of note, when patient preference of pacing mode was assessed, there was a clear advantage for AV-synchronous pacing modes; this can be ascertained only in crossover trials. All the randomized large-scale studies comparing single-chamber ventricular and dual-chamber



10  Clinical Trials of Atrial and Ventricular Pacing Modes

TABLE

235

Studies Comparing VVI and VVIR Pacing*

10-1 

Study (year) Lipkin et al.6

Pacing Indication Third-degree AV block (9 of 10 patients with retrograde AV block) Third-degree AV block (6) or SND (5) Third-degree AV block (AV node ablation in 29) AV block (13) or SND (2)

N 10

Sensor Piezocrystal

Control VVI 70 bpm

11

VVI (rate: na)

46

Minute ventilation Different

Result Long-term improvement in breathlessness and increased maximal oxygen consumption with VVIR Similar improvement in oxygen consumption at anaerobic threshold Improved exercise capacity and better quality of life with VVIR

VVI 70 bpm

Improved exercise duration

15

Piezocrystal

VVI 70 bpm

AV block

18

QT interval

VVI 70 bpm

Rossi et al.11

Third-degree AV block

13

VVI 70 bpm

Gammage et al.12

AV block and atrial fibrillation

12

Minute ventilation Piezocrystal

13 of 15 preferred VVIR (less dyspnea, tiredness) Exercise capacity improved significantly on bicycle and on treadmill Exercise tolerance and dyspnea improved with VVIR, patient preference (61%) Angina with VVIR in 2 Improved exercise capacity (maximal exercise time, oxygen uptake at anaerobic threshold) Improved maximum exercise capacity, decreased perceived difficulty of submaximal exercise

Oto et al.7 8

Lau et al.

Smedgard et al.9

VVI 60 bpm

*Small numbers (N) of patients randomized to fixed-rate ventricular single-chamber pacing (VVI) versus rate-adaptive ventricular pacing (VVIR). AV, Atrioventricular; SND, sinus node disease; na, not available.

pacing had a parallel trial design and therefore lack this information (apart from crossover patients, who showed a clear preference for dualchamber pacing mode in PASE and MOST). Ventricular Single-Chamber Pacing Versus Atrial Synchronized Ventricular Pacing (VVI vs. VDD) The question if dual-chamber pacing with ventricular pacing synchronized to atrial activity was superior to single-chamber ventricular pacing was evaluated early. In 16 patients with high-degree AV block, Kruse and Rydén21 found a significant increase in maximal exercise capacity in VDD compared to VVI pacing. Interestingly, the extent of improvement was the same for patients older and younger than 65 years. At comparable exercise levels, the atrial rate was significantly lower in VDD than VVI pacing. In a crossover design, 13 patients underwent invasive hemodynamic measurements after 3 months of VDD and VVI pacing.22 During VDD pacing, cardiac output was significantly higher (>30%), particularly during exercise, because of the heart rate increase in VDD and despite a stroke volume increase in VVI pacing. Arteriovenous oxygen difference was significantly higher during VVI pacing. Arterial blood lactate was significantly higher in VVI than VDD pacing during exercise. Heart size was significantly smaller with VDD pacing. In a questionnaire on symptoms and pacemaker choice, patients preferred the VDD mode. These early observations favoring dual-chamber pacing significantly in all respects over VVI pacing were an important part of initiating the TABLE

10-2 

strong belief in AV synchronous dual-chamber pacing as the “physiologic” and preferred pacing mode. Single-Lead VDD Pacing Versus Dual-Chamber DDD Pacing in Atrioventricular Block The VDD pacing mode offers the advantage of using only one lead, typically tripolar or quadripolar, with two floating rings that sense atrial activity.23 This pacing mode may be similar to DDD pacing with two leads in patients with AV block and normal sinus node function. However, no RCTs have been performed comparing VDD and DDD pacing. A retrospective study analyzed 1214 consecutive patients with pacemaker implantation for AV block (36.5% VVI; 32.9% DDD; 30.6% VDD).24 At implantation, operation and fluoroscopic times were longer in DDD than in VDD and VVI systems. During follow-up of 5 years, complications requiring surgical interventions occurred 2.3 times more frequently for DDD systems than VDD systems, mainly because of a higher incidence of early atrial lead dysfunction. Dual-Chamber Pacing in Chronotropic Incompetence or Paroxysmal Atrial Fibrillation: DDD(R) with Mode Switching There are few studies prospectively comparing different pacing modes within dual-chamber pacing, such as triggered versus inhibited mode. Sulke et al.25 compared DDDR, DDD, DDIR, and VVIR pacing modes in 22 patients with high-degree AV block and chronotropic

Studies Comparing VVIR and DDD(R)/AAI(R)

Study Lau et sl.13 Jutzy et al.14 15

Menozzi et al.

Oldroyd et al.16 Linde-Edelstamet al.17 Lau et al.18 Lau et al.19 Deharo et al.20

Pacing Indication Third-degree AV block

N 10

Study Mode DDD

Control Mode VVIR

SND (12) or third-degree AV block (2) High-degree AV block

14

DDDR

VVIR

14

DDD

VVIR

Third-degree AV block, normal sinus node function High-degree AV block

10

DDD

VVIR

17

DDD

VVIR

SND (18) or third-degree AV block (15) SND

33

DDDR, DDD

VVIR

15

DDDR, AAIR

VVIR

Third-degree AV block, normal sinus function

18

DDD

VVIR

Result Cardiac output (rest, exercise) and systolic blood pressure better with DDD Exercise capacity, cardiac output, and maximal oxygen consumption better with DDDR Double-blind; patients preferred DDD; cardiac output at rest, ANP, and symptom scores better with DDD ANP better with DDD; no difference in symptom scores Less symptoms in DDD; no difference in exercise time, central hemodynamics, norepinephrine, or myocardial oxygen consumption Double blind; quality of life better in DDD and DDDR More arrhythmias (PVCs, AF) and palpitations in VVIR; better blood pressure in AAIR/DDDR; no significant difference in NYHA Trend toward better well-being with DDD; no significant difference in CPx parameters

AF, Atrial fibrillation; ANP, atrial natriuretic peptide; CPx, cardiopulmonary exercise testing; NYHA, New York Heart Association functional class; PVCs, premature ventricular contractions; SND, sinus node disease.

236

SECTION 2  Clinical Concepts

incompetence. In a randomized double-blind crossover design, patients were paced in each of these modes for 4 weeks. Patients were asked their preference, received three questionnaires for subjective assessment, and underwent treadmill testing, mental stress testing, testing of everyday activities (e.g., suitcase lifting, staircase climbing), and echocardiographic evaluation. Scores for subjective grading of well-being were highest for DDDR pacing, similar for DDD and DDIR modes, and lowest for VVIR pacing. DDDR pacing was the preferred mode in 59% of patients, VVIR mode was the least acceptable mode for 73% of patients. Treadmill testing was best in DDDR mode; nontracking modes underresponded to mental stress; and all rate-adaptive modes overreacted to staircase descent. Cardiac output was best in DDDR mode and non-tracking modes showed varying values in patients with AV block. This study suggested that rate-responsive dual-chamber tracking mode is superior to nontracking dual-chamber pacing, dualchamber pacing without rate-response, and single-chamber ventricular pacing in patients with AV block and chronotropic incompetence, based on both objective and subjective measurements. Another study compared different pacing modes in 48 patients with AV block and paroxysmal atrial tachyarrhythmias.26 Patients received dual-chamber systems programmed to DDIR mode for 30 days. In a randomized double-blind crossover manner, devices were then programmed for 4 weeks each to DDDR with mode switching, DDDR with limitation of the upper tracking rate, and VVIR. Patients received transtelephonic self-activated devices to transmit electrocardiograms whenever they perceived symptoms. In addition, at the end of each 4-week study period, devices were interrogated; patients underwent 24-hour Holter recordings, received three symptom questionnaires, and at the end of the study were asked for their preferred pacing period. Patients with intolerable symptoms were allowed to cross over early to the next pacing mode. Different devices with fast- and slowreacting mode-switching algorithms were used. In this study, one third of patients requested early crossover from VVIR to another mode because of intolerable symptoms, most likely pacemaker syndrome. In DDDR pacing without mode switching but limited upper tracking rate, 19% of patients requested early crossover (29% of patients with documented atrial tachyarrhythmias during this period). Only one patient with DDDR and mode switching requested early crossover because of inappropriate tracking of atrial tachyarrhythmia. Patients with fast-reacting mode-switching algorithms in particular preferred DDDR over VVIR mode. Symptom questionnaires favored DDDR with mode switching over DDDR with limited upper racking rates, DDIR, and VVIR pacing. The authors conclude that dual-chamber pacing with tracking and mode switching to a nontracking mode, whenever this automatic function is fast and reliable, is the preferred pacing mode for patients with AV block and paroxysmal atrial tachyarrhythmias (Fig. 10-1). Dual-Chamber Pacing with Versus Without Rate Response (DDD vs. DDDR) The need for a sensor in patients with chronotropic incompetence has received little attention after dual-chamber pacing became available and resolved this problem for patients with AV block and normal sinus function. Most studies subsequently compared different sensors.27,28 Additionally, the definition of “chronotropic incompetence” varied widely. An early study evaluated cardiopulmonary exercise testing with the DDDR versus DDD pacing modes in eight patients.29 Unfortunately, this was a mix of patients, five with AV block and three with sinus node disease, and five with and three without chronotropic incompetence. Chronotropic incompetence was defined as a maximum heart rate at exercise before pacemaker implantation of less than 110 beats per minute (bpm), but not whether it was caused by AV block (resolved with DDD pacing alone) or sinus node dysfunction (requires rateadaptive pacing). In a crossover study, patients were randomized to DDD or DDDR, each for 3 weeks, and performed an exercise test and completed a symptom evaluation form at the end of each study period. Rate-adaptive pacing was associated with a higher oxygen uptake at

19%

14%

67%

A

Dual-chamber mode None

Ventricular single-chamber mode

33%

0%

B

Dual-chamber mode None

67%

Ventricular single-chamber mode

Figure 10-1  Patient preference of pacing mode. A, Overall patient preference. B, Preference in patients without atrial tachyarrhythmias during the study period.

the anaerobic threshold and maximum exercise. However, exercise time and subjective symptoms were not different in the whole patient group, only in patients with chronotropic incompetence, and symptoms of exercise intolerance were better with DDDR pacing. In a study in 63 patients with a DDD pacemaker, a symptom-limited exercise test was performed 1 month after implantation.30 With chronotropic (sinus node) incompetence defined as a maximum heart rate of less than 60% of the age-predicted maximum or less than 100 bpm, 25 patients were then randomized to perform exercise testing in DDD or DDDR mode on two consecutive days. To minimize bias, patients and physicians were blinded with respect to the pacing mode. Paired analysis revealed a statistically significant improvement in the DDDR mode, with higher heart rates at maximum exercise (113 vs. 84 bpm), longer duration of total exercise and time to anaerobic threshold, and higher oxygen uptake at maximum exercise and anaerobic threshold. Only one large RCT performed according to the principles of evidence-based medicine (EBM) specifically assessed the benefit of rate-adaptive pacing in the dual-chamber mode in patients with sinus rhythm.31 Unfortunately, the single-blind Advanced Elements of Pacing Randomized Controlled Trial (ADEPT) included a mix of patients with SND (~66%) and AV block. After an exercise test 1 month after implantation, 872 patients were enrolled. To be eligible, patients needed to complete at least stage 2 on the Chronotropic Assessment Exercise Protocol and to have a heart rate at peak exercise of 80% or greater of the age-predicted maximum. The mean age was 71 years,



however, so patients with a maximum heart rate not exceeding 120 bpm at maximum exercise could be included. Patients were randomized to DDD versus DDDR pacing (dual-sensor system; maximum adaptive rate, 220 bpm minus age) with rate-adaptive AV delay shortening in a parallel study design. After 12 months, general QOL (measured by Short-Form 36 General Health Survey [SF-36], Ferrans and Powers Quality of Life Index) and cardiovascular functional status (Specific Activity Scale and Duke Activity Status Index) were assessed by questionnaires, together with the maximum exercise time at treadmill testing 6 months after randomization. ADEPT found no specific or general differences in scores of the activity and QOL questionnaires. The total exercise time was not different between DDD and DDDR pacing. Independent of discussions about the ideal sensor(s), severe limitations included the following: • The definition of “chronotropic incompetence” was too broad to demonstrate an improvement by rate-adaptive pacing. Previous studies suggest that rate-adaptive pacing can improve exercise capacity only in patients with a maximum sinus rate less than 90 to 100 bpm.32,33 Although patients with a maximum heart rate of 80% or less of the age-predicted maximum have by definition chronotropic incompetence, this is too mild to be improved by rate-adaptive pacing. • Patients with AV block causing limitation of heart rate increase at maximum exercise (one third of patients enrolled in ADEPT) will substantially benefit from DDD pacing alone. If sinus node function is normal, no further improvement can reasonably be expected from the addition of rate-adaptive pacing. • Because of the negative consequences of right ventricular pacing, programming the AV delay to 150 to 200 msec in patients with SND, particularly activating a rate-adaptive AV delay–shortening algorithm, may have severely biased the results and limited exercise capacity, particularly during DDDR pacing. CONCLUSION Insufficient data from large RCTs exist to clarify if and to what extent rate-adaptive pacing in addition to the DDD mode improves exercise capacity in patients with chronotropic sinus node incompetence. For clinical reasons, only advanced chronotropic incompetence (i.e., sinus node unable to achieve rates >90-100 bpm during exercise) should be taken into account; only in this situation will pacing have a significant potential to improve exercise capacity and relieve symptoms. Caution must be used in patients with coronary artery disease in whom (paced) heart rates greater than 120 bpm may induce ischemia. Sensors should be programmed conservatively (i.e., with limited increase in heart rate during exercise) because “overpacing” is more symptomatic than pacing with rates a little too slow for metabolic needs.

Atrial Versus Ventricular Single-Chamber Pacing in Sinus Node Disease In 1994, Andersen et al.34 published the first RCT on pacing mode. A total of 225 patients with SND were randomized to receive a singlechamber pacemaker in the right atrium or ventricle. Of note, the study excluded patients with AV block of any degree (including first-degree AV block with PQ interval >220/260 msec), Wenckebach block at less than 100 bpm, atrial fibrillation (AF) more than 50% of the time (or with pauses >3 seconds or ventricular rates <40 bpm), or bifascicular bundle branch block. In total, 827 of 1052 screened patients were excluded from study participation, predominantly because of AV block (n = 552). Study outcome parameters were mortality, AF, thromboembolism (TE), and heart failure (HF). From retrospective studies, the authors expected AF in 30%, TE in 15%, and mortality in 15% of patients in the ventricular pacing group. The study intent was to demonstrate a 50% reduction in AF and HF and a 66% reduction in TE and mortality with atrial single-chamber pacing, which would have required 100 patients in each group. This rather optimistic prediction

10  Clinical Trials of Atrial and Ventricular Pacing Modes

TABLE

10-3 

237

Clinical Events in Atrial versus Ventricular Pacing for Sick Sinus Syndrome (Danish Study)*

Clinical Event All-cause mortality Cardiovascular mortality Stroke (cerebrovascular accident) NYHA functional class Permanent atrial fibrillation

Ventricular (n = 115) 50% 34% 23% Mean 1.3 8%

Atrial (n = 110) 34%† 17%† 12%† Mean 1.5† 19%†

From Andersen HR, Nielsen JC, Thomsen PE, et al: Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 350:1210-1216, 1997. *Results from long-term follow-up. †P < .05 for lower incidence respectively; better value with AAIR.

of the capabilities of physiologic pacing reflects the widespread belief in its superiority over ventricular pacing at the time of conception of this study. During a follow-up of 3.3 years, all-cause mortality was similar (22% with ventricular vs. 19% with atrial pacing). There was no significant difference in the risk of AF (in the ECG of at least one follow-up visit in 23% of patients with ventricular vs. 14% with atrial pacing). However, TE was significantly more frequent with ventricular pacing (17% vs. 5%; P = .008). At the same time, ventricular pacing was associated with a significant increase in left atrial diameter compared to baseline and to patients randomized to atrial pacing. Andersen et al.35 extended the follow-up until the last patient completed 5 years in the assigned pacing mode. By that time, the first patients enrolled into the trial had completed an 8-year follow-up (mean, 5.5 years). This prolonged follow-up demonstrated a significantly lower mortality in atrial versus ventricular pacing (relative risk reduction [RRR], 34%), mainly from a reduction in cardiovascular mortality (Table 10-3). Similarly, atrial fibrillation was less likely in the atrial pacing group (RRR, 46% vs. ventricular pacing) as were TE events (RRR, 53%). Only 4 of 110 patients developed AV block during the study period (annual rate, 0.6%), two of whom had a right bundle branch block at baseline. The authors detected retrograde conduction in 63% of patients randomized to VVI pacing. CRITICAL APPRAISAL OF DANISH STUDY The Danish study34,35 was the first large-scale RCT on pacing mode selection, at a time when the discussion was whether it was ethically possible to implant VVI(R) pacemaker systems in SND patients. Also, it is as yet the most positive RCT in favor of atrial-based pacing. Compared with RCTs on dual- versus single-chamber ventricular pacing, however, the number of patients in the Danish trial was rather small; the expectations of a 50% AF and HF reduction and even 66% TE and mortality reduction by atrial versus ventricular single-chamber pacing were too optimistic to show a significant difference in such a small patient group. Prolongation of follow-up to cope with this error in sample size calculation was not prespecified, thus arguably not allowed in a prospective trial. Therefore, results resemble a “post hoc” analysis and are only hypothesis generating. However, all results at 3.3 and 5.5 years point to atrial pacing being associated with more favorable clinical results than ventricular pacing. In no study outcome parameter was ventricular better (significantly or nonsignificantly) than atrial pacing. The Danish trial proposed effective criteria to select patients for AAIR pacing with low risk of AV block. The need to measure the Wenckebach block point at study entry in addition to the PQ interval, however, is not clear. During the study, no development of AV block was predictable by a progressive reduction in the heart rate at the Wenckebach block point.36 However, only a few patients who had documented second-degree or third-degree AV block received an upgrade from AAI to DDD. An observational study found an annual incidence of upgrade from AAI to DDD of 1.7% as a result of documented AV block or AF with slow ventricular rate in 399 patients followed for 4.6 years.37 Also of note was a 0.8% additional annual reoperation rate for the addition of a ventricular lead, mainly because

238

TABLE

10-4 

SECTION 2  Clinical Concepts

Evaluation Parameters for Impact of Pacing Modes on Cardiac Performance

Area Clinical

Exercise capacity Echocardiographic

Clinical events Invasive hemodynamics Blood serum Coronary artery perfusion Arrhythmias

Parameters Dyspnea (NYHA class) Symptom scores Edema, dose of diuretics Systolic blood pressure Pacemaker syndrome Quality of life (questionnaires, scores) Patient preference Exercise duration, maximum workload Anaerobic threshold, maximum oxygen uptake Mitral regurgitation Cardiac output LV end-diastolic diameter, LV ejection fraction/fraction shortening Left atrial diameter Mortality (cardiovascular, all-cause) Thromboembolism/stroke Heart failure hospitalization Cardiac output Pulmonary capillary wedge pressure, V wave Myocardial oxygen consumption Atrial natriuretic peptide, brain natriuretic peptide (Nor-)Epinephrine levels Positron emission tomography (PET) Scintigraphy Atrial fibrillation Ventricular arrhythmias

LV, Left ventricular; NYHA, New York Heart Association.

of atrial lead problems. Therefore, 2.5% of AAI systems were surgically changed to VVIR or DDDR per year. There is renewed interest in the Andersen et al.34,35 data because of the deleterious effects of unnecessary right ventricular pacing observed in the DDDR mode38 (see later). In this context, observations from the Danish trial on development of heart failure with VVI pacing in sinus node disease are important.39 The Danish trial observed an increase in New York Heart Association (NYHA) functional class during follow-up in 31% of patients in the ventricular versus 9% in the atrial group (P < .0005). The incidence of crural edema and dyspnea, together with the need for diuretics during the 5.5-year study period, was significantly higher in patients with ventricular pacing, and the left ventricular fractional shortening decreased significantly only in the ventricular group, not in the atrial pacing group. At the same time, the left atrial diameter increased significantly more during ventricular pacing, from 34 to 41 mm. Interestingly, despite the left atrial dilatation in ventricular pacing in SND, a higher incidence of AF was evident only after 5.5 years, not at 3.3 years of follow-up, despite that TE events were observed more frequently in ventricular pacing already at 3.3 years. Of note, 12 TABLE

10-5 

of the 39 patients who developed TE during follow-up never had documentation of AF, neither before randomization nor during follow-up.40 Documentation may have missed AF in a significant number of patients because only 12-lead ECG was used at follow-up. Pacemaker memory functions likely would have documented a much higher incidence of AF.41

Ventricular Versus Dual-Chamber Pacing NONRANDOMIZED EARLY STUDIES Starting from impressive observations of improved hemodynamics with VAT and VDD compared to VVI pacing in patients with AV block,22 many publications documented the benefits of “physiologic” versus ventricular pacing from the earlier 1980s to the late 1990s. Various parameters were used to define the presence or absence of this benefit (Table 10-4). Outcomes of dual-chamber or atrial versus ventricular single-chamber pacing particularly note hemodynamic improvement with dual-chamber pacing and range from case reports to patient series.42 Of these multiple outcome parameters, four were frequently chosen as endpoints in prospective, large-scale RCTs: mortality, stroke, atrial fibrillation, and heart failure. Whereas studies of the early 1980s usually focused on hemodynamic parameters, the concept of clinical studies on pacing shifted toward investigating the impact of different pacing modes on clinical events such as mortality, particularly after the CAST study, in which antiarrhythmic drugs successfully suppressed ventricular ectopy but were associated with an increased mortality. Mortality Retrospective early trials showed a significant reduction of mortality for atrial and dual-chamber pacing compared to ventricular singlechamber pacing, predominantly in patients with sinus node disease43-52 (Tables 10-5 and 10-6). However, mortality rates varied widely for VVI (15%-48%) compared to atrial or dual-chamber pacing (7%-27%).50 In high-degree AV block, Alpert et al.53 found no difference in allcause mortality between 132 patients with ventricular compared to 48 patients with dual-chamber systems. Similarly, in 148 patients with AV block (74 with VVI and 74 with VDD pacemaker systems), LindeEdelstam et al.54 found no difference in mortality in the entire patient group. However, both studies found that in patients with preexisting heart failure, VVI pacing was associated with a significantly higher mortality than VDD pacing. A study of 1245 patients (77% with AV block; ventricular pacing in 97%, dual-chamber pacing in only 3%), suggested that survival was related to the mode of pacing.48 Analyzing 391 patients with AV block or carotid sinus hypersensitivity, Hesselson

Survival in Patients with Sinus Node Disease in Relation to Pacing Mode* Physiologic

Study/Year Rosenqvist43/1988 Sasaki44/1988 Bianconi45/1989 Santini46/1990 Stangl47/1990 Zanini48/1990 Nürnberg49/1991 Hesselson50 1992 Sgarbossa51/1993 Tung et al.52/1994 Weighted means and totals

Patients (N) 89 19 153 214 110 53 37 308 395 36 1414

Follow-up (mo) 44 20 44 61 52 45 41 30 66 44 50

Ventricular Patients (N) 79 25 150 125 112 57 93 193 112 112 1058

*Results from retrospective observational studies. †P ≤ .05. PHYS, Physiologic pacing mode; RRR, relative risk reduction; VENT, ventricular pacing mode.

Follow-up (mo) 47 35 59 47 54 40 41 44 66 44 49

Death (%/yr) PHYS 2.1 7.6 3.8 2.8 4.0 2.5 7.1 8.3 3.9 8.3 4.8

VENT 5.9 8.2 6.3 7.7 6.2 5.3 13.8 12.8 7.5 16.5 9.4

RRR (%) −64† −7 −40 −64† −35 −53 −49† −35† −48† −50† −49



239

10  Clinical Trials of Atrial and Ventricular Pacing Modes

TABLE

10-6 

Survival in Patients with Atrioventricular Block and Other Indications in Relation to Pacing Mode* Physiologic

Study/Year Alpert53/1986 Linde-Edelstam54/1992 Zanini48/1990 Hesselson50/1992

Patients (N) 48 74 53 299

Ventricular

Follow-up (mo) 60 65 45 30

Patients (N) 132 74 57 92

Death (%/yr)

Follow-up (mo) 60 65 40 44

PHYS 6.0 6.6 2.5 10.4

VENT 7.4 5.9 5.3 14.9

RRR (%) −19 +11 −53 −30†

*Results from retrospective observational studies. †P ≤ .05. PHYS, Physiologic mode; RRR, relative risk reduction; VENT, ventricular mode.

et al.50 demonstrated a significant mortality benefit during a 7 year follow-up with DDD (54%) versus VVI pacing (33%). Atrial Fibrillation and Thromboembolism Starting in the 1980s, almost all retrospective studies showed a lower incidence of AF in patients with atrial/dual-chamber pacing compared to ventricular single-chamber pacing43-52,54-59 (Table 10-7). This was particularly evident for SND. Heart Failure Several studies identified ventricular versus “physiologic” pacing mode as an independent predictor of mortality in patients with congestive heart failure (CHF),54 whereas others did not confirm this observation.51 Overall, retrospective studies suggest a large improvement in clinical outcomes with the use of atrial and dual-chamber pacing versus ventricular pacing systems, with a 45% RRR in mortality, 62% reduction in HF, 66% reduction in stroke, and a 72% reduction in AF (see Table 10-7). These data were used to calculate sample size in the Danish trial of AAI versus VVI pacing.34 Medicare Trial As with other investigators in the late 1980s, Lamas60 noted the problem of “retrograde,” or ventriculoatrial (VA) conduction during VVI pacing at Brigham and Women’s Hospital (Boston). This was a common phenomenon in pacemaker patients and a significant cause of adverse symptoms after VVI pacemaker implantation. Also, only a properly timed atrial systole contributed positively to systolic ventricular performance by the Frank-Starling mechanism which states that the extent of systolic myocardial fiber shortening depends on the degree TABLE

10-7 

of diastolic fiber stretch, or preload. Therefore, with the important atrial contribution to cardiac performance, dual-chamber pacing with restoration of normal cardiac physiology (AV synchrony and appropriate rate response) may be advantageous in patients with AV block or SND. Lamas et al.61 sought to confirm the theoretical advantages of dualchamber pacing in a large, retrospective analysis of a 20% random sample of all Medicare beneficiaries 65 or older who received a first pacemaker implantation (1988-1990) and whose vital status information was available for at least 1 year (n = 36,312). Dual-chamber pacemaker selection was an independent predictor of survival at 1 and 2 years, with a relative mortality risk reduction of 18%, even after controlling for potentially confounding factors. However, choice of dualversus single-chamber pacing mode was biased by patient age, gender, indication for pacing, presence of CHF, and AF. Additionally, implantation in the western United States, rural provider, and hospitalization in a facility with 500 beds or more, a private hospital, or a hospital with a catheterization laboratory were also associated with dual- instead of single-chamber pacemaker selection. For this potential bias, the authors performed a prospective trial. RANDOMIZED STUDIES In the early 1980s, double-blind crossover studies prospectively compared VVI to dual-chamber pacing. Perrins et al.62 randomized 13 patients with AV block and a VDD pacemaker to dual-chamber or VVI mode. They found a better exercise capacity and reduction of symptoms during the period with dual-chamber pacing, as documented by patients’ diaries and monthly symptom scores. Similarly, Kristensson

Pacing Mode, Atrial Fibrillation (AF), Stroke/Thromboembolism (CVA/TE), Heart Failure (HF), and Mortality* AF (%/yr)

Study Sutton55 Markewitz56 Ebagosti57 Langerfeld58 Rosenqvist43 Sasaki44 Bianconi45 Feuer59 Santini46 Stangl47 Zanini48 Nürnberg49 Hesselsson50 Linde-Edelstam54 Sgarbossa51 Tung52 Total/mean

P-yr 3239 592 408 1265 636 112 1301 807 1582 981 389 444 2498 799 2789 543 18385

P 1.4 3.1 2.0 0.9 1.8 0 4.8 2.5 1.4 1.5 1.0 4.8 1.4 – – – 1.9

V 6.8 10.0 5.2 5.4 12.1 12.3 7.9 4.5 11.8 4.2 5.3 11.0 5.3 – – – 7.0

CVA/TE (%/yr) R −85† −69 −62† −83 −85† −100† −39† −44† −88† −64 −81† −56 −74 – – – −72

P – – 0 – 3.3 0 1.2 – 0.5 – 0 0 – – – – 0.9

V – – 1.4 – 3.9 6.8 2.1 – 2.6 – 2.1 3.1 – – – – 2.7

HF (%/yr) R – – −100 – −15 −100 −43 – −81 – −100 −100 – – – – −66

P – – – – 3.9 2.6 – – – – 0.5 – – – – – 2.6

*Results from nonrandomized observational studies. †Multivariate analysis identified ventricular pacing as an independent predictor of chronic atrial fibrillation and stroke. P [PHYS], physiologic pacing mode; P-yr, Patient-years; R [RRR], relative risk reduction; V [VENT], ventricular pacing mode.

V – – – – 9.4 9.6 – – – – 1.6 – – – – – 6.8

Death (%/yr) R – – – – −59† −73 – – – – −69 – – – – – −62

P – – 3.5 – 2.1 7.6 3.8 2.2 2.8 4.0 2.5 7.1 9.0 5.8 3.9 8.3 4.8

V – – 4.8 – 5.9 8.2 6.3 3.9 7.7 6.2 5.3 13.8 13.6 7.0 7.5 16.5 8.9

R – – −27 – −64† −7 −40 −44 −64† −35 −53 −49† −34 −17 −48 −50 −45

240

SECTION 2  Clinical Concepts

et al.63 randomized 44 patients to VVI or VDD for 3 weeks for each mode. They observed a statistically significant improvement of maximal exercise tolerance of 14% with AV synchronous pacing. Arterial lactate, respiratory rates, and perceived exertion ratings during submaximal exercise were higher on ventricular inhibited pacing. Symptom scores during the 3-week periods with VVI pacing were worse than with dual-chamber pacing. Most patients had a better functional class during AV synchronous pacing and preferred this pacing mode. Importantly, these two studies attempted to reduce any bias by double-blinding patients and the physicians who performed exercise testing. Also, in-patient comparison was done between ventricular and dual-chamber pacing modes, not available in later trials, which used a parallel trial design to avoid carryover effects. In one of the first prospective randomized, intention-to-treat trials on pacing mode selection, Mattioli et al.64 compared ventricular (VVI or VVIR) with physiologic pacing (AAI, DDD, DDDR, VDD) in 210 patients (SND in 110, AV block in 100) with a median age of 77 years. Only six patients received an AAI pacemaker. Patients with previously known AF were excluded from this study. A total of 56 patients (27%) developed AF during follow-up. The incidence of AF was 10% at 1 year, 23% at 3 years, and 31% at 5 years. The investigators observed an increased incidence of chronic AF in patients receiving ventricular pacing (P < .05). No difference was observed in the incidence of chronic AF between patients paced for AV block and patients paced for SND. In the subgroup of SND patients, the incidence of chronic AF was significantly less in patients receiving a physiologic than in those receiving a ventricular pacemaker (see Table 10-7). Pacemaker Selection in the Elderly Study (PASE) After their observations in the Medicare trial, Lamas et al.65 randomized 407 patients 65 or older with sinus rhythm and an indication for permanent pacing (SND or AV block) to single- or dual-chamber pacemaker therapy in the Pacemaker Selection in the Elderly Study. All patients received a dual-chamber device programmed to VVIR or DDDR according to the randomization result. The primary endpoint was health-related QOL (measured by SF-36); average age was 76. During the 30-month follow-up, QOL improved significantly after pacemaker implantation, but without a significant difference between VVIR and DDDR pacing modes, neither in QOL nor in clinical outcomes (cardiovascular events or death; Table 10-8). However, this refers to the intention-to-treat analysis while “on-treatment”, 26% percent of patients assigned to ventricular pacing were crossed over and paced in the dual-chamber mode because of symptoms of pacemaker syndrome. The PASE subgroup of patients with SND had a significantly better QOL in some subscales of the SF-36 and a better cardiovascular functional status with dual-chamber pacing than with ventricular pacing. A trend toward lower all-cause mortality, lower incidence of AF, and reduced incidence of the combined endpoint of stroke, hospitalization for heart failure, or all-cause mortality favoring dual-chamber pacing was seen in patients with SND, but not in those with AV block (see Table 10-8). The authors concluded that pacemaker therapy improves QOL, but that the benefits associated with dual-chamber pacing versus

TABLE

10-8 

Clinical Events in Pacemaker Selection in the Elderly Study (PASE) All Patients (n = 407)

Event All-cause mortality Atrial fibrillation

VVIR 17% 19%

DDDR 16% 17%

SND (n = 175) VVIR 20% 28%

DDDR 12%* 19%*

AV Block (n = 201) VVIR 15% 11%

DDDR 17% 16%

Data from Lamas GA, Orav J, Stambler BS, et al: Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. N Engl J Med 338:1097-1104, 1998. *Trend (P < 0.10) toward lower incidence with DDDR. SND, Sinus node disease.

ventricular pacing were moderate and observed only in the subgroup of SND patients. Critical Appraisal.  PASE was the first large multicenter RCT on dualchamber versus ventricular single-chamber pacing performed according to EBM guidelines. The results were primarily interpreted as disappointing, showing only a marginal or even no advantage of dualchamber pacing. However, the most relevant clinical finding may be the crossover rate of 26% from VVIR to DDDR pacing because of symptoms potentially caused or worsened by single-chamber pacing. In PASE, all patients had received dual-chamber devices, and randomization to single- or dual-chamber pacing was performed by device programming (“software randomization”). Patients randomized to VVIR pacing thus were fortunate because crossover did not require an additional surgical intervention, only reprogramming. Therefore, it was argued that crossover may have been performed because of bias on the side of physicians who attributed symptoms during VVIR pacing inappropriately to “pacemaker syndrome,” despite that per protocol, investigators were required to discuss each case individually with the principal investigator. An analysis of causes and results of crossover from VVIR to DDDR pacing, however, showed that the most common reason for crossover was “severe pacemaker syndrome” (77%), defined as a constellation of fatigue, dyspnea, effort intolerance, paroxysmal nocturnal dyspnea, neck fullness, presyncope, cannon A waves, blood pressure (BP) reduction with ventricular pacing, and CHF initiation or exacerbation.66 The most common individual symptoms were fatigue (62%), effort intolerance (64%), dyspnea (55%), and presyncope (34%). The diagnosis “pacemaker syndrome” or “intolerance to VVIR” in these patients with crossover is supported by the observation that, in contrast to other patients, their QOL deteriorated significantly after pacemaker implantation before crossover and improved significantly after reprogramming to dual-chamber pacing. The use of β-blockers, the presence of nonischemic cardiomyopathy, and systolic BP less than 110 mm Hg during ventricular pacing (relative risk of crossing over = 2.6) predicted intolerance to VVIR. However, the sensitivity of a decrease in paced systolic BP to less than 110 mm Hg at implantation for predicting intolerance to VVIR pacing was only 36%, the positive predictive power only 48%. The presence of VA conduction at implant did not predict the development of intolerance to VVIR pacing, although VA conduction or cannon A waves were present in almost 50% of crossover patients. Similar to results of later trials, the incidence of AF was significantly higher in patients with sinus node disease randomized to VVIR compared to DDDR (28% versus 16% at 18 months). There was no difference between VVIR and DDDR with regard to the development of AF in patients with AV block. In conclusion, the PASE trial suggests that symptoms of a pacemaker syndrome during VVIR pacing are frequent in an elderly population with sinus rhythm and sinus node disease or atrioventricular block. If the crossover rate of 26% translates into 26% of patients requiring surgical reintervention if they are implanted with a ventricular singlechamber device, this complication rate is clinically unacceptable and not cost-effective. Mode Selection Trial in Sinus Node Dysfunction (MOST) The group of investigators of PASE followed their observation that differences in outcome parameters between VVIR and DDDR were (if present at all) more pronounced in sinus node disease, performing a pacing mode comparison in SND patients.67 A total of 2010 patients were randomized to dual-chamber (1014) or ventricular pacing (996) and followed for 33 months. The incidence of the primary endpoint (all-cause mortality or nonfatal stroke) did not differ significantly (21.5% in DDDR, 23.0% in VVIR). Adjusted analyses revealed that in patients assigned to DDDR pacing, the risk of AF was 23% lower (21% vs. 27%) and HF scores were better. Heart failure hospitalization was reduced by 27%, the composite endpoint death, stroke, or HF hospitalization was reduced by 15% (Table 10-9). Dual-chamber pacing resulted in significantly better QOL for six of the eight SF-36 subscales



10  Clinical Trials of Atrial and Ventricular Pacing Modes

TABLE

10-9 

Clinical Events in Mode Selection Trial in Sinus Node Dysfunction (MOST)

Clinical Event Death Stroke Heart failure hospitalization Atrial fibrillation

VVIR (n = 996) 23.0% 4.9% 12.3% 27.1%

DDDR (n = 1014) 21.5% 4.0% 10.2%* 21.4%*

Data from Lamas GA, Lee KL, Sweeney MO, et al: Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 346:1854-1862, 2002. *P < .05 for lower incidence with DDDR.

during the 4 years of follow-up. The authors concluded that in SND patients, dual-chamber pacing does not increase stroke-free survival compared to ventricular single-chamber pacing, but DDDR significantly reduces AF risk and HF symptoms and improves QOL. Critical Appraisal.  The MOST trial had the ambitious aim to assess clinical events (mortality, stroke), AF incidence, and symptoms (HF, pacemaker syndrome, QOL) in VVIR versus DDDR pacing for SND. While the latter two endpoints favored dual-chamber pacing, the first and most important endpoint (mortality) did not demonstrate a significant difference. Therefore, the MOST trial was frequently regarded as a negative trial, showing no significant benefit of dual-chamber compared to ventricular single-chamber pacing. In-depth analyses of mortality68 and stroke risk69 showed no advantage of dual-chamber pacing, and QOL was better in dual-chamber mode in several items, particularly related to physical function.70 However, there were two important lessons from MOST: (1) pacemaker syndrome is frequent in SND and VVIR pacing,71 and (2) unnecessary right ventricular pacing in SND is detrimental.38 A strong argument in favor of dual-chamber pacing is the observation of severe pacemaker syndrome in approximately 20% of SND patients treated by VVIR pacing.71 The investigators in MOST attempted to prevent the major weakness of PASE, where the crossover rate from single- to dual-chamber pacing of 26% was so high that it may have prevented any meaningful intention-to-treat analysis of the difference between the two pacing modes. In MOST, therefore, the diagnosis of pacemaker syndrome strictly required documentation of new symptoms (e.g., dyspnea, syncope) together with VA conduction

or systolic BP reduction of 20 mm Hg or more during VVI pacing compared to intrinsic rhythm. Even in the presence of pacemaker syndrome, crossover of pacing mode had to be confirmed by the clinical coordinating center; other attempts to resolve pacemaker syndrome (e.g., reprogram pacing rate, deactivate sensor) were required; and only if these failed, the centers could ask the principal investigator to review the indication for crossover to dual-chamber mode. Despite these rigid requirements, 20% of patients programmed to VVIR met criteria for pacemaker syndrome and required crossover from single- to dual-chamber. Interestingly, pacemaker syndrome could basically develop at any time after implantation: At 6 months, it was present and required reprogramming in 14% of patients with VVIR pacing, in 16% at 1 year, in 18% at 2 years, and in 20% at 4 years. Slow sinus rates but not the presence or absence of VA conduction before pacemaker implantation predicted the development of pacemaker syndrome. QOL in patients with pacemaker syndrome was significantly worse than in patients without this complication of VVIR pacing, and it improved significantly after crossover to dual-chamber mode. Therefore, pacemaker syndrome with 20% incidence can be regarded as the most frequent complication of ventricular singlechamber pacing in SND, with significant impact on patients’ symptoms and QOL (Fig. 10-2). A second post hoc analysis of MOST detected one of the basic problems of studies on mode selection and changed the practice of cardiac pacing. Sweeney et al.38 found that the percentage of right ventricular (RV) pacing was strongly associated with the risk of developing HF and AF. This refers to patients with SND and narrow QRS at baseline. Interestingly, this association was more striking for dualchamber than single-chamber pacing. From these results, hypothetically, a “badly timed” (i.e., too early) ventricular stimulus may be more detrimental in dual-chamber pacing, where the pacing mode forces adverse AV timing to be present in every cycle, versus single-chamber ventricular pacing, where (besides pacemaker syndrome with VA conduction) only some cycles have by chance a detrimental AV relation, whereas in most cardiac cycles, atrium and ventricle are dissociated. The potential adverse effects of unnecessary RV pacing and inappropriate AV timing are problems not only in PASE and MOST, but in all trials comparing ventricular single- and dual-chamber pacing and may partly explain the lack of a positive effect of dual-chamber pacing in these studies.

Criterion 1: New or worsened dyspnea, orthopnea, elevated jugular venous pressure, rales, and edema with ventriculoatrial (VA) conduction during ventricular pacing

Criterion 2: Symptoms of dizziness, weakness, presyncope or syncope, and a ≥20 mm Hg reduction of systolic blood pressure when the patient had VVIR pacing compared with atrial pacing or sinus rhythm

23% Figure 10-2  Pacemaker syndrome in MOST. Percentage of patients meeting criterion 1 or 2 or both criteria in Mode Selection Trial in Sinus Node Dysfunction.

241

42%

35% Criterion 1

Criterion 2

Both criteria

242

TABLE

10-10 

SECTION 2  Clinical Concepts

Clinical Events in Canadian Trial of Physiologic Pacing (CTOPP)

Clinical Event (annual) Stroke Heart failure hospitalization Atrial fibrillation

VVIR (n = 1474) 1.1% 3.5% 6.6%

AAIR/DDDR (n = 1094) 1.0% 3.1% 5.3%*

Data from Connolly SJ, Kerr CR, Gent M, et al: Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. N Engl J Med 342:1385-1391, 2000. *P ≤ .05 for lower incidence with DDDR.

Canadian Trial of Physiologic Pacing (CTOPP) After PASE in 1998, the Canadian Trial of Physiologic Pacing was the second large RCT on pacing mode selection.72 It enrolled patients scheduled for pacemaker implantation without permanent atrial fibrillation at 32 Canadian centers. Patients were randomized to receive either a ventricular pacemaker or a “physiologic pacemaker” (i.e., atrial single or dual chamber) and followed for an average of 3 years. The primary outcome was stroke or death from a cardiovascular cause; secondary outcomes were all-cause mortality, AF development, and hospitalization for heart failure. CTOPP randomized 2568 patients, 1094 received a physiologic system (dual-chamber or atrial singlechamber pacemaker), and 1474 a ventricular single-chamber device. The annual rate of stroke and death from cardiovascular causes were similar in both groups (5.5% with ventricular pacing, 4.9% with physiologic pacing; P = 0.33) (Table 10-10). The incidence of AF was lower with physiologic versus ventricular pacing (annual rate, 5.3% vs. 6.6%; P = .05) with the difference emerging only 2 years after implantation. All-cause mortality and HF hospitalization were not significantly different, whereas postoperative complications occurred more frequently with physiologic pacing (9.0%), which consisted of atrial singlechamber pacing in only 5% and ventricular single-chamber pacing in another 5% of patients because of problems to implant the atrial lead. The authors of CTOPP concluded that physiologic pacing provides little or no benefit over ventricular pacing with regard to stroke prevention or cardiovascular death. Critical Appraisal.  Of the many questions about CTOPP, the authors cite the most important: in 56% of 1931 eligible patients who were not enrolled, it was the physician who declined participation. Heart failure of NYHA Class II or higher was present in significantly more eligible patients who were not enrolled (49%) than in those who were enrolled (39%). Because many physicians believed dual-chamber pacing to be superior to ventricular single-chamber pacing at patient recruitment in CTOPP, they likely declined to enroll patients when they were concerned about worse outcomes with ventricular single-chamber pacing, namely, HF patients and those who might require pacing most of the time. Therefore, CTOPP probably represents primarily patients with intermittent bradycardia, such as intermittent sinoatrial and atrioventricular block. A post hoc analysis supported the criticism that the lack of benefit of physiologic pacing may derive from CTOPP including many patients with only intermittent and rare bradycardia. Tang et al.73 compared patients with an unpaced heart rate before pacemaker implantation of ≤60 bpm to patients with an unpaced heart rate above 60 bpm. Risk of cardiovascular death or stroke was significantly higher in patients with ventricular single-chamber pacing than with physiologic pacing, if the unpaced heart rate before pacemaker implantation was ≤60 bpm, whereas patients with an unpaced heart rate greater than 60 bpm derived no benefit in this study endpoint from physiologic pacing. Similarly, only patients with an unpaced heart rate ≤60 bpm showed a better exercise capacity, as measured by 6-minute hall walk test with dual-chamber pacing, whereas pacing mode did not affect exercise capacity in patients with an unpaced heart rate greater than 60 bpm.74 One of the major criticisms of CTOPP refers to the lack of experience with atrial leads and dual-chamber pacing by many centers that enrolled a large number of patients.75 The results that centers were

unable to implant an atrial lead in 5% of patients, that incidence of postoperative complications for dual-chamber pacemaker implantation was 9%, and that more than 17% of dual-chamber devices were reprogrammed to VVI at 5-year follow-up reflect the lack of experience in implanting and following dual-chamber devices in some of the centers that participated in CTOPP. As an argument in favor of dual-chamber pacing, a prespecified subanalysis found “chronic atrial fibrillation” (defined as AF lasting >1 week) occurred significantly more often in ventricular single-chamber pacing.76 This trend was even more pronounced in 1474 patients from CTOPP in whom follow-up was extended to a mean of 6.4 years.77 However, even in this extended study period, no difference could be observed between dual-chamber and ventricular single-chamber pacing with regard to cardiovascular mortality and stroke. Additionally, the effect of pacing mode on AF incidence was regarded as less important after publication of the AFFIRM trial.78 In conclusion, CTOPP showed for the first time that even in a study with a large patient group and a long follow-up period, it is difficult to demonstrate an advantage in “hard endpoints” of dual- over singlechamber ventricular pacing. However, CTOPP was frequently regarded as a study with the “apparent intent of the trial to pattern cost control instead of optimize patient care.”75 Even in Canada, it never had an impact on pacing mode selection, which was characterized by a constant increase of the percentage of dual-chamber systems. United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial Complementary to MOST, which randomized patients with SND to ventricular single- or dual-chamber pacing, the UKPACE trial randomized patients with AV block; 2021 patients age 70 or older with high-degree AV block randomly received a ventricular single-chamber or a dual-chamber pacemaker.79 In the single-chamber group, patients were further randomized to receive either fixed-rate or rate-adaptive pacing. The primary outcome was all-cause mortality; secondary outcomes were AF, heart failure, and stroke/transient ischemic attack (TIA)/systemic embolism. During the follow-up of 4.6 years, annual mortality did not differ (7.2% vs. 7.4% in single- vs. dual-chamber group) (Table 10-11). Surprisingly, there were also no significant differences between both groups in the incidence of AF, HF, or stroke/ TIA/embolism. The authors concluded that in elderly patients with high-degree AV block, pacing mode does not influence all-cause mortality or the incidence of cardiovascular events. Critical Appraisal.  It had been expected that results of the UKPACE trial might favor dual-chamber pacing, because patients with highdegree AV block are frequently pacemaker dependent and require ventricular pacing continuously. Patients with SND in MOST were usually not pacemaker dependent and may therefore have had periods when they did not require pacing. This could dilute the advantageous effects of “physiologic” compared to ventricular single-chamber pacing. Elderly patients with AV block enrolled in UKPACE may have been particularly sensitive to suboptimal hemodynamic conditions produced by asynchronous pacing in the VVI and VVIR modes. In their trial design paper, the authors of UKPACE therefore hypothesized that “it may be that such patients have much to gain from the superior hemodynamics of optimal pacing in terms of functional capacity and

TABLE

10-11 

Clinical Events in United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial

Clinical Event (annual) All-cause mortality Cardiovascular mortality Thromboembolism Heart failure hospitalization Atrial fibrillation

VVI/VVIR (n = 1009) 7.2% 3.9% 2.1% 3.2% 3.0%

*P < .05 for higher incidence with DDDR.

DDDR (n = 1012) 7.4% 4.5%* 1.7% 3.3% 2.8%



10  Clinical Trials of Atrial and Ventricular Pacing Modes

Study

Physiologic

Ventricular

Wt%

Danish

39/110

57/115

4.1

0.66 [0.44,0.99]

CTOPP

390/1094

565/1474

40.8

0.92 [0.81,1.05]

PASE

32/203

34/204

2.9

0.94 [0.58,1.52]

MOST

200/1014

204/996

17.8

0.97 [0.8,1.18]

UKPACE

393/1012

387/1009

34.4

1.01 [0.88,1.16]

Overall

1054/3433

1247/3798

100

0.95 [0.87,1.03]

243

HR [95% CI]

Homogeneity: chi-square = 3.99 df = 4 p = 0.41 Association: chi-square = 1.69 p = 0.19 0.1

0.5

1.0

2.0

Hazard ratio Figure 10-3  Pooled estimate of mortality in randomized trials of pacing mode. Danish, Atrial versus ventricular pacing in sick sinus syndrome (Andersen et al.34,35); CI, Confidence interval; CTOPP, canadian Trial of Physiologic Pacing; HR, hazard ratio; MOST, Mode of Selection Trial in Sinus Node Dysfunction; PASE, Pacemaker Selection in the Elderly; UKPACE, United Kingdom Pacing and Cardiovascular Events trial.

quality of life, in addition to the possibility of reduced cardiovascular morbidity and improved survival.”80 The main finding of UKPACE, that dual-chamber pacing did not convey any advantages in terms of mortality, AF, stroke, or heart failure in elderly patients with AV block compared with single-chamber ventricular pacing, was therefore particularly disappointing. UKPACE was the only large RCT that found no difference in AF between single- and dual-chamber pacing. In fact, AF was detected more frequently in dualchamber pacing during the first 18 months of the study, perhaps from a systematic bias. In dual-chamber devices, AF can easily be diagnosed by the atrial lead and electrogram (EGM). In VVI and VVIR devices, the detection of AF is limited to the surface electrocardiogram (ECG) and can be difficult in patients with complete AV block and VVIR pacing.81 Explanations for the contradictory results between a number of hemodynamic studies demonstrating unequivocally a significant advantage of dual-chamber pacing on one side, and the lack of any clinically meaningful benefit of dual-chamber pacing in UKPACE on the other side, are difficult. Three prespecified UKPACE subanalyses (nuclear assessment of left ventricular function, Holter recording to assess prevalence of atrial arrhythmias, assessment of QOL and cognitive function) to date have not been published. Some studies on hemodynamics in pacing, particularly in the context of cardiac resynchronization therapy, have emphasized the importance of timing the AV delay to achieve acceptable results in dual-chamber pacing.82,83 Hemodynamic optimization of the AV delay had not been performed in UKPACE. On the contrary, programming instructions in UKPACE suggested the use of short AV delays (150 msec, with rate-adaptive shortening to 75 msec)80 to facilitate and ensure continuous ventricular pacing. In view of the deleterious effects of RV pacing, this may have negatively affected patients with dual-chamber devices (see Role of Prevention of Unnecessary Right Ventricular Pacing). It was not reported how many patients had only intermittent versus permanent second-degree or third-degree AV block. Continuous ventricular pacing may have been unnecessary and therefore disadvantageous in these patients. Programming of such short AV delays caused a significantly (P < .001) higher percentage of ventricular pacing in patients with dual-chamber pacing: Counters (available in 65% of patients) demonstrated a median of 99% RV pacing in dualchamber mode versus 94% in VVI and 93% in VVIR at 1 month.79 Inappropriately short AV delays can lead to premature mitral valve closure, causing pulmonary venous regurgitation by nonphysiologic

flow reversal during atrial systole.84 Because of device programming, this may have occurred more frequently in UKPACE than in other RCTs of pacing mode, leading to disadvantageous side effects that counteracted and precluded any potential benefit of dual-chamber pacing. META-ANALYSIS OF VENTRICULAR VERSUS ATRIAL-BASED PACING After UKPACE, Healey et al.85 performed a meta-analysis of the large trials on pacing mode selection (Danish study,34,35 PASE,65 CTOPP,72 MOST,67 UKPACE79). As expected, no advantage of dual-chamber pacing was found for mortality, for the combination of mortality and stroke, or for heart failure hospitalization (Figs. 10-3 to 10-8). The incidence of atrial fibrillation was lower in dual-chamber pacing. However, predominantly because of UKPACE results, a subanalysis showed a lower incidence of AF only for dual-chamber pacing in sinus node disease, but not in AV block. Even though this meta-analysis included the impressive number of 7231 patients, results cannot overcome the general limitations of the individual trials, such as selection bias and biased detection of AF when an atrial lead is present.

Atrial Single-Chamber Versus Dual-Chamber Pacing: Clinical Trials In 2004, Masumoto et al.86 performed a retrospective analysis of 196 patients with sinus node disease who were implanted with dualchamber devices programmed to DDD (n = 101) or AAI (n = 95) mode. Consecutive patients implanted between 1979 and 2000 were included if they had no second- or third-degree AV block, a maximum PR interval of 220 msec, and no left bundle branch block or bifascicular block. During a mean follow-up of 8 years, eight AAI devices had to be switched to DDD because high-degree AV block developed (incidence, 1.1%/yr). At 10 years, there was no need to add a ventricular lead in 89% of patients with AAI pacing. Excluding generator exchanges, 18 patients with DDD versus 17 with AAI system underwent reoperation, predominantly for lead failure. All-cause mortality was similar in both groups (10-year survival: 88% in AAI, 93% in DDD), as was freedom from permanent AF (94% in AAI, 91% in DDD) (Table 10-12). The authors concluded that AAI pacing can achieve similar clinical benefits as DDD pacing in sinus node disease with relevant AV or infrahisian conduction disturbances.

244

SECTION 2  Clinical Concepts

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

Danish

25/110

45/115

4.2

0.54 [0.33,0.87]

CTOPP

307/1094

452/1474

47.6

0.91 [0.78,1.05]

MOST

112/982

124/958

15.3

0.88 [0.68,1.13]

UKPACE

266/1011

863/3551

33

1.09 [0.91,1.29]

Overall

710/3197

242/1004

100

0.94 [0.85,1.04]

Homogeneity: chi-square = 8.31 df = 3 p = 0.04 Association: chi-square = 1.64 p = 0.2 0.25

0.50

1.00

2.00

Hazard ratio Figure 10-4  Pooled estimate of cardiovascular mortality or stroke in randomized trials of pacing mode.

TABLE

10-12 

Clinical Events in AAI versus DDD pacing

Pacing Mode Atrial Dual chamber

All-Cause Mortality 12% 7%

Permanent AF 4% 8%

Lead Failure 15% 23%

Data from Masumoto H, Ueda Y, Kato R, et al: Long-term clinical performance of AAI pacing in patients with sick sinus syndrome: a comparison with dual-chamber pacing. Europace 6:444-450, 2004. AF, Atrial fibrillation.

Nielsen et al.87 compared myocardial blood flow and left ventricular ejection fraction (LVEF) in 30 patients with SND randomized to AAI versus DDD pacing. After 22 months of pacing in the assigned mode, myocardial blood flow was assessed with positron emission tomography (PET) and LVEF measured with echocardiography. Patients with dual-chamber pacemakers were temporarily programmed to AAI to obtain an intraindividual comparison. Myocardial blood flow was

similar in the groups with AAI and DDD pacing. However, blood flow significantly improved if the patient’s DDD pacing was temporarily programmed to AAI mode. LVEF was similar to baseline results after 22 months in AAI but had become significantly lower in patients with DDD pacing, from 61% to 56% (P = .01). However, if DDD pacing was temporarily changed to AAI, measurements of LVEF returned to baseline results. The authors concluded that dual-chamber compared with single-chamber AAI pacing has detrimental effects on myocardial blood flow and LVEF, which are still reversible after 22 months. In a single-center pilot study, consecutive patients with sinus node disease were screened and enrolled if they had no bundle branch block (BBB), and the spontaneous PQ interval did not exceed 220 msec (patients ≤70 years) or 260 msec (patients >70 years).88 Of 952 patients with a first pacemaker implantation between 1994 and 1999, 755 were excluded from the study, mainly for AV block (48%), permanent AF (10%), or BBB (5%), and only 2% of patients did not give consent. The 177 enrolled patients were randomized to receive an AAIR pacing system (n = 54) or a DDDR system programmed to a short AV delay

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

Danish

26/110

40/115

4.5

0.54 [0.33,0.89]

CTOPP

224/1094

367/1474

40.3

0.8 [0.68,0.95]

PASE

35/203

38/204

5.3

0.91 [0.57,1.44]

MOST

217/1014

270/996

34.9

0.79 [0.66,0.94]

UKPACE

98/1012

111/1009

15.1

0.88 [0.67,1.16]

Overall

600/3433

826/3798

100

0.8 [0.72,0.89]

Homogeneity: chi-square = 3.26 df = 4 p = 0.52 Association: chi-square = 17.43 p = 3e–05 0.25

0.50

1.00

2.00

Hazard ratio Figure 10-5  Pooled estimate of atrial fibrillation in randomized trials of pacing mode.



10  Clinical Trials of Atrial and Ventricular Pacing Modes

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

105/1094

156/1474

34.5

0.9 [0.7,1.15]

PASE

14/203

24/204

4.9

0.55 [0.28,1.06]

MOST

104/1014

123/996

31

0.82 [0.63,1.06]

UKPACE

111/1012

105/1009

29.7

1.04 [0.8,1.36]

Overall

334/3323

408/3683

100

0.89 [0.77,1.03]

CTOPP

245

Homogeneity: chi-square = 3.76 df = 3 p = 0.29 Association: chi-square = 2.46 p = 0.12 0.25

0.50

1.00

2.00

Hazard ratio Figure 10-6  Pooled estimate of hospitalization for heart failure in randomized trials of pacing mode.

(150 msec, DDDR-s, n = 60) or a long AV delay (300 msec, DDDR-l, n = 63). Echocardiographic (left atrial diameter, left ventricular function and size) and clinical (AF, stroke or arterial embolism, mortality, heart failure) outcomes were assessed in these three modes of pacing in SND. During the study, patients in the DDDR-s group received pacing for a mean of 90%. Patients in the DDDR-l group still received 17% of (a priori unnecessary) ventricular pacing. After a mean follow-up of 3 years, patients randomized to AAIR did not show a significant change in left atrial diameter, left ventricular diameter or LVEF shortening compared to baseline. In contrast, left atrial diameter was increased and left ventricular shortening fraction decreased significantly in the DDDR-s patients. In the DDDR-l group, the left atrial diameter and the left ventricular end-systolic and end-diastolic diameters increased significantly during the 3-year follow-up. Atrial fibrillation in the 12-lead ECG during at least one follow-up visit was significantly less common in AAIR (7.4%) than in DDDR-s (23.3%) or DDDR-l (17.5%).89 During the study, 16 strokes occurred in 14 patients, but no peripheral embolism was observed. Clinical events, including all-cause mortality, cardiovascular mortality, development of CHF, and increased use of diuretics, did not differ among the three groups. However, progression of HF symptoms, although not significantly different among the groups, was seen, with an increase of at least one NYHA class in 31% of patients paced in AAIR mode versus 30% in DDDR-s and 46% in DDDR-l. The study by Nielsen et al.87 would have required 450 patients for an 80% power to detect clinical or echocardiographic differences between AAIR and DDDR (no differences between DDDR-s and DDDR-l were expected). Inclusion was stopped when a multicenter trial (DANPACE) randomizing SND patients to AAIR versus DDDR pacing was initiated. However, the results of this study from Aarhus suggest that in patients with SND, narrow QRS and normal AV conduction dual-chamber pacing compared to AAIR pacing may result in deleterious effects in terms of left atrial enlargement, left ventricular volumes and ejection fraction, and AF incidence. Surprisingly, even in these select patients, programming the AV delay to very long values was unable to prevent a significant proportion of unnecessary right ventricular pacing. The observed proportion of ventricular pacing of 17% had detrimental effects in terms of left atrial dilatation and incidence of AF similar to DDDR pacing with short AV delay. In a study following these observations, Albertsen et al.90 randomized 50 patients with sinus node disease to AAIR or DDDR (AV delay 220 msec paced and 200 msec sensed). Primary endpoint was dyssynchrony (evaluated by tissue-Doppler imaging with at least 1 segment

with delayed longitudinal contraction) and LVEF (evaluated by 3D echocardiography) after 12 months compared to baseline. Physicians performing echocardiography were blinded with regard to pacing mode. Secondary endpoints referred to 6-minute walking test and NT-proBNP. During follow-up, patients with DDDR pacing received ventricular pacing for 66% of the time. Dyssynchrony slightly increased with DDDR pacing (mean of 1.3 delayed segments at baseline vs. 2.1 after 12 months) but not in AAIR pacing. Although LVEF decreased statistically significant with DDDR pacing (63% at baseline vs. 59% after 12 months; no change observed in AAIR pacing), there was no difference between AAIR and DDDR pacing after 12 months in NYHA class or NT-proBNP. These results confirm other observations of deteriorated left ventricular function with unnecessary right ventricular pacing, and suggest the development of left ventricular dyssynchrony as one cause. At the same time, echocardiographic changes from baseline did not translate into significant clinical changes in this small study. The Danish multicenter randomized trial on single-lead atrial versus dual-chamber pacing in patients with sick sinus syndrome (DANPACE) was started in 1999.91 It compared AAIR and DDDR pacing in patients with SND but with no BBB or AV block (except for PR interval ≤220 msec for patients <70 years and ≤260 msec for those ≥70 years). This trial used hardware randomization. Primary endpoint was all-cause mortality; secondary endpoints included detection of atrial fibrillation during scheduled follow-up, progression to permanent AF, incidence of stroke, heart failure, and the need for reoperation. It planned to include 1900 patients followed for a mean of 5.5 years to detect an absolute 6% difference in all-cause mortality with a power of 80%. The trial was terminated after 1415 patients, implanted in 20 centers in Denmark, United Kingdom, and Canada, were followed for a mean of 5.5 years. No patient was lost to follow-up. Patients in the DDDR group had been programmed to an AV delay of ≤220 msec paced and ≤200 msec sensed with rateadaptive shortening. This caused ventricular pacing for a mean of 65% of the time in DANPACE. All-cause mortality (30% in AAIR, 27% in DDDR) was not significantly different (P = 0.53) nor was there a difference in stroke, NYHA functional class, use of diuretics, or hospitalization for heart failure. To the surprise of the investigators, the incidence of paroxysmal AF was significantly lower in patients paced in the DDDR mode (RRR, 21%; P = .024). This difference appeared already within 6 months after randomization and was still observed in a multivariate analysis. However, permanent AF was similar in both pacing modes. Of clinical

246

SECTION 2  Clinical Concepts

SINUS NODE DISEASE Study

Physiologic

Ventricular

Wt%

HR [95% CI]

Danish

25/110

45/115

10

0.54 [0.33,0.87]

CTOPP

141/512

213/689

53.1

0.91 [0.74,1.13]

MOST

112/982

124/958

36.8

0.88 [0.68,1.13]

Overall

278/1604

382/1762

100

0.85 [0.73,1]

Homogeneity: chi-square = 3.92 df = 2 p = 0.14 Association: chi-square = 4.07 p = 0.044 0.25

A

1.00

0.50

2.00

Hazard ratio NO SINUS NODE DISEASE

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

CTOPP

166/582

239/785

43.6

0.9 [0.74,1.1]

UKPACE

266/1010

242/1002

56.4

1.09 [0.91,1.13]

Overall

432/1592

481/1787

100

1 [0.88,1.14]

Homogeneity: chi-square = 2.01 df = 1 p = 0.16 Association: chi-square = 0 p = 0.98 0.80

B

1.00

1.25

Hazard ratio

Figure 10-7  Cardiovascular mortality or stroke, based on indication for pacing. A, Sinus node disease. B, Pacing indications other than sinus node disease.

significance is the observation of a doubling of the need for a reoperation during follow-up in AAIR pacing (hazard ratio = 2.0 with AAIR; 95% confidence interval = 1.54-2.61; P < .001), mainly for the need of a ventricular lead. Only one patient in the DDDR pacing group had to be upgraded to a biventricular system. The authors concluded that DDDR systems programmed to an AV delay of ≤220 msec instead of AAIR systems should be used in sinus node disease. The incidence of AF related to pacing mode is different in DANPACE compared to results from a 2003 study by Nielsen et al.88 In this pilot study in 177 patients, the incidence of AF was significantly lower with AAIR pacing (7.4%) compared to DDDR with long AV delay (17.5%) and DDDR with short AV delay (23.3%). In the SAVE PACe trial, patients had significantly less persistent AF if randomized to a dualchamber mode allowing single nonconducted P waves not to be tracked, to minimize ventricular pacing in the dual-chamber mode, than patients with conventional DDDR pacing92 (see Role of

Prevention of Unnecessary Right Ventricular Pacing). However, patients with SND and conventional dual-chamber pacing in DANPACE received RV pacing for only 65% of the time versus 99% in SAVE PACe. In conclusion, several earlier studies comparing AAIR and DDDR pacing in patients with sinus node disease and narrow QRS complex suggested an advantage of the single-chamber atrial pacing mode that systematically rules out unnecessary ventricular pacing. This was strongly confirmed by post hoc analyses from MOST, in which unnecessary RV pacing was associated with worse clinical outcome. However, two randomized prospective trials (DANPACE and MVP trial; see later) did not confirm a benefit of AAIR pacing (DANPACE) or DDDR pacing with strict prevention of RV pacing in patients with an implantable cardioverter-defibrillator (ICD). Most likely, the development of first-degree AV block with long PR intervals or higher-degree AV block adversely affects hemodynamics if the ventricle is left unpaced. AV



10  Clinical Trials of Atrial and Ventricular Pacing Modes

247

SINUS NODE DISEASE Study

Physiologic

Ventricular

Wt%

HR [95% CI]

Danish

26/110

40/115

6.4

0.54 [0.33,0.89]

CTOPP

150/512

252/689

39.2

0.78 [0.64,0.96]

PASE

17/91

24/85

4.1

0.57 [0.31,1.07]

MOST

217/1014

270/996

50.2

0.79 [0.66,0.94]

Overall

410/1727

586/1885

100

0.76 [0.67,0.86]

Homogeneity: chi-square = 2.84 df = 3 p = 0.42 Association: chi-square = 18.62 p = 1.6a–05 0.25

A

1.00

0.50

2.0

Hazard ratio NO SINUS NODE DISEASE

Study

Physiologic

Ventricular

Wt%

HR [95% CI]

CTOPP

74/582

115/785

42.9

0.84 [0.63,1.12]

PASE

18/112

14/119

7.5

1.46 [0.73,2.94]

UKPACE

98/1011

111/1007

49.6

0.88 [0.67,1.16]

Overall

190/1705

111/1911

100

0.9 [0.74,1.09]

Homogeneity: chi-square = 2.09 df = 2 p = 0.35 Association: chi-square = 1.24 p = 0.27 0.5

B

1.0

2.0

Hazard ratio

Figure 10-8  Atrial fibrillation based on indication for pacing. A, Sinus node disease. B, Pacing indications other than sinus node disease.

block may also enhance the development of AF, thus questioning the concept that RV pacing should always be systematically avoided for its associated ventricular dyssynchrony. Therefore, at present, there are no firm recommendations on the ideal pacing mode in sinus node disease. AAI pacing does not appear as desirable as before DANPACE. Potentially, implantation of a dualchamber device programmed to maintain AAI pacing as long as sufficient for proper AV synchrony may be the best option, avoiding reoperation whenever first-degree AV block or higher develops. The role of first-degree AV block induced by atrial pacing from sites far from the septum (e.g., right atrial appendage, lateral right atrial wall) needs to be further evaluated. Atrial pacing–induced AV desynchronization with first-degree paced AV block may be one mechanism limiting the potential benefits of atrial and dual-chamber pacing in patients with SND.

Dual-Chamber Versus Ventricular Pacing in Defibrillator Patients The possibility of physiologic pacing in patients with an indication for an ICD and dual-chamber pacing was highly desired before it was available.93 However, the first studies on dual- versus single-chamber ICDs were disappointing, failing to show improved discrimination between ventricular and supraventricular tachycardia.94-96 Some newer studies question if single-chamber ICDs are comparable to dualchamber ICDs in prevention of inappropriate therapy.97-99 However, one of the aims of dual-chamber pacing in ICD patients is the reduction in clinical events, particularly heart failure and HF progression caused by bradycardia, which frequently develops during treatment with β-blockers and amiodarone. Even an increased risk of ventricular tachyarrhythmia (e.g., from bradycardia-dependent

TABLE

10-13 

SECTION 2  Clinical Concepts

Clinical Endpoints in Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial at 1 Year

Pacing DDDR (70 bpm) VVI (40 bpm)

All-Cause Mortality 10.1% 6.5%

HF Hospitalization 22.6% 13.3%

Combined 26.7%* 16.1%*

Data from Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. *P < .05. HF, Heart failure.

arrhythmias) has been observed in ICDs that were programmed to a VVI 40-bpm backup pacing mode.100 The Dual Chamber and VVI Implantable Defibrillator (DAVID) trial therefore evaluated if dualchamber pacing reduced the incidence of HF hospitalization and allcause mortality compared to backup ventricular pacing in patients with a conventional indication for ICD therapy and heart failure (LVEF ≤40%) but no standard indication for antibradycardia pacing.101 In 37 U.S. centers, 506 patients were enrolled and randomized to DDDR pacing at 70 bpm versus VVI backup pacing at 40 bpm (software randomization, DDDR systems implanted in all patients). Programming of other parameters, particularly the AV delay, was left to the individual investigator. The mean sinus rate at baseline was 72 bpm, the mean PR interval of patients in DAVID was 184 msec, and 27% of patients had a BBB. At 6 months, 86% of patients received β-blockers and 27%, amiodarone. The trial was prematurely stopped at a mean follow-up of 8 months because, unexpectedly, patients with dual-chamber ICDs had a significantly higher incidence of HF hospitalization (43 [23%] at 1-year follow-up) and death (23 [10%] at 1 year) than patients with single-chamber ICDs (30 and 15, equivalent to 1-year incidence of 13% and 6.5%). This difference reached statistical significance in favor of single-chamber ICDs (Table 10-13). One major difference in patients with single-chamber ICDs was the significantly lower proportion of ventricular pacing. At the 6-month control, device counters documented that VVI 40-bpm back-up pacing was associated with a mean proportion of ventricular pacing of only 0.6% in these patients without bradycardia compared to 59.6% ventricular pacing in the DDDR mode. A post hoc analysis corroborated the hypothesis that right ventricular pacing was the cause of worse outcome in patients with dual-chamber ICDs.102 In 380 patients who had a 3-month follow-up and had not yet reached a study endpoint, a multivariate analysis demonstrated that the percent of cumulative RV pacing was correlated with death or HF hospitalization during further study. If patients with dual-chamber ICDs had RV pacing more than 40% of the time, they had a more than fivefold higher risk of HF hospitalization or death than patients with a dual-chamber ICD and RV pacing for 40% or less of the time (P = .02). Patients with DDDR pacing at 70 bpm and ≤40% RV pacing trended toward a better outcome than those with VVI 40-bpm backup pacing. Another analysis assessed data in patients with “soft” indications for pacing, such as bradycardia, defined as sinus bradycardia of less than 60 bpm, and without a conventional indication for pacing.103 Results similar to the overall analysis were observed in these patients. However, the two soft indications are fundamentally different; patients with firstdegree AV block may have experienced specifically deleterious effects of dual-chamber pacing because they likely were continuously paced (and unpaced in VVI 40-bpm group), whereas patients with sinus bradycardia might have specifically benefited from dual-chamber pacing as long as a sufficiently long programmed AV delay prohibited unnecessary RV pacing. However, this was not reported in this post hoc analysis. These data were partly replicated in the second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II), although differences between pacing modes in a primary prevention ICD trial did not reach statistical significance.104 In 404 patients who received a singlechamber ICD and 313 patients with a dual-chamber ICD for primary prevention of sudden cardiac death after myocardial infarction (LVEF ≤30%), the trend was toward an increase in hospitalization for heart

failure in patients with dual-chamber devices. Because of the nonrandomized assignment to dual-chamber ICDs, however, patients who had received dual-chamber devices were older and had higher NYHA functional class, more frequent prior coronary artery bypass surgery, wider QRS complex, more frequent left BBB, atrial tachyarrhythmias, and higher nitrate urea levels. The DAVID investigators performed a second study with VVI backup pacing at 40 bpm in patients with heart failure, an indication for ICD therapy, and no conventional indication for bradycardia pacing (DAVID-II).105 This time the dual-chamber group was programmed to AAI 70 bpm and tested for “non-inferiority” compared to backup VVI pacing at 40 bpm. In 29 U.S. centers, 543 patients were enrolled and implanted with a dual-chamber ICD programmable to the VVI and AAI pacing modes. Of note, 57 patients from the first DAVID trial who did not reach a study endpoint were also included. During a mean follow-up of 2.7 years, no significant difference was seen in the primary combined endpoint of time to HF hospitalization or death (incidence 11%, 17%, and 25% at 1, 2, and 3 years, respectively). In a subanalysis, asymptomatic sinus bradycardia at baseline was associated with a lower incidence of adverse outcome (12% vs. 26%) in patients randomized to VVI 40-bpm back-up or AAIR 70-bpm pacing.106 The question if dual-chamber ICDs have any potential to reduce adverse clinical events compared to single-chamber ICDs was assessed in the Dual Chamber and Atrial Tachyarrhythmias and Adverse Events Study (DATAS).107 Patients with Class I indication for an ICD (according to ACC/AHA 1998 guidelines) were included if permanent atrial tachyarrhythmias and an indication for dual-chamber pacing were absent. A total of 334 patients were then randomized to single-chamber ICD, dual-chamber ICD, or “simulated single-chamber ICD” (i.e., dual-chamber ICD implanted but programmed to single-chamber mode for pacing and discrimination between supraventricular and ventricular tachyarrhythmia). With crossover of the latter two groups after 8 months, all patients were followed for 16 months. The primary outcome was a composite of all-cause-mortality, need for cardiovascular hospitalization or intervention, two or more inappropriate shocks, and sustained symptomatic atrial tachyarrhythmia for 48 hours or longer. This composite was expressed as a prespecified score. Any one of these endpoints occurred in 65 patients with dual-chamber ICD (58%), 82 patients with single-chamber ICD (74%), and 84 patients with a dual-chamber ICD programmed to single-chamber parameters (76%). Mortality was 4% in dual-chamber, 9% in singlechamber, and 10% in simulated single-chamber ICD patients. The composite endpoint score was 33% lower for patients with dualchamber ICDs (Fig. 10-9). 50

46

45

42

40 Percent

248

38

35 30 25 20 15 10 5

16

13

9 10

12 5

4

3

6

0 Death Dual-chamber

Hospitalization Single-chamber

HF Inappropriate hospitalizations shocks Simulated single-chamber

Figure 10-9  Clinical events in DATAS. All numbers represent percentages in Dual Chamber and Atrial Tachyarrhythmias Adverse Events Study. HF, heart failure.

249



10  Clinical Trials of Atrial and Ventricular Pacing Modes

In ICD patients, study results suggest that prevention of unnecessary right ventricular pacing plays a major role. Comparing single- and dual-chamber devices, trials showed a significant increase particularly in HF hospitalization with dual-chamber ICDs that was not caused by the dual-chamber mode itself but by RV pacing. This can lead to severe deterioration of ventricular function, most likely through desynchronization of right and left ventricular contraction, especially in preexisting HF. Of note, studies randomizing ICD patients to single- or dual-chamber pacing enrolled only patients without an indication for antibradycardia pacing. Results therefore do not apply to ICD patients with SND or AV block. Also, patients without structural heart disease where overdrive pacing may play a role (e.g., patients with long QT syndrome) are not represented in studies randomizing patients to single-chamber versus dual-chamber ICDs. Other, “soft” indications have not been systematically studied. Although patients with firstdegree AV block seem to have a particularly high percentage of unnecessary RV pacing with implications for HF progression (see below), sinus bradycardia, which may contribute and aggravate HF in some patients, may have a different outcome if ventricular pacing is prevented. Newer studies and post hoc analyses avoiding unnecessary RV pacing and using dedicated programming for better discrimination between supraventricular and ventricular tachyarrhythmias suggest some advantage for dual-chamber ICDs over single-chamber ICDs with 40-bpm backup VVI pacing.

difference in the development of AF emerged only after 2 years, and in light of the results of AFFIRM,78 was deemed not clinically relevant. At the same time, in patients who required pacing most of the time (“unpaced heart rate <60 bpm”), physiologic pacing significantly reduced stroke, cardiovascular mortality, and even all-cause mortality, rendering CTOPP the most positive trial on pacing mode selection in favor of physiologic pacing.

Critical Appraisal of Pacing Mode Trials

UKPACE

The large randomized trials on pacing mode dramatically changed the perception of “physiologic pacing.” In studies of the late 1980s, the addition of an atrial lead to a ventricular lead was perceived as a great step forward in cardiac pacing. The dual-chamber pacing mode enabled ventricular pacing at a programmable time after atrial sensing (AV-synchronous pacing), which improved cardiac output significantly compared with “asynchronous” ventricular pacing in the VVI(R) mode, as well as reducing mitral regurgitation, right atrial pressure, and pulmonary capillary wedge pressure and resolving pacemaker syndrome in a significant number of patients. Retrospective studies confirmed these hemodynamic advantages of dual-chamber pacing by clinical data. However, these clinical data from retrospective and nonrandomized studies were questioned108,109 when selection bias became evident.61,110 It is disappointing and difficult to explain why the theoretical advantages and the positive results of early studies did not translate into positive results in large, randomized clinical trials. However, some findings deserve special mention. PASE The Pacemaker Selection in the Elderly Study could be seen as evidence that elderly patients with conventional indications for permanent pacing do not seem to derive any benefit from dual-chamber over single-chamber pacing in terms of QOL, cardiovascular events, or mortality. However, PASE could also be viewed as evidence that approximately 25% of patients with sinus rhythm develop severe symptoms with VVIR pacing, which can be resolved by dual-chamber pacing in most cases. The high crossover rate in PASE precludes any firm interpretation of the results. Therefore, PASE does not answer the question if DDDR pacing provides an advantage over VVIR pacing in elderly patients. CTOPP The Canadian Trial of Physiologic Pacing is usually regarded as negative because three of four endpoints (stroke/cardiovascular events, allcause mortality, heart failure) were not reduced with physiologic compared to ventricular pacing. Even the statistically significant

MOST Although the Mode Selection Trial in Sinus Node Dysfunction was negative with regard to a difference in stroke, all-cause mortality, cardiovascular mortality, and HF hospitalization in patients with SND paced in VVIR versus DDDR mode (confirming lower incidence of AF with dual-chamber pacing and showing some superiority of dualchamber pacing in QOL), MOST demonstrated a surprisingly high incidence of severe pacemaker syndrome and, despite special precautions in the study protocol, an even higher crossover rate from VVIR to DDDR as a result of problems with single-chamber pacing. If these results would translate into daily clinical practice, MOST would suggest that every third patient with SND and VVIR pacing would require a second surgery for an upgrade to dual-chamber pacing, an economic and medical disaster. The most important observation in MOST may be the deleterious effect of unnecessary RV pacing (see later).

From the information published, the United Kingdom Pacing and Cardiovascular Events study is the most negative trial on pacing mode selection. It clearly showed that death can be prevented in AV block as effectively by single-chamber as by dual-chamber pacemakers. Any difference between these pacing modes with regard to exercise capacity, symptoms, and QOL remains unclear. The lack of difference between single- and dual-chamber pacing in AV block could be explained by patient selection bias in UKPACE (only 45% of eligible patients were enrolled) and by inappropriately short AV delays (per protocol 75-150 ms) with adverse hemodynamic consequences. The “forced” proportion of ventricular pacing of 99% in the dual-chamber mode which was significantly more than in VVI and VVIR pacing (93 and 94%) may theoretically have further deteriorated clinical results of dualchamber pacing (see Role of Prevention of Unnecessary Right Ventricular Pacing). OTHER ISSUES In addition to interpretations of the findings in the large RCTs on pacing mode selection, the following issues should be considered when evaluating the clinical implications of these trials: 1. Experience of study centers with the more complex, dual-chamber systems (atrial lead dislodgement, atrial over/undersensing, programming issues). 2. Lack of delineation of patient subgroups, such as patients with permanent bradycardia and pacemaker dependence. 3. Insufficient instruments to quantify pacing-associated symptoms, quality of life, and exercise capacity, particularly in elderly patients with comorbidity. 4. Unequal diagnostic tools to detect atrial fibrillation, an endpoint in all trials. The atrial lead allows easy detection of AF with the atrial EGM, whereas in ventricular devices, detection of AF relies on the surface ECG and may be difficult in complete AV block.81 5. Too few trials with sufficient long-term follow-up. The randomized trials on pacing mode selection demonstrate that mortality is similar with ventricular single- compared to dual-chamber pacing. This mainly refers to patients with atrioventricular block; for those with sinus node disease, it has not been convincingly shown that pacing improves survival compared to the natural course. It also became quite evident that dual-chamber pacing is associated with less AF than ventricular single-chamber pacing. However, the central

250

SECTION 2  Clinical Concepts

35

optimized to the patient (lead position, AV delay, pacing rates), (3) dual-chamber pacing is more complex and therefore associated with more pitfalls and potential for complications (atrial lead dislodgement, pacemaker mediated tachycardia), and (4) dual-chamber pacing is not as “innocent” as previously thought because it may cause more poorly timed right ventricular pacing than VVI(R), with potentially deleterious effects.

31 Intolerance to VVI (R) in %

30 26 25 20 15

Role of Prevention of Unnecessary Right Ventricular Pacing

10 4

5

3

0 PASE

MOST

CTOPP

UKPACE

Figure 10-10  Intolerance to VVI(R) in PASE, MOST, CTOPP, and UKPACE trials. Blue columns, Studies with software randomization requiring only reprogramming to crossover to DDD(R). Red columns, Studies with hardware randomization requiring reoperation to crossover to DDDR.

question is whether dual-chamber pacing is associated with improved hemodynamics that translate into less heart failure, less symptoms, and better QOL and exercise capacity; this remains unanswered even after randomizing more than 7000 patients. Beyond criticism about how such “soft endpoints” should best be evaluated (e.g., SF-36 unable to detect subtle, pacing-related QOL differences; symptom scores not sufficiently validated and not used), there are some critical, unresolved issues. First, randomized trials on pacing mode selection suffer from selection bias, particularly if hardware randomization is applied. From theoretical considerations and earlier studies, investigators have ethical concerns regarding whether pacemaker-dependent patients are at an increased risk for adverse events with ventricular single-chamber pacing. It is a strength of published trials (particularly CTOPP and UKPACE, which were hardware randomized) to keep track of why eligible patients were not enrolled into the trial: In CTOPP, only 16% of eligible but not enrolled patients declined consent, whereas in 56% the physician declined.72 Second, in a blinded trial, patient preference would be a powerful argument in favor of or against a pacing mode.25,26,62,63 Unfortunately, but logically, all large RCTs on pacing mode selection had a parallel trial design preventing intraindividual comparisons. Intraindividual comparisons could only be made in crossover patients (because of suspected pacemaker syndrome) from VVIR to DDDR pacing in PASE and MOST, showing a striking preference for DDDR pacing in these select patients. Third, the choice of software versus hardware randomization has both advantages and problems. If a patient “software randomized” to VVIR expresses symptoms, it is easy to reprogram the device to DDDR and see if symptoms are resolved. This may lead to an overestimation of the incidence of “VVIR intolerance” (26-31% in PASE and MOST). On the other hand, in hardware randomization, crossover to dualchamber pacing requires surgical intervention with potential complications, medically and legally. It is therefore evident that the incidence of “VVIR intolerance” is underestimated in hardware-randomized trials (3.1% in UKPACE, 4.3% in CTOPP) (Fig. 10-10). In summary, despite the RCT results on pacing mode selection, the perception that dual-chamber pacing is superior to single-chamber ventricular pacing in sinus rhythm still governs current guidelines111,112 and international physicians’ choices75,113 of pacing mode selection. However, trials have shown that (1) the beneficial effects of dualchamber pacing may have been overestimated (see rationale and sample size calculation of the Danish trial and UKPACE), (2) dualchamber pacing by itself may not convey hemodynamic benefits if not

Surprising data from the DAVID trial showed that compared with VVI 40-bpm backup pacing, DDDR pacing at 70 bpm produced more, not less, heart failure hospitalization and a slight, statistically not significant increase risk of mortality in patients with an ICD and no bradycardia101 (see earlier). In search of an explanation, it became obvious that right ventricular pacing was present in dual-chamber pacing much more frequently than in ventricular backup pacing (56% vs. 3% of patients with paced ventricular rhythm after 6 months). Similar results have been reported (independent of the presence of a single- or dual-chamber ICD) for patients in MADIT-II, where a cumulative proportion of ventricular pacing of more than 50% was associated with an almost twofold increased risk of new or worsened heart failure.114 A number of studies on histology,115 hemodynamics,116 and echocardiography117 have demonstrated deleterious acute and long-term consequences of RV apical pacing, their full clinical impact emerged only after DAVID. The MOST trial enrolled only patients with sinus node disease; apart from 11% of patients with additional second- or third-degree AV block,67 patients who did not require ventricular pacing. Sweeney et al.38 investigated the effect of unnecessary RV pacing in patients with SND. They selected 1339 patients from MOST who had a narrow QRS (<120 msec) at baseline before pacing was instituted. Taken from pacemaker memory functions, 707 patients randomized to DDDR received RV pacing at an average 90% of the time. In contrast, in patients randomized to VVIR, RV pacing was present only 58% of the time. In a Cox proportional hazard model, RV pacing (again, unnecessary in SND patients) was a strong predictor of HF hospitalization in DDDR mode (Table 10-14). For percentages of RV pacing in the AV-synchronous mode up to 40%, every 10% increase in ventricular pacing linearly increased the relative risk increase for HF hospitalization by 54%. RV pacing in the DDDR mode more than 40% of the time versus less than 40% was associated with a 2.6-fold increased risk of HF hospitalization. This association was much more striking for DDDR than for VVIR pacing, in which RV pacing up to 80% of the time had only a minor impact on HF development, whereas pacing more than 80% of the time resulted in a 2.5-fold increased risk of HF hospitalization. Similar to the increased risk of heart failure hospitalization, unnecessary right ventricular pacing also increased the risk of atrial fibrillation.38 Up to 80% to 85% of RV pacing in the DDDR or VVIR modes, the risk of AF linearly increased by approximately 1% for every percent increase in cumulative ventricular pacing. The authors concluded that

TABLE

10-14 

Association of Percentage of Ventricular Pacing (VP) with Heart Failure Hospitalization (HF Hosp) and Atrial Fibrillation (AF) for Dual-Chamber and Single-Chamber Ventricular Pacing DDDR (n = 707)

VP (%) <10 10-50 50-90 >90 Total

HF Hosp 2% 9% 9% 12% 10%

AF 16% 19% 32% 17% 21%

VVIR (n = 6432) HF Hosp 7% 6% 8% 16% 9%

AF 21% 23% 29% 18% 24%

251



10  Clinical Trials of Atrial and Ventricular Pacing Modes

unnecessary RV pacing in SND leads to ventricular desynchronization in asynchronous as well as in AV-synchronous RV pacing, and over a broad range of cumulative percentages of pacing, linearly increases the risk of development of HF and AF in patients without BBB. The higher percentage of RV pacing in dual-chamber than in ventricular single-chamber pacing may be one explanation for the lack of superiority of this pacing mode in large trials. A post hoc analysis confirmed this for the DAVID trial.102 The authors dichotomized the group of patients with DDDR pacing at 70 bpm into those with 40% or less versus those with more than 40% RV pacing. In a Cox regression analysis, ventricular pacing 40% or less of the time was associated with slightly fewer clinical events than with VVI 40-bpm backup (P = .07). Patients with ventricular pacing more than 40% of the time in DDDR mode had a 5.3-fold increased risk of a study endpoint (death or HF hospitalization) than patients with 40% or less ventricular pacing. Prevention of unnecessary RV pacing in patients with a dualchamber pacemaker or ICD is difficult to achieve with prolonged settings for the AV delay alone. In a pilot study with 177 patients with SND and normal AV conduction, Nielsen et al.88 observed ventricular pacing still for 17% of the time in DDDR mode with a fixed AV delay as long as 300 msec. Beyond being ineffective, programming AV delays to such long values creates new problems, such as limitations of the upper tracking rate or AV desynchronization arrhythmias.118,119 A better way to prevent unnecessary RV pacing is therefore an automatic algorithm to provide AAIR pacing, with monitoring of AV conduction and an automatic switch to DDDR when AV block occurs beyond a single dropped beat. Two such algorithms developed for minimized ventricular pacing are MVP (Medtronic, Minneapolis) and SafeR (Sorin, Milano). For the SafeR algorithm, a reduction in RV pacing to less than 1% in patients without permanent AV conduction block (SND, paroxysmal AV block) was shown, together with safe switching to DDDR mode when necessary.120-122 For the MVP algorithm, its superiority in prevention of unnecessary RV pacing versus an extended AV search hysteresis has been demonstrated (0.9% in firstdegree AV block vs. 80.6% ventricular pacing),123 maintaining 99% ventricular pacing in patients with permanent third-degree AV block. In SND patients, MVP consistently reduced the percentage of ventricular pacing to 1.4%,124,125 with a relative reduction of ventricular pacing of 99% in SND and 60% in paroxysmal AV block.125 Similar reductions in RV pacing have been achieved in ICD patients.126 The effect of consequent prevention of RV pacing on clinical outcomes was tested in 1065 SND patients in the SAVE-PACe trial.92 All patients had normal AV conduction and QRS duration less than 120 msec. After randomization to conventional dual-chamber pacing versus dual-chamber pacing with the addition of algorithms that specifically promote intrinsic AV conduction, patients were followed for 1.7 years, when the trial was stopped. RV pacing had been present for a median of 99% of the time in patients with conventional pacing; the addition of algorithms to promote spontaneous AV conduction and to preserve a narrow QRS limited unnecessary ventricular pacing to a median of 9%. The incidence of persistent AF was significantly lower (7.9%) in patients with dedicated algorithms to promote intrinsic AV conduction compared to patients with conventional dualchamber pacing (12.7%; RRR, 40%). The need for any intervention for AF (cardioversion, catheter ablation) was also significantly reduced by 38%. Mortality was not significantly different (4.9% with minimized ventricular pacing, 5.4% with conventional dual-chamber pacing). The MVP algorithm was also tested in DAVID-like patients with an indication for ICD therapy.127 In a non-inferiority design, the MVP trial enrolled 1030 patients with an ICD indication, sinus rhythm and no indication for pacing to dual-chamber/minimal pacing at 60 bpm versus VVI 40 bpm backup pacing. The primary endpoint was time to death, HF hospitalization, or HF-related urgent care. The trial was stopped after 2.4 years after an interim analysis suggested that it was highly unlikely that there would be a statistically significant difference with regard to the primary endpoint regardless of follow-up duration.

In these patients with a mean LVEF of 35%, all-cause mortality was slightly but not significantly higher in the dual-chamber group (11% vs. 9%), mainly driven by a difference in noncardiac death (4.1% vs. 3.1%). Heart failure hospitalizations and related urgent care was necessary in 20.8% of patients with a dual-chamber device, versus 18.8% in patients randomized to VVI 40-bpm backup pacing. These differences were not statistically significantly different (P = 0.873). However, because of fewer events than expected, the confidence interval crossed the prespecified border for non-inferiority. Therefore, the MVP trial was unable to demonstrate non-inferiority of dual-chamber ICDs incorporating an algorithm for prevention of RV pacing compared to VVI backup pacing at 40 bpm. Of note (even though not prespecified), a striking difference in outcome was observed in a post hoc analysis for patients with a baseline PR interval ≥230 msec (mean, 260 msec). Although event rates in patients with PR <230 msec were virtually identical between single- and dual-chamber ICDs, patients with a PR ≥230 msec had a significantly higher event rate with dual-chamber pacing promoting intrinsic AV conduction. Similarly, the Inhibition of Unnecessary RV Pacing with AVSH in ICDs (INTRINSIC) trial investigated if dual-chamber ICDs are “noninferior” to single-chamber ICDs with VVI 40-bpm backup, if an AV hysteresis algorithm prevents unnecessary RV pacing. Patients with a standard indication for an ICD were enrolled. All patients whose AV search hysteresis algorithm achieved ventricular pacing less than 20% of the time at the 1-week control visit were randomized to receive VVI 40-bpm or DDDR 60-bpm pacing. Investigators had to amend the study protocol (prolong AV delay during activity of AV search hysteresis) because a larger-than-expected number of patients would otherwise have been excluded from randomization.128 Thus, of 1530 patients enrolled, a total of 988 with ventricular pacing less than 20% at the 1-week visit were randomized.129 During a mean follow-up of 10.4 months, the endpoints of death and HF hospitalization were more frequent in VVI backup 40 bpm (9.5%) than in DDDR pacing with AV search hysteresis (6.4%). Non-inferiority of DDDR with AV search hysteresis met a significance of P <.001, even with a trend for superiority of DDDR with AV search hysteresis (P = .07) with regard to primary endpoints. Also, all-cause mortality was nonsignificantly lower in the dual-chamber ICD arm (3.6% vs. 5.1%; P = 0.23). Of note, the event rate was higher in the observational arm (patients excluded from randomization because ventricular pacing was present >20% of the time despite use of AV search hysteresis algorithm), with a total of 12.5% events and an all-cause mortality of 5.5%. In summary, it has been shown impressively that unnecessary right ventricular pacing promotes the development of heart failure and atrial fibrillation, most likely through ventricular desynchronization and hemodynamic deterioration. In ICD patients with severely impaired left ventricular function, this leads to an increase in HF hospitalization and mortality. Even in patients with sinus node disease and normal LV function, RV pacing is associated with increased HF hospitalization. The higher proportion of unnecessary RV pacing in dualchamber pacing than in single-chamber ventricular pacing likely helps explain the disappointing results of mode selection, particularly in SND patients. However, prevention of ventricular pacing is not automatically the better option. Patients with a normal PR interval at baseline and patients with a low percentage (<20%) of ventricular pacing achieved by simple means (e.g., intermittent prolongation of AV delay) seem to be ideal candidates for dual-chamber pacing with dedicated algorithms that prevent RV pacing. In contrast, patients with first-degree AV block, particularly with a baseline PR interval greater than 230 msec (or >260 msec) and those with more than 20% ventricular pacing despite prolongation of the AV delay do not seem to benefit from prevention of ventricular pacing; in these patients, ventricular pacing may not be entirely “unnecessary.” However, if prevention of ventricular pacing is not the better option in all patients, and if RV pacing is associated with deleterious hemodynamic and structural side effects, biventricular pacing or pacing from an alternative RV site, such as the midseptum, may be superior in patients who require ventricular pacing.

252

SECTION 2  Clinical Concepts

Trials Evaluating Right Ventricular Versus Biventricular Pacing A growing body of evidence indicates that RV pacing leads to newonset heart failure in a significant proportion (~25%) of patients with high-grade AV block and normal left ventricular function over the long term (>5 years), typically in patients who are older at implantation, those with a particularly wide QRS, and those with coronary artery disease.130 To date, however few prospective randomized controlled trials have compared biventricular (BiV) to conventional pacing for standard bradycardia indications. In the left ventricular–based cardiac stimulation post–AV nodal ablation evaluation (PAVE) trial, Doshi et al.131 randomized 184 patients with permanent AF and AV node ablation to BiV versus RV pacing. After 6 months, LVEF was significantly better in patients with BiV pacing (46% vs. 41%; P = .03) as was the 6-minute walking distance (6MWD), but no significant difference in perceived QOL. Patients with LVEF less than 45% or NYHA Class II and III at baseline had greater improvement in 6MWD by BiV pacing compared to patients with normal LVEF or no HF symptoms. Although PAVE was an important step in the evaluation of cardiac resynchronization therapy (CRT) for standard pacing indications outside hemodynamic indications in HF patients, it was certainly too small with insufficient follow-up to investigate the full impact of CRT in patients without symptomatic HF. Biventricular pacing was tested in patients with standard bradycardia indications and heart failure in the Homburg Biventricular Pacing Evaluation (HOBIPACE) study.132 In 30 patients with AV block and LVEF of 40% or less, BiV devices were implanted and randomized to RV versus BiV pacing for 3 months, then a 3-month crossover phase. In patients with and without AF, BiV pacing induced improvements in LVEF and left ventricular end-diastolic as well as end-systolic volumes, a reduction in NT-proBNP by 31%, an improved QOL score, improved exercise capacity, and improved maximum oxygen consumption and oxygen uptake at the anaerobic threshold during cardiopulmonary exercise testing. Although these were impressive results, 63% of the patients in HOBIPACE had a left BBB (mean QRS duration, 174 msec), meeting the conventional indication for CRT. In the RD-CHF study, 44 permanently paced patients with continuous single-chamber RV pacing for a standard pacing indication (worsening CHF) who required a pacemaker generator change for battery depletion were upgraded to a BiV system and completed a randomized crossover study.133 All patients had NYHA Class III or IV with LVEF of 35% or less and echocardiographic signs of interventricular or intra-LV dyssynchrony. The mean paced QRS duration at baseline was 200 msec. During crossover with pacing in RV and BiV mode for 3 months each, QRS duration and LV preejection delay were significantly shortened by BiV pacing, and NYHA functional class, 6MWD, and QOL were significantly improved. Although these are important data in a population with a pacemaker indication, there is almost 100% overlap with current indications for CRT. Albertsen et al.134 randomized 50 patients with AV block (permanent or paroxysmal) who were referred for a first pacemaker implantation to either RV dual-chamber or BiV pacing.134 Only four patients had a left BBB, and mean LVEF was 60% at baseline. All patients received a pacemaker capable of BiV pacing with three lead connectors, but only BiV-randomized patients received an LV lead (implantation success, 100%). During follow-up of 12 months, LVEF was unchanged in BiV pacing, with a minimal but statistically significant decrease to 57% with RV pacing. Tissue Doppler imaging revealed more LV dyssynchrony after 12 months with RV than BiV pacing (1.8 vs. 0.8 segments with delayed longitudinal contraction; P = .02). NT-proBNP levels, which were not high at baseline (122 pmol/L in DDDR: 91 pmol/L in BiV) remained unchanged with dual-chamber pacing but were significantly lower after 12 months with BiV pacing. In summary, Albertsen et al.134 were the first to investigate BiV pacing in a group of patients with AV block (unrelated to AV node ablation) requiring ventricular pacing, without an indication for CRT. Although

only surrogate parameters for outcome were analyzed, the 12-month follow-up was sufficient to produce echocardiographic and serologic results that indicate a hemodynamic superiority of BiV pacing in patients with AV block and normal LV function at baseline. To date, PACE represents the largest trial on biventricular pacing for standard pacing indications.135 In 177 patients with a pacing indication (AV block in 102, SND in 71, other indication in 4 patients) and normal systolic LV function (defined as LVEF >45%), a BiV pacemaker was implanted. Another 16 patients were excluded from randomization after an unsuccessful attempt of implantation of the LV lead. After stratification according to the presence or absence of diastolic dysfunction, patients were randomized to receive DDDR pacing (60-140 bpm) or BiV pacing. In patients with SND, the AV delay was programmed 20 msec shorter than intrinsic AV conduction. After 12 months, the primary endpoints (LVEF and LV end-systolic volume) were assessed. Left ventricular function was much better preserved in BiV pacing (LVEF = 62% vs. 55%, P <.001; end-systolic volume = 28 vs. 36 mL, P <.001) in patients with and without diastolic dysfunction at baseline. A significant deterioration in LVEF to less than 45% occurred in one patient (1%) during BiV versus eight (9%) during RV pacing (P = .02). Six patients with RV pacing and five with BiV pacing were hospitalized for heart failure; one patient with RV pacing died during the study. There was no significant difference in 6MWD or QOL using the SF-36 questionnaire. Echocardiographic data suggest that BiV pacing can prevent pacing-induced ventricular remodeling and heart failure in patients without significant systolic ventricular dysfunction. However, these are only surrogate parameters. PACE must be criticized for failed implant procedures that do not appear in the analysis, and for including SND patients with presumably normal PR interval and QRS duration, who underwent “forced” RV or BiV pacing. At least for RV pacing, it is known that heart failure can be caused by unnecessary pacing in these patients. The results of PACE therefore must be interpreted with caution. Several studies on biventricular pacing for conventional pacing indications are ongoing. The PREVENT-HF trial has completed enrollment and follow-up of 108 randomized patients with a standard Class I or IIa indication for cardiac pacing and a projected need for ventricular pacing of at least 80% to RV or BiV pacing.136 After 12 months, LV end-diastolic volume is compared as the primary endpoint. The Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) study enrolled 1800 patients in 2007 with a conventional indication for pacing, with a high probability that the ventricle will be predominantly paced.137 Patients with all NYHA functional classes were eligible, with no restriction in LVEF. Patients with an indication for primary prophylaxis of sudden cardiac death were allowed to receive an ICD instead of a pacemaker. There was a hardware randomization to RV versus BiV devices. The study is endpoint driven; follow-up will be terminated when 635 endpoints (all-cause mortality) have occurred. In contrast, BLOCK-HF is a double-blind, software-randomized trial enrolling patients with a Class I or IIa pacing indication for second-degree or third-degree AV block or other pacing indications (e.g., first-degree AV block with pseudo–pacemaker syndrome, Wenckebach block rates <100 bpm, PR >300 msec).138 Patients must have LVEF of 50% or less (NYHA Class I-III) and are softwarerandomized to RV versus BiV pacing (ICD if an indication for primary prevention of sudden cardiac death is present). During a follow-up of at least 12 months, the primary endpoint in the projected 1636 enrolled patients will be a combination of all-cause mortality, HF-related urgent care, or a 15% or more increase in LV end-systolic volume index. In summary, there is some evidence that biventricular pacing can prevent the deleterious effects of right ventricular pacing in a significant number of patients. However, the results of BioPace and BLOCK-HF should be evaluated before BiV pacing, with the additional expenditure of time, money, and effort at implantation and the additional hardware, as well as potential short-term and long-term complications, is applied in patients with a pacing indication involving an expected high percentage of ventricular pacing. In the meantime,

253



10  Clinical Trials of Atrial and Ventricular Pacing Modes

routine placement of an LV lead for patients with AV block is not recommended by the pacing guidelines. Patients with an indication for CRT, according to REVERSE, MADIT-CRT, and RAFT (LVEF ≤40%; NYHA I-III if positive history of ≥Class II),139-141 may represent candidates that can benefit from biventricular devices based on the assumption that they would otherwise have a (paced) broad left bundle branch block (LBBB).

of AF and pacemaker syndrome in dual-chamber pacing, particularly in patients with SND.145 The higher incidence of complications in dual-chamber devices at implantation was also considered. The cost of the dual-chamber system, including all costs of complications and clinical events during a 5-year period, was assumed to be 7400 £− . The cost difference compared to single-chamber systems was small, about 700 £− during 5 years. The cost for dual-chamber versus single-chamber ventricular pacing over 5 years was therefore estimated to be 8500 £− per QOL-year saved in patients with AV block and 9500 £− in patients with SND. This cost was reduced to approximately 5500 £− over 10 years. However, these calculations would dramatically change, to approximately 30,000 £− per QOL-year saved, if a lower incidence of pacemaker syndrome, similar to the CTOPP, would have been used. A “cost-efficacy analysis” has been performed retrospectively in patients with single-chamber versus dual-chamber ICDs using the Yale University Electrophysiology database.146 It included 453 patients who had received a single- or dual-chamber ICD between June 1997 (when the first dual-chamber ICD received FDA approval) and July 2001. Three strategies of pacing mode selection were assessed: (1) implantation of a single-chamber ICD with upgrade whenever needed, (2) implantation of a dual-chamber ICD in all patients, and (3) electrophysiologic (EP) study and implantation of a dual-chamber ICD only in patients with results indicating abnormal sinus or AV nodal function. Interestingly, the targeted, EP-guided device selection was the most expensive strategy (>$41,000); implantation of single-chamber ICDs with need for upgrade in an estimated 20% of patients cost $39,000. Surprisingly, implantation of dual-chamber ICDs in all patients would have been the least expensive strategy, only $36,000. Subsequent sensitivity analyses demonstrated that even with need to upgrade single-chamber ICDs in only 10% or even 5%, implantation of a dual-chamber ICD remained less expensive as long as it was no more than $1500 over a single-chamber ICD. An EP-guided approach would be least expensive in patients who underwent EP testing for other reasons (e.g., inducibility of ventricular tachyarrhythmias). A recent analysis with assumptions representative for current systems calculated cost-effectiveness in a statistical model.147 The authors assumed that the implantation of dual-chamber devices instead of VVIR systems in 1000 patients would prevent AF in 36 and severe pacemaker syndrome in 168 patients, while requiring 13 additional hospitalizations from complications over 5 years. In this model, health benefits would need an incremental cost of 23 ' per patient and 0.09 QOL-years, equal to incremental costs of 260 ' per QOLyear gained. Similar to other analyses, upgrade procedures for pacemaker syndrome would have the greatest impact on costs. In summary, the majority of calculations of cost-effectiveness show that dual-chamber pacing provides benefits at an acceptable price. However, these analyses are weak and depend on a large number of hazy assumptions.

Cost-Effectiveness of Dual-Chamber Pacing Analyses of cost-effectiveness in pacemakers and ICDs have limited applicability because of the varied and highly time-dependent costs of devices. This is particularly important in countries where health care providers and industry can negotiate a mixed calculation (i.e., singleand dual-chamber devices sold at same price). Costs also depend on the outpatient availability of pacemaker (and ICD) implantation and cost of the operation room and staff need for anesthesiologist, conscious sedation vs. general anesthesia in ICD implantation), which vary greatly according to routine practices and legal issues. Given this background, cost-effectiveness calculations from study data must be considered in the study’s context. Interestingly, even data from large randomized trials can be interpreted so differently that costeffectiveness can range from “highly ineffective” to “highly effective” based on the same data. Similar to diverging assumptions on costs, assumptions on “efficacy” also vary widely. Cost-effectiveness in terms of “cost per life-year gained” depends only on mortality and the studies included in the analysis. However, “cost per quality-of-life year” (QOL-year) depends on the reliability of the QOL instruments used and inclusion of associated effects (e.g., AF, pacemaker syndrome, stroke, HF, exercise capacity). This may be even more important in the evaluation of pacing modes, but it is much more difficult to assess in a statistical model and less robust. In 1996, Sutton and Bourgeois142 published a cost-effectiveness analysis based on the (nonrandomized) studies available. They found a 10-year survival in sinus node disease with DDD pacing of 71%, versus only 57% with VVI pacing. The numbers for AV block were 61% with DDD and 51% with VVI pacing. For QOL, prevalence of heart failure was 60% lower with dual-chamber pacing; severe disability was present with VVI pacing in 36% of SND patients and 22% of AV block patients, but only for 8% and 3% of patients paced in dual-chamber mode. Assuming the implantation of a dual-chamber system costs 1.5 times more than a VVI system, this higher cost was offset by the higher cost of complications and side effects (stroke, disability, upgrade) during VVI pacing after 3 years. Assuming a battery life of 10 years, dual-chamber pacing was highly cost-effective in this analysis. Cost-effectiveness was calculated for a subset of patients from the Canadian Trial of Physiologic Pacing.143 CTOPP authors calculated additional costs of approximately 3000 Canadian dollars ($) for implantation and follow-up of a dual-chamber versus single-chamber device. With a (nonsignificant) relative mortality reduction of 9.4% with dual-chamber pacing, the authors calculated a gain of 0.01 lifeyears with dual-chamber pacing, with costs of approximately $300,000 per life-year saved. Only in the subgroup of patients with an intrinsic heart rate less than 60 bpm would the cost per life-year be acceptable, at $16,000. A key consideration in this analysis is the need for reoperation because of pacemaker syndrome. In CTOPP, this was necessary in only 4.3% of patients randomized to VVI during 5 years,72 versus 25% to 30% in PASE and MOST, where “reoperation” could be replaced by reprogramming the devices.65,67 An analysis of the U.S. MOST trial found that dual-chamber pacing in patients with sinus node disease was cost-effective, with an average of $53,000 per life-year saved.144 However, depending on the statistical model and method, and exclusion or inclusion of QOL data, results varied between $3200 and $334,000. A cost-effectiveness analysis by the British National Health Service in 2005 (before UKPACE results) took into account the lower incidence

Current Guidelines on Pacing Mode Selection The current American College of Cardiology/American Heart Association (ACC/AHA/HRS) guidelines on cardiac pacing reference the five pacing mode selection trials discussed (Danish, PASE, MOST, CTOPP, UKPACE).148 A major limitation of these trials was a rate of crossover and dropout of assigned pacing mode greater than 37%. Whenever a low percentage of pacing is expected (e.g., “very infrequent sinus pauses or infrequent AV block”), maintenance of AV synchrony during pacing likely does not seem important, and ventricular single-chamber pacing may be used as an alternative to dual-chamber pacing. However, progression of bradycardia is difficult to predict. Therefore, some patients with a seemingly rare need for pacing may develop bradycardia with permanent need of pacing (e.g., caused by β-blockers and antiarrhythmic drugs) and may then require a reoperation for an upgrade to dual-chamber pacing. The current European Society of Cardiology (ESC) guidelines on pacing recommend only AAIR pacing and DDDR, with dedicated

254

SECTION 2  Clinical Concepts

algorithms to prevent unnecessary right ventricular pacing in sinus node disease.149 Single-chamber ventricular pacing is discarded because of the higher risk of atrial fibrillation and the trend toward lower exercise capacity and more pacemaker syndrome in a Cochrane review.150 In patients with AV block, VVIR is recommended only in those without sinus rhythm. Otherwise, VDD, DDD, and DDDR devices are recommended, depending on chronotropic sinus node function. VVIR is mentioned only as a Class IIb indication (i.e., majority of experts would not chose this pacing mode in patients with AV block and sinus rhythm). Alternative RV pacing sites, such as septal, hisian, parahisian, and biventricular, are mentioned. However, no recommendation is provided for these pacing sites in AV block with narrow QRS.

Future Perspectives in Pacing Mode Evaluation The studies assessing whether any pacing mode is preferable in different indications for permanent pacing have gathered a tremendous amount of information. Unfortunately, the results are frequently contradictory and difficult to interpret, even in many well-conducted and designed trials. It was the explicit aim of this chapter to outline the difficulties in interpretation of results of pacing mode selection trials. On the other hand, these trials have made it clear that, although it is easy to demonstrate a benefit of pacing regardless of mode in patients with life-threatening bradycardia, it is more difficult to show added benefit for any specific pacing mode, particularly in patients with less severe bradycardia. However, data from randomized trials suggest that implanting a more complex pacemaker system alone does not necessarily translate into better outcome; the pacing system must also be optimized to the patient’s needs. Despite some contradictory results, programmed parameters and algorithms should prevent unnecessary RV pacing in the ventricular single-chamber and perhaps even more

in dual-chamber modes. At present, it is not clear which patients most need prevention of RV pacing or what alternative exists for different pacing indications. For patients with usually unavoidable ventricular pacing, conventional dual-chamber pacing must be tested against BiV pacing also in the absence of heart failure and wide QRS. In patients with intermittent AV block and particularly for patients with firstdegree AV block, the ideal pacing mode at present is not clear. In patients with intermittent AV block and narrow QRS, BiV pacing in periods with AV block alternating with facilitation of intrinsic conduction in periods of normal AV nodal function may be superior to conventional dual-chamber pacing, particularly in patients with LV dysfunction and clinical HF. In patients without LV dysfunction or HF, it remains unclear what the best pacing mode currently is. In patients with AV block, there seems to be a turning point (intrinsic PR interval >260 msec) after which prevention of ventricular pacing and spontaneous AV conduction may be worse than RV pacing. This turning point may differ in patient with and without HF. The diagnostic benefit of atrial leads has not been systematically evaluated. Information on the atrial rhythm may be particularly useful in ICDs, to discriminate between supraventricular and ventricular tachyarrhythmias, but potentially even more to detect asymptomatic, paroxysmal atrial fibrillation, particularly in patients with a high CHADS2 score to establish anticoagulation. Future trials on pacing mode selection should also take into account optimized programming of devices. Activation of useful algorithms (mode switching, prevention of unnecessary ventricular pacing), deactivation of useless algorithms (AV delay prolongation in patients with permanent AV block), optimization of algorithms (rate response), and optimization of parameters (atrial sensitivity to avoid AF undersensing; sensed and paced AV delay) may play a role. Similarly, the role of atrial lead position (septal, Bachmann bundle) and ECG-guided ventricular lead placement may further improve results of different pacing modes and should be investigated.

REFERENCES 1. Ohm OJ, Brejvik K: Patients with high-grade atrioventricular block treated and not treated with a pacemaker. Acta Med Scand 203:521-528, 1978. 2. Sasaki Y, Shimotori M, Akahane K, et al: Long-term follow-up of patients with sick sinus syndrome: a comparison of clinical aspects among unpaced, ventricular inhibited paced and physiologically paced groups. Pacing Clin Electrophysiol 11:1575-1583, 1988. 3. Ausubel K, Furman S: The pacemaker syndrome. Ann Intern Med 103:420-429, 1985. 4. Rosenqvist M, Brandt J, Schüller H: Long-term pacing in sinus node disease: effects of stimulation mode on cardiovascular morbidity and mortality. Am Heart J 116:16-22, 1988. 5. Barold SS: Permanent single chamber atrial pacing is obsolete. Pacing Clin Electrophysiol 24:271-275, 2001. 6. Lipkin DP, Buller N, Frenneaux M, et al: Randomised crossover trial of rate responsive Activitrax and conventional fixed rate ventricular pacing. Br Heart J 58:613-616, 1987. 7. Oto MA, Muderrisoglu H, Ozin MB, et al: Quality of life in patients with rate responsive pacemakers: a randomized, crossover study. Pacing Clin Electrophysiol 14:800-806, 1991. 8. Lau CP, Rushby J, Leigh-Jones M, et al: Symptomatology and quality of life in patients with rate-responsive pacemakers: a double-blind, randomized, crossover study. Clin Cardiol 12:505512, 1989. 9. Smedgard P, Kristensson BE, Kruse I, et al: Rate-responsive pacing by means of activity sensing versus single rate ventricular pacing. Pacing Clin Electrophysiol 10:902-915, 1987. 10. Hedman A, Nordlander R: QT sensing rate responsive pacing compared to fixed rate ventricular inhibited pacing. Pacing Clin Electrophysiol 12:374-385, 1989. 11. Rossi P, Rognoni G, Occhetta E, et al: Respiration-dependent ventricular pacing compared with fixed ventricular and atrialventricular synchronous pacing: aerobic and hemodynamic variables. J Am Coll Cardiol 6:646-652, 1985. 12. Gammage M, Schofield S, Rankin I, et al: Benefit of single setting rate responsive ventricular pacing compared with fixed rate demand pacing in elderly patients. Pacing Clin Electrophysiol 14:174-180, 1991. 13. Lau CP, Wong CK, Leung WH, Liu WX: Superior cardiac hemodynamics of atrioventricular synchrony over rate responsive pacing at submaximal exercise: observations in activity sensing DDDR pacemakers. Pacing Clin Electrophysiol 13:1832-1837, 1990.

14. Jutzy RV, Florio J, Isaeff DM, et al: Comparative evaluation of rate modulated dual chamber and VVIR pacing. Pacing Clin Electrophysiol 13:1838-1846, 1990. 15. Menozzi C, Brignole M, Moracchini PV, et al: Intrapatient comparison between chronic VVIR and DDD pacing in patients affected by high degree AV block without heart failure. Pacing Clin Electrophysiol 13:1816-1822, 1990. 16. Oldroyd KG, Rae AP, Carter R, et al: Double blind crossover comparison of the effects of dual chamber pacing [DDD] and ventricular rate adaptive [VVIR] pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block. Br Heart J 65:188-193, 1991. 17. Linde-Edelstam C, Nordlander R, Unden AL, et al: Quality of life in patients treated with atrioventricular synchronous pacing compared to rate modulated ventricular pacing: a long-term, double-blind, crossover study. Pacing Clin Electrophysiol 17:1844-1848, 1992. 18. Lau CP, Tai YT, Lee PW, et al: Quality-of-life in DDDR pacing: atrioventricular synchrony or rate adaptation? Pacing Clin Electrophysiol 17:1838-1843, 1994. 19. Lau CP, Tai YT, Leung WH, et al: Rate adaptive pacing in sick sinus syndrome: effects of pacing modes and intrinsic conduction on physiological responses, arrhythmias, symptomatology and quality of life. Eur Heart J 15:1445-1455, 1994. 20. Deharo JC, Badier M, Thirion X, et al: A randomized, singleblind crossover comparison of the effects of chronic DDD and dual sensor VVIR pacing mode on quality-of-life and cardiopulmonary performance in complete heart block. Pacing Clin Electrophysiol 19:1320-1326, 1996. 21. Kruse I, Rydén L: Comparison of physical work capacity and systolic time intervals with ventricular inhibited and atrial synchronous ventricular inhibited pacing. Br Heart J 46:129-136, 1981. 22. Kruse I, Arnman K, Conradson TB, Rydén L: A comparison of the acute and long-term hemodynamic effects of ventricular inhibited and atrial synchronous ventricular inhibited pacing. Circulation 65:846-855, 1982. 23. Antonioli GE, Ansani L, Barbieri D, et al: Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing. Pacing Clin Electrophysiol 15:1890-1893, 1992. 24. Wiegand UK, Bode F, Bonnemeier H, et al: Long-term complication rates in ventricular, single lead VDD, and dual chamber pacing. Pacing Clin Electrophysiol 26:1961-1969, 2003.

25. Sulke AN, Chambers J, Dristas A, et al: A randomized doubleblind crossover comparison of four rate-responsive pacing modes. J Am Coll Cardiol 17:696-706, 1991. 26. Kamalvand K, Tan K, Kotsakis A, et al: Is mode switching beneficial? A randomized study in patients with paroxysmal atrial tachyarrhythmias. J Am Coll Cardiol 30:496-504, 1997. 27. Lau CP, Butrous GS, Ward DE, Camm AJ: Comparison of exercise performance of six rate-adaptive right ventricular cardiac pacemakers. Am J Cardiol 63:833-838, 1989. 28. Shukla HH, Flaker GC, Hellkamp AS, et al: Clinical and quality of life comparison of accelerometer, piezoelectric crystal, and blended sensors in DDDR-paced patients with sinus node dysfunction in the Mode Selection Trial (MOST). Pacing Clin Electrophysiol 28:762-770, 2005. 29. Capucci A, Boriani G, Specchia S, et al: Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing. Pacing Clin Electrophysiol 15:1908-1913, 1992. 30. Lazarus A, Mitchell K: A prospective multicenter study demonstrating clinical benefit with a new accelerometer-based DDDR pacemaker. Pacing Clin Electrophysiol 19:1694-1697, 1996. 31. Lamas GA, Knight JD, Sweeney MO, et al: Impact of ratemodulated pacing on quality of life and exercise capacity: evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT). Heart Rhythm 4:1125-1132, 2007. 32. Kindermann M, Schwaab B, Finkler N, et al: Defining the optimum upper heart rate limit during exercise: a study in pacemaker patients with heart failure. Eur Heart J 23:1301-1308, 2002. 33. Camm AJ, Fei L: Chronotropic incompetence. Part II. Clinical implications. Clin Cardiol 19:503-508, 1996. 34. Andersen HR, Thuesen L, Bagger JP, et al: Prospective randomised trial of atrial versus ventricular pacing in sick-sinus syndrome. Lancet 344:1523-1528, 1994. 35. Andersen HR, Nielsen JC, Thomsen PE, et al: Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 350:12101216, 1997. 36. Andersen HR, Nielsen JC, Thomsen PE, et al: Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome. Circulation 98:1315-1321, 1998. 37. Kristensen L, Nielsen JC, Pedersen AK, et al: AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker. Pacing Clin Electrophysiol 24:358-365, 2001.



10  Clinical Trials of Atrial and Ventricular Pacing Modes 38. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 107:2932-2937, 2003. 39. Nielsen JC, Andersen HR, Thomsen PE, et al: Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to singlechamber atrial or ventricular pacing. Circulation 97:987-995, 1998. 40. Andersen HR, Nielsen JC, Thomsen PE, et al: Arterial thromboembolism in patients with sick sinus syndrome: prediction from pacing mode, atrial fibrillation, and echocardiographic findings. Heart 81:412-418, 1999. 41. Israel CW, Grönefeld G, Ehrlich JR, et al: Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. J Am Coll Cardiol 43:47-52, 2004. 42. Rediker DE, Eagle KA, Homma S, et al: Clinical and hemodynamic comparison of VVI versus DDD pacing in patients with DDD pacemakers. Am J Cardiol 61:323-329, 1988. 43. Rosenqvist M, Brandt J, Schüller H: Long-term pacing in sinus node disease: effects of stimulation mode on cardiovascular morbidity and mortality. Am Heart J 116:16-22, 1988. 44. Sasaki Y, Shimotori M, Akahane K, et al: Long-term follow-up of patients with sick sinus syndrome: a comparison of clinical aspects among unpaced, ventricular inhibited paced and physiologically paced groups. Pacing Clin Electrophysiol 11:1575-1583, 1988. 45. Bianconi L, Boccadamo R, Di Florio A, et al: Atrial versus ventricular stimulation in sick sinus syndrome: effect on morbidity and mortality [abstract]. Pacing Clin Electrophysiol 12:1236, 1989. 46. Santini M, Alexidou G, Ansalone G, et al: Relation of prognosis in sick sinus syndrome to age, conduction defect, and modes of permanent cardiac pacing. Am J Cardiol 65:729-735, 1990. 47. Stangl K, Seitz K, Wirtzfeld A, et al: Differences between atrial single chamber pacing (AAI) and ventricular single chamber pacing (VVI) with respect to prognosis and antiarrhythmic effect in patients with sick sinus syndrome. Pacing Clin Electrophysiol 13:2080-2085, 1990. 48. Zanini R, Facchinetti AI, Gallo G, et al: Morbidity and mortality of patients with sinus node disease: comparative effects of atrial and ventricular pacing. Pacing Clin Electrophysiol 13:2076-2079, 1990. 49. Nürnberg M, Frohner K, Podczeck A, et al: Is VVI pacing more dangerous than AV sequential pacing in patients with sick sinus syndrome? [abstract]. Pacing Clin Electrophysiol 14:674, 1991. 50. Hesselson AB, Parsonnet V, Bernstein AD, et al: Deleterious effect of long-term single-chamber ventricular pacing in patients with sick sinus syndrome: the hidden benefits of dual chamber pacing. J Am Coll Cardiol 19:1542-1549, 1992. 51. Sgarbossa EB, Pinski SL, Maloney JD, et al: Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities. Circulation 88:1045-1053, 1993. 52. Tung RT, Shen WK, Hayes DL, et al: Long-term survival after permanent pacemaker implantation for sick sinus syndrome. Am J Cardiol 74:1016-1020, 1994. 53. Alpert MA, Curtis JJ, Sanfelippo JF, et al: Comparative survival after permanent ventricular and dual chamber pacing for patients with chronic high degree atrioventricular block with and without preexistent congestive heart failure. J Am Coll Cardiol 7:925-932, 1986. 54. Linde-Edelstam C, Gullberg B, Norlander R, et al: Longevity in patients with high degree atrioventricular block paced in the atrial synchronous or the fixed rate ventricular inhibited mode. Pacing Clin Electrophysiol 15:304-313, 1992. 55. Sutton R, Kenny RA: The natural history of sick sinus syndrome. Pacing Clin Electrophysiol 9:1114-1116, 1986. 56. Markewitz A, Schad N, Hemmer W, et al: What is the most appropriate stimulation mode in patients with sinus node dysfunction? Pacing Clin Electrophysiol 9:1115-1120, 1986. 57. Ebagosti A, Guenoun M, Saadjian A, et al: Long-term follow-up of patients treated with VVI pacing and sequential pacing with reference to VA retrograde conduction. Pacing Clin Electrophysiol 11:1929-1934, 1988. 58. Langenfeld H, Schneider B, Grimm W, et al: The six-minute walk: an adequate exercise for pacemaker patients? Pacing Clin Electrophysiol 13:1761-1765, 1990. 59. Feuer JM, Shandling AH, Messenger JC, et al: Influence of cardiac pacing mode on the long-term development of atrial fibrillation. Am J Cardiol 64:1376-1379, 1989. 60. Lamas GA: Physiological consequences of normal atrioventricular conduction: applicability to modern cardiac pacing. J Card Surg 4:89-98, 1989. 61. Lamas GA, Pashos CL, Normand SL, McNeil B: Permanent pacemaker selection and subsequent survival in elderly Medicare pacemaker recipients. Circulation 91:1063-1069, 1995. 62. Perrins EJ, Morley CA, Chan SL, Sutton R: Randomized controlled trial of physiological and ventricular pacing. Br Heart J 50:112-117, 1983. 63. Kristensson BE, Amman K, Smedgard P, Ryden L: Physiological versus single-rate ventricular pacing: a double-blind cross-over study. Pacing Clin Electrophysiol 8:73-84, 1986.

64. Mattioli AV, Vivoli D, Mattioli G: Influence of pacing modalities on the incidence of atrial fibrillation in patients without prior atrial fibrillation. Eur Heart J 19:282-286, 1998. 65. Lamas GA, Orav J, Stambler BS, et al: Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. N Engl J Med 338:10971104, 1998. 66. Ellenbogen KA, Stambler BS, Orav EJ, et al: Clinical characteristics of patients intolerant to VVIR pacing. Am J Cardiol 86:5963, 2000. 67. Lamas GA, Lee KL, Sweeney MO, et al: Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 346:1854-1862, 2002. 68. Flaker G, Greenspon A, Tardiff B, et al: Death in patients with permanent pacemakers for sick sinus syndrome. Am Heart J 146:887-893, 2003. 69. Greenspon AJ, Hart RG, Dawson D, et al: Predictors of stroke in patients paced for sick sinus syndrome. J Am Coll Cardiol 43:1617-1622, 2004. 70. Fleischmann KE, Orav EJ, Lamas GA, et al: Atrial fibrillation and quality of life after pacemaker implantation for sick sinus syndrome: data from the Mode Selection Trial (MOST). Am Heart J 158:78-83, 2009. 71. Link MS, Hellkamp AS, Estes NA 3rd, et al: High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST). J Am Coll Cardiol 43:2066-2071, 2004. 72. Connolly SJ, Kerr CR, Gent M, et al: Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 342:1385-1391, 2000. 73. Tang AS, Roberts RS, Kerr C, et al: Relationship between pacemaker dependency and the effect of pacing mode on cardiovascular outcomes. Circulation 103:3081-3085, 2001. 74. Baranchuk A, Healey JS, Thorpe KE, et al: The effect of atrialbased pacing on exercise capacity as measured by the 6-minute walk test: a substudy of the Canadian Trial of Physiologic Pacing (CTOPP). Heart Rhythm 4:1024-1028, 2007. 75. Tyers GF, Gao M, Hayden RI, et al: Use of physiologic pacing after the Canadian Trial of Physiologic Pacing. Pacing Clin Electrophysiol 28(suppl 1):68-69, 2005. 76. Skanes AC, Krahn AD, Yee R, et al: Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. CTOPP Investigators. J Am Coll Cardiol 38:167-172, 2001. 77. Kerr CR, Connolly SJ, Abdollah H, et al: Canadian Trial of Physiological Pacing: effects of physiological pacing during long-term follow-up. Circulation 109:357-362, 2004. 78. Wyse DG, Waldo AL, DiMarco JP, et al: A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347:1825-1833, 2002. 79. Toff WD, Camm AJ, Skehan JD: Single-chamber versus dualchamber pacing for high-grade atrioventricular block. N Engl J Med 353:145-155, 2005. 80. Toff WD, Skehan JD, De Bono DP, Camm AJ: The United Kingdom Pacing and Cardiovascular Events (UKPACE) trial. Heart 78:221-223, 1997. 81. Patel AM, Westveer DC, Man KC, et al: Treatment of underlying atrial fibrillation: paced rhythm obscures recognition. J Am Coll Cardiol 36:784-787, 2000. 82. Auricchio A, Stellbrink C, Block M, et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 99:29933001, 1999. 83. Auricchio A, Ding J, Spinelli JC, et al: Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. J Am Coll Cardiol 39:1163-1169, 2002. 84. Stierle U, Kruger D, Mitusch R, et al: Adverse pacemaker hemodynamics evaluated by pulmonary venous flow monitoring. Pacing Clin Electrophysiol 18:2028-2034, 1995. 85. Healey JS, Toff WD, Lamas GA, et al: Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation 114:11-17, 2006. 86. Masumoto H, Ueda Y, Kato R, et al: Long-term clinical performance of AAI pacing in patients with sick sinus syndrome: a comparison with dual-chamber pacing. Europace 6:444-450, 2004. 87. Nielsen JC, Bøttcher M, Nielsen TT, et al: Regional myocardial blood flow in patients with sick sinus syndrome randomized to long-term single chamber atrial or dual chamber pacing: effect of pacing mode and rate. J Am Coll Cardiol 35:1453-1461, 2000. 88. Nielsen JC, Kristensen L, Andersen HR, et al: A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 42:614-623, 2003. 89. Kristensen L, Nielsen JC, Mortensen PT, et al: Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome. Heart 90:661-666, 2004. 90. Albertsen AE, Nielsen JC, Poulsen SH, et al: DDD(R)-pacing, but not AAI(R)-pacing, induces left ventricular desynchronization in patients with sick sinus syndrome: tissue-Doppler and 3D echocardiographic evaluation in a randomized controlled comparison. Europace 10:127-133, 2008.

255

91. Nielsen JC, Thomsen PE, Højberg S, et al: A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J 32:686-696, 2011. 92. Sweeney MO, Bank AJ, Nsah E, et al: Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 357:1000-1008, 2007. 93. Best PJ, Hayes DL, Stanton MS: The potential usage of dual chamber pacing in patients with implantable cardioverterdefibrillators. Pacing Clin Electrophysiol 22:79-85, 1999. 94. Kühlkamp V, Dörnberger V, Mewis C, et al: Clinical experience with the new detection algorithms for atrial fibrillation of a defibrillator with dual chamber sensing and pacing. J Cardiovasc Electrophysiol 10:905-915, 1999. 95. Deisenhofer I, Kolb C, Ndrepepa G, et al: Do current dual chamber cardioverter defibrillators have advantages over conventional single chamber cardioverter-defibrillators in reducing inappropriate therapies? A randomized, prospective study. J Cardiovasc Electrophysiol 12:134-142, 2001. 96. Theuns DA, Rivero-Ayerza M, Boersma E, Jordaens L: Prevention of inappropriate therapy in implantable defibrillators: a meta-analysis of clinical trials comparing single-chamber and dual-chamber arrhythmia discrimination algorithms. Int J Cardiol 125:352-357, 2008. 97. Friedman PA, McClelland RL, Bamlet WR, et al: Dual-chamber versus single-chamber detection enhancements for implantable defibrillator rhythm diagnosis: the detect supraventricular tachycardia study. Circulation 113:2871-2879, 2006. 98. Bänsch D, Steffgen F, Grönefeld G, et al: The 1+1 trial: a prospective trial of a dual- versus a single-chamber implantable defibrillator in patients with slow ventricular tachycardias. Circulation 110:1022-1029, 2004. 99. Dorian P, Philippon F, Thibault B, et al: Randomized controlled study of detection enhancements versus rate-only detection to prevent inappropriate therapy in a dual-chamber implantable cardioverter-defibrillator. Heart Rhythm 1:540-547, 2004. 100. Wietholt D, Kuehlkamp V, Meisel E, et al: Prevention of sustained ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators: the PREVENT study. J Interv Card Electrophysiol 9:383-389, 2003. 101. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. 102. Sharma AD, Rizo-Patron C, Hallstrom AP, et al: Percent right ventricular pacing predicts outcomes in the DAVID Trial. Heart Rhythm 2(8):830-834, 2005. 103. Kutalek SP, Sharma AD, McWilliams MJ, et al: Effect of pacing for soft indications on mortality and heart failure in the dual chamber and VVI implantable defibrillator (DAVID) trial. Pacing Clin Electrophysiol 31:828-837, 2008. 104. Berenbom LD, Weiford BC, Vacek JL, et al: Differences in outcomes between patients treated with single- versus dualchamber implantable cardioverter defibrillators: a substudy of the Multicenter Automatic Defibrillator Implantation Trial II. Ann Noninvasive Electrocardiol 10:429-435, 2005. 105. Wilkoff BL, Kudenchuk PJ, Buxton AE, et al: The DAVID (Dual Chamber and VVI Implantable Defibrillator) II trial. J Am Coll Cardiol 53:872-880, 2009. 106. Kudenchuk PJ, Hallstrom AP, Herre JM, Wilkoff BL: Heart rate, pacing, and outcome in the Dual Chamber and VVI Implantable Defibrillator (DAVID) trials. Heart Rhythm 6:1129-1135, 2009. 107. Almendral J, Arribas F, Wolpert C, et al: Dual-chamber defibrillators reduce clinically significant adverse events compared with single-chamber devices: results from the DATAS (Dual Chamber and Atrial Tachyarrhythmias Adverse Events Study) trial. Europace 10:528-535, 2008. 108. Connolly SJ, Kerr C, Gent M, Yusuf S: Dual-chamber versus ventricular pacing: critical appraisal of current data. Circulation 94:578-583, 1996. 109. Lamas GA, Estes NM 3rd, Schneller S, Flaker GC: Does dual chamber or atrial pacing prevent atrial fibrillation? The need for a randomized controlled trial. Pacing Clin Electrophysiol 15:1109-1113, 1992. 110. Lamas GA, Prosser AP, Edery TP, et al: Age and sex bias in pacemaker selection [abstract]. Circulation 86(suppl I):449, 1992. 111. Vardas PE, Auricchio A, Blanc JJ, et al: Guidelines for cardiac pacing and cardiac resynchronization therapy. The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Europace 9:959-998, 2007. 112. Epstein AE, Dimarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities. Heart Rhythm 5:934-955, 2008. 113. Markewitz A: Annual report 2007 of the German Pacemaker Registry. Herzschrittmacherther Elektrophysiol 20:191-218, 2009. 114. Steinberg JS, Fischer A, Wang P et al: The clinical implications of cumulative right ventricular pacing in the Multicenter Automatic Defibrillator Implantation Trial II. J Cardiovasc Electrophysiol 16:359-365, 2005. 115. Karpawich PP, Rabah R, Haas JE: Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block. Pacing Clin Electrophysiol 22:1372-1377, 1999. 116. Lieberman R, Padeletti L, Schreuder J, et al: Ventricular pacing lead location alters systemic hemodynamics and left ventricular

256

SECTION 2  Clinical Concepts

function in patients with and without reduced ejection fraction. J Am Coll Cardiol 48:1634-1641, 2006. 117. Thambo JB, Bordachar P, Garrigue S, et al: Detrimental ventricular remodeling in patients with congenital complete heart block and chronic right ventricular apical pacing. Circulation 110:3766-3772, 2004. 118. Barold SS, Levine PA: Pacemaker repetitive nonreentrant ventriculoatrial synchronous rhythm. J Interv Card Electrophysiol 5:45-58, 2001. 119. Sweeney MO: Novel cause of spurious mode switching in dualchamber pacemakers: atrioventricular desynchronization arrhythmia. J Cardiovasc Electrophysiol 13:616-619, 2002. 120. Fröhlig G, Gras D, Victor J, et al: Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular pacing. Europace 8:96-101, 2006. 121. Savouré A, Fröhlig G, Galley D, et al: A new dual-chamber pacing mode to minimize ventricular pacing. Pacing Clin Electrophysiol 28(suppl 1):43-46, 2005. 122. Thibault B, Simpson C, Gagné CE, et al: Impact of AV conduction disorders on SafeR mode performance. Pacing Clin Electrophysiol 32(suppl 1):231-235, 2009. 123. Pürerfellner H, Brandt J, Israel C, et al: Comparison of two strategies to reduce ventricular pacing in pacemaker patients. Pacing Clin Electrophysiol 31:167-176, 2008. 124. Milasinovic G, Tscheliessnigg K, Boehmer A, et al: Percent ventricular pacing with managed ventricular pacing mode in standard pacemaker population. Europace 10:151-155, 2008. 125. Gillis AM, Pürerfellner H, Israel CW, et al: Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Pacing Clin Electrophysiol 29:697-705, 2006. 126. Sweeney MO, Ellenbogen KA, Casavant D, et al: Multicenter, prospective, randomized safety and efficacy study of a new atrial-based managed ventricular pacing mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol 16:811-817, 2005. 127. Sweeney MO, Ellenbogen KA, Tang AS, et al: Atrial pacing or ventricular backup-only pacing in implantable cardioverterdefibrillator patients. Heart Rhythm 7:1552-1560, 2010. 128. Olshansky B, Day J, McGuire M, et al: Reduction of right ventricular pacing in patients with dual-chamber ICDs. Pacing Clin Electrophysiol 29:237-243, 2006. 129. Olshansky B, Day JD, Moore S, et al: Is dual-chamber programming inferior to single-chamber programming in an implantable cardioverter-defibrillator? Results of the INTRINSIC RV

(Inhibition of Unnecessary RV Pacing with AVSH in ICDs) study. Circulation 115:9-16, 2007. 130. Zhang XH, Chen H, Siu CW, et al: New-onset heart failure after permanent right ventricular apical pacing in patients with acquired high-grade atrioventricular block and normal left ventricular function. J Cardiovasc Electrophysiol 19:136-141, 2008. 131. Doshi RN, Daoud EG, Fellows C, et al: Left ventricular–based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 16:1160-1165, 2005. 132. Kindermann M, Hennen B, Jung J, et al: Biventricular versus conventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg Biventricular Pacing Evaluation (HOBIPACE). J Am Coll Cardiol 47:1927-1937, 2006. 133. Leclercq C, Cazeau S, Lellouche D, et al: Upgrading from single chamber right ventricular to biventricular pacing in permanently paced patients with worsening heart failure: the RD-CHF Study. Pacing Clin Electrophysiol 30(suppl 1):23-30, 2007. 134. Albertsen AE, Nielsen JC, Poulsen SH, et al: Biventricular pacing preserves left ventricular performance in patients with highgrade atrioventricular block: a randomized comparison with DDD(R) pacing in 50 consecutive patients. Europace 10:314-320, 2008. 135. Yu CM, Chan JY, Zhang Q, et al: Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 361:2123-2134, 2009. 136. De Teresa E, Gómez-Doblas JJ, Lamas G, et al: Preventing ventricular dysfunction in pacemaker patients without advanced heart failure: rationale and design of the PREVENT-HF study. Europace 9:442-446, 2007. 137. Funck RC, Blanc JJ, Mueller HH, et al: Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) study. Europace 8:629-635, 2006. 138. Curtis AB, Adamson PB, Chung E, et al: Biventricular versus right ventricular pacing in patients with AV block (BLOCK HF): clinical study design and rationale. J Cardiovasc Electrophysiol 18:965-971, 2007. 139. Linde C, Abraham WT, Gold MR, et al: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 52:1834-1843, 2008.

140. Moss AJ, Hall WJ, Cannom DS, et al: Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361:1329-1338, 2009. 141. Tang AS, Wells GA, Talajic M, et al: Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363:2385-2395, 2010. 142. Sutton R, Bourgeois I: Cost-benefit analysis of single- and dualchamber pacing for sick sinus syndrome and atrioventricular block: an economic sensitivity analysis of the literature. Eur Heart J 17:574-582, 1996. 143. O’Brien BJ, Blackhouse G, Goeree R, et al: Cost-effectiveness of physiologic pacing: results of the Canadian Health Economic Assessment of Physiologic Pacing. Heart Rhythm 2:270-275, 2005. 144. Rinfret S, Cohen DJ, Lamas GA, et al: Cost-effectiveness of dualchamber pacing compared with ventricular pacing for sinus node dysfunction. Circulation 111:165-172, 2005. 145. Castelnuovo E, Stein K, Pitt M, et al: The effectiveness and costeffectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation. Health Technol Assess 9(43):iii, xi-xiii, 1-246, 2005. 146. Goldberger Z, Elbel B, McPherson CA, et al: Cost advantage of dual-chamber versus single-chamber cardioverter-defibrillator implantation. J Am Coll Cardiol 46:850-857, 2005. 147. Deniz HB, Caro JJ, Ward A, et al: Economic and health consequences of managing bradycardia with dual-chamber compared to single-chamber ventricular pacemakers in Italy. J Cardiovasc Med 9:43-50, 2008. 148. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation 117:e350e-408, 2008. 149. Vardas PE, Auricchio A, Blanc JJ, et al: Guidelines for cardiac pacing and cardiac resynchronization therapy. The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. Europace 9:959998, 2007. 150. Dretzke J, Toff WD, Lip GY, et al: Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block. Cochrane Database Syst Rev 2:CD003710, 2004.

11  11

Clinical Trials of Defibrillator Therapy DEREK V. EXNER

This chapter reviews the findings from randomized trials of implant-

able cardioverter-defibrillator (ICD) therapy, from observational studies of ICD therapy in less common disorders, and from ongoing studies, as well as indications and guidelines for ICD therapy. Sudden cardiac death, risk stratification, impact on quality of life, costeffectiveness, evolution of ICD therapy, and its potential limitations are discussed to provide insight into past studies and the direction of future research.

Sudden Death: Definition and Implication for Clinical Trials Sudden cardiac death is defined as a death attributable to cardiac cause that occurs soon after the onset of symptoms. A 49% reduction in the incidence of sudden death has been documented over more than 50 years.1 The incidence of out-of-hospital cardiac arrest from ventricular fibrillation (VF) has also been reduced.2 These reductions largely appear to be related to improved management of coronary heart disease risk factors and prevention strategies that include prophylactic insertion of ICD systems.3 Despite these advances, sudden death remains a major public health problem. Worldwide, more than 3 million lives are ended prematurely because of sudden death,4 many in ambulatory populations from sustained ventricular tachycardia (VT) or VF.5,6 Bradyarrhythmic events and electromechanical dissociation may be more common mechanisms in patients with end-stage heart failure.7 A definition of sudden death that includes events that occur within 1 hour of symptom onset has been considered reliable in identifying deaths related to arrhythmias.8 Definitions of sudden death that also incorporate the circumstances surrounding these events may provide additional value in separating arrhythmic from nonarrhythmic causes.9 Despite these refinements, however, misclassification occurs.10 Autopsy data from a large study of patients who survived a myocardial infarction (MI), had residual left ventricular (LV) dysfunction, and later suffered sudden death found that half of deaths categorized as “sudden” were nonarrhythmic. Most of these nonarrhythmic sudden deaths were related to a recurrent MI or cardiac rupture and were more frequent in the initial 6 months after the initial MI.11 Another study found that VT or VF were responsible for most sudden deaths in a group of post-MI patients with moderate LV dysfunction in whom the cardiac rhythm was monitored at the time of these events. Bradyarrhythmias were responsible for a minority of these sudden arrhythmic deaths, and VT or VF was the underlying rhythm for some deaths categorized as nonarrhythmic.6 Thus, clinical definitions of sudden death and arrhythmic death are imperfect. Categorizing deaths as “arrhythmic” or “nonarrhythmic” is useful for hypothesis generation, but inherently unreliable. Because of these issues, total mortality is the preferred term as the primary outcome in randomized trials assessing the efficacy of ICD therapy.

Evolution of Therapy: Implication for Clinical Trials The first implantation of an automated defibrillator occurred in the 1970s.12 Over the past three decades, improvements have been made

in device capability and size. The contemporary tiered-therapy ICD is capable of delivering antitachycardia pacing (ATP), low-energy cardioversion, and high-energy defibrillation therapies. In addition, it provides backup bradycardia pacing. The ICD effectively terminates the vast majority of sustained VT or VF events and most bradyarrhythmias.13 Enhancements that include painless ATP therapies,14,15 algorithms to reduce the likelihood of unnecessary ICD therapies,16 and remote monitoring17,18 have added to the appeal of the ICD. The addition of cardiac resynchronization therapy (CRT) offers the potential to improve LV function, reduce morbidity, and further decrease mortality in select patients.19 Most contemporary ICD systems are placed in a subcutaneous or submuscular position in the chest and use the venous anatomy for lead delivery. The risk of death related to placement of nonthoracotomy, transvenous ICD systems approaches 0%. In contrast, earlier ICD systems that required a thoracotomy or sternotomy for lead placement were associated with a 5% mortality risk in the first 30 postoperative days.20,21 The ease of implantation and relatively low risk of surgical morbidity and mortality with contemporary ICD system placement have altered the direction of studies examining ICD efficacy. Initial trials were limited to patients considered at “very high risk” of cardiac arrest, whereas later trials have included patients at somewhat lower risk. The results of clinical trials over the past two decades have established the ICD as a cornerstone of therapy for patients at risk for sudden death.22,23 The number of ICD implantations worldwide now exceeds 250,000 per year.24 The exponential increase in the number of ICD systems implanted over the past decade mirrors the quantity of patient data obtained from randomized clinical trials4,24 (Fig. 11-1).

Quality of Life In contrast to antiarrhythmic drugs, which are designed to prevent arrhythmias, the ICD treats arrhythmias that have already developed. Because the ICD prolongs life, patients may experience deterioration in underlying health that might not have otherwise occurred. Stress, anxiety, depression, mood disturbance, sexual dysfunction, and a sense of uncertainty or loss of control have been described in ICD recipients.25 The ICD also provides a sense of reassurance to some patients, enhancing their quality of life (QOL). The use of an ICD with CRT may further enhance QOL by reducing heart failure symptoms and preventing hospitalizations.19 Six large trials have published data related to QOL with ICD therapy. Two trials included patients with spontaneous or inducible ventricular arrhythmias and found that ICD therapy and amiodarone were associated with similar alterations in QOL.26,27 Results from the four trials that included patients without a history of these arrhythmias are less consistent. The Coronary Artery Bypass Graft (CABG) Patch trial found reduced QOL with ICD therapy,28 as did the Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II).29 In contrast, the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial30 and the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) found no significant difference in QOL over time.31 Details regarding the QOL assessment methods and potential explanations for these differences are provided later in the individual reviews of these trials.

257

258

SECTION 2  Clinical Concepts

14,000

250,000

Trial participants

10,000 8000

Trial participants ICD implants

6000

200,000 150,000 100,000

4000

50,000

2000 0

Implants worldwide

12,000

0 1991 1994 1997 2000 2003 2006 2009

Year Figure 11-1  Growth of the use of defibrillator system implantations worldwide and of the knowledge from randomized clinical trials of defibrillator therapy. An exponential increase in the number of implantable cardioverter-defibrillator (ICD) systems worldwide has occurred since 1990. This increase is a reflection of the number of patients included in randomized trials evaluating the efficacy of ICD therapy to reduce mortality and sudden death. (Modified from Josephson M, Wellens HJ: Implantable defibrillators and sudden cardiac death. Circulation 109:2685-2691, 2004; and Camm AJ, Nisam S: European utilization of the implantable defibrillator: has 10 years changed the “enigma”? Europace 12:1063-1069, 2010.)

Limitations of Therapy SHOCKS Even sporadic ICD shocks are associated with significant, independent reductions in QOL. Compared with patients who did not experience shocks, patients in the Antiarrhythmics versus Implantable Defibrillators (AVID) trial who experienced at least one shock during the initial year of follow-up had reduced QOL, independent of LV ejection fraction (EF), social circumstances, and medication use.26 The reductions in QOL associated with shocks in AVID were similar in magnitude to clinically important adverse effects from amiodarone. In MADIT-II, a higher prevalence of heart failure and the development of shocks in ICD-treated patients were associated with reductions in QOL among ICD recipients.29 ICD shocks were also associated with reduced QOL in the DEFINITE trial.30 In SCD-HeFT, QOL was diminished over the short term following ICD shocks, but subsequently improved.31 This implies a direct association between ICD shocks and reduced QOL. The development of clusters of life-threatening arrhythmias identifies patients at high risk of death in the near term. Patients in AVID who experienced electrical storm (at least three episodes of VT or VF in a 24-hour period) had a greater than fivefold higher risk of death in the subsequent 3 months.32 The majority of these deaths are related to progressive heart failure, supporting a link between electrical storm and deteriorating LV function. The MADIT-II investigators found that inappropriate ICD shocks were common, representing over 30% of all shocks, and were associated with a twofold higher risk of death. Most of these inappropriate shocks were related to atrial fibrillation or a supraventricular tachycardia.33 In SCD-HeFT, risk of death with appropriate ICD shocks was fivefold higher, and risk of death with inappropriate ICD shocks was twofold higher. Most of the deaths in the patients who received shocks and later died in SCD-HeFT were attributed to progressive heart failure.34 It is not known whether the development of isolated or multiple ICD shocks identifies patients with worsening LV function or whether the ICD therapies themselves contribute to progressive LV dysfunction. Evidence links multiple shocks with myocardial injury and fibrosis.35,36 There is also evidence in animal models that ICD shocks may be proarrhythmic.37 Data from human studies support a proarrhythmic effect of some shocks and suggest that multiple shocks can result in myocardial stunning and electromechanical dissociation.38,39 Also, observational data indicate that ICD shocks, but not ATP therapies, are

associated with a higher risk of death.40 However, other studies did not find a difference in outcome if arrhythmias were terminated by ATP or by shocks.32 Nonetheless, strategies to reduce the likelihood of inappropriate and appropriate shocks, and alternative methods to terminate ventricular arrhythmias, are vital avenues of investigation.16 Antiarrhythmic drugs can be used to reduce the likelihood of ICD shocks,41,42 but may negatively affect QOL because of their adverse effects.26 ATP therapies painlessly interrupt reentrant ventricular arrhythmias using brief, rapid bursts of overdrive pacing. ATP has long been used to terminate slower ventricular arrhythmias (rates <188 beats per minute [bpm]) with an efficacy exceeding 90% and a low (<5%) risk of accelerating these slower arrhythmias to a more rapid one that requires a defibrillation shock. ATP has also been shown to be useful for terminating fast VT (188-250 bpm)43 and should be used as the initial treatment for treating these arrhythmias.16 The use of ATP for fast VT has been demonstrated to enhance QOL,43 both in patients with, and in those without, a history of sustained arrhythmias before ICD implantation.44 Extending the time to detect and treat a ventricular arrhythmia, from 4 to 5 seconds to 9 to 12 seconds, also appears to be useful in reducing the number of ICD shocks,45 because even fast VT episodes will spontaneously terminate 30% of the time.43 The combined use of algorithms that avoid shocks from external and intracardiac noise, provide enhanced redetection, and maximize the use of ATP therapies has been estimated to reduce unnecessary ICD shocks by more than 80%.46 It is important to note that the safety and efficacy of delaying the detection of these arrhythmias or the use of multiple algorithms to reduce shocks are not known. Ongoing studies are in progress to address these and other relevant issues. RELIABILITY Despite the intuitive appeal of the ICD, the clinician must recognize that it is an imperfect therapeutic device. Present ICD systems have a limited working life and are subject to both complications and unexpected failure over time.47-49 However, the life expectancy of patients receiving ICD systems has improved over time. One study found that 75% of ICD recipients were alive at 5 years and more than 40% were alive at 10 years after ICD placement.48 This is consistent with a 49% survival rate after a median follow-up of over 7 years in MADIT-II ICD recipients.50 A contemporary ICD battery is anticipated to last 4 to 7 years, but clinical experience is that the average in-service time for an ICD is typically 3 to 5 years due to premature battery depletion, device advisories, need for system upgrades, and infections.51 Therefore, recipients are likely to require multiple devices over their lifetime. With recent trials showing benefit in patients with less advanced forms of heart disease, this mismatch will continue to grow. Research related to assessing reliability and longevity is required. Longer-term follow-up of ICD patients in clinical trials is also needed to obtain reliable data on long-term efficacy and cost-effectiveness of ICD therapy. COST Cost-effectiveness is crucial in the setting of limited or restricted health care resources. This is particularly relevant as use of ICD and CRT devices expands to include patients sharing only some similarities with patient populations in whom these devices have been shown to be effective, so-called indication creep or indication extrapolation.52 For example, a large survey of 141 centers in Western Europe found that at least 1 in 5 patients undergoing a CRT procedure had clinical or electrocardiographic characteristics that placed them outside of published guidelines.53 Analysis of data from the National Cardiovascular Data Registry (NCDR) ICD Registry similarly found that over 20% of patients receiving CRT devices did not meet guideline-based indications.54 A major limitation of cost analyses in randomized trials is that these analyses invariably inflate the cost of ICD therapy and devalue the life-years gained. The estimate of life-years gained from randomized trials depends heavily on the duration of follow-up assessing benefit. The cost of an ICD is heavily front-loaded, yet its benefit accrues over



11  Clinical Trials of Defibrillator Therapy

time. Thus, short-term data from randomized trials may artificially underestimate the cost-effectiveness of ICD therapy.55 For example, the mortality reduction observed with long-term follow-up in MADIT-II was much larger than that initially observed, despite many patients in the conventional group crossing over to ICD therapy at the conclusion of the trial.50 At a median follow-up of over 7 years, the absolute reduction in mortality with ICD therapy was 13%. This is much larger than the 5.6% reduction in mortality at the trial’s conclusion, where median follow-up was 1.5 years.56 An in-depth analysis of randomized trials of ICD therapy found a modest, incremental cost-effectiveness of ICD therapy that ranged between $25,000 and $50,000 per quality-adjusted life-year.57 Similar estimates have been found in most randomized trials. These data indicate that ICD therapy is cost-effective. However, it is important to recognize that cost-effectiveness likely differs in the real world versus the populations from whom these estimates were derived. For example, only sparse data exist on the cost-effectiveness of ICD therapy in elderlypersons.58 Additional data regarding cost-effectiveness are included in the discussion of individual trials. UTILIZATION There are marked differences in the use of ICD therapy in different regions of the world. In the United States, the rate of ICD implantations is approximately 600 implants per 1 million population. In Western Europe and Canada, the rates are approximately one quarter of the U.S. rate.24 The reasons for these differences are complex, but likely relate to differing perceptions of need, variability in guidelines, perceived cost-effectiveness, and concerns over inappropriate ICD therapies and device malfunction.59 This underutilization has also been attributed to a shortage of electrophysiologists, poorly developed local referral strategies and care pathways, and difficult or confusing financial circumstances.24 Solutions to some of these barriers are more obvious than others. For example, an entirely subcutaneous ICD system may address limited implantation resources.60 However, issues then arise related to how these patients and devices will be followed. Studies assessing the long-term effectiveness and safety of subcutaneous ICD systems are in progress. Underuse of ICD therapy is concerning and has significant consequences for patients in whom an ICD is clearly indicated, but not prescribed. Additional efforts to identify and address barriers to patient referral and implantation rates are required.

Individual risk of sudden death

259

Groups at Risk for Sudden Death The term primary prevention has been used to describe the use of ICD therapy in individuals without a history of spontaneous life-threatening arrhythmias. Secondary prevention has been used to describe the use of an ICD in a patient with a previously documented life-threatening arrhythmia. This dichotomy is both problematic and inexact, as evidenced by the inclusion criteria and results of completed trials to be discussed. Instead of these descriptors, the populations studied are categorized as belonging to one of the following four patient groups: • Spontaneous or inducible ventricular arrhythmias • Heart failure or left ventricular dysfunction alone • Left ventricular dysfunction in specific circumstances • Less common inherited or acquired cardiac disease IDENTIFYING INDIVIDUALS AT RISK A major barrier to preventing sudden death is the lack of accurate and reliable methods of identifying the majority of individuals at risk and those in whom an ICD would be most beneficial.61 Individuals who can be identified before experiencing sudden death can be categorized as belonging to one of the four groups previously listed. Patients with spontaneous or inducible ventricular arrhythmias are known to be at high risk for cardiac arrest, but they represent only a fraction of those who will experience sudden death62,63 (Fig. 11-2). Patients with structural heart disease, notably a previous MI or LV dysfunction, represent a significant proportion of those at risk for sudden death and have an intermediate risk of cardiac arrest in the near term. To date, only two approaches have proved useful in guiding prophylactic ICD therapy in this group. LV dysfunction alone (LVEF ≤ 0.35) or in combination with the induction of sustained VT/VF with invasive programmed electrical stimulation.56,64,65 However, invasive programmed electrical stimulation does not appear useful early after MI,66,67 and arrhythmia inducibility is unreliable in predicting longterm outcome.68 Although individuals with LV dysfunction after MI have a heightened risk of sudden death, most will not experience a cardiac arrest in the near term. Further, the majority of sudden deaths occur in post-MI patients with better-preserved LV function69,70 (Fig. 11-3). If a left ventricular ejection fraction cutoff value of 0.35 or less (LVEF ≤ 0.35) is used to identify those at risk, fewer than one third of patients who will

Proportion of sudden deaths

Sudden death (%)

40

30 Minor disease

20

Prior MI Heart failure

10

0 Ventricular arrhythmia

Heart failure

Prior MI

Minor disease

Ventricular arrhythmia

Figure 11-2  Sudden death: individual risk versus population impact. Individuals with spontaneous or inducible sustained ventricular arrhythmias (blue) have a large individual risk of cardiac arrest in the near term. However, only a small number of patients have these ventricular arrhythmias, so the number of sudden deaths in this group is relatively small. Patients with heart failure (green) and those with a myocardial infarction (MI) (purple) have an intermediate risk of cardiac arrest in the near term. Because of the large number of patients with these conditions, many more sudden deaths occur in this group. Trials of ICD therapy in patients with heart failure have been conducted to reduce more effectively the burden of sudden death. (Modified from Rea TD, Pearce RM, Raghunathan TE, et al: Incidence of out-of-hospital cardiac arrest. Am J Cardiol 93:1455-1460, 2004.)

260

SECTION 2  Clinical Concepts

Patients with an ejection fraction less than or equal to 0.35 (specific measure)

Patients who have survived a myocardial infarction

Those with an ejection fraction less than or equal to 0.35 who will suffer sudden arrhythmic death

Individuals who will suffer a sudden arrhythmic death Patients with an ejection fraction less than or equal to 0.50 (sensitive measure)

Figure 11-3  Identifying individuals at risk for sudden death: specificity versus sensitivity. Patients who have survived a myocardial infarction (gray) are at risk for sudden death, but only a fraction of these individuals will experience sudden death in the near term (purple). Although patients with severe left ventricular (LV) dysfunction (ejection fraction ≤0.35; green circle) have a high risk of death, most of these deaths are not sudden, and less than one third of all sudden deaths will occur in these patients. Patients with mild LV dysfunction (ejection fraction ≤0.50; blue circle) are less likely to die but account for the majority of those who will experience sudden death in the near term. Risk assessment strategies, in addition to the use of ejection fraction, may allow better identification of patients with a history of myocardial infarction who are more likely to benefit from an implantable cardioverter-defibrillator. (Modified from La Rovere MT, Bigger JT Jr, Marcus FI, et al. Baroreflex sensitivity and heart rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes after Myocardial Infarction) Investigators. Lancet 351:478-484, 1998; and Exner DV, Kavanagh KM, Slawnych MP, et al: Noninvasive risk assessment early after a myocardial infarction: the REFINE study. J Am Coll Cardiol 50:2275-2284, 2007.)

suffer sudden death are identified.69-72 In contrast, a cutoff of 0.50 or less (LVEF ≤ 0.50) will identify most patients at risk.69,70 However, an LVEF ≤ 0.50 alone is a nonspecific selection method, and additional risk assessment is required to better identify those at risk for sudden death. Individuals with mild or subclinical heart disease account for the majority of sudden deaths,63,73 but the likelihood that an individual in this group will experience a cardiac arrest over a decade is very low (see Fig. 11-2).74 Many of the cardiac arrests in this group appear to be triggered by unstable coronary artery plaques.75 Appropriate attention to therapy with antiplatelet agents, statins, fish oils, and other drugs has the potential to significantly reduce the burden of sudden death.76 The widespread use of automated external defibrillators (AEDs) has been advocated as one method to improve survival from sudden death, but the Home AED Trial (HAT) found that an AED plus cardiopulmonary resuscitation (CPR) offered no advantage over CPR alone in patients at risk for sudden death because of a history of prior MI.77 The efficacy of a wearable AED in patients considered at risk for sudden death, but who are not candidates for an ICD (e.g., LV dysfunction early after MI), is presently under investigation. Noninvasive methods to assess the location and extent of myocardial scarring,78 cardiac denervation,79 ventricular conduction, cardiac repolarization, and autonomic tone61,80 have been developed to identify patients at risk for sudden death. However, although noninvasive techniques such as T-wave alternans (TWA), heart rate turbulence (HRT), other Holter monitor indices, imaging methods, and genetic assessment may be useful in some patients, these methods have not been useful in identifying groups of patients likely to benefit from an ICD. The signal-averaged electrocardiogram (signal-averaged ECG) was considered a reliable means to identify patients at risk for sudden death, but failed to predict ICD efficacy in the CABG Patch study.81 Similarly, heart rate variability was regarded as a reliable marker for predicating sudden death after MI, but no survival benefit was identified with ICD therapy in the Defibrillators in Acute Myocardial Infarction Trial (DINAMIT).82 The Microvolt T Wave Alternans Testing for Risk Stratification of Post–Myocardial Infarction Patients (MASTER) study, although not randomized, found that microvolt TWA results were not helpful in identifying post-MI patients with LV dysfunction at risk for arrhythmic death or in predicting ICD effectiveness.83 It is essential that risk assessment strategies be subjected to the rigor of a randomized trial to assess whether they do, in fact, identify patients likely to benefit from an ICD or other preventive therapy. Additional details related to these studies are provided later, along with a discussion of ongoing randomized studies assessing the utility of cardiac magnetic resonance imaging and noninvasive measures of risk to predict ICD efficacy.

In addition to those with primary electrical disorders, patients with hypertrophic cardiomyopathy, cardiac sarcoidosis, and arrhythmogenic right ventricular cardiomyopathy are also at risk of sudden death. These conditions are uncommon on a population level and difficult to study in randomized clinical trials. Thus, guidelines and clinical decision making must rely on nonrandomized data. The use of ICD therapy in these conditions is discussed later in this chapter. RELATIVE VS. ABSOLUTE RISK REDUCTION AND NUMBER NEEDED TO TREAT When assessing the impact of a therapy, one must consider its relative and absolute benefit. The absolute risk reduction is the difference between control and intervention group rates. For example, ICD therapy reduced mortality by 5.6% (19.8% control vs. 14.2% ICD) after a median follow-up of 1.5 years in MADIT-II. At a median follow-up of more than 7 years, the absolute risk reduction was 13% (62% control vs. 49% ICD).50 The relative risk reduction is the percentage reduction in rates with the intervention. For this same example, the relative risk reduction at 1.5 years in MADIT-II was 31% (5.6% absolute reduction ÷ 19.8% control rate) and at 7 years was 21% (13% absolute reduction ÷ 62% control rate). The number of patients needing to be treated in order to prevent one event is often used to describe the absolute impact of a therapy. The number needed to treat (NNT) is the reciprocal of the absolute risk reduction. In MADIT-II the NNT after 1.5 years was 17.9 (100% ÷ 5.6%) and at 7 years was 7.7 (100% ÷ 13%). This information is important for clinical decision making and health policy.

Evolution of ICD Therapy Initial observational studies and smaller randomized trials suggested that ICD implantation was associated with a greater than 60% relative reduction in mortality compared with conventional strategies.84 Because of limitations in the design of these initial studies, a series of larger, adequately powered, randomized trials were conducted either to confirm or to refute these initial observations. Because of the risk of ICD system placement (via thoracotomy or sternotomy), initial randomized trials focused on patients with the highest individual risk for a fatal cardiac arrest, those with a history of spontaneous ventricular arrhythmias (see Fig. 11-2). The next group of studies evaluated patients with an extremely high risk of a fatal cardiac arrest caused by a history of a prior MI, severe LV dysfunction, and arrhythmias inducible by invasive programmed electrical stimulation. During this time, studies were also designed to minimize the risk of ICD



11  Clinical Trials of Defibrillator Therapy Odds ratio (95% confidence interval)

Risk groups

Spontaneous or inducible ventricular arrhythmias

Heart failure or LV dysfunction alone

LV dysfunction in specific circumstances

Mortality reduction

AVID (n = 1,016) CIDS (n = 659) CASH (n = 288) MADIT I (n = 196) MUSTT (n = 514)

0.59 (0.43, 0.81) 0.81 (0.57, 1.14) 0.71 (0.43, 1.18) 0.30 (0.15, 0.59) 0.34 (0.22, 0.53)

8.2% 4.3% 8.1% 22.8% 23.0%

MADIT II (n = 1,232) AMIOVIRT (n = 103) CAT (n = 104) COMPANION (n = 903) SCD-HEFT (n = 1,676) DEFINITE (n = 458)

0.68 (0.50, 0.92) 0.86, (0.27, 2.75) 0.76 (0.33, 1.80) 0.64 (0.46, 0.90) 0.70 (0.56, 0.87) 0.66 (0.39, 1.11)

5.4% 1.7% 5.4% 7.3% 6.8% 5.2%

CABG-Patch (n = 900) DINAMIT (n = 674) BEST-ICD (n = 138) IRIS (n = 898)

1.11 (0.81, 1.52) 1.12 (0.76, 1.67) 1.17 (0.39, 3.58) 1.01 (0.75, 1.36)

Overall

0.72 ( 0.60, 0.86) 0.2

0.5

1

261

2

Favors ICD Figure 11-4  Summary of published randomized trials of defibrillator therapy. A large number of randomized trials have evaluated the efficacy of the implantable cardioverter-defibrillator (ICD) versus drug therapy or usual medical care. These patient populations can be separated into those with (1) spontaneous or inducible ventricular arrhythmias (purple), (2) heart failure or left ventricular (LV) dysfunction alone (green), and (3) LV dysfunction in specific circumstances (orange). The ICD has been proved to reduce mortality in the first two groups but not in the third. The relative benefits (odds ratios) in the first two groups are similar, and the absolute reduction in mortality with ICD therapy is approximately twice as large in patients with spontaneous or inducible ventricular arrhythmias as in patients with heart failure or LV dysfunction alone. AMIOVIRT, Amiodarone versus Implantable Cardioverter-Defibrillator Trial; AVID, Antiarrhythmics versus Implantable Defibrillators trial; BEST ICD, BEta-blocker STrategy plus ICD study; CABG-Patch, Coronary Artery Bypass Graft (CABG) Patch trial; CASH, Cardiac Arrest Study Hamburg; CAT, Cardiomyopathy Trial; CIDS, Canadian Implantable Defibrillator Study; COMPANION, Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure study; DEFINITE, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation; DINAMIT, Defibrillators in Acute Myocardial Infarction Trial; IRIS, Immediate Risk-Stzratification Improves Survival; MADIT, Multicenter Automatic Defibrillator Implantation Trial; MUSTT, Multicenter Unsustained Tachycardia Trial; SCD-HEFT, Sudden Cardiac Death-Heart Failure Trial.

system implantation by limiting therapy to patients who required a sternotomy for another reason (e.g., CABG surgery).81 After the mostly positive results of these early trials, studies in populations with lower but significant risk of sudden death were initiated. These trials have mostly been limited to patients with heart failure and LV dysfunction. A number of randomized studies have compared ICD therapy with amiodarone or other medical therapy. The relative benefit of ICD was consistent in most of these studies. However, no benefit of ICD therapy was found in four adequately powered trials (Fig. 11-4). These four trials included patients with LV dysfunction in specific circumstances. Three studies enrolled patients very early after MI,82,85,86 and the other included patients undergoing CABG surgery.81 The lack of ICD efficacy in these populations can be explained by (1) post-MI coronary artery revascularization and remodeling dramatically reducing the risk of sudden death, thus reducing ICD efficacy,87 or (2) use of inadequate risk assessment methods to select patients. Given the utility of most of these tests,80 the second explanation appears less likely. The neutral results from these four trials emphasize the need for randomized trials to assess ICD efficacy definitively in new populations and highlight the pitfalls of using a therapy for an indication beyond what has been shown to be efficacious.

Efficacy: Review of Randomized Trials PATIENTS WITH SPONTANEOUS OR INDUCIBLE VENTRICULAR ARRHYTHMIAS Table 11-1 summarizes the inclusion criteria, primary endpoints, and main results for five studies involving patients with spontaneous or inducible ventricular arrhythmias. Table 11-2 presents details of the

study populations, risk of the untreated population (annual control group mortality), and relative and absolute changes in mortality with ICD therapy. Two large randomized trials88,89 and one small trial90 provide convincing evidence that ICD therapy is superior to class III antiarrhythmic drugs in reducing mortality among patients with mostly spontaneous life-threatening arrhythmias. These studies generally included patients who survived a cardiac arrest caused by VT or VF. Another small randomized trial compared ICD therapy with conventional care that generally included amiodarone,64 and a large randomized trial in which ICD therapy was used in a nonrandomized manner91 assessed the efficacy of ICD therapy in patients with LV dysfunction and inducible ventricular arrhythmias. Both trials showed a benefit from ICD therapy similar to that in the three studies of patients who survived a cardiac arrest. Antiarrhythmics versus Implantable Defibrillators Trial The Antiarrhythmics versus Implantable Defibrillators (AVID) trial was a large (n = 1016) multicenter trial conducted in the United States and Canada. Patients entered into the trial were resuscitated from VT, had sustained VT with syncope, or had sustained VT with an LVEF of 0.40 or less and symptoms suggesting severe hemodynamic compromise (near-syncope, heart failure, and angina).88 Patients were excluded if the ventricular arrhythmia was attributed to a reversible cause or if the episode of VT was categorized as stable. The LVEF was required to be ≤0.40 in patients who underwent revascularization after the index arrhythmia, regardless of the qualifying arrhythmia. The primary outcome of AVID was all-cause mortality. The AVID trial began recruitment in mid-1993 and was terminated in 1997, when patients randomly assigned to ICD therapy were found

262

TABLE

11-1 

SECTION 2  Clinical Concepts

Clinical Trials of ICD Therapy for Spontaneous or Inducible Ventricular Arrhythmias: Inclusion Criteria, Comparison Groups, and Main Results

Trial Antiarrhythmics versus Implantable Defibrillators (AVID) (1999) Canadian Implantable Defibrillator Study (CIDS) (2000) Cardiac Arrest Study Hamburg (CASH) (2000) First Multicenter Automatic Defibrillator Implantation Trial (MADIT-I) (1996) Multicenter Unsustained Tachycardia Trial (MUSTT) (1999)*

Inclusion Criteria Resuscitated VF, sustained VT and syncope, or sustained VT with EF ≤ 0.40 and severe symptoms; no reversible cause Resuscitated VF, sustained VT and syncope, sustained VT and EF ≤ 0.35, or unmonitored syncope with subsequent spontaneous or inducible VT; no reversible cause Cardiac arrest secondary to VF or VT not related to a reversible cause Age 25-80 yr, NYHA I-III, EF ≤ 0.35, nonrecent MI (>3 wk) or CABG (>3 mo), spontaneous NSVT, and inducible VT Age < 80 yr; NYHA I, II, or III; EF ≤ 0.40; nonrecent MI (≥4 days); spontaneous NSVT; and inducible VT

Comparison ICD vs. antiarrhythmic drugs (amiodarone)

Primary Endpoint All-cause mortality

Main Findings 31% relative reduction in primary endpoint (P < .02) with ICD

ICD vs. amiodarone

All-cause mortality

20% relative reduction in primary endpoint (P = .1) with ICD

ICD vs. drug therapy (amiodarone, metoprolol) ICD vs. best medical therapy, which could include amiodarone

All-cause mortality

23% relative reduction in primary endpoint (P = .2) with ICD

All-cause mortality

56% risk reduction in primary endpoint (P = .009) with ICD

ICD vs. antiarrhythmic therapy (amiodarone and class I agents)

Cardiac arrest or death from arrhythmia

76% relative reduction in primary endpoint (P < .001) with ICD

CABG, Coronary artery bypass graft; EF, ejection fraction; ICD, implantable cardioverter-defibrillator; MI, myocardial infarction; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association functional class; VF, ventricular fibrillation; VT, ventricular tachycardia. *Nonrandomized ICD use.

to have a 31% relative reduction in the risk of death compared with patients receiving antiarrhythmic drug therapy, mostly amiodarone (95% confidence interval [CI] = 10% to 52%). This mortality benefit translates into an average life extension of 2.7 months during 18 months of follow-up.92 The NNT over 36 months is approximately 9 (11.3% absolute risk reduction) and the incremental cost of an ICD at 3 years was approximately $67,000 (U.S.) per life-year saved. However, the early termination of the AVID trial has two important implications: (1) premature termination may overestimate the magnitude of benefit with ICD therapy compared with amiodarone,93 and (2) the resultant shorter average duration of follow-up may lead to underestimation of the true cost-effectiveness of ICD therapy.94 Analyses were undertaken to identify groups more likely to benefit from ICD therapy. The 61% of patients with LVEF values less than 0.35 had a large (40%) relative reduction in the risk of death with ICD compared with drug therapy, whereas patients with higher values did not significantly benefit.95 AVID included relatively few patients with advanced heart failure, marked reductions in LVEF, or advanced age and thus had limited power to assess the relative efficacy of ICD therapy versus amiodarone in these and other subgroups.96 As a prespecified secondary endpoint, the AVID investigators also collected QOL data before and at 3, 6, and 12 months after randomization.26 Data were available for 905 of 1016 (89%) patients enrolled. Of these, 800 patients survived 1 year or longer and constituted the QOL study population. Moderate to severe impairment in both physical functioning and mental well-being were evident in both treatment groups at baseline. Patients who received an ICD had better physical functioning over the subsequent year, but no significant changes were noted in mental well-being. No significant difference in QOL over time

TABLE

11-2 

was observed between the ICD-treated and amiodarone-treated patients. Adverse symptoms were associated with a decrease in QOL in both groups. As previously discussed, there was an independent association between ICD shocks and reduced QOL. The reduction in QOL with multiple ICD shocks was of similar magnitude to the reduction in QOL observed among patients with severe adverse symptoms from amiodarone. One criticism of AVID was an imbalance in β-blocker use between patients assigned to an ICD (38% at 1 year) versus amiodarone (11% at 1 year). However, β-blocker use did not alter survival among those treated with an ICD or amiodarone. In contrast, patients who were eligible for the AVID trial, but were not randomly assigned to and did not receive amiodarone or an ICD, had a 53% lower risk of death with a β-blocker versus similar patients who did not receive β-blockers.97 These data suggest that β-blockers may reduce sudden death, but this effect is mitigated with the use of an ICD or amiodarone. Another intriguing result from AVID was that patients with sustained VT or VF caused by a reversible cause had a similar, or perhaps higher, risk of death compared with patients in whom the event was considered a primary episode of VT or VF.98 A separate analysis found that the prognosis of patients with stable VT was similar to those with unstable VT.99 These analyses question the dogma that patients with stable VT and those with a potentially reversible cause of sustained VT or VF have a good prognosis and are not candidates for an ICD. Canadian Implantable Defibrillator Study The Canadian Implantable Defibrillator Study (CIDS) was a large (n = 659) multicenter trial conducted in Canada, Australia, and the United States from 1990 to 1997.89 Patients were eligible if they had VF, sustained VT causing syncope, sustained VT and an LVEF ≤ 0.35, or

Clinical Trials of ICD Therapy for Spontaneous or Inducible Ventricular Arrhythmias: Population Details and Mortality Results Mortality Results: ICD vs. Other (%)

Trial AVID (1999) CIDS (2000) CASH (2000) MADIT-I (1996) MUSTT* (1999)

N 1016 659 228 196 704

Age (yr) 65 64 58 63 65

Women (%) 20 16 20 8 10

NYHA, New York Heart Association functional class. *ICD use was not randomized.

NYHA >II (%) 8 11 19 — 24

Mean Ejection Fraction 0.35 0.34 0.45 0.26 0.28

Mean Follow-up (mo) 18 36 57 27 39

Annual Rate in Controls 12 10 9 17 13

Relative Risk Reduction 31 20 23 54 51

Absolute Risk Reduction 8.2 4.3 8.1 22.8 23

Number Needed to Treat (36 mo) 9 23 20 3 5



unmonitored syncope with subsequent spontaneous or inducible VT. Patients who had experienced a recent MI (within 72 hours) or had an electrolyte imbalance were excluded. The average follow-up in CIDS (36 months) was twice that of AVID, but the number of deaths was somewhat fewer in CIDS (181) than in AVID (202). The primary outcome in CIDS was all-cause mortality. This study demonstrated a 20% lower relative (95% CI = 8% increase to 40%) risk of death with an ICD than with amiodarone (P = .14). On the basis of this 4.3% absolute reduction in mortality, the NNT over 36 months was 23. A subsequent single-center analysis of 120 patients found a high rate of cessation of amiodarone because of adverse effects (82% of patients) and a reduction in mortality with an ICD (16 deaths; 27% mortality) versus amiodarone (28 deaths; 47% mortality) over 11 years of follow-up.100 The incremental cost of an ICD was approximately $150,000 (U.S.) per life-year gained.101 Patients in CIDS with low LVEF values benefited from ICD therapy to a greater extent than those with better-preserved LV function. The selective use of an ICD for patients with LVEF values less than 0.35 lowers the incremental cost of an ICD to less than $70,000 per life-year gained.102 Another analysis demonstrated that patients with two or more of three characteristics that included age 70 years or older, LVEF ≤0.35, and New York Heart Association functional class (NYHA Class) greater than II benefited from ICD therapy, whereas patients with one or no characteristics did not.103 However, the CIDS risk score was imperfect when applied to AVID.104 Quality of life was assessed in CIDS using the Rand Corporation’s 38-item Mental Health Inventory and the Nottingham Health Profile.27 Of the initial 400 enrolled patients, only 178 (45%) provided analyzable QOL data at 1 year. Patients randomly assigned to ICD therapy had significant improvements in several QOL measures over 1 year of follow-up. In patients undergoing amiodarone therapy, these QOL measures either did not improve or deteriorated. Patients with at least five ICD shocks during follow-up had reduced QOL. Whether ICD therapy truly provides better QOL than amiodarone therapy is uncertain because of the conflicting results from the AVID trial and the methodologic issues related to the CIDS analysis.105 Cardiac Arrest Study Hamburg The Cardiac Arrest Study Hamburg (CASH) was a smaller randomized trial (n = 288) that compared the use of an ICD with drug therapy.90 Patients were enrolled from 1987 to 1996. A significant number of patients underwent a thoracotomy or sternotomy for ICD system placement (before July 1991). The study population included patients resuscitated from a cardiac arrest secondary to a documented sustained VT or VF. Patients were excluded if the cardiac arrest occurred within 72 hours of an MI or cardiac surgery or was related to an electrolyte abnormality or proarrhythmic drug. The primary endpoint was allcause mortality. The average follow-up in CASH (57 months) was substantially longer than that of other secondary prevention trials. However, there were fewer deaths (72) because of the smaller overall study population. A trend toward a lower risk of death with ICD therapy (23% relative reduction; P = .16) was observed. The 8.1% absolute reduction in risk of death over 57 months with an ICD is similar to that found in AVID over 18 months and translates into an NNT of 12. Pooled Analysis of the Three Studies The combined results of the AVID, CIDS, and CASH data demonstrate that mortality is reduced by 27% (95% CI = 13% to 40%; P <.001) with an ICD compared with amiodarone.22 Death attributed to an arrhythmia was reduced by 51% (95% CI = 33% to 64%; P < .001). No significant difference between treatment groups in the risk of death from nonarrhythmic causes was evident. This reduction in mortality corresponded to an average extension in life of 2.1 months. The annual mortality with an ICD was 12.3% per year, versus 8.8% per year with amiodarone. The absolute reduction in mortality (10.5%) over 36 months translates into needing to treat fewer than 10 patients in order to prevent one death.

11  Clinical Trials of Defibrillator Therapy

263

Patients with LVEF values ≤0.35 benefited from ICD therapy to a greater extent than did patients with better-preserved LV function (P = .01). Patients who required a thoracotomy or sternotomy for ICD placement (before 1991) did not exhibit any evidence of benefit with an ICD, whereas patients who received nonthoracotomy systems did (31% relative reduction; 95% CI = 15% to 44%). A trend toward a greater benefit from ICD therapy than from amiodarone was evident among patients treated with β-blockers compared with those who were not (P = .10). Patients with a history of CABG surgery also tended to benefit from ICD therapy to a greater extent than patients without such a history (P = .10). First Multicenter Automatic Defibrillator Implantation Trial The First Multicenter Automatic Defibrillator Implantation Trial (MADIT-I) was a small (n = 196) multicenter trial conducted in the United States, Germany, and Italy from December 1990 to March 1996.64 The first one half of the patients received epicardial ICD systems, and the remaining half received nonthoracotomy, transvenous systems. ICD therapy was compared with conventional care, mostly empiric amiodarone therapy, in patients with ischemic LV dysfunction, asymptomatic nonsustained VT (NSVT), and inducible, nonsuppressible, sustained VT/VF with programmed stimulation. Most MADIT-I patients (93%) had nonsuppressible, monomorphic VT. The MADIT-I demonstrated a large, 54% (95% CI = 18% to 74%) relative reduction in mortality (P = .009). The MADIT-I population has been considered distinct from the patients in the AVID trial, CIDS, and CASH, but the populations are similar. Both CIDS and AVID included patients with VT unrelated to a cardiac arrest. CIDS also included patients with a history of syncope and a low LVEF value plus inducible VT. The average extension of life with an ICD was 10 months. This large reduction in mortality (26.2% absolute reduction over 27 months) represents an NNT of only 3 over 36 months. This translates into a modest incremental cost of $27,000 per life-year gained, making ICD therapy in this population very economically attractive.106 The annual mortality rate in the MADIT-I control group appears to be somewhat higher than that observed in the three trials evaluating ICD therapy in patients with mostly spontaneous sustained ventricular arrhythmias (see Table 11-2). The likely explanation is that all the patients in MADIT-I had LVEF ≤0.35, whereas LVEF was not a primary inclusion criterion in AVID, CIDS, or CASH. If only those patients in AVID, CIDS, and CASH with LVEF ≤0.35 are studied, a similar 16% annual mortality rate is observed in patients receiving amiodarone.22 Moreover, the relative reduction in risk of death with an ICD versus amiodarone among patients with LVEF ≤0.35 in AVID, CIDS, and CASH (44%; 95% CI = 17% to 47%; P <.001) is similar to that found in MADIT-I (54%; 95% CI = 18% to 74% reduction). Thus, patients with spontaneous or inducible sustained ventricular arrhythmias have a similar risk of death and benefit to a similar extent with ICD therapy. A major limitation of MADIT-I is the lack of information about how many patients with ischemic LV dysfunction and NSVT would have to be screened to identify one patient fulfilling all the inclusion criteria for this trial. This number is estimated to be large because these criteria are present in very few (<2%) patients after MI.107 Also, targeting ICD therapy to only those at highest risk apparently has a marginal effect on reducing the burden of sudden death (see Fig. 11-2). Another concern regarding MADIT-I is the non-protocol-driven use of antiarrhythmic drugs. For example, 23% of patients assigned to conventional therapy were not receiving antiarrhythmic drug therapy at last follow-up, and only 55% of patients were receiving amiodarone at that time. The significance of this issue is questionable, given the results of SCD-HeFT (see later), which found no significant benefit or harm from amiodarone. Multicenter Unsustained Tachycardia Trial The randomized Multicenter Unsustained Tachycardia Trial (MUSTT) compared antiarrhythmic therapy with best medical therapy in 704 patients with coronary artery disease, LVEF ≤ 0.40, NSVT, and

264

SECTION 2  Clinical Concepts

inducible sustained VT/VF during programmed electrical stimulation.91 It is important to emphasize that although the use or nonuse of ICD therapy in MUSTT was not randomly assigned, the results are often considered when interpreting data from the previously discussed trials. Patients were recruited from 85 centers in the United States and Canada from 1990 through 1996. Most (1435; 65%) of the 2202 patients evaluated did not have inducible ventricular arrhythmias and were not eligible for therapy randomization. Of the 767 eligible patients, only 63 (8%) refused randomization, strengthening the generalizability of the results. The 351 patients randomly assigned to electrophysiologically guided therapy underwent serial drug testing, followed by random assignment to receive antiarrhythmic drugs. ICD therapy could be used only after failure of at least one antiarrhythmic drug, and amiodarone could be tested only after at least two failed drug trials. Similar proportions of patients assigned to this strategy were discharged with drug therapy (158; 45%) versus an ICD (161; 46%). Of the 158 patients discharged with drug therapy, most received a class I agent (26%). Amiodarone (10%) and sotalol (9%) were used in the remaining patients. β-blockers were less frequently used in patients assigned to electrophysiologically guided therapy (29%) than in those who received no antiarrhythmic therapy (51%). Over an average follow-up of 39 months, the risk of the primary endpoint—cardiac arrest or death attributed to an arrhythmia—was significantly lower among patients randomly assigned to electrophysiologically guided therapy than in those receiving conventional care (27% relative risk reduction; 95% CI = 1% to 47%; P = .04). The absolute risk of death (secondary endpoint) in patients assigned to electrophysiologically guided therapy was 6% over 5 years. However, the benefits in terms of overall survival and the risk of arrhythmic death or cardiac arrest in patients in the electrophysiologically guided therapy group were limited to patients who received an ICD. The risk of death over 5 years was substantially lower in patients discharged with an ICD (24%) than in those discharged with drug therapy (55%), translating into a 49% lower relative risk. This result is similar to that found in MADIT-I and among patients with low LVEF values in AVID, CIDS, and CASH. The large absolute reduction in the risk of death in MUSTT (31%) translates into an NNT of 5 over 36 months. Drug therapy was not associated with a survival advantage over best medical therapy. The prognostic significance of inducible arrhythmias during invasive electrophysiologic testing was also evaluated in MUSTT.108 During 5 years of follow-up, patients with an inducible sustained ventricular arrhythmia had a significantly higher risk of cardiac arrest or death

TABLE

11-3 

caused by arrhythmia (32%) than patients in whom a sustained arrhythmia was not inducible (24%; P <.001). Overall mortality was also statistically higher in patients in whom a sustained arrhythmia was inducible (48% vs. 44%; P = .005). However, the absolute difference in mortality (4% over 5 years) was small and of questionable clinical significance. Also, LVEF alone was unreliable in predicting long-term outcome.109 Baseline clinical variables (functional class, NSVT, age, QRS duration, inducible VT/VF, and atrial fibrillation) were found to better estimate the risks of arrhythmic death and total mortality than LVEF ≤0.30 versus >0.30. PATIENTS WITH HEART FAILURE OR LEFT VENTRICULAR DYSFUNCTION ALONE Table 11-3 summarizes the inclusion criteria, primary endpoints, and main results for six studies that involved patients with heart failure or LV dysfunction alone. Table 11-4 presents details of the study populations, the risk of the population untreated (annual control group mortality), and the relative and absolute alterations in mortality with ICD therapy. These trials are often dichotomized on the basis of the underlying etiology of LV dysfunction (ischemic vs. nonischemic). Three trials (CAT, AMIOVIRT, DEFINITE) included only patients with nonischemic LV dysfunction; two (COMPANION, SCD-HeFT) included patients with both ischemic and nonischemic etiologies, and one (MADIT-II) was limited to patients with ischemic LV dysfunction. It is important to recognize that number of patients, duration of follow-up, and resultant statistical power of these trials differ greatly. COMPANION was also different from the other trials in that all patients were required to have a QRS duration of greater than 120 msec and symptoms of advanced heart failure. COMPANION also assessed the combined use of CRT and ICD, whereas the other trials evaluated non-CRT ICD therapy. The two larger and long-term trials that used non-CRT ICD therapy, SCD-HeFT and MADIT-II, provide the most reliable information on the efficacy of ICD therapy in patients with heart failure or LV dysfunction alone. Second Multicenter Automatic Defibrillator Implantation Trial Although MADIT-I showed a large benefit from ICD therapy, its study population represented a highly select group of patients (see Figs. 11-2 and 11-3). MADIT-II evaluated ICD therapy in a lower-risk group that accounts for a larger proportion of patients who will experience sudden death. MADIT-II enrolled 1232 patients from 71 U.S. centers and five

Clinical Trials of ICD Therapy for Heart Failure or Left Ventricular Dysfunction Alone: Inclusion Criteria, Comparison Groups, and Main Results

Trial Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) (2002) Amiodarone versus Implantable Cardioverter-Defibrillator Trial (AMIOVIRT) (2003) Cardiomyopathy Trial (CAT) (2002) Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) (2004) Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) (2005) Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evalution (DEFINITE) (2005)

NYHA I-III, EF ≤ 0.30, remote MI (>1 mo)

Inclusion Criteria

Comparison ICD vs. best medical therapy

Primary Endpoint All-cause mortality

Main Findings 31% relative reduction in primary endpoint (P = .02) with ICD No significant alteration (P = .8) with ICD

NYHA I-IV, EF ≤ 0.35, dilated cardiomyopathy, NSVT

ICD vs. best medical therapy

All-cause mortality

NYHA II-III, EF ≤ 0.30, dilated cardiomyopathy, recent-onset heart failure (≤9 mo) NYHA III-IV, EF ≤ 0.35, nonrecent MI or CABG (≥60 days), QRS ≥120 msec, PR ≥150 msec, recent heart failure hospitalization (≤12 mo), and nonrecent onset of heart failure (>6 mo) NYHA II-III, EF ≤ 0.35, nonrecent MI or revascularization (>30 days), nonrecent heart failure onset (>3 mo) NYHA I-III, EF ≤ 0.35, dilated cardiomyopathy NSVT, or ≥10 PVCs/hr

ICD vs. best medical therapy

All-cause mortality

No significant alteration (P = .6) with ICD

Resynchronization ICD vs. best medical therapy

All-cause death or hospitalization

20% relative reduction in primary endpoint (P = .01) with resynchronization ICD

ICD vs. placebo

All-cause mortality

ICD vs. best medical therapy

All-cause mortality

23% relative reduction in primary endpoint (P < .01) with ICD 35% relative reduction in primary endpoint (P = .08) with ICD

CABG, Coronary artery bypass graft surgery; EF, ejection fraction; MI, myocardial infarction; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association functional class; PVCs, premature ventricular complexes.



11  Clinical Trials of Defibrillator Therapy

TABLE

11-4 

265

Clinical Trials of ICD Therapy for Heart Failure or Left Ventricular Dysfunction Alone: Population Details and Mortality Results Mortality Results: ICD vs. Other (%)

Trial MADIT-II (2002) AMIOVIRT (2003) CAT (2002) COMPANION* (2004) SCD-HeFT* (2005) DEFINITE (2005)

N 1232 103 104 903 1676 458

Age (yr) 64 52 52 67 60 58

Women (%) 16 30 20 32 23 29

NYHA >II (%) 29 20 35 100 30 21

Mean Ejection Fraction 0.23 0.23 0.24 0.22 0.25 0.21

Mean Followup (mo) 20 24 23 15 46 29

Annual Relative Rate in Controls 10 4 4 19 7 7

Relative Risk Reduction 31 13 17 36 23 35

Absolute Risk Reduction 5.4 1.7 5.4 7.3 6.8 5.2

Number Needed to Treat (36 mo) 10 39 12 5 23 24

NYHA, New York Heart Association functional class. *Patient numbers reflect assignment to an ICD or medical therapy (COMPANION)/placebo (SCD-HeFT).

European centers from July 1997 to January 2002.56 ICD therapy was compared with usual care in patients with ischemic LV dysfunction (LVEF ≤0.30). Patients who had experienced a recent MI (within 1 month of evaluation) or revascularization procedure (within 3 months of evaluation) were not eligible. Patients who underwent invasive electrophysiologic testing and had inducible sustained arrhythmias, fulfilling the criteria for MADIT-I, were also ineligible.Angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and lipid-lowering therapies were prescribed to 70%, 70%, and 66% of participants, respectively, on the basis of data from the last follow-up visit. These rates are higher than in the trials evaluating ICD efficacy in patients with spontaneous or inducible ventricular arrhythmias conducted before the wider recognition of the importance of these medications. Patients were followed up for an average of 20 months. ICD therapy was associated with a 31% relative reduction in mortality (95% CI = 7% to 49%; P <.02). Over the 20 months, 19.8% of patients in the conventional therapy group died, versus 14.2% in the ICD group (5.4% absolute reduction). This translates into an NNT for ICD therapy of approximately 10 over 36 months. These risk reductions are large but not as great as those observed in patients with similar characteristics in whom inducible sustained ventricular arrhythmias were provoked. The NNT for ICD therapy in MADIT-II is more than three times larger than the NNT in MADIT-I. The cost-effectiveness of ICD therapy in MADIT-II was assessed using data from 1095 U.S. patients randomized to an ICD or conventional care. Utilization data were converted to costs using national and hospital-specific data. The incremental cost-effectiveness ratio was calculated as the difference in discounted costs divided by the difference in discounted life expectancy within 3.5 years. Secondary analyses included projections of survival (using three alternative assumptions), corresponding cost assumptions, and the resulting cost-effectiveness ratios out to 12 years after randomization. Assumptions included the cost of ICD therapy was $33,000 (device and implant) and a survival rate of ICD recipients ranging from 13% to 26% at 12 years.110 The actual long-term survival of ICD recipients in MADIT-II is in keeping with the more optimistic projection.50 This survival estimate results in an incremental cost-effectiveness ratio in the range of $50,000. This result is similar to that estimated for other trials when results were extrapolated over time.57 These data indicate that ICD therapy is economically beneficial in these patients. The MADIT-II researchers noted that the effect of ICD therapy was similar in subgroup analyses stratified by age, gender, LVEF, and NYHA class. However, patients with longer QRS durations (>120 msec) had larger absolute and relative risk reductions that trended toward statistical significance. Some considered this finding to indicate that patients with QRS values greater than 120 msec benefit from ICD therapy and that those with shorter QRS values do not, but this remains controversial.111 Delayed ventricular conduction has also been shown to predict a higher risk of death among patients receiving contemporary medical therapy.80 Other noninvasive risk assessment tools, such as T-wave alternans, have been advocated for selecting patients for ICD therapy,112 but their usefulness remains unproved83 (see Ongoing Trials).

The ability of electrophysiologic testing to predict mortality and ICD efficacy was also assessed in MADIT-II.68,113 Electrophysiologic inducibility was performed on 593 patients randomly assigned to ICD therapy. A sustained ventricular arrhythmia was inducible in 36% of patients, who were more likely to demonstrate spontaneous VT in follow-up. In contrast, patients who did not have a sustained inducible ventricular arrhythmia were more likely to experience spontaneous VF. Overall, patients in MADIT-II had a 20% rate of appropriate ICD therapies for VT or VF over 4 years of follow-up. The likelihood of VT or VF was similar for patients with and without inducible arrhythmias at baseline. As with the findings in MUSTT, the MADIT-II data indicate that electrophysiologic testing is suboptimal in identifying patients who will benefit from an ICD. Analyses from MADIT-II include clinical risk factors associated with benefit from ICD therapy114 and with mortality in ICD recipients115 and utility of noninvasive tests to predict ICD benefit. Although both dynamic alterations in QT duration116 and morphology117 predicted an increased risk of death and arrhythmias in MADIT-II, neither measure was useful in discriminating between patients likely versus unlikely to benefit from an ICD. A risk score comprised of five clinical factors (NYHA Class >II, age >70, BUN >26 mg/dL, QRS duration >120 msec, atrial fibrillation) was derived after excluding patients with blood urea nitrogen (BUN) values of at least 50 mg/dL and/or serum creatinine values of at least 2.5 mg/dL. Conventional therapy patients with none of these risk factors had an 8% mortality rate, and those with at least one risk factor had a 28% mortality rate. ICD therapy was not associated with a significant alteration in mortality among the 345 patients with no risk factors (hazard ratio 0.96; P = .91), but was associated with a 49% relative reduction in the risk of death in the 786 patients with at least one risk factor (P <.001). This score is interesting in that it is similar to that proposed in CIDS103 and contains some of the same variables that in MUSTT predicted the long-term risks of arrhythmic death and total mortality.109 The utility of the MADIT-II risk score is unclear because it has not been validated, and its components largely overlap with those shown to predict death despite ICD use in MADIT-II participants.115 Another interesting analysis in MADIT-II evaluated the efficacy of ICD therapy based on the time from MI to study enrollment.118 An inclusion criterion for MADIT-II was that patients had their MI at least 1 month before evaluation; however, the average time from MI to enrollment in MADIT-II was much longer (mean, 81 months). Patients were subdivided into quartiles of time from MI to enrollment: less than18 months (300 patients), 18 to 59 months (283), 60 to 119 months (284), and 120 months or longer (292). A survival benefit from ICD therapy was apparent in the three groups with a longer duration between MI and enrollment (relative risk reductions of 38% to 50% with ICD therapy), but no benefit from ICD therapy was evident among patients whose MI events had occurred within 18 months of enrollment (2% reduction). These data, along with those of DINAMIT and IRIS, suggest that ICD therapy may not be effective early after MI. This may relate to the mechanisms of sudden death early after MI,11 a

266

SECTION 2  Clinical Concepts

differential risk of sudden versus nonsudden death early after MI, or other factors.119 Amiodarone versus Implantable Cardioverter-Defibrillator Trial The Amiodarone versus Implantable Cardioverter-Defibrillator Trial (AMIOVIRT) compared ICD therapy versus amiodarone in patients with nonischemic LV dysfunction and asymptomatic nonsustained ventricular tachycardia (NSVT) at 10 U.S. centers from 1996 and 2000.120 Patients were required to have a nonrecent (at least 6 months) diagnosis of LV dysfunction. The primary endpoint was total mortality. A total of 103 patients were enrolled, and average follow-up was 2 years. Of 13 deaths, six were in the ICD group and seven in the amiodarone group (P = .8). AMIOVIRT was terminated early because of futility. The trial was powered to detect a 50% relative (10% absolute) reduction in mortality with an ICD versus amiodarone. The observed mortality rate in amiodarone-treated patients was 12% at 3 years. AMIOVIRT neither supports nor refutes the value of ICD therapy in patients with nonischemic LV dysfunction and NSVT. Cardiomyopathy Trial The Cardiomyopathy Trial (CAT), conducted in 15 German centers from 1991 to 1997, compared ICD therapy with standard medical therapy in 104 patients with nonischemic LV dysfunction.121 Unlike the other trials of ICD therapy in patients with heart failure or LV dysfunction alone, patients in CAT were required to have recently diagnosed heart failure (<9 months before enrollment). The primary endpoint of CAT was all-cause mortality. Only 30 deaths were observed over a mean follow-up of 5.5 years. Of these, 13 occurred in the ICD group and 17 in the control group (P = .6). CAT was also terminated because of futility. The observed mortality rate in patients randomly assigned to standard therapy alone at 1 year was 3.7%. This value was much lower than the anticipated mortality rate of 30%. The trial has been interpreted as providing evidence that prophylactic ICD implantation is ineffective in patients with dilated cardiomyopathy and recent onset heart failure. As with AMIOVIRT, however, CAT was grossly underpowered, precluding any firm conclusions to be drawn (see DEFINITE discussion). Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) study evaluated the efficacy of CRT plus ICD (595 patients) versus medical therapy (308), and CRT plus pacemaker (617) versus medical therapy in patients with advanced heart failure (NYHA Class III or IV) and QRS durations over 120 msec.122 The 1520 patients were enrolled at 128 sites in the United States between January 2000 and December 2002. Patients with ischemic (55%) and nonischemic (45%) LV dysfunction were included. Patients with a recent (<2 months before consideration) MI or revascularization were not eligible. The primary endpoint was a composite of death or hospitalization from any cause. Secondary endpoints were mortality and cardiac morbidity. Median follow-up was 12 months in the medical therapy group and 16 months in the pacemaker and ICD groups. ACE inhibitors or angiotensin receptor antagonists (90%), β-blockers (68%), and spironolactone (54%) were prescribed frequently at baseline. Medication use during follow-up was not reported. The remainder of this review focuses on the 903 patients randomly assigned to medical therapy versus CRT plus ICD. The 12-month rate of death or hospitalization from any cause (primary endpoint) was 68% in the medical therapy group versus 56% in the CRT plus ICD group. This represents a 21% relative reduction (95% CI = 4% to 31%; P = .014). The 12% absolute reduction indicates that fewer than eight patients need to be treated with CRT plus ICD to prevent one death or hospitalization over 12 months. This is a very large effect size and reflects the risk of the population and the use of the combined outcome of death or hospitalization from any cause.

There were 77 deaths (25%) in the medical therapy group and 105 deaths (18%) in the CRT plus ICD group, reflecting a 36% relative risk reduction (95% CI = 14% to 52%; P = .003). The 7% absolute risk reduction indicates that slightly more than 14 patients need to be treated with CRT plus ICD to prevent one death over 12 months. The effects of CRT plus ICD and medical therapy on mortality were compared in a range of patient subgroups. Consistent benefit was evident when data were stratified by age, gender, QRS duration, severity of LV dysfunction, etiology of LV dysfunction, blood pressure, and medication use. The reason for this large reduction in mortality is unclear but may relate to the combined effect of CRT plus an ICD, because large reductions in mortality were observed with CRT plus a pacemaker in COMPANION (4% absolute mortality reduction over 12 months) and the Cardiac Resynchronisation in Heart Failure (CARE-HF) study (10% absolute mortality reduction over 29 months).123 It is important to note that, although most of the baseline characteristics of patients in COMPANION are similar to those of participants in the other trials of ICD in heart failure or LV dysfunction alone (see Table 11-4), the annual control group mortality rate in COMPANION is two to five times greater than that of the other trials. Whether this reflects that all patients in COMPANION had advanced heart failure symptoms, had QRS values above 120 msec, or other factors is not known. The 1-year mortality rate among patients assigned to medical therapy in CARE-HF, involving similar patients, was approximately 13%.123 The brief follow-up in COMPANION or other factors may also explain the high mortality rate in the medical care group. A number of potential limitations related to COMPANION merit attention. Concern surrounds the unequal randomization used in favor of ICD or pacemaker therapy. However, this strategy has been used in other randomized trials, including MADIT-II. A more significant issue is that 26% of the patients assigned to medical therapy withdrew prematurely from the study. This problem was addressed in part through censoring the data of lost participants on the date of last contact, but this strategy is not without risk. Another concern is that the definition of “all-cause hospitalization” was changed after the trial was under way, potentially influencing the primary endpoint. Specifically, “the treatment of decompensated heart failure with vasoactive drugs for more than 4 hours in an urgent care setting” was included as a hospitalization. Sudden Cardiac Death–Heart Failure Trial The Sudden Cardiac Death–Heart Failure Trial (SCD-HeFT) compared the efficacy of an ICD (829 patients) to placebo (847) and amiodarone versus placebo in patients with heart failure (NYHA II or III).65 The 2521 patients were enrolled at 148 sites in the United States, Canada, and New Zealand from 1997 to 2001. Randomization was stratified according to etiology of LV dysfunction and NYHA functional class. Similar proportions of patients with ischemic (52%) and nonischemic (48%) etiologies of LV dysfunction were enrolled. The majority of patients (70%) had NYHA II functional status limitation at baseline. Patients with a recent (1 month of evaluation) MI or revascularization procedure were not eligible. The primary endpoint was all-cause mortality. Secondary endpoints were arrhythmic death, nonarrhythmic death, morbidity, costeffectiveness, and QOL. Patients were required to receive therapy with a vasodilator for at least 3 months before enrollment, and use of β-blockers and spironolactone was strongly encouraged. An ACE inhibitor or angiotensin receptor antagonist was prescribed to 96% of patients at baseline, 87% of whom continued to receive these agents at last follow-up. β-Blockers and spironolactone were prescribed to 69% and 19% of participants at baseline, respectively, and to 78% and 31% at last follow-up. Rates of heart failure medication use in SCD-HeFT were higher than those in MADIT-II and COMPANION; this must be taken into consideration when comparing outcomes and ICD efficacy results for these trials. Median follow-up in SCD-HeFT was 45.5 months. The vital status for every patient was available for last scheduled follow-up. During 60



months of follow-up, 36.1% of patients randomly assigned to placebo died. Patients randomly assigned to amiodarone therapy had a similar risk of death (34%) over this time. Patients randomly assigned to an ICD had a significantly lower risk of death (28.9%) over the 60 months. This difference translates into a 23% relative reduction in mortality with ICD therapy versus placebo (95% CI = 4% to 38%; P = .007). The relative benefit of ICD therapy was similar in patients with nonischemic (27% reduction) and ischemic (21% reduction) etiologies of LV dysfunction. The absolute reduction in mortality of 7.2% over 60 months indicates that almost 14 patients would need to be treated with an ICD to prevent one death. The absolute mortality reductions with ICD therapy over 60 months were also similar in patients with nonischemic (6.5%) and ischemic (7.3%) etiologies for LV dysfunction. To allow comparison with the other trials, one can calculate the absolute mortality reduction in SCD-HeFT over 36 months to be about 4.3%, which translates into needing to treat 23 patients over this time to prevent one death. Several subanalyses have been performed in SCD-HeFT. One assessed the modes of death and found that ICD therapy reduced cardiac mortality and sudden death overall, but had no effect on heart failure mortality.124 ICD therapy was also not associated with a reduction in mortality in patients with NYHA Class III limitation. Amiodarone had no overall effect on all-cause mortality or its cause-specific components. Amiodarone was associated with an increased risk of noncardiac mortality in NYHA Class III patients. The lack of benefit from ICD therapy and increased risk of noncardiac mortality in Class III patients treated with amiodarone were unexpected. The greater proportion of nonsudden versus sudden deaths in Class III patients, misclassification of deaths due to a lack of ICD data or clinical data, and statistical chance may all explain these findings. As noted earlier, the impact of ICD shocks on outcome was assessed in SCD-HeFT.34 Of the 829 patients randomized to ICD therapy, 811 had an ICD successfully implanted. More than 99% of patients received a single-chamber ICD system. The ICD systems used were intentionally programmed to intervene only for rapid arrhythmias (cycle lengths ≤320 msec or rates >188 bpm). An episode of tachycardia was defined as lasting at least 18 of 24 bpm. Up to six shocks could be delivered per episode. ATP was not permitted, and the devices had no capability to determine if the episode had spontaneously terminated before delivery of a shock (i.e., no reconfirmation). A group of experts adjudicated all ICD shock episodes. ICD shocks that followed the onset of VT or VF were considered appropriate. Thus, by definition, “appropriate” episodes included longer runs of NSVT that fulfilled the detection criteria, but spontaneously terminated. This is problematic; up to 30% of fast VT episodes will spontaneously terminate.43 All other ICD shocks were considered to be inappropriate. Over a median follow-up of 46 months, 269 patients (33%) received at least one ICD shock. Of these, 128 (48%) received only appropriate shocks, 87 (32%) only inappropriate shocks, and 54 (20%) both appropriate and inappropriate shocks. Recurrent appropriate ICD shocks occurred in 97 of the 182 patients (53%) and recurrent inappropriate shocks in 61 of 141 patients (43%). Appropriate ICD shocks were independently associated with a 5.7-fold higher risk of death (P <.001). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death was threefold higher (P <.001). Thus, appropriate shocks were associated with a substantial risk of death over the short term. Inappropriate shocks were associated with a twofold higher risk of death (P = .002). The most common cause of death among patients who received ICD shocks was progressive heart failure. A second appropriate shock was associated with a further significant increase in the risk of death by a factor of 2 (P = .005). The association of electrical storm with mortality could not be assessed because of the limited memory capacity of the ICD systems used in SCD-HeFT (i.e., data were overwritten when repetitive arrhythmic events occurred over a short period). The ICD systems used in SCD-HeFT precluded documenting slower VT, which may have impacted the outcomes of ICD recipients and the classification of deaths.

11  Clinical Trials of Defibrillator Therapy

267

Quality of life was measured in SCD-HeFT using structured interviews at baseline and at 3, 12, and 30 months.31 The two prespecified primary outcomes were the Duke Activity Status Index (DASI), reflecting cardiac-specific physical functioning, and the Medical Outcomes Study 36-Item Short-Form (SF-36) Mental Health Inventory 5 (MHI5), reflecting psychological well-being. QOL data collection was 93% to 98% complete. Psychological well-being was significantly improved at 3 months (P = .01) and 12 months (P = .003) but not at 30 months (P = 0.8) with ICD therapy versus medical care. The Minnesota Living with Heart Failure Questionnaire was also used, with scores generally better in the ICD group than the medical care group at each follow-up assessment, but of borderline statistical significance. ICD shocks in the month preceding a scheduled assessment were associated with a decreased QOL in multiple domains. As noted, electrical storm events were not recorded in SCD-HeFT. The use of amiodarone had no significant effects on QOL. An analysis of the impact of significant adverse effects on QOL was not reported. These results provide the largest, most comprehensive assessment of QOL in patients receiving a primary prevention ICD. The results are reassuring in that ICD therapy, including the occurrence of appropriate and inappropriate shocks, is not associated with altered QOL. The cost-effectiveness of ICD therapy in SCD-HeFT was estimated using hospital billing data and the Medicare Fee Schedule. The “base case cost-effectiveness analysis” used empirical clinical and cost data to estimate the lifetime incremental cost of saving an extra life-year with ICD therapy relative to medical therapy alone. At 5 years, the amiodarone arm had survival equivalent to the placebo arm but higher costs. For ICD relative to medical therapy alone, the base case lifetime cost-effectiveness and cost-utility ratios (discounted at 3%) were $38,389 per life-year saved and $41,530 per quality-adjusted life-year saved, respectively. At 12 years the cost effectiveness ratio was $58,510 per life-year saved. The cost-effectiveness ratio was only $29,872 per life-year saved for NYHA Class II patients, whereas incremental cost but no incremental benefit was observed in Class III patients. These data indicate that ICD therapy is cost-effective. The substantially longer follow-up in SCD-HeFT provides a more reliable and realistic estimate of cost, for reasons previously discussed.125 A substudy in SCD-HeFT included 490 patients at 37 clinical sites and evaluated the utility of microvolt T-wave alternans (TWA).126 Masked readers, using standard criteria, classified the tests as positive (37%), negative (22%), or indeterminate (41%). The composite primary endpoint was the first occurrence of sudden cardiac death, sustained VT or VF, or an appropriate ICD shock. During a median follow-up of 30 months, no significant differences in the composite rate were found in TWA-positive versus TWA-negative patients (hazard ratio 1.2; P = 0.6) or in TWA-nonnegative (positive and indeterminate) versus TWA-negative subjects (hazard ratio 1.3; P = 0.5). Similar results were observed when patients randomized to an ICD and those randomized to amiodarone were separately evaluated. Thus, microvolt TWA assessment was not useful in predicting arrhythmic events death in SCD-HeFT. These results are similar to those in the MASTER study.127 Although unclear, the reasons for this finding support the need for additional studies on noninvasive risk assessment methods. A Holter substudy was also conducted in SCD-HeFT, but those results have not yet been reported. Another analysis in SCD-HeFT investigated whether defibrillation testing during ICD implantation was associated with outcome.128 This analysis included the 811 patients randomized to ICD therapy and had a device implanted. The testing protocol in SCD-HeFT was designed to limit shock testing. Baseline data were available in 717 patients (88%). All 717 patients were successfully defibrillated with energies of 30 J or less, the maximum output of the ICD systems used. Energies were 20 J or less in 98% of patients. No survival difference between the 547 patients converted with low (≤10 J) versus the 170 patients with higher (>10 J) energy values (P = .4) were observed. The use of routine defibrillation testing in primary prevention patients remains controversial129 and is being addressed in ongoing randomized trials.

268

SECTION 2  Clinical Concepts

Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) study compared ICD therapy versus medical care in 488 patients with nonischemic LV dysfunction.130 Patients were enrolled from participating sites in the United States from 1998 to 2003. In addition to an LVEF ≤ 0.35, patients were required to have ambient arrhythmias (frequent premature ventricular beats or NSVT). Unlike CAT, duration of heart failure was neither an inclusion nor an exclusion criterion in DEFINITE. The primary endpoint was death from any cause. The secondary endpoint was sudden death. Mean follow-up was 29 months. ACE inhibitors (86%), angiotensin receptor blockers (11%), and β-blockers (85%) were prescribed to the majority of patients. As shown in Table 11-4, the mean LVEF in DEFINITE was somewhat lower (0.21) than the average values for patients in CAT (0.24) and SCD-HeFT (0.25). More than half (57%) of the patients in DEFINITE had NYHA Class II symptoms. During the 29 months of average follow-up, there were 28 deaths in the ICD group and 40 in the medical therapy group. This difference represents a 35% relative reduction in mortality with an ICD versus no ICD (95% CI = 6% increase to 60% decrease; P = .08). The absolute reduction in mortality at 2 years was 6.2%. This translates into treating 24 patients with an ICD over 36 months to prevent one death. A significant reduction in sudden death (80%; 95% CI = 29% to 94%; P = .006) was also observed with ICD therapy. Quality of life was assessed using the Medical Outcomes 12-Item Short-Form Survey (SF-12) and the Minnesota Living with Heart Failure Questionnaire in 458 of the 488 (94%) participants.30 QOL was assessed at baseline, 1 month after randomization, and every 3 months thereafter. Overall, there were no significant differences in QOL between patients randomized to an ICD or standard medical therapy. In patients with at least one ICD shock, QOL declined on the emotional scale of the Minnesota Living with Heart Failure Questionnaire (P = .04) and the mental component score of SF-12 (P = .04). As in most other analyses, QOL was similar in patients with and without an ICD, even when shocks are considered. An interesting analysis of DEFINITE explored the relationship between ICD shocks and otherwise fatal events.131 A masked committee reviewed the shock electrograms and categorized cause of death. There were 15 clinical sudden deaths or cardiac arrests in the con­ ventional group and three in the ICD group. Of the 229 patients randomized to an ICD, 33 patients (14%) received a total of 70 appropriate shocks. The number of events that included syncope plus sudden death or cardiac arrest in the conventional arm and appropriate ICD shocks with syncope in the ICD arm was similar (approximately 7%). Thus, using appropriate ICD shocks as a surrogate for sudden death overestimates the risk twofold. These data highlight

TABLE

11-5 

the need for caution when “appropriate ICD therapies” are used to estimate survival. Given the lack of benefit from ICD therapy in CAT, where patients were randomly assigned to therapy within 9 months of the onset of heart failure, a post hoc analysis of data from DEFINITE was undertaken to assess the impact of time from heart failure diagnosis on survival and ICD efficacy.132 Patients were divided into those with a recent (within 3 months) or remote (beyond 9 months) diagnosis of nonischemic cardiomyopathy. Randomization was also stratified by this categorization. Those with recently diagnosed cardiomyopathy had improved survival with an ICD. This benefit was significant at 3 months (P = .05) and of borderline significance at 9 months of follow-up (P = .06). Patients with remotely diagnosed cardiomyopathy did not have a significant survival benefit with an ICD. Thus, patients who have a recent cardiomyopathy diagnosis do not appear to have any less ICD benefit than those with a remote diagnosis. Given the divergent results in DEFINITE and CAT,121 it would reason that recently diagnosed cardiomyopathy should not be used as an exclusion criterion in patients with nonreversible LV dysfunction and LVEF ≤0.35 after an adequate trial of medical therapy. Pooled Analysis of Trials in Patients with Heart Failure or Left Ventricular Dysfunction Alone A systematic review found a 26% relative reduction in mortality with ICD therapy when the results of the MADIT-II, AMIOVIRT, CAT, COMPANION, SCD-HeFT, and DEFINITE trials were combined with the MADIT-I results (95% CI = 17% to 33%).133 With the MADIT-I data removed, a smaller but statistically significant relative risk reduction in mortality, 21%, was observed (95% CI = 6% to 34%; P = .009). The absolute mortality reduction in those patients with heart failure or LV dysfunction alone ranged from 5.8% to 7.9%, depending on the trials included. This translates into an NNT of 14 to 18 over 36 months. These absolute mortality reductions with ICD therapy are in addition to the 6.1% absolute risk reduction seen with ACE inhibitors and 4.4% absolute risk reduction seen with β-blockers. Thus, an ICD importantly reduces mortality beyond the benefits of β-blockers, ACE inhibitors, and other medical therapy. Patients with Left Ventricular Dysfunction in Specific Circumstances Table 11-5 summarizes the inclusion criteria, primary endpoint, and main result for three studies that included patients with LV dysfunction in specific circumstances. Table 11-6 provides details of the study populations, the risk of the population untreated (annual control group mortality), and the relative and absolute alterations in mortality with ICD therapy. These trials are considered separately because the other studies invariably excluded patients with recent coronary artery bypass surgery or a recent myocardial infarction, the specific populations in which ICD therapy was evaluated in the four studies discussed here.

Clinical Trials of ICD Therapy for Left Ventricular Dysfunction in Specific Circumstances: Inclusion Criteria, Comparison Groups, and Main Result

Trial Coronary Artery Bypass Graft Patch (CABG Patch) (1996) Defibrillators in Acute Myocardial Infarction Trial (DINAMIT) (2005) BEta-blocker STrategy plus ICD (BEST-ICD) (2005) Immediate Risk-Stratification Improves Survival (IRIS) (2009)

Inclusion Criteria EF ≤ 0.35, undergoing CABG, abnormal signal-averaged ECG NYHA I-III, EF ≤ 0.35, recent MI (6-40 days), depressed heart rate variability or elevated average 24-hr heart rate EF ≤ 0.3 and one or more of following: ≥10 PVCs/hr, reduced heart rate variability, abnormal signal-averaged ECG, recent MI (>1 mo) EF ≤ 0.4 and one or both of following: Heart rate ≥90 bpm, nonsustained VT

Comparison ICD vs. best medical therapy ICD vs. best medical therapy Invasive strategy (ICD if inducible VT, otherwise medical therapy) vs. conservative strategy (medical therapy) ICD vs. best medical therapy

Primary Endpoint All-cause mortality All-cause mortality All-cause mortality All-cause mortality

Main Finding No significant alteration (P = .6) with ICD No significant alteration (P = .7) with ICD No significant alteration (P = .4) with invasive strategy vs. conservative strategy No significant alteration (P = .8) with ICD

ECG, Electrocardiogram; EF, ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association functional class; PVCs, premature ventricular complexes; VT, ventricular tachycardia.



11  Clinical Trials of Defibrillator Therapy

TABLE

11-6 

269

Clinical Trials of ICD Therapy for Left Ventricular Dysfunction in Specific Circumstances: Population Details and Mortality Results Mortality Results: ICD vs. Other (%)

Trial CABG Patch DINAMIT BEST-ICD IRIS

N 900 674 148 898

Age (yr) 64 62 66 62

Women (%) 16 24 29 23

NYHA > II (%) — 13 — 12

Mean Ejection Fraction 0.27 0.28 0.31 0.37

Mean Followup (mo) 32 30 17 37

Annual Rate in Control Group 8 7 14 8

Relative Risk Alteration 7 (increase) 8 (increase) 13 (increase) 4 (increase)

Absolute Risk Alteration 1.7 (increase) 1.7 (increase) 2.4 (increase) 0.2 (increase)

NYHA, New York Heart Association functional class.

Coronary Artery Bypass Graft Patch Trial

Defibrillators in Acute Myocardial Infarction Trial

The CABG Patch trial was conducted at 35 U.S. centers and two German centers between 1990 and 1997. Prophylactic ICD therapy was compared with usual care in 900 patients with LVEF values ≤0.35 and abnormal signal-averaged ECG recordings undergoing CABG surgery.81 No significant reduction in mortality was observed with ICD therapy (relative increased risk 7%; P = .6) over an average follow-up of 32 months. A secondary analysis found that the ICD significantly reduced the risk of sudden death compared with medical therapy. Despite the attempt to identify a group of patients at high risk for sudden death, most of the deaths in CABG Patch (71%) were nonarrhythmic.134 Thus, the lack of benefit from ICD therapy appears to be related to a low risk of sudden death. The reasons for the divergent results in the CABG Patch trial will likely never be fully understood. Characteristics of the patients in the trial were similar to those of patients with ischemic LV dysfunction and no history of sustained or inducible ventricular arrhythmias who were enrolled in MADIT-II and the other ICD trials, apart from higher mean LVEF values (see Table 11-6). Whether this finding relates to the use of a signal-averaged ECG to select patients, the effect of revascularization, or statistical chance is not known. Early studies suggested that the presence of late potentials on signal-averaged ECG analysis were predictive of death and serious arrhythmias.135 Later data suggested that signal-averaged ECG recordings do not provide useful prognostic information in patients who have undergone revascularization.136 One analysis that evaluated the impact of CABG on outcome in patients with LV dysfunction found that revascularization was associated with a 25% reduction in risk of death and a 46% reduction in risk of sudden death, independent of LVEF and severity of heart failure.87 As baseline LVEF declined, absolute reduction in risk of sudden death with prior CABG rose. When these data were applied to a group of patients with LV dysfunction who had not undergone prior surgery (Coronary Artery Surgery Study Registry), the predicted annual rates of death (8.2%) and sudden death (2.4%) were similar to those observed in CABG Patch (7.9% and 2.3%, respectively).87 An analysis from SCD-HeFT found no relationship between prior CABG and outcome,137 whereas analysis from MADIT-CRT found a significant reduction in the risk of VT/VF or death in patients with (32% risk) versus without (42%) prior coronary revascularization (P = .02).138 Regardless of the reasons why ICD therapy did not alter mortality in CABG Patch, this result highlights the need for restraint in the use of ICD therapy for the prevention of sudden death in patient groups in whom data on ICD efficacy are lacking. Quality of life was assessed in the CABG Patch trial.28 Six months after surgery, 490 of the 900 enrolled patients completed QOL assessments. Compared with the ICD group, control patients were more likely to think their health status had improved over the preceding year, and controls had both higher emotional role functioning and greater psychological well-being. The ICD and control groups were similar on other QOL measures. These results are at odds with other trials, which found no reduction in QOL with ICD therapy. Whether these differences in QOL with ICD therapy in CABG Patch relate to the population assessed, the use of thoracotomy versus nonthoracotomy ICD systems, rates of incomplete data, or other factors is unknown.

The Defibrillators in Acute Myocardial Infarction Trial (DINAMIT) tested the hypothesis that an ICD will reduce mortality in patients with a recent MI who are at high risk of arrhythmic death because of LV dysfunction and impaired autonomic tone, manifesting as low heart rate variability or a high resting heart rate.82 A total of 674 patients were enrolled at 73 sites from 12 countries between 1998 and 2002. Patients were enrolled 6 to 40 days after the index MI. Patients with NYHA Class IV symptoms, or in whom CABG surgery or three-vessel coronary angioplasty had been performed or was planned, were excluded. The primary outcome was death from any cause. Arrhythmic death was a secondary outcome. Mean follow-up was 30 months. Most of the characteristics of patients in DINAMIT (see Table 11-6) were similar to those of patients with ischemic LV dysfunction and no history of sustained or inducible ventricular arrhythmias enrolled in MADIT-II and the other ICD trials involving patients without a history of sustained or inducible ventricular arrhythmias, apart from higher mean LVEF values (see Table 11-6). Mean LVEF values in the CABG Patch trial and DINAMIT were similar. In DINAMIT, 62 deaths occurred in the ICD group versus 58 deaths in the conventional therapy group, translating into a statistically nonsignificant 8% higher (95% CI = 24% lower to 55% higher) risk of death with an ICD. In terms of the secondary endpoint, there were 12 arrhythmic deaths in the ICD group compared with 29 in the conventional therapy group, translating into a significant 58% (95% CI = 17% to 78%) lower risk in the ICD versus conventional group (P = .009). However, the reduction in arrhythmic death was offset by a 75% (95% CI = 11% to 176%) higher risk of nonarrhythmic death in the ICD versus the conventional therapy group. An important analysis related to the development of arrhythmias requiring appropriate ICD therapies and subsequent mortality in DINAMIT patients has been presented, but not published.139 Over the 2.5 years of follow-up, 18% of patients randomly assigned to receive an ICD in DINAMIT had appropriate ICD therapies. On average, these patients had baseline LVEF values and degrees of autonomic tone impairment similar to patients who did not have appropriate ICD therapies. However, patients who received shocks were more likely to have NSVT. Most patients who received shocks experienced multiple shocks. The mortality rate in those who experienced appropriate ICD therapies (36%) was significantly greater than that in patients who experienced no therapies (15%) or were randomly assigned to not receive an ICD (17%). Three quarters of deaths in patients experiencing appropriate ICD therapies were categorized as nonarrhythmic. As in AVID38 and SCD-HeFT,34 patients who experienced appropriate ICD therapies in DINAMIT were subsequently at high risk of death from progressive heart failure. The reasons for lack of benefit from ICD therapy in DINAMIT will likely never be fully understood. The inclusion of patients very early after MI may partly explain these results. As discussed, no benefit from ICD therapy was evident among patients within 18 months of an MI in MADIT-II.118 The lack of ICD efficacy may relate to alterations in cardiac structural remodeling,140 electrical remodeling,70 autonomic remodeling,141 or other factors early after MI. Recent insights on the mechanisms of sudden death in early post-MI patients with LV dysfunction are also likely relevant. As noted, almost half of the sudden

270

SECTION 2  Clinical Concepts

deaths thought to be arrhythmic were in fact related to recurrent MI events or cardiac rupture.11 The choice of an elevated heart rate or impaired heart rate variability as inclusion criteria may have selected a group of patients at high risk for death but, necessarily, death related to ventricular arrhythmias. Although impaired heart rate variability does identify patients at high risk of presumed arrhythmic death early after MI,69 it is also a potent predictor of death from progressive pump failure in patients with LV dysfunction.142 Moreover, alterations in heart rate variability early versus later after MI provide similar different prognostic information.70 The high risk of nonarrhythmic death after appropriate ICD therapies in DINAMIT also suggests that ventricular arrhythmias in these patients may simply be a marker for progressive heart failure given the population enrolled (severe LV dysfunction). Other studies assessing ICD efficacy early after MI are ongoing (see Ongoing Trials). BEta-blocker STrategy plus Implantable Cardioverter-Defibrillator Study The BEta-blocker STrategy plus ICD (BEST-ICD) study evaluated the usefulness of an electrophysiologically guided ICD strategy in patients at high risk of sudden death early (<1 month) after MI.85 Patients were enrolled between 1998 and 2003. The overall study design was complex. Patients were required to have LV dysfunction, to be able to tolerate therapy with a β-blocker, and to have at least one of the following abnormal findings on noninvasive tests: 10 or more premature ventricular complexes per hour (≥10 PVCs/hr), depressed heart rate variability, and an abnormal signal-averaged ECG. Eligible patients who agreed to participate were then randomly assigned (with a ratio of 3 : 2) to usual medical care (conventional therapy) or to an invasive electrophysiologic study (invasive strategy). Patients in the invasive strategy group who had inducible sustained VT/VF received an ICD, whereas those who had no sustained arrhythmia induced were crossed over to receive conventional therapy. On the basis of this algorithm, 59 patients were randomly assigned to conventional therapy and 79 to the invasive strategy. A sustained ventricular arrhythmia was induced in 24 of the 79 patients in the invasive strategy group; these 24 patients received an ICD. The remaining 114 patients received usual medical care. All participants received metoprolol, with an average dose of 68 mg/day at baseline. The majority of patients were prescribed an ACE inhibitor (81% at discharge and 78% at last follow-up) and aspirin (81% at baseline and 82% at last follow-up). The rate of statin use was low (22% at baseline and 25% at last follow-up). A few patients received amiodarone (7% at baseline and 12% at follow-up). Similar to CABG Patch and DINAMIT, patients in the BEST-ICD study had a lesser degree of LV dysfunction than those in MADIT-II and the other trials of patients with heart failure or LV dysfunction alone (see Table 11-6). During a mean follow-up of 17 months, 26 patients (19%) died. Only nine deaths (7%) were categorized as sudden. Overall, 22% of the patients randomly assigned to conventional therapy died compared with 16% of patients randomly assigned to an invasive strategy (P = .4). The mortality rates were similar among patients who received an ICD because of an inducible arrhythmia (21%), those randomly assigned to the invasive strategy without an inducible arrhythmia (15%), and those randomly assigned to conventional therapy (22%). A major limitation of the BEST-ICD study is the small number of patients (138), which prevents any conclusion related to the efficacy or lack of efficacy of ICD therapy in this group of patients. Another limitation is that the population was highly selected. More than 15,000 patients were screened. Of these, 8% had an LVEF ≤0.35. The majority (92%) of these patients had at least one abnormal noninvasive test. A large number of patients were excluded for other reasons, including lack of informed consent (40%), intolerance of β-blocker (18%), early revascularization (16%), and NSVT (7%). These data question the external validity of the BEST-ICD results. Further, other data indicate that invasive programmed electrical stimulation does not appear useful early after MI.66,67

Immediate Risk-Stratification Improves Survival Study The Immediate Risk-Stratification Improves Survival (IRIS) study compared ICD therapy with usual medical care in 898 patients enrolled 5 to 31 days after MI. Participants were considered at risk for sudden death because of LVEF ≤0.40 plus a heart rate of ≥90 bpm on the first available ECG and/or NSVT of at least 150 bpm during Holter monitoring.86 Two thirds of participants (602; 67%) were included because of an elevated ECG heart rate. Remaining patients were enrolled with both elevated heart rate and NSVT (88; 10%) or NSVT alone (208; 23%). Patients were enrolled at 92 European sites between 2002 and 2007. The 898 patients were selected from a group of 62,944 patients with recent MI (screen/enroll ratio 70 : 1). Participants were equally assigned to standard medical care alone (453) or standard care plus an ICD (445). The primary endpoint was all-cause mortality. An independent events committee further categorized deaths as sudden or nonsudden. The trial was extended by the data and safety monitoring board in late 2005 when a lower-than-expected mortality rate was observed. The mean age of IRIS participants was 63 years, and 23% were female. Most of the qualifying MI events were categorized as “anterior” (65%), and 77% were ST elevation in nature. The mean LVEF was 0.37 in the study population overall but varied depending on enrollment criteria met. Patients who qualified for inclusion because of elevated ECG heart rate alone (mean LVEF 0.32) or both elevated heart rate and NSVT (mean LVEF ~0.30) had greater LV dysfunction versus those with NSVT alone (mean LVEF ~0.45). Most patients had NYHA Class I (28%) or Class II (60%) symptoms. Direct percutaneous intervention was used as the revascularization strategy in 72% of patients, a thrombolytic agent in 15%, and neither intervention in the remaining 13% of patients. A history of atrial fibrillation was present in 14%, diabetes in one third, and hypertension in two thirds of participants. Antiplatelet agents (98%), β-blockers (87%), and ACE inhibitors (82%) were prescribed frequently. Median follow-up in IRIS was 37 months. Over this time, 233 patients died: 116 in the ICD group and 117 in the control group. The risk of death was similar in the ICD versus control group (hazard ratio 1.04; 95% CI 0.81 to 1.35; P = .8). The risk of sudden death was reduced by almost 50% with ICD therapy (P = .049), but this was offset by almost doubling in the risk of nonsudden death (P = .001). Results were similar among patients who qualified on the basis of an elevated ECG heart rate, NSVT, or both. The results of IRIS mirror those of DINAMIT; inclusion of patients very early after MI may partly explain the lack of benefit.11,70,118,140,141 As noted, post-MI patients with LV dysfunction have a high risk of nonarrhythmic sudden death early after MI,11 and ICD shocks may be particularly deleterious in this patient population. The IRIS results have been criticized for the inclusion of patients with LVEF values outside present guidelines.143 However, IRIS was designed to assess the utility of ICD therapy in patients selected by other criteria. The choice of using an elevated heart rate or NSVT may also explain the clear lack of efficacy in IRIS. Although shown to predict risk, these parameters do not discriminate between sudden death and deaths from progressive heart failure.80 Other studies assessing the efficacy of ICD therapy after MI are ongoing (see Ongoing Trials). Summary It is clear from all four studies of patients with LV dysfunction in specific circumstances that prospective evaluation of risk assessment tools is required to determine whether their use can identify patients likely to benefit from an ICD. These trials emphasize the need for continued research on ICD therapy, particularly patients with a recent MI. NONRANDOMIZED STUDIES OF ICD THERAPY: A NOTE OF CAUTION Randomized trials of ICD therapy have not been undertaken in certain situations because of concerns regarding feasibility (e.g., uncommon condition, complex study design, cost) or a lack of equipoise (i.e.,



unwillingness of physicians to randomize patients or patients to accept no ICD therapy). It is important to note that some of the early landmark trials, including AVID, faced harsh criticism regarding the randomization of patients to no ICD,144 but the investigators persisted,145 altering clinical practice. In the absence of randomized trial data, nonrandomized studies have been undertaken to inform decision making. These studies have typically used appropriate ICD therapies or a composite of appropriate ICD therapies or death as an outcome.146-150 Findings suggesting that frequent ICD therapies during follow-up justify an ICD in patients with similar characteristics should be interpreted with caution. As discussed, data from DEFINITE131 and other trials151,152 indicate that appropriate ICD therapies are not a reliable surrogate for mortality and overestimate therapeutic benefit. For example, two studies of patients with nonischemic LV dysfunction found high rates (36%51%) of appropriate ICD therapies over 36 months of follow-up.153,154 However, randomized trials of similar patients found mortality rates of only 12% to 21% over a similar period65,120,130 (see Table 11-3). These data indicate that caution must be used when only nonrandomized data are available to guide clinical decision making. PATIENTS WITH LESS COMMON INHERITED OR ACQUIRED CARDIAC DISEASE Implantable cardioverter-defibrillator therapy has a clear role in several less common inherited or acquired forms of cardiac disease. These include, but are not limited to, hypertrophic cardiomyopathy, cardiac sarcoidosis, and arrhythmogenic right ventricular cardiomyopathy. These diseases are discussed here with an emphasis on the patient selection for ICD therapy. A more in-depth review of ICD therapy in familial sudden death syndromes can be found in the 2010 Heart Rhythm UK position statement.155 Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is usually inherited in an autosomal dominant pattern and is estimated to affect 0.2% of the population. It is characterized by hypertrophy of the interventricular septum, apex, or other LV regions. HCM is the most common cause of sudden death in persons younger than 40, and a cardiac arrest may be the first manifestation of the disease. The arrhythmias that lead to cardiac arrest in HCM are thought to result from cardiac myocyte disarray. The reported annual incidence of sudden death attributed to HCM has declined from 5% to less than 1% per year, likely reflecting enhanced surveillance.155-157 There have been no randomized trials of ICD therapy in HCM, so observational data must be relied on to aid clinical decision making.146,148 Deciding to use an ICD in patients with HCM can be challenging. These patients are often young and active and have paroxysmal atrial fibrillation. Thus, they will require many devices over their lifetime and may be at higher risk for unnecessary shocks.33,51 However, these patients typically have minimal comorbidity and are unlikely to survive a cardiac arrest. Thus, clinicians need to consider risk factors for sudden death in patients with HCM when deciding whether to use an ICD. Risk factors for HCM fall into three categories: (1) those that mandate an ICD if the patient is otherwise an appropriate candidate, (2) those that favor ICD therapy if the patient is otherwise an appropriate candidate, and (3) less certain risk factors that do not provide clear guidance with respect to ICD insertion. Patients with HCM who have survived a cardiac arrest should receive an ICD,155 as should those with a history of spontaneous sustained VT.155 Less certain risk factors for sudden death in HCM include the presence of atrial fibrillation, LV outflow tract obstruction, myocardial ischemia, presence of a high-risk mutation, and a patient’s desire to pursue competitive physical exercise.155 At present, these less certain risk factors do not aid the decision to insert an ICD in a patient with HCM. Risk factors that favor insertion of an ICD include a family history of sudden death related to HCM, unexplained syncope, LV wall thickness of 30 mm or greater, a drop in systolic blood pressure with

11  Clinical Trials of Defibrillator Therapy

271

exercise, and NSVT. Some advocate that an ICD is warranted when one of these risk factors is present,148 whereas others believe that at least two of these factors are required.158 The presence of two or more risk factors identifies HCM patients with an annual sudden death risk of about 3%, whereas a single risk factor is associated with an annual risk of about 1%.159 The UK Heart Rhythm position paper states that “patients with HCM and two or more recognized risk factors for sudden death should be considered for ICD implantation. Patients with HCM and a single recognized risk factor for sudden death may, according to individual circumstances, be considered for ICD implantation.” The use of contrast-enhanced cardiac magnetic resonance (CMR) imaging to determine the extent of myocardial scarring and fibrosis has been advocated for sudden death risk assessment in HCM patients160-162 and may be helpful when the decision to use an ICD is unclear. Cardiac Sarcoidosis Sarcoidosis is an idiopathic, multisystem disorder characterized by infiltrative, noncaseating granulomas in multiple organ systems. Clinically evident cardiac involvement is observed in about 5% of patients with sarcoidosis and includes tachyarrhythmias, conduction disturbance, heart failure, and sudden death.163 Antiarrhythmic drugs are thought to be of limited value in cardiac sarcoidosis because of poor efficacy, the frequent presence of concomitant conduction disease, and diagnostic issues related to adverse effect surveillance (e.g., amiodarone pulmonary toxicity).164,165 Sudden death in cardiac sarcoidosis is thought to relate to heart block or reentrant ventricular arrhythmias.164 There have been no randomized trials of ICD therapy in cardiac sarcoidosis, and only sparse observational data are available to guide clinical decision making.164,165 Identification of high-risk patients using invasive programmed ventricular stimulation has been advocated, but its sensitivity and accuracy are questionable.166 An invasive study may be useful in patients with cardiac sarcoidosis and unexplained syncope. It is recommended that patients with cardiac sarcoidosis who have survived a cardiac arrest or who have sustained VT should receive an ICD if they are otherwise appropriate candidates.143 It would also seem reasonable to use an ICD for a patient with sarcoidosis and significant LV dysfunction if an otherwise appropriate candidate. Some believe that an ICD is also warranted when chronic pacing is indicated in a patient with cardiac sarcoid.165 It is less certain whether patients with evidence of cardiac sarcoidosis, lesser impairment of LV function, and no indication for pacing warrant an ICD. Contrast-enhanced CMR may be of value in these patients.167 The presence versus absence of significant delayed enhancement, a measure of scarring, was found to have significant prognostic value in a group of 81 patients with biopsyproven extracardiac sarcoidosis and preserved LV function (median LVEF = 0.56). Significant delayed enhancement on CMR was present in 21 patients (26%). Increased delayed enhancement was associated with a ninefold higher rate of adverse events (death, appropriate ICD shock, or requirement for permanent pacemaker) and an 11.5-fold higher risk of cardiac death. These data indicate that CMR may play a role in selection of patients for prophylactic ICD therapy in the future, but data should be considered preliminary. Arrhythmogenic Right Ventricular Cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiomyopathy characterized by fibrofatty infiltration of the right ventricle and less often the left ventricle. It is typically autosomal dominant with variable penetrance. Disease-causing mutations in genes encoding cell adhesion proteins (e.g., plakoglobin and desmoplakin) indicate a disorder of the cell-to-cell junction. ARVC has a predilection for the thinnest areas, the so-called triangle of dysplasia, which includes the diaphragmatic, infundibular, and apical regions of the right ventricle. These structural changes disrupt normal electrical activity and are thought to form the basis for reentrant VT and VF.155,168 The criteria for diagnosing ARVC were recently revised to improve their clinical utility.168 Briefly, major criteria now include global or regional dysfunction and structural alterations in the right ventricle

272

SECTION 2  Clinical Concepts

(regional RV akinesia, dyskinesia, or aneurysm identified using echocardiography, CMR, or RV angiography), abnormal RV endomyocardial biopsy findings (abnormal morphometric analysis with or without fatty infiltration), specific ECG findings (epsilon wave in leads V1 to V3), less specific ECG findings (inverted T waves in leads V1, V2, and V3 in the absence of RBBB), arrhythmias (NSVT or sustained VT of LBB morphology with superior axis), and a family history of confirmed ARVC. No randomized trials of ICD therapy have been done in ARVC patients, so clinicians must rely on observational data to aid clinical decision making. Observational studies have consistently found a high frequency of appropriate ICD use for life-threatening ventricular arrhythmias and a low rate of arrhythmic death in patients with ARVC treated with ICD therapy.143,147,169 Most experts would agree that patients with ARVC who have survived a cardiac arrest, have poorly tolerated VT, or have syncope, when VT/VF cannot be excluded, should receive an ICD if they are otherwise appropriate candidates.155 ARVC patients presenting with ventricular arrhythmias and severe structural disease should also be considered for an ICD if otherwise appropriate candidates.155 The UK Heart Rhythm position paper further states, “ARVC patients who are asymptomatic with mild disease are at low risk of sudden death, and the risks of ICD therapy may outweigh the benefits in this group.”155 The signal-averaged ECG is helpful in confirming a diagnosis of ARVC, but invasive electrophysiologic assessment and programmed electrical stimulation are of limited value in identifying ARVC patients at risk of sudden death, a result of the low predictive accuracy and unacceptably high false-positive and falsenegative results with this assessment method.170 OTHER INFORMATIVE ICD TRIALS Microvolt T Wave Alternans Testing for Risk Stratification of Post–Myocardial Infarction Patients Microvolt T Wave Alternans Testing for Risk Stratification of Post– Myocardial Infarction Patients (MASTER) was an observational study that evaluated the association of baseline microvolt TWA results with outcomes.83 A total of 768 patients with ischemic LV dysfunction (LVEF ≤0.35) and no prior sustained ventricular arrhythmia were enrolled. Of these, 392 (51%) received an ICD. The mean follow-up was 27 months. The 514 (67%) patients with nonnegative microvolt TWA results had an 8.6% rate of sudden death, and the remaining 254 patients with negative results had a rate of 5.1%. Patients with nonnegative TWA results had a 19.3% mortality rate, significantly larger than the 11.8% mortality rate in patients with a negative TWA result. A 70% reduction in arrhythmic death was observed with ICD therapy, but the effectiveness of ICD therapy was not consistent across the microvolt TWA subgroups. Data interpretation indicates that microvolt TWA assessment has limited value in identifying patients for ICD therapy and should not be used to decide whether a patient should receive an ICD. Alternans Before Cardioverter-Defibrillator The Alternans Before Cardioverter-Defibrillator (ABCD) observational study included 566 patients who underwent microvolt TWA testing and attempted induction of VT/VF with invasive electrophysiologic testing.149 Patients with LVEF < 0.40 values attributable to ischemic heart disease and NSVT were followed for a median of 1.9 years. The primary outcome was ICD shocks, ATP-terminated rhythms, or sudden death. Patients with abnormal microvolt TWA or inducible VT/VF were recommended to receive an ICD; 495 of the 566 patients (87%) received an ICD. A total of 65 events were observed, including 51 ICD shocks, four ATP-terminated rhythms, and 10 sudden deaths. Seven of the 10 sudden deaths occurred despite the patients being treated with an ICD. The event rate in patients with negative TWA and no inducible VT/VF (10.1%) was similar to the event rate in patients with a positive microvolt TWA result but no inducible VT/VF (12%). Patients with inducible VT/VF but a negative microvolt TWA result

had a slightly higher event rate (15.5%), as did patients with both a positive microvolt TWA result and an inducible VT/VF (15.7%). Patients with inducible VT/VF and an indeterminate TWA were at highest risk (22.9%). These data suggest that microvolt TWA assessment may provide additive value to the results of invasive electrophysiologic testing. Given the uncertainty about the usefulness of appropriate ICD therapies as a surrogate for sudden death, the implications of MASTER and ABCD are unclear. Combined with the previously discussed SCDHeFT TWA substudy, these results indicate that microvolt TWA testing alone is not useful in selecting patients for prophylactic ICD therapy. The ABCD results suggest that combining TWA assessment with invasive electrophysiologic testing may be useful in selecting patients at particular risk for sudden death, but that appropriately designed studies, in which results are used to guide therapy, are required before recommending this strategy. Inhibition of Unnecessary RV Pacing with AVSH in ICDs The Inhibition of Unnecessary RV Pacing with AVSH in ICDs (INTRINSIC-RV) study compared dual-chamber rate-responsive (DDDR) with atrioventricular search hysteresis (AVSH) versus backup single-chamber (VVI at 40 bpm) programming. The primary outcome was death or heart failure hospitalization.170a A total of 1530 ICD recipients entered a 1-week period for assessment of percent RV pacing. The 988 patients with less than 20% RV pacing were randomized to DDDR (502) versus VVI (486). LVEF values were not collected. A history of atrial fibrillation or atrial flutter was present in about 12% of participants. Over mean follow-up of 10 months, 32 DDDR (6.4%) and 46 VVI (9.5%) patients died or were hospitalized with heart failure (P = .07) The mean percent RV pacing in the DDDR arm was 10% (median 4%) versus 3% (median 0%) in the VVI arm. Thus, DDDR pacing with AVSH was associated with similar outcomes as VVI backup pacing. Second Dual Chamber and VVI Implantable Defibrillator Trial The Second Dual Chamber and VVI Implantable Defibrillator (DAVID-II) trial included 600 patients from 29 sites in North America.171 It assessed whether AAI pacing was a safe alternative to backup VVI ventricular pacing in 600 ICD recipients with LV dysfunction. DAVID-I had found that forced atrial-RV pacing increased the risk of death or heart failure hospitalization in ICD recipients with LV dysfunction.172 Patients receiving an ICD for primary or secondary prevention, with no clinical indication for pacing, were randomly assigned to AAI (70 bpm) versus VVI pacing (at 40 bpm). The mean LVEF of participants was 0.26, a history of atrial fibrillation was present in 14%, and 20% had a PR interval greater than 200 msec. Over a mean follow-up of 2.7 years, the risk of death or heart failure hospitalization was similar in patients assigned to AAI versus VVI pacing (P = .95). No differences in QOL or the rates of atrial fibrillation, syncope, or appropriate or inappropriate shocks were observed. Thus, AAI pacing appears to be a safe alternative when pacing is desired in ICD recipients. Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy The Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) evaluated the capacity of ICD plus CRT versus ICD therapy alone to reduce the risk of death or heart failure events in 1820 patients with LVEF values ≤0.30, QRS duration ≥130 msec, and NYHA Class I or II limitation.173 Heart failure events were diagnosed by physicians aware of treatment assignment, but adjudicated by a masked committee. During an average follow-up of 2.4 years, the composite outcome occurred in 187 of 1089 patients in the CRT-ICD group (17.2%) and 185 of 731 patients in the ICD group (25.3%), with a resultant hazard ratio of 0.66 (95% CI = 0.52 to 0.84; P = .001). Similar results were observed in patients with ischemic and nonischemic LV dysfunction. CRT was particularly effective in patients with wide QRS durations (≥150 msec). The benefit of CRT



was solely attributable to a 41% reduction in the risk of heart failure events. No difference in the risk of death was observed in the two groups (each with 3% annual mortality). Echocardiographic studies were obtained at baseline and at 1 year in 1372 of the 1820 (75%) patients. The CRT-ICD group had greater improvement in various chamber dimensions versus the ICD group. Most notably, LV end-systolic volume index was reduced by an average of 28.7 versus 9.1 mL/m2, and LVEF increased in absolute terms by 0.11 versus 0.03 in the CRT-D versus ICD groups, respectively. Remodeling at 1 year was predictive of subsequent death or heart failure (P <.001).174 The MADIT-CRT data suggest a benefit from providing CRT earlier in the course of disease. Recent European guidelines now recommend CRT for patients with NYHA Class II limitation175 (see Guidelines for ICD Therapy). Resynchronization/Defibrillation for Advanced Heart Failure Trial The Resynchronization/Defibrillation for Advanced Heart Failure Trial (RAFT) compared ICD plus CRT versus an ICD therapy alone in 1798 patients with LVEF values ≤0.30, NYHA Class II or III symptoms, intrinsic QRS duration ≥120 msec, or paced QRS durations ≥200 msec. Patients with ischemic or nonischemic LV dysfunction were eligible. Unlike MADIT-CRT, patients with atrial fibrillation were included if the ventricular rate was controlled.176 The primary objective of RAFT was to determine if the addition of CRT to ICD and optimized medical therapy would reduce total mortality and hospitalizations for heart failure in patients with mild to moderate heart failure symptoms. Patients with NYHA Class II or III limitation were initially eligible, but enrollment was restricted to patients with Class II limitation after completion of CARE-HF.123 The 1798 patients were followed for a mean of 40 months. The primary outcome of death or hospitalization occurred in 297 of 894 patients assigned to ICD-CRT (33.2%) versus 364 of 904 patients in the ICD group (40.3%), which resulted in a 25% relative risk reduction (HR 0.75; 95% CI 0.64 to 0.87; P < 0.001). The 7.1% absolute reduction in the risk of the primary outcome translates into needing to treat 14 patients with CRT-ICD versus an ICD for 40 months to prevent one event. Patients assigned to ICD-CRT also had a 25% lower risk of death from any cause. The 5-year actuarial rate of death in the CRT-ICD group was 28.6% versus 34.6% in the ICD group (HR 0.75; 95% CI 0.62 to 0.91; P = 0.003). Thus, 14 patients would need to be treated for 5 years with ICD-CRT versus an ICD alone to save one life. Further, 32% fewer patients in the ICD-CRT group were hospitalized for heart failure (174 hospitalizations) versus the ICD group (236 hospitalizations; HR 0.68; 95% CI 0.56 to 0.83; P < 0.001). The ICD-CRT patients had more adverse events, largely attributed to left ventricular lead– related complications. RAFT was the first study to demonstrate improved survival with ICD-CRT versus ICD alone in patients with class II symptoms. A total of 193 the 708 class II patients randomized to ICD-CRT (27.3%) experienced the primary outcome of death or hospitalization, while 253 of the 730 patients randomized to an ICD (34.7%) experienced the primary outcome. Fewer class II patients randomized to CRT-ICD (15.5%) versus an ICD (21.1%) died during follow-up, representing a 5.6% absolute reduction in mortality over the 40 months of follow-up. Thus, only 12 patients with class II symptoms would need to be treated for 5 years with ICD-CRT versus an ICD to save one life. Similar to what was identified in MADIT-CRT, patients with very wide QRS durations in RAFT also benefited from CRT to a greater extent. Significant interaction between treatment and QRS duration was observed (P = 0.003), with ICD–CRT therapy being more effective in patients with an intrinsic QRS duration of ≥150 msec. RAFT also found a weak interaction between treatment and QRS morphologic type (P = 0.046) in that patients with left bundle branch block appeared to have a greater benefit than patients with nonspecific intraventricular conduction delay. Patients with chronic atrial fibrillation were also found to benefit to a lesser extent versus patients in sinus rhythm. Whether patients with non-left bundle branch QRS patterns or chronic

11  Clinical Trials of Defibrillator Therapy

TABLE

11-7 

Standard Definitions: Classification of Recommendations and Level of Evidence

Classification I II IIa IIb III Level of Evidence A B C

273

Details Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective. Conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/efficacy of a procedure or treatment. Weight of evidence/opinion is in favor of usefulness/ efficacy. Usefulness/efficacy is less well established by evidence/ opinion. Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/ effective and in some cases may be harmful. Definition Data derived from multiple randomized clinical trials or meta-analyses. Data derived from a single randomized trial or nonrandomized studies. Only consensus opinion of experts, case studies, or standard of care.

atrial fibrillation benefit from CRT remains in question. Studies designed to definitively address the efficacy of CRT in these patient groups are presently being planned.

Guidelines for ICD Therapy The American College of Cardiology (ACC) and the American Heart Association (AHA) have proposed standard definitions for categorizing levels of evidence143 (Table 11-7). The latest published ACC, AHA, and Heart Rhythm Society (HRS) guidelines for the use of ICD therapy are from 2008.143 Table 11-8 summarizes the conditions in which ICD therapy is considered to be useful or may be useful (classes I and II). Table 11-9 summarizes the conditions for which there is evidence or general agreement that ICD therapy is not useful or may be harmful (class III). Some important randomized trials have been published since the 2008 ACC/AHA/HRS guidelines were released, including IRIS and several CRT studies (REVERSE, MADIT-CRT, and RAFT). As noted, recent European Society of Cardiology (ESC) Guidelines now recommend CRT (class I, level A) for patients in sinus rhythm, with LVEF values of 0.35 or greater, NYHA Class II limitation, and QRS duration of 150 msec or longer.175 Whether all patients with the characteristics in Table 11-8 should receive an ICD is controversial.177,178 Some believe that additional risk assessment is required to identify patients who are most likely to benefit from an ICD because of the concerns over device longevity, cost, accessibility, unnecessary shocks, and consequence of shocks. Others believe that ICD therapy saves lives, does not appreciably alter QOL over time (even when ICD shocks are included), and is costeffective (see previous discussion).

Ongoing Trials Table 11-10 provides details on three ongoing trials assessing the efficacy of an ICD or a wearable AED after MI and another evaluating ICD efficacy in nonischemic cardiomyopathy. Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation The Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) trial is assessing the efficacy of prophylactic ICD therapy in patients with ischemic heart disease, LVEF values greater than 0.35, and extensive myocardial scar as assessed using CMR imaging. It includes patients with a documented MI and those with

274

TABLE

11-8 

SECTION 2  Clinical Concepts

Indications for ICD Therapy

Recommendations Level of Evidence Class I (General Agreement of Benefit with ICD Therapy)   1.  Cardiac arrest due to VF or unstable sustained VT A after evaluation in the absence of completely reversible causes. B   2.  Structural heart disease and spontaneous sustained VT, whether hemodynamically stable or unstable.   3.  Syncope of undetermined origin and clinically B relevant, sustained VT or VF induced at electrophysiologic study. A   4.  LVEF ≤0.35 due to prior MI who are at least 40 days post-MI and NYHA II or III. B   5.  LVEF ≤0.35 due to a nonischemic cause and NYHA II or III. A   6.  LVEF ≤0.30 due to prior MI, at least 40 days post-MI and are NYHA I. B   7.  Nonsustained VT due to prior MI, LVEF ≤0.40, and inducible VF or sustained VT at electrophysiologic study. Class IIa (Weight of Evidence in Favor of Usefulness of ICD Therapy) C   1.  Unexplained syncope, significant LV dysfunction related to a nonischemic cause. C   2.  Sustained VT and normal or near-normal left ventricular systolic function. C   3.  Hypertrophic cardiomyopathy with one or more major risk factors for sudden death (see text).   4.  Arrhythmogenic right ventricular cardiomyopathy C (ARVC) with one or more risk factors for sudden death. B   5.  Long-QT syndrome with syncope and/or VT while receiving β-blockers.   6.  Nonhospitalized patients awaiting transplantation. C   7.  Brugada syndrome with syncope. C C   8.  Brugada syndrome with documented VT that has not resulted in cardiac arrest.   9.  Catecholaminergic polymorphic VT with syncope C and/or documented sustained VT while receiving β-blockers. C 10.  Cardiac sarcoidosis, giant cell myocarditis, or Chagas disease. Class IIb (Efficacy of ICD Therapy Is Less Well Established) C   1.  LVEF ≤ 0.35 due to nonischemic cause and NYHA I.   2.  Long-QT syndrome and risk factors for sudden death. B   3.  Advanced structural heart disease and syncope of C unknown cause despite invasive and noninvasive investigations. C   4.  Familial cardiomyopathy associated with sudden death.   5.  Left ventricular noncompaction. C LVEF, Left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association functional class; VF, ventricular fibrillation; VT, ventricular tachycardia.

significant stenosis of a major epicardial vessel. Patients with LVEF of 0.30 to 0.35 and NYHA Class I limitation, no prior VT or VF, and no inducible VT/VF with invasive electrophysiologic testing are also eligible. “Extensive scar” is defined as an infarct mass more than 15% of the left ventricle on a core laboratory-assessed, contrast-enhanced CMR study. Patients receiving antiarrhythmic drug therapy and those with a recent MI (within 40 days), recent revascularization (within 90

TABLE

11-9 

days), or existing cardiac devices are ineligible. Total survival will be evaluated 2 years after the last patient is randomized. Vest Prevention of Early Sudden Death Trial and Prediction of ICD Therapies Study The Vest Prevention of Early Sudden Death Trial (VEST) is a randomized comparison of the LifeVest versus standard care in a large number of patients with a recent MI and an LVEF ≤0.35. Patients are enrolled within the initial week after their MI (STEMI or NSTEMI). Patients with planned early CABG, an indication for or an existing ICD, chronic renal failure requiring hemodialysis, or a chest circumference too small or too large for the LifeVest garment are ineligible. The primary outcome is adjudicated sudden death, within 3 months of enrollment. Once patients complete the 2- to 3-month participation in VEST, they receive an ICD if their LVEF remains ≤0.35 or an implantable loop recorder (ILR) if LVEF is greater than 0.35. They are then followed in the Prediction of ICD Therapies Study (PREDICTS). This observational study is assessing the stability of noninvasive parameters over time and the optimal combination that predicts outcome. Patients who did not participate in the VEST phase can participate in PREDICTS if they have had a confirmed MI in the past 6 months and no exclusion criteria. The endpoint in PREDICTS is the occurrence of ventricular arrhythmias, defined as an ICD- or ILR-recorded ventricular tachyarrhythmia of at least 18 beats in duration. Risk Estimation Following Infarction Noninvasive Evaluation–ICD Efficacy The Risk Estimation Following Infarction Noninvasive Evaluation– ICD efficacy (REFINE-ICD) trial is testing if post-MI patients with a high-risk Holter monitor will benefit from an ICD. Patients with a confirmed MI in the preceding 2 to 14 months, LVEF of 0.36 to 0.49, and abnormalities in TWA and HRT, as determined by a core Holter laboratory, are randomized to medical care with or without an ICD. Medical care includes a β-blocker, ACE inhibitor or angiotensin receptor blocker, statin, and antiplatelet agent as clinically indicated. Patients not in sinus rhythm and those with active ischemia amenable to revascularization, recent revascularization, receiving antiarrhythmic drugs, in chronic renal failure, or with an indication for or an existing ICD, pacemaker, or CRT device are ineligible. Programming to minimize unnecessary ICD therapies is used. Patients are followed an average of 5 years. The primary outcome is all-cause mortality. Secondary outcomes include cost-effectiveness and QOL assessment. Efficacy of ICD in Patients with Non-Ischemic Systolic Heart Failure Trial The Efficacy of ICD in Patients with Non-Ischemic Systolic Heart Failure (DANISH) trial includes patients with nonischemic heart failure (NYHA Class I-IV), LVEF values ≤0.35, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>200 pg/mL). Patients with NYHA Class IV limitation are only eligible if they are candidates for a CRT system. Patients are randomized to standard medical therapy or standard medical therapy plus an ICD or a CRT-D if eligible. Standard medical therapy includes an ACE inhibitor or angiotensin receptor blocker and a β-blocker, unless not

Circumstances in which ICD Therapy Is Not Indicated

Recommendations Class III (General Agreement that An ICD Is Not Effective and May Be Harmful) 1.  No reasonable expectation of survival for at least 1 year, even when class I or II implantation criteria are present. 2.  Incessant VT or VF. 3.  Significant psychiatric illnesses that may be aggravated by ICD implantation or that may preclude systematic follow-up. 4.  Drug-refractory, NYHA IV heart failure and not a candidate for cardiac transplantation or CRT-D. 5.  Syncope of undetermined without inducible ventricular tachyarrhythmias and without structural heart disease. 6.  VF or VT is amenable to surgical or catheter ablation (e.g., Wolff-Parkinson-White syndrome, outflow tract VT, idiopathic VT, or fascicular VT without structural heart disease). 7.  VT or VF caused by a completely reversible disorder in the absence of structural heart disease (e.g., electrolyte imbalance, drugs, trauma).

Level of Evidence

CRT-D, Cardiac resynchronization therapy–defibrillation; NYHA, New York Heart Association functional class; VF, ventricular fibrillation; VT, ventricular tachycardia.

C C C C C B



11  Clinical Trials of Defibrillator Therapy

TABLE

11-10 

275

Ongoing ICD Trials Assessing Mortality

Trial Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) Vest Prevention of Early Sudden Death (VEST) Risk Estimation Following Infarction Noninvasive Evaluation–ICD efficacy (REFINE ICD) Efficacy of ICD in Patients with Non-Ischemic Systolic Heart Failure (DANISH)

Population Prior MI (any) LVEF > 0.35 Extensive myocardial scar (MRI) MI (within 7 days) LVEF ≤ 0.35 MI (2-14 months) LVEF 0.36-0.49 Abnormal T wave alternans and hear rate turbulence (Holter) Non-ischemic heart failure (LVEF ≤0.35) NYHA II-III NT-BNP > 200 pg/mL

Comparison ICD vs. usual care (1 : 1)

N 1550

Primary Endpoint Mortality

Identifier NCT00487279

Status Enrolling

Wearable AED vs. usual care (1 : 1) ICD vs. usual care (1 : 1)

2400

NCT00628966

Enrolling

1400

Sudden death mortality Mortality

NCT00673842

Enrolling

ICD vs. usual care (1 : 1)

1000

Mortality

NCT00541268 NCT00542945

Enrolling

AED, Automated external defibrillator; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MRI, magnetic resonance imaging; NT-BNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association functional class.

tolerated. The primary outcome is time to death from any cause. It is expected to require 2 years of enrollment, with at least 36 months of follow-up. Other Trials Other randomized trials (not listed) are assessing the safety and efficacy of methods to reduce the likelihood of ICD shocks, the utility of CRT in patient groups in whom there is insufficient evidence to date (e.g., narrow QRS duration), and the value of remote monitoring of implanted devices. Several other observational studies assessing risk prediction tools (Holter, imaging, genetic) are also ongoing.

Other Issues COST-EFFECTIVE, NOT INEXPENSIVE Regardless of a clinician’s philosophy related to costly interventions, a fundamental principle is that the choice to implant an ICD must be based on a reasonable probability of success. This principle must be considered in terms of a broad perspective (mortality, QOL, potential complications, cost). Although therapies are labeled as “cost-effective” if they are similar in cost to other interventions (e.g., renal dialysis), this label does not mean that they are “inexpensive.” This issue is of particular relevance when a physician concurrently uses multiple interventions in a single patient (e.g., renal dialysis, CABG, ICD). Ultimately, because of the evolving face of health care delivery, issues of cost influence the practice of medicine. It is also paramount to appreciate that estimates of cost-effectiveness derived from clinical trials may not mirror “real-world” costs. IS THERE A NEED FOR ADDITIONAL RISK ASSESSMENT? Controversy surrounds the use of ICD therapy in all patients with an LVEF of 0.35 or less.177,178 Although widespread use of ICD therapy for prevention of arrhythmic death is understandable, this approach still carries the risk of complications related to implantation and subsequent revisions, besides the cost. Although extrapolation of the findings of past studies is reasonable and often necessary, it is prudent to consider a reasonable probability of success, including assessment of sudden death risk versus the risk of competing modes of death. The analyses from CIDS,103 MUSTT,109 and MADIT-II114 indicate that patients with significant comorbidity, particularly chronic renal impairment,179 may benefit from ICD therapy to a lesser extent. Other sources of data, including large registries, may aid in better selection of appropriate candidates for ICD therapy (see Real-World Effectiveness). In an attempt to include a greater proportion of patients at risk for sudden death (see Fig. 11-2), LV dysfunction has been a major inclusion criterion for most of the completed ICD trials (see Table 11-3).

However, many of these patients do not experience life-threatening arrhythmias in the near term. The incidence of appropriate ICD therapies ranges from 28% to 68% over the initial 2 to 5 years after ICD implantation, depending on the population studied and the duration of follow-up.151,154,180 Patients receiving an ICD on the basis of heart failure or LV dysfunction alone have a twofold to threefold lower risk of life-threatening arrhythmias in the initial 2 to 5 years of follow-up than patients with a history of spontaneous sustained VT/VF181-183 or inducible sustained VT/VF.184 Identifying higher-risk groups in those receiving an ICD for heart failure or LV dysfunction alone has been undertaken.103,109,114 Although useful in helping physicians better understand which patients may benefit from an ICD, these clinical scores should be used as “hypothesis-generating” tools, given the lack of prospective validation to date. Although the relative efficacy of an ICD is similar in most of the ICD trials (see Fig. 11-4), the absolute effect differs substantially. Among sudden death survivors22 and patients with ischemic LV dysfunction and inducible arrhythmias,64,91 the average absolute risk reduction was about 12%. Therefore, the NNT for ICD therapy in this group is approximately 8. In contrast, among patients with only LV dysfunction,23,133 the average absolute benefit was about 6%, translating into an NNT of 16. These data have been used to support the need for methods to better identify patients in whom ICD therapy leads to a greater absolute risk reduction and a lower NNT. The long-term data from MADIT-II identify a large, 13% absolute reduction in mortality with ICD therapy in patients with LV dysfunction.50 This reduction in mortality is similar to that in the randomized trials of ICD therapy in secondary prevention patients, although over shorter follow-up (see Fig. 11-4). The results of RAFT provide further evidence of the cost effectiveness of adding CRT to ICD therapy in patients with prolonged QRS durations and symptomatic heart failure (see Other Informative ICD Trials). Given the consequence of sudden death, it is imperative that a balance is reached between identifying patients with a significant absolute mortality reduction with ICD therapy (specificity) but not excluding most who will die from sudden death (sensitivity) (see Fig. 11-3). Noninvasive tools have also been advocated to better identify patients likely versus unlikely to benefit from an ICD. As discussed, these methods have not proved useful in guiding ICD therapy to date. Ongoing trials (e.g., DETERMINE, REFINE ICD) are assessing whether these tools can be used to select patients in whom an ICD will reduce mortality. Until these and other trials have been completed, it is unclear what role, if any, these methods have in guiding ICD therapy. REAL-WORLD EFFECTIVENESS The sites participating in the reviewed randomized trials are typically high-volume, academically oriented centers. The success rates and complication rates achieved in these trials may not reflect the

276

SECTION 2  Clinical Concepts

results in other centers. Until recently, little was known about the real-world success rates and complications of ICD placement. This issue is particularly relevant when the results of more complex ICD systems that include CRT are applied to less experienced centers, given the steep learning curve associated with implantation of LV leads.185 Large registries have been initiated to assess real-world effectiveness of ICD therapy, most notably the U.S. National Cardiovascular Data Registry (NCDR) Registry. Insights from the NCDR and other registries include improved outcomes when devices are implanted by electrophysiologists versus non-electrophysiologists,186 better outcomes in higher-volume than lower-volume implant centers,187 and significantly impaired outcomes in ICD recipients from comorbidities such as chronic renal disease.188 These data complement the findings from randomized trials. Registry data have also provided insight into implant complications, showing a twofold higher rate of complications with dual-chamber and CRT systems versus single-chamber ICD systems.189 Registry data have also helped in identifying barriers related to device implantation190,191 and the off-label use of devices.53,54 Despite limitations, registry data are providing important insights into real-world application of ICD systems.

Conclusion With advances in implantable cardioverter-defibrillator technology, the patient populations who may benefit from ICD therapy continue to expand. Many trials evaluating ICD efficacy in a variety of settings have convincingly demonstrated that the ICD is superior to antiarrhythmic drug therapy in patients with spontaneous or inducible ventricular arrhythmias. Also, ICD therapy improves the survival of patients with heart failure or LV dysfunction caused by ischemic heart disease or dilated cardiomyopathy. However, patients with LV dysfunction in specific circumstances, notably those with recent myocardial infarction, do not appear to benefit from ICD therapy. Ongoing and future studies will address the role of the ICD early after MI, as well as which patients benefit most from ICD therapy. Issues of reliability, cost, quality of life, and real-world outcomes will also feature prominently in future studies. A tremendous debt of gratitude is owed to the thousands of patients who have helped us learn so much about the usefulness and limitations of ICD therapy over the past 25 years. Without the time and effort of these individuals, we would know far less, and our capacity to reduce the burden of sudden death and improve the lives of so many individuals would be greatly diminished.

REFERENCES 1. Fox CS, Evans JC, Larson MG, et al: Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study. Circulation 110:522-527, 2004. 2. Bunch TJ, White RD, Friedman PA, et al: Trends in treated ventricular fibrillation out-of-hospital cardiac arrest: a 17-year population-based study. Heart Rhythm 1:255-259, 2004. 3. Kuller LH, Traven ND, Rutan GH, et al: Marked decline of coronary heart disease mortality in 35-44-year-old white men in Allegheny County, Pennsylvania. Circulation 80:261-266, 1989. 4. Josephson M, Wellens HJ: Implantable defibrillators and sudden cardiac death. Circulation 109:2685-2691, 2004. 5. Bayes de Luna A, Coumel P, Leclercq JF: Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 117:151-159, 1989. 6. Gang UJ, Jons C, Jorgensen RM, et al: Heart rhythm at the time of death documented by an implantable loop recorder. Europace 12:254-260, 2010. 7. Luu M, Stevenson WG, Stevenson LW, et al: Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 80:1675-1680, 1989. 8. Hinkle LE, Jr, Thaler HT: Clinical classification of cardiac deaths. Circulation 65:457-464, 1982. 9. Narang R, Cleland JG, Erhardt L, et al: Mode of death in chronic heart failure: a request and proposition for more accurate classification. Eur Heart J 17:1390-1403, 1996. 10. Greenberg H, Case RB, Moss AJ, et al: Analysis of mortality events in the Multicenter Automatic Defibrillator Implantation Trial (MADIT-II). J Am Coll Cardiol 43:1459-1465, 2004. 11. Pouleur AC, Barkoudah E, Uno H, et al: Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. Circulation 122:597-602, 2010. 12. Mirowski M, Mower MM, Langer A, et al: A chronically implanted system for automatic defibrillation in active conscious dogs: experimental model for treatment of sudden death from ventricular fibrillation. Circulation 58:90-94, 1978. 13. Exner DV, Klein GJ, Prystowsky EN: Primary prevention of sudden death with implantable defibrillator therapy in patients with cardiac disease: Can we afford to do it? (Can we afford not to?) Circulation 104:1564-1570, 2001. 14. Wilkoff BL, Ousdigian KT, Sterns LD, et al: A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective randomized multicenter EMPIRIC trial. J Am Coll Cardiol 48:330-339, 2006. 15. Saeed M, Neason CG, Razavi M, et al: Programming antitachycardia pacing for primary prevention in patients with implantable cardioverter defibrillators: results from the PROVE trial. J Cardiovasc Electrophysiol 21:1349-1354, 2010. 16. Schwab JO: Optimizing ICD programming for shock reduction. Fundam Clin Pharmacol 24:653-659, 2010. 17. Steinhaus D, Reynolds DW, Gadler F, et al: Implant experience with an implantable hemodynamic monitor for the management of symptomatic heart failure. Pacing Clin Electrophysiol 28:747-753, 2005. 18. Varma N, Epstein AE, Irimpen A, et al: Efficacy and safety of automatic remote monitoring for implantable cardioverterdefibrillator follow-up: the Lumos-T Safely Reduces Routine Office Device Follow-up (TRUST) trial. Circulation 122:325332, 2010.

19. McAlister FA, Ezekowitz J, Hooton N, et al: Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA 297:2502-2514, 2007. 20. Kleman JM, Castle LW, Kidwell GA, et al: Nonthoracotomyversus thoracotomy-implantable defibrillators: intention-totreat comparison of clinical outcomes. Circulation 90:2833-2842, 1994. 21. Kim SG, Pathapati R, Fisher JD, et al: Comparison of long-term outcomes of patients treated with nonthoracotomy and thoracotomy implantable defibrillators. Am J Cardiol 78:1109-1112, 1996. 22. Connolly SJ, Hallstrom AP, Cappato R, et al: Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies; Antiarrhythmics vs Implantable Defibrillator study; Cardiac Arrest Study Hamburg; Canadian Implantable Defibrillator Study. Eur Heart J 21:20712078, 2000. 23. Ezekowitz JA, Rowe BH, Dryden DM, et al: Systematic review: implantable cardioverter defibrillators for adults with left ventricular systolic dysfunction. Ann Intern Med 147:251-262, 2007. 24. Camm AJ, Nisam S: European utilization of the implantable defibrillator: has 10 years changed the “enigma”? Europace 12:1063-1069, 2010. 25. McCready MJ, Exner DV: Quality of life and psychological impact of implantable cardioverter-defibrillators: focus on randomized controlled trial data. Card Electrophysiol Rev 7:63-70, 2003. 26. Schron EB, Exner DV, Yao Q, et al: Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation 105:589-594, 2002. 27. Irvine J, Dorian P, Baker B, et al: Quality of life in the Canadian Implantable Defibrillator Study (CIDS). Am Heart J 144:282289, 2002. 28. Namerow PB, Firth BR, Heywood GM, et al: Quality-of-life six months after CABG surgery in patients randomized to ICD versus no ICD therapy: findings from the CABG Patch trial. Pacing Clin Electrophysiol 22:1305-1313, 1999. 29. Noyes K, Corona E, Veazie P, et al: Examination of the effect of implantable cardioverter-defibrillators on health-related quality of life: based on results from the Multicenter Automatic Defibrillator Trial-II. Am J Cardiovasc Drugs 9:393-400, 2009. 30. Passman R, Subacius H, Ruo B, et al: Implantable cardioverter defibrillators and quality of life: results from the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation study. Arch Intern Med 167:2226-2232, 2007. 31. Mark DB, Anstrom KJ, Sun JL, et al: Quality of life with defibrillator therapy or amiodarone in heart failure. N Engl J Med 359:999-1008, 2008. 32. Exner DV, Pinski SL, Wyse DG, et al: Electrical storm presages nonsudden death: the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. Circulation 103:2066-2071, 2001. 33. Daubert JP, Zareba W, Cannom DS, et al: Inappropriate implantable cardioverter-defibrillator shocks in MADIT-II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 51:1357-1365, 2008. 34. Poole JE, Johnson GW, Hellkamp AS, et al: Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 359:1009-1017, 2008. 35. Epstein AE, Kay GN, Plumb VJ, et al: Gross and microscopic pathological changes associated with nonthoracotomy

implantable defibrillator leads. Circulation 98:1517-1524, 1998. 36. Hurst TM, Hinrichs M, Breidenbach C, et al: Detection of myocardial injury during transvenous implantation of automatic cardioverter-defibrillators. J Am Coll Cardiol 34:402-408, 1999. 37. Trayanova N, Eason J: Shock-induced arrhythmogenesis in the myocardium. Chaos 12:962-972, 2002. 38. Pires LA, Lehmann MH, Steinman RT, et al: Sudden death in implantable cardioverter-defibrillator recipients: clinical context, arrhythmic events and device responses. J Am Coll Cardiol 33:24-32, 1999. 39. Mitchell LB, Pineda EA, Titus JL, et al: Sudden death in patients with implantable cardioverter defibrillators: the importance of post-shock electromechanical dissociation. J Am Coll Cardiol 39:1323-1328, 2002. 40. Sweeney MO, Sherfesee L, DeGroot PJ, et al: Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients. Heart Rhythm 7:353-360, 2010. 41. Pacifico A, Hohnloser SH, Williams JH, et al: Prevention of implantable-defibrillator shocks by treatment with sotalol. d,lSotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 340:1855-1862, 1999. 42. Dorian P, Borggrefe M, Al-Khalidi HR, et al: Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Circulation 110:3646-3654, 2004. 43. Wathen MS, DeGroot PJ, Sweeney MO, et al: Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 110:2591-2596, 2004. 44. Sweeney MO, Wathen MS, Volosin K, et al: Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT Reduces Shock Therapies (PainFREE Rx II) trial. Circulation 111:2898-2905, 2005. 45. Wilkoff BL, Williamson BD, Stern RS, et al: Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 52:541-550, 2008. 46. Volosin KJ, Exner DV, Wathen M, et al: Combining Shock Reduction Strategies to Enhance ICD Therapy: a role for computer modeling. J Cardiovasc Electrophysiol 22:280-289, 2011. 47. Mehta D, Nayak HM, Singson M, et al: Late complications in patients with pectoral defibrillator implants with transvenous defibrillator lead systems: high incidence of insulation breakdown. Pacing Clin Electrophysiol 21:1893-1900, 1998. 48. Hauser RG: The growing mismatch between patient longevity and the service life of implantable cardioverter-defibrillators. J Am Coll Cardiol 45:2022-2025, 2005. 49. Krahn AD, Champagne J, Healey JS, et al: Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: a report from the Canadian Heart Rhythm Society Device Advisory Committee. Heart Rhythm 5:639-642, 2008. 50. Goldenberg I, Gillespie J, Moss AJ, et al: Long-term benefit of primary prevention with an implantable cardioverterdefibrillator: an extended 8-year follow-up study of the



11  Clinical Trials of Defibrillator Therapy Multicenter Automatic Defibrillator Implantation Trial II. Circulation 122:1265-1271, 2010. 51. Knops P, Theuns DA, Res JC, Jordaens L: Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection. Pacing Clin Electrophysiol 32:1276-1285, 2009. 52. Simpson CS, Klein GJ, Hoffmaster B: Expensive medical technologies and “indication extrapolation”: the case of implantable cardioverter-defibrillators. Am Heart J 140:419-422, 2000. 53. Dickstein K, Bogale N, Priori S, et al: The European Cardiac Resynchronization Therapy Survey. Eur Heart J 30:2450-2460, 2009. 54. Fein AS, Wang Y, Curtis JP, et al: Prevalence and predictors of off-label use of cardiac resynchronization therapy in patients enrolled in the National Cardiovascular Data Registry Implantable Cardiac-Defibrillator Registry. J Am Coll Cardiol 56:766773, 2010. 55. Salukhe TV, Dimopoulos K, Sutton R, et al: Life-years gained from defibrillator implantation: markedly nonlinear increase during 3 years of follow-up and its implications. Circulation 109:1848-1853, 2004. 56. Moss AJ, Zareba W, Hall WJ, et al: Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346:877-883, 2002. 57. Sanders GD, Hlatky MA, Owens DK: Cost-effectiveness of implantable cardioverter-defibrillators. N Engl J Med 353:14711480, 2005. 58. Sanders GD, Kong MH, Al-Khatib SM, Peterson ED: Costeffectiveness of implantable cardioverter defibrillators in patients ≥65 years of age. Am Heart J 160:122-131, 2010. 59. Myerburg RJ, Reddy V, Castellanos A: Indications for implantable cardioverter-defibrillators based on evidence and judgment. J Am Coll Cardiol 54:747-763, 2009. 60. Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 363:3644, 2010. 61. Exner DV: Noninvasive risk stratification after myocardial infarction: rationale, current evidence and the need for definitive trials. Can J Cardiol 25(Suppl A):21-27, 2009. 62. Myerburg RJ: Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc Electrophysiol 12:369-381, 2001. 63. Rea TD, Pearce RM, Raghunathan TE, et al: Incidence of out-ofhospital cardiac arrest. Am J Cardiol 93:1455-1460, 2004. 64. Moss AJ, Hall WJ, Cannom DS, et al: Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 335:19331940, 1996. 65. Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352:225-237, 2005. 66. Roy D, Marchand E, Theroux P, et al: Programmed ventricular stimulation in survivors of an acute myocardial infarction. Circulation 72:487-494, 1985. 67. Al-Khatib SM, Hafley G, Lee KL, Buxton AE: Relation between time from myocardial infarction to enrolment and patient outcomes in the Multicenter Unsustained Tachycardia Trial. Europace 12:1112-1118, 2010. 68. Daubert JP, Zareba W, Hall WJ, et al: Predictive value of ventricular arrhythmia inducibility for subsequent ventricular tachycardia or ventricular fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients. J Am Coll Cardiol 47:98-107, 2006. 69. La Rovere MT, Bigger JT, Jr, Marcus FI, et al: Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes after Myocardial Infarction) Investigators. Lancet 351:478-484, 1998. 70. Exner DV, Kavanagh KM, Slawnych MP, et al: Noninvasive risk assessment early after a myocardial infarction the REFINE study. J Am Coll Cardiol 50:2275-2284, 2007. 71. Schmidt G, Malik M, Barthel P, et al: Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction. Lancet 353:1390-1396, 1999. 72. Gorgels AP, Gijsbers C, de Vreede–Swagemakers J, et al: Out-ofhospital cardiac arrest: the relevance of heart failure. The Maastricht Circulatory Arrest Registry. Eur Heart J 24:1204-1209, 2003. 73. Traven ND, Kuller LH, Ives DG, et al: Coronary heart disease mortality and sudden death: trends and patterns in 35- to 44-year-old white males, 1970-1990. Am J Epidemiol 142:45-52, 1995. 74. Jouven X, Desnos M, Guerot C, Ducimetiere P: Predicting sudden death in the population: the Paris Prospective Study I. Circulation 99:1978-1983, 1999. 75. Adabag AS, Peterson G, Apple FS, et al: Etiology of sudden death in the community: results of anatomical, metabolic, and genetic evaluation. Am Heart J 159:33-39, 2010. 76. Antman EM, Hand M, Armstrong PW, et al: 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 51:210247, 2008. 77. Bardy GH, Lee KL, Mark DB, et al: Home use of automated external defibrillators for sudden cardiac arrest. N Engl J Med 358:1793-1804, 2008.

78. Heidary S, Patel H, Chung J, et al: Quantitative tissue characterization of infarct core and border zone in patients with ischemic cardiomyopathy by magnetic resonance is associated with future cardiovascular events. J Am Coll Cardiol 55:2762-2768, 2010. 79. Boogers MJ, Borleffs CJ, Henneman MM, et al: Cardiac sympathetic denervation assessed with 123-iodine metaiodobenzylguanidine imaging predicts ventricular arrhythmias in implantable cardioverter-defibrillator patients. J Am Coll Cardiol 55:2769-2777, 2010. 80. Goldberger JJ, Cain ME, Hohnloser SH, et al: American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death. A scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. J Am Coll Cardiol 52:1179-1199, 2008. 81. Bigger JT, Jr: Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 337:15691575, 1997. 82. Hohnloser SH, Kuck KH, Dorian P, et al: Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 351:2481-2488, 2004. 83. Chow T, Kereiakes DJ, Onufer J, et al: Does microvolt T-wave alternans testing predict ventricular tachyarrhythmias in patients with ischemic cardiomyopathy and prophylactic defibrillators? The MASTER (Microvolt T Wave Alternans Testing for Risk Stratification of Post–Myocardial Infarction Patients) trial. J Am Coll Cardiol 52:1607-1615, 2008. 84. Wever EF, Hauer RN, Schrijvers G, et al: Cost-effectiveness of implantable defibrillator as first-choice therapy versus electrophysiologically guided, tiered strategy in postinfarct sudden death survivors: a randomized study [see comments]. Circulation 93:489-496, 1996. 85. Raviele A, Bongiorni MG, Brignole M, et al: Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial. Europace 7:327-337, 2005. 86. Steinbeck G, Andresen D, Seidl K, et al: Defibrillator implantation early after myocardial infarction. N Engl J Med 361:14271436, 2009. 87. Veenhuyzen GD, Singh SN, McAreavey D, et al: Prior coronary artery bypass surgery and risk of death among patients with ischemic left ventricular dysfunction. Circulation 104:14891493, 2001. 88. AVID Investigators: A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators [see comments]. N Engl J Med 337:1576-1583, 1997. 89. Connolly SJ, Gent M, Roberts RS, et al: Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 101:1297-1302, 2000. 90. Kuck KH, Cappato R, Siebels J, Ruppel R: Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 102:748-754, 2000. 91. Buxton AE, Lee KL, Fisher JD, et al: A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 341:1882-1890, 1999. 92. Larsen G, Hallstrom A, McAnulty J, et al: Cost-effectiveness of the implantable cardioverter-defibrillator versus antiarrhythmic drugs in survivors of serious ventricular tachyarrhythmias: results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) economic analysis substudy. Circulation 105:2049-2057, 2002. 93. DeMets DL, Hardy R, Friedman LM, Lan KK: Statistical aspects of early termination in the beta-blocker heart attack trial. Control Clin Trials 5:362-372, 1984. 94. Stanton MS, Bell GK: Economic outcomes of implantable cardioverter-defibrillators. Circulation 101:1067-1074, 2000. 95. Domanski MJ, Sakseena S, Epstein AE, et al: Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics versus Implantable Defibrillators. J Am Coll Cardiol 34:1090-1095, 1999. 96. Assmann SF, Pocock SJ, Enos LE, Kasten LE: Subgroup analysis and other (mis)uses of baseline data in clinical trials [see comments]. Lancet 355:1064-1069, 2000. 97. Exner DV, Reiffel JA, Epstein AE, et al: Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. J Am Coll Cardiol 34:325-333, 1999. 98. Wyse DG, Friedman PL, Brodsky MA, et al: Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up. J Am Coll Cardiol 38:1718-1724, 2001. 99. Raitt MH, Renfroe EG, Epstein AE, et al: “Stable” ventricular tachycardia is not a benign rhythm: insights from the

277

Antiarrhythmics versus Implantable Defibrillators (AVID) Registry. Circulation 103:244-252, 2001. 100. Bokhari F, Newman D, Greene M, et al: Long-term comparison of the implantable cardioverter defibrillator versus amiodarone: eleven-year follow-up of a subset of patients in the Canadian Implantable Defibrillator Study (CIDS). Circulation 110:112116, 2004. 101. O’Brien BJ, Connolly SJ, Goeree R, et al: Cost-effectiveness of the implantable cardioverter-defibrillator : results from the Canadian Implantable Defibrillator Study (CIDS). Circulation 103:1416-1421, 2001. 102. Sheldon R, O’Brien BJ, Blackhouse G, et al: Effect of clinical risk stratification on cost-effectiveness of the implantable cardioverter-defibrillator: the Canadian Implantable Defibrillator Study. Circulation 104:1622-1626, 2001. 103. Sheldon R, Connolly S, Krahn A, et al: Identification of patients most likely to benefit from implantable cardioverter-defibrillator therapy: the Canadian Implantable Defibrillator Study. Circulation 101:1660-1664, 2000. 104. Exner DV, Sheldon RS, Pinski SL, et al: Do baseline characteristics accurately discriminate between patients likely versus unlikely to benefit from implantable defibrillator therapy? Evaluation of the Canadian Implantable Defibrillator Study Implantable Cardioverter Defibrillatory Efficacy Score in the Antiarrhythmics versus Implantable Defibrillators trial. Am Heart J 141:99-104, 2001. 105. Exner DV: Quality of life in patients with life-threatening arrhythmias: does choice of therapy make a difference? Am Heart J 144:208-211, 2002. 106. Mushlin AI, Hall WJ, Zwanziger J, et al: The cost-effectiveness of automatic implantable cardiac defibrillators: results from MADIT. Multicenter Automatic Defibrillator Implantation Trial. Circulation 97:2129-2135, 1998. 107. Andresen D, Steinbeck G, Bruggemann T, et al: Can the MADIT results be applied to myocardial infarction patients at hospital discharge? J Am Coll Cardiol 31:308A, 1998. 108. Buxton AE, Lee KL, DiCarlo L, et al: Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 342:1937-1945, 2000. 109. Buxton AE, Lee KL, Hafley GE, et al: Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study. J Am Coll Cardiol 50:1150-1157, 2007. 110. Zwanziger J, Hall WJ, Dick AW, et al: The cost effectiveness of implantable cardioverter-defibrillators: results from the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. J Am Coll Cardiol 47:2310-2318, 2006. 111. Buxton AE, Sweeney MO, Wathen MS, et al: QRS duration does not predict occurrence of ventricular tachyarrhythmias in patients with implanted cardioverter-defibrillators. J Am Coll Cardiol 46:310-316, 2005. 112. Bloomfield DM, Steinman RC, Namerow PB, et al: Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: a solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum. Circulation 110:1885-1889, 2004. 113. Moss AJ: Correcting misconceptions. Ann Noninvas Electrocardiol 8:177-178, 2003. 114. Goldenberg I, Vyas AK, Hall WJ, et al: Risk stratification for primary implantation of a cardioverter-defibrillator in patients with ischemic left ventricular dysfunction. J Am Coll Cardiol 51:288-296, 2008. 115. Cygankiewicz I, Gillespie J, Zareba W, et al: Predictors of longterm mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) patients with implantable cardioverter-defibrillators. Heart Rhythm 6:468-473, 2009. 116. Haigney MC, Zareba W, Gentlesk PJ, et al: QT interval variability and spontaneous ventricular tachycardia or fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients. J Am Coll Cardiol 44:1481-1487, 2004. 117. Couderc JP, Zareba W, McNitt S, et al: Repolarization variability in the risk stratification of MADIT-II patients. Europace 2007. 118. Wilber DJ, Zareba W, Hall WJ, et al: Time dependence of mortality risk and defibrillator benefit after myocardial infarction. Circulation 109:1082-1084, 2004. 119. Goldenberg I, Moss AJ, Hall WJ, et al: Causes and consequences of heart failure after prophylactic implantation of a defibrillator in the Multicenter Automatic Defibrillator Implantation Trial II. Circulation 113:2810-2817, 2006. 120. Strickberger SA, Hummel JD, Bartlett TG, et al: Amiodarone versus Implantable Cardioverter-Defibrillator Trial: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia. AMIOVIRT. J Am Coll Cardiol 41:1707-1712, 2003. 121. Bansch D, Antz M, Boczor S, et al: Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation 105:1453-1458, 2002. 122. Bristow MR, Saxon LA, Boehmer J, et al: Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004. 123. Cleland JG, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005.

278

SECTION 2  Clinical Concepts

124. Packer DL, Prutkin JM, Hellkamp AS, et al: Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the Sudden Cardiac Death in Heart Failure Trial. Circulation 120:2170-2176, 2009. 125. Mark DB, Nelson CL, Anstrom KJ, et al: Cost-effectiveness of defibrillator therapy or amiodarone in chronic stable heart failure: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Circulation 114:135-142, 2006. 126. Gold MR, Ip JH, Costantini O, et al: Role of microvolt T-wave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction: primary results from the T-Wave Alternans Sudden Cardiac Death in Heart Failure trial substudy. Circulation 118:2022-2028, 2008. 127. Chow T, Kereiakes DJ, Bartone C, et al: Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy. J Am Coll Cardiol 47:1820-1827, 2006. 128. Blatt JA, Poole JE, Johnson GW, et al: No benefit from defibrillation threshold testing in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). J Am Coll Cardiol 52:551-556, 2008. 129. Healey JS, Birnie DH, Lee DS, et al: Defibrillation Testing at the Time of ICD Insertion: An Analysis from the Ontario ICD Registry. J Cardiovasc Electrophysiol 21:1344-1348, 2010. 130. Kadish A, Dyer A, Daubert JP, et al: Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 350:2151-2158, 2004. 131. Ellenbogen KA, Levine JH, Berger RD, et al: Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac death in patients with nonischemic cardiomyopathy? Circulation 113:776-782, 2006. 132. Kadish A, Schaechter A, Subacius H, et al: Patients with recently diagnosed nonischemic cardiomyopathy benefit from implantable cardioverter-defibrillators. J Am Coll Cardiol 47:2477-2482, 2006. 133. Nanthakumar K, Epstein AE, Kay GN, et al: Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials. J Am Coll Cardiol 44:2166-2172, 2004. 134. Bigger JT, Jr, Whang W, Rottman JN, et al: Mechanisms of death in the CABG Patch trial: a randomized trial of implantable cardiac defibrillator prophylaxis in patients at high risk of death after coronary artery bypass graft surgery. Circulation 99:14161421, 1999. 135. Bailey JJ, Berson AS, Handelsman H, Hodges M: Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction. J Am Coll Cardiol 38:19021911, 2001. 136. Bauer A, Guzik P, Barthel P, et al: Reduced prognostic power of ventricular late potentials in post-infarction patients of the reperfusion era. Eur Heart J 26:755-761, 2005. 137. Al-Khatib SM, Hellkamp AS, Lee KL, et al: Implantable cardioverter defibrillator therapy in patients with prior coronary revascularization in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). J Cardiovasc Electrophysiol 19:1059-1065, 2008. 138. Barsheshet A, Goldenberg I, Narins CR, et al: Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT. Heart Rhythm 7:1421-1427, 2010. 139. Dorian P, Connolly S, Hohnloser SH: Why don’t ICDs decrease all-cause mortality after MI? Insights from the DINAMIT study. Circulation 110:502, 2004. 140. Savoye C, Equine O, Tricot O, et al: Left ventricular remodeling after anterior wall acute myocardial infarction in modern clinical practice (from the REmodelage VEntriculaire [REVE] study group). Am J Cardiol 98:1144-1149, 2006. 141. Huikuri HV, Exner DV, Kavanagh KM, et al: Attenuated recovery of heart rate turbulence early after myocardial infarction identifies patients at high risk for fatal or near-fatal arrhythmic events. Heart Rhythm 7:229-235, 2010. 142. Nolan J, Batin PD, Andrews R, et al: Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom Heart Failure Evaluation and Assessment of Risk Trial (UK-Heart). Circulation 98:1510-1516, 1998. 143. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51:e1-e62, 2008. 144. Fogoros RN: An AVID dissent (editorial) [see comments]. Pacing Clin Electrophysiol 17:1707-1711, 1994. 145. Epstein AE: AVID necessity. Pacing Clin Electrophysiol 16:17731775, 1993. 146. Maron BJ, Shen WK, Link MS, et al: Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy [see comments]. N Engl J Med 342:365-373, 2000.

147. Piccini JP, Dalal D, Roguin A, et al: Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia. Heart Rhythm 2:1188-1194, 2005. 148. Maron BJ, Spirito P, Shen WK, et al: Implantable cardioverterdefibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy. JAMA 298:405-412, 2007. 149. Costantini O, Hohnloser SH, Kirk MM, et al: The ABCD (Alternans Before Cardioverter Defibrillator) Trial: strategies using T-wave alternans to improve efficiency of sudden cardiac death prevention. J Am Coll Cardiol 53:471-479, 2009. 150. Chow T, Kereiakes DJ, Bartone C, et al: Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy. J Am Coll Cardiol 49:50-58, 2007. 151. Klein RC, Raitt MH, Wilkoff BL, et al: Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics versus Implantable Defibrillators (AVID) Trial. J Cardiovasc Electrophysiol 14:940-948, 2003. 152. Wathen M: Implantable cardioverter defibrillator shock reduction using new antitachycardia pacing therapies. Am Heart J 153:44-52, 2007. 153. Grimm W, Flores BT, Marchlinski FE: Shock occurrence and survival in 241 patients with implantable cardioverterdefibrillator therapy. Circulation 87:1880-1888, 1993. 154. Grimm W, Hoffmann JJ, Muller HH, Maisch B: Implantable defibrillator event rates in patients with idiopathic dilated cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left ventricular ejection fraction below 30%. J Am Coll Cardiol 39:780-787, 2002. 155. Garratt CJ, Elliott P, Behr E, et al: Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes. Europace 12:1156-1175, 2010. 156. Maron BJ, Olivotto I, Spirito P, et al: Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large nonreferral-based patient population. Circulation 102:858-864, 2000. 157. Maron BJ, Casey SA, Hauser RG, Aeppli DM: Clinical course of hypertrophic cardiomyopathy with survival to advanced age. J Am Coll Cardiol 42:882-888, 2003. 158. Elliott P, Gimeno J, Mahon N, et al: Relation between severity of left-ventricular hypertrophy and prognosis in patients with hypertrophic cardiomyopathy. Lancet 357:420-424, 2001. 159. Maron BJ, Thompson PD, Ackerman MJ, et al: Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 115:1643-1655, 2007. 160. O’Hanlon R, Grasso A, Roughton M, et al: Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy. J Am Coll Cardiol 56:867-874, 2010. 161. Bruder O, Wagner A, Jensen CJ, et al: Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 56:875-887, 2010. 162. Gosling OE, Bellenger N, Spurrell P: Risk assessment with cardiac magnetic resonance imaging in hypertrophic cardiomyopathy. Heart 95:1843, 2009. 163. Pierre-Louis B, Prasad A, Frishman WH: Cardiac manifestations of sarcoidosis and therapeutic options. Cardiol Rev 17:153-158, 2009. 164. Syed J, Myers R: Sarcoid heart disease. Can J Cardiol 20:89-93, 2004. 165. Kim JS, Judson MA, Donnino R, et al: Cardiac sarcoidosis. Am Heart J 157:9-21, 2009. 166. Aizer A, Stern EH, Gomes JA, et al: Usefulness of programmed ventricular stimulation in predicting future arrhythmic events in patients with cardiac sarcoidosis. Am J Cardiol 96:276-282, 2005. 167. Patel MR, Cawley PJ, Heitner JF, et al: Detection of myocardial damage in patients with sarcoidosis. Circulation 120:1969-1977, 2009. 168. Marcus FI, McKenna WJ, Sherrill D, et al: Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 121:15331541, 2010. 169. Dalal D, Nasir K, Bomma C, et al: Arrhythmogenic right ventricular dysplasia: a United States experience. Circulation 112:3823-3832, 2005. 170. Corrado D, Leoni L, Link MS, et al: Implantable cardioverterdefibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/ dysplasia. Circulation 108:3084-3091, 2003. 170a.  Olshansky B, Day JD, Moore S, et al: Is dual-chamber programming inferior to single chamber programming in an implantable cardioverter-defibrillator? Results of the INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AVSH in ICDs) study. Circulation 115:9-16, 2007.

171. Wilkoff BL, Kudenchuk PJ, Buxton AE, et al: The DAVID (Dual Chamber and VVI Implantable Defibrillator) II trial. J Am Coll Cardiol 53:872-880, 2009. 172. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. 173. Moss AJ, Hall WJ, Cannom DS, et al: Cardiac-resynchronization therapy for the prevention of heart failure events. N Engl J Med 361:1329-1338, 2009. 174. Solomon SD, Foster E, Bourgoun M, et al: Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: Multicenter Automatic Defibrillator Implantation Trial: cardiac resynchronization therapy. Circulation 122:985992, 2010. 175. Dickstein K, Vardas PE, Auricchio A, et al: 2010 focused update of ESC Guidelines on Device Therapy in Heart Failure: an update of the 2008 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and the 2007 ESC Guidelines for Cardiac Resynchronization Therapy. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J 31:2677-2687, 2010. 176. Tang AS, Wells GA, Talajic M, et al: Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators; Cardiac resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363:2385-2395, 2010. 177. Moss AJ: Should everyone with an ejection fraction less than or equal to 30% receive an implantable cardioverter-defibrillator? Everyone with an ejection fraction ≤30% should receive an implantable cardioverter-defibrillator. Circulation 111:25372549, discussion 2549, 2005. 178. Buxton AE: Should everyone with an ejection fraction less than or equal to 30% receive an implantable cardioverter-defibrillator? Not everyone with an ejection fraction ≤30% should receive an implantable cardioverter-defibrillator. Circulation 111:25372549, 2005. 179. Goldenberg I, Moss AJ: Implantable cardioverter defibrillator efficacy and chronic kidney disease: competing risks of arrhythmic and nonarrhythmic mortality. J Cardiovasc Electrophysiol 19:1281-1283, 2008. 180. Theuns DA, Klootwijk AP, Simoons ML, Jordaens LJ: Clinical variables predicting inappropriate use of implantable cardioverter-defibrillator in patients with coronary heart disease or nonischemic dilated cardiomyopathy. Am J Cardiol 95:271274, 2005. 181. Capoferri M, Schwick N, Tanner H, et al: Incidence of arrhythmic events in patients with implantable cardioverter-defibrillator for primary and secondary prevention of sudden cardiac death. Swiss Med Wkly 134:154-158, 2004. 182. Wilkoff BL, Hess M, Young J, Abraham WT: Differences in tachyarrhythmia detection and implantable cardioverter defibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 15:1002-1009, 2004. 183. Theuns DA, Thornton AS, Klootwijk AP, et al: Outcome in patients with an ICD incorporating cardiac resynchronisation therapy: differences between primary and secondary prophylaxis. Eur J Heart Fail 7:1027-1032, 2005. 184. Backenkohler U, Erdogan A, Steen-Mueller MK, et al: Long-term incidence of malignant ventricular arrhythmia and shock therapy in patients with primary defibrillator implantation does not differ from event rates in patients treated for survived cardiac arrest. J Cardiovasc Electrophysiol 16:478-482, 2005. 185. Kautzner J, Riedlbauchova L, Cihak R, et al: Technical aspects of implantation of LV lead for cardiac resynchronization therapy in chronic heart failure. Pacing Clin Electrophysiol 27:783-790, 2004. 186. Curtis JP, Luebbert JJ, Wang Y, et al: Association of physician certification and outcomes among patients receiving an implantable cardioverter-defibrillator. JAMA 301:1661-1670, 2009. 187. Freeman JV, Wang Y, Curtis JP, et al: The relation between hospital procedure volume and complications of cardioverterdefibrillator implantation from the Implantable CardioverterDefibrillator Registry. J Am Coll Cardiol 56:1133-1139, 2010. 188. Aggarwal A, Wang Y, Rumsfeld JS, et al: Clinical characteristics and in-hospital outcome of patients with end-stage renal disease on dialysis referred for implantable cardioverter-defibrillator implantation. Heart Rhythm 6:1565-1571, 2009. 189. Lee DS, Krahn AD, Healey JS, et al: Evaluation of early complications related to de novo cardioverter-defibrillator implantation: insights from the Ontario ICD database. J Am Coll Cardiol 55:774-782, 2010. 190. Daugherty SL, Peterson PN, Wang Y, et al: Use of implantable cardioverter-defibrillators for primary prevention in the community: do women and men equally meet trial enrollment criteria? Am Heart J 158:224-229, 2009. 191. Curtis AB, Yancy CW, Albert NM, et al: Cardiac resynchronization therapy utilization for heart failure: findings from IMPROVE HF. Am Heart J 158:956-964, 2009.

12  12

Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators SANDEEP TALWAR  |  LESLIE A. SAXON

A

paradigm shift in the treatment of heart failure from purely pharmacologic therapy to a strategy that now includes electrical therapy was heralded by the outcomes of major landmark trials of cardiac resynchronization therapy (CRT), which are reviewed in this chapter. These trials have elucidated the relative roles of pacing, defibrillation, and intraventricular conduction delay in the natural history of heart failure. They have helped to identify patient populations who benefit from device therapy as well as limitations in selecting patients based on measures other than QRS width (duration). Advances in remote device follow-up technology are further refining daily management and improving outcomes in heart failure patients. Treatment of the heart failure disease substrate with device-based therapy such as CRT has expanded the potential of a heart failure device that not only treats heart failure, but also diagnoses and prevents heart failure exacerbations and arrhythmic events, aiding overall patient management and tracking. Patients with advanced heart failure can receive contemporary medical therapy combined appropriately with electrical resynchronization. Also, their outcome may be predicted by powerful point-of-source data sets that allow for daily diagnostic measures and patient participation in disease management.1-10 Resynchronization devices now represent about 40% of all implantable cardioverter-defibrillators (ICDs) used in the United States.11 Review of clinical trial data shows that at least one third of patients for whom ICDs are indicated also qualify for a CRT with defibrillator (CRT-D) device.12,13 This proportion is likely to increase with expansion of CRT therapy to patients with mild to moderate heart failure.14 Although the implant procedure for a CRT-D is technically more challenging than that for an ICD, CRT has the added advantages of making patients feel better, causing reverse ventricular remodeling, and reducing heart failure hospitalizations—three important goals when offering device therapy to a population with heart failure.2,9,15,16 Despite the evidence base and guidelines, CRT is underutilized in eligible patients, with significant variation in age, gender, QRS duration, care provider, insurance status, and geographic location of practices.17 This chapter also reviews advances in lead technology, and device features for delivering CRT itself or expanding CRT, such as remote device follow-up and enhanced CRT–heart failure diagnostic devices.18-23

Heart Failure and QRS Delay: Scope of the Problem The greatest expense for the U.S. Medicare Trust Fund is the treatment of heart failure.24-28 The majority of this expense is in the acute management of heart failure hospitalizations, which often require intensive care unit management.26 There are not only about 1 million heart failure hospitalizations yearly, but also 300,000 heart failure deaths. These deaths are primarily caused by progressive pump dysfunction and sudden cardiac death, both of which can be addressed with a CRT and pacemaker (CRT-P) or CRT-D device.8,9 As heart failure severity

increases, characterized by both mechanical and electrical remodeling, the primary cause of cardiovascular death typically is pump failure. Conversely, as heart failure functional class improves, electrical instability plays a more prominent role, such that the absolute number of sudden deaths in the patient with advanced heart failure and QRS prolongation is significant, accounting for about one third of all deaths.29,30 When it accompanies heart failure from systolic dysfunction, QRS delay (≥120 msec) itself adds significant morbidity and mortality.31-36 In fact, mortality rates progressively increase as intraventricular conduction delay increases. The latter may also predispose heart failure patients to an increased risk of ventricular arrhythmias by acting as a substrate for reentrant ventricular tachycardia.37 Affecting 30% to 50% of patients with New York Heart Association (NYHA) Class III or IV heart failure, QRS delay, predominantly left bundle branch block (LBBB), impairs cardiac function by introducing intraventricular dyssynchrony. Severe mechanical left ventricular (LV) dyssynchrony is observed in 60% to 70% of patients with QRS duration of 120 msec or greater. It was previously thought that this group of patients with advanced heart failure would be most likely to benefit from resynchronization therapy; this chapter reviews data disproving this assumption. Conduction delay also worsens atrioventricular (AV) and interventricular (VV) dyssynchrony, whereas intraventricular dyssynchrony results in worsening LV function, as measured by the rise of left ventricular pressure (dP/dt) and filling times.38-41 Interestingly, even in patients with right bundle branch block (RBBB) or intraventricular conduction delay, significant electrical delay to the left ventricle is observed on detailed activation mapping, suggesting that RBBB in this setting often represents “concealed” LBBB.42,43

Studies of CRT in the Acute Setting: How Does It Work? Cardiac resynchronization therapy is defined as the stimulation of the left ventricle or simultaneous stimulation of both the right and the left ventricle after atrial sensed or paced events or in atrial fibrillation (AF). CRT works by multiple mechanisms, ranging from structural changes (e.g., favorable ventricular remodeling, improved peak oxygen consumption, reduced mitral regurgitation) to cellular and molecular changes (e.g., improved adrenergic-stimulated myocyte function, decreased neurohormonal activation, altered ionic currents and calcium homeostasis). In an elegant study, Tomaselli’s group recently demonstrated that CRT abbreviates the dyssynchronous heart failure–induced prolongation of action potential in cells isolated from the LV lateral wall. Aiba et al.44 conclude that CRT partially reverses the cellular triggers and substrate for arrhythmias in this pacing-induced model of heart failure. CRT works by partially or totally correcting AV, VV, and most importantly left intraventricular dyssynchronies, leading to reverse remodeling and restoring adverse electrophysiologic, neurohormonal, and anatomic changes that result from heart failure.40,44-50 The predominant beneficial effects are on measures of systolic function, as summarized in Table 12-1 and discussed in detail in Chapter 9.

279

280

TABLE

12-1 

SECTION 2  Clinical Concepts

Mechanisms of Acute Improvement in Cardiac Function with Cardiac Resynchronization Therapy (CRT)

Type of CRT Atrioventricular (AV) resynchronization Inter/intraventricular resynchronization

Mechanisms Diminished mitral regurgitation Lengthened diastolic filling time Optimization of filling pattern Increases in left ventricular efficiency/systolic blood pressure, dP/dt, pulse pressure, stroke volume, and stroke work Decrease in left ventricular end-systolic volume

In the first closed-chest study of CRT, in 27 subjects with heart failure and QRS delay, Blanc et al.45 demonstrated improvements in systolic blood pressure, pulmonary capillary wedge pressure, and V-wave amplitude with LV or biventricular (BiV) stimulation compared with baseline or right ventricular (RV) pacing. Kass et al.39 and Aurrichio et al.46 subsequently demonstrated that the effects of CRT could be further optimized by AV delay timing to achieve immediate increases in dP/dt and pulse pressure of 12% to 25% with LV or BiV stimulation, in a total of 45 patients. Figure 12-1 demonstrates the effects of pacing site on pressure-volume loops obtained in a patient with heart failure and LBBB. Neither RV pacing site alters the abnormal

loop. However, both left ventricular free wall (LVFW) and BiV stimulation result in reduced LV end-systolic volume and increased stroke volume and stroke work (increased loop width and area). These changes correlated with improved pulse pressure. Interestingly, in the patient with AF and heart block, greater immediate improvement in LV function is achieved with BiV or LV-RV offset stimulation than with single-site LV stimulation, presumably because VV dyssynchrony induced by LV-only stimulation is avoided in the setting of heart block.49 Acute predictors of a beneficial hemodynamic response to CRT were identified to be baseline extent of QRS delay (but not subsequent shortening with pacing) and mechanical dyssynchrony.41,50 LVFW rather than true anterior LV stimulation sites appear to elicit a more robust acute hemodynamic response.48 However, rigorous endocardial mapping has recently shown a high degree of individual variability for the best pacing site.51 The authors concluded that in a homogeneous group of patients with nonischemic dilated cardiomyopathy, the optimal pacing site cannot be predicted, and pacing from the coronary sinus or midlateral wall is rarely optimal. Speckle tracking analysis of torsion suggests that an acute improvement in LV twist after CRT predicts LV reverse remodeling.52 Similar findings in the PROMISE-CRT study support the hypothesis that acute changes in radial mechanical dyssynchrony are associated with LV reverse remodeling.53

RV SEPTUM

LV pressure (mm Hg)

RV APEX 120

120

80

80

40

40

0

0 0

100

200

300

0

LV pressure (mm Hg)

LV FREE WALL

100

200

300

BIVENTRICULAR

120

120

80

80

40

40

0

0 0

100

200

0

300

LV volume (mL)

100

200

300

LV volume (mL)

Intrinsic Paced Figure 12-1  Pressure-volume graphs from a patient with baseline left bundle branch block as a function of varying pacing sites. Data are shown for optimal atrioventricular interval (averaging 125 ± 48 msec) at each site; solid line, NSR control; dashed line, VDD pacing. The difference was negligible between right ventricular (RV) apex and septum pacing. However, left ventricular (LV) pacing produced loops with greater area (stroke work) and width (stroke volume) and a reduced systolic volume. The last finding is consistent with increased contractile function and thus elevation of dP/dtmax. These results were similar in a subset of patients with measurable data. (From Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 30:1567-1573, 1999.)



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Controlled Trials of CRT Devices Table 12-2 summarizes the design, inclusion criteria, and results of the early controlled clinical trials of CRT-P and CRT-D devices. In general, inclusion criteria were similar: symptomatic, mostly NYHA Class III and IV heart failure (except REVERSE and MADIT-CRT, later trials that enrolled NYHA I and II patients), left ventricular ejection fraction (LVEF) of less than 0.35, prolonged QRS duration (>120, >130, or >150 msec), and stability of proved medical therapies for heart failure before enrollment.3,5,7-10,54-57 TABLE

12-2 

281

Only two early trials used epicardial LV leads, placed through limited thoracotomy for LV stimulation.4,54 The Multisite Stimulation in Cardiomyopathy–Sinus Rhythm (MUSTIC-SR) trial used a styletdriven coronary sinus lead; the other trials used over-the-wire leads to achieve LV stimulation through a coronary sinus branch vein.3,7-10,54-57 The earliest U.S. CRT study using an epicardial LV lead, the VIGORCHF trial, was not completed because of insufficient patient enrollment for the primary functional endpoint of peak oxygen uptake (peak Vo2). In addition, with the emergence of the coronary sinus branch vein lead, patients and physicians became reluctant to continue using

Early Controlled Trials of CRT Alone or with Implantable Cardioverter-Defibrillator (ICD) Enrollment (Pub) Dates 1998-1999 (2001)

Study (Location) Multisite Stimulation in Cardiomyopathy–Sinus Rhythm (MUSTIC-SR) (Europe)

Type (Duration) Prospective, randomized, single-blind crossover study of HF (3 months)

Multisite Stimulation in Cardiomyopathy–Atrial Fibrillation (MUSTIC-AF) (Europe)

Prospective, randomized, single-blind crossover VVIR-BiV study of HF (2-3 months)

1998-1999 (2002)

Pacing Therapies in Congestive Heart Failure (PATH-CHF) (Europe)

Longitudinal study of CRT with second placebo control phase; first and third periods are crossovers between LV and BiV (3 months) Crossover randomized trial of no CRT vs. CRT in LV only; 2 patient groups: QRS 120150 msec and QRS >150 msec (3 months)

1995-1998 (2002)

PATH-CHF II (Europe)

N* 67

NYHA >III LVEF <0.35 LVEDD >60 mm QRS ≥200 msec during ventricular pacing 6MWD <450 m NYHA III or IV QRS >120 msec Sinus rate ≥55 bpm PR ≥150 msec

6MWD, peak Vo2, QOL, NYHA,† hospitalization, patient treatment preference, all-cause mortality, echo indices

59

Peak Vo2, 6MWD, NYHA, QOL†

41

86

NYHA II-IV LVEF ≤0.30 QRS ≥120 msec Optimal therapy for HF; patients with ICDs may be included

Peak Vo2, peak Vo2 AT, 6MWD, QOL, NYHA,† hospitalization

NYHA III-IV LVEF ≤0.35 LVEDD ≥55 mm QRS ≥130 msec Patients with pacing indication not admitted; stable optimal medical therapy NYHA III-IV LVEF ≤0.35 LVEDD ≥55 mm QRS ≥130 msec ICD indication

NYHA, 6MWD, QOL,† echo indices, peak Vo2, mortality, hospitalization, QRS duration, neurohormone levels

453

QOL, NYHA, 6MWD,† peak Vo2, echo indices, exercise duration, HF composite (death, HF hospitalization, NYHA, and patient global self-assessment), safety of CRT-D Combined all-cause mortality and all-cause hospitalization,† QOL, functional capacity, peak exercise performance, cardiac morbidity

369

Prospective, randomized, double-blind, parallel, controlled trial (6 months)

1998-2000 (2002)

Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLEICD) (U.S.)

Prospective, randomized, double-blind, parallel, controlled trial evaluating safety and efficacy of CRT in patients with HF and indication for ICD (6 months) Randomized (1:2:2), open-label, 3-arm study to determine if optimal drug therapy + CRT or drug therapy + CRT-D is superior to drug therapy alone (12 months)

1999-2001 (2003)

Open-label, randomized, controlled trial of CRT + optimal medical therapy vs. optimal medical therapy alone (mean: 29.4 mo)

2001-2003 (2004)

Cardiac Resynchronization in Heart Failure (CARE-HF) (Europe)

Endpoints 6MWD, peak Vo2, QOL, NYHA,† hospitalization, patient treatment preference, all-cause mortality, echo indices

1998 (2003)

Multicenter InSync Randomized Clinical Evaluation (MIRACLE) (U.S.)

Comparison of Medical Therapy Pacing and Defibrillation in Heart Failure (COMPANION) (U.S.)

Inclusion Criteria NYHA III LVEF <0.35 LVEDD >60 mm QRS ≥150 msec 6MWD <450 m

2000-2002 (2004)

NYHA III or IV LVEF ≤0.35 QRS ≥120 msec PR >150 msec No indication for pacemaker or ICD HF hospitalization in past year NYHA III or IV LVEF ≤0.35 LVEDD ≥30 mm/m (height) QRS >150 msec or QRS ≥120 msec plus echo criteria of dyssynchrony; stable optimal medical therapy

All-cause mortality or unplanned cardiovascular hospitalization,† all-cause mortality or hospitalization for HF, NYHA, QOL, echo LV function, neurohormone levels, economic impact

1520

800

Results Improvements in 6MWD, peak Vo2, QOL, and NYHA; reduced hospitalizations; patients preferred CRT Improvements in 6MWD, peak Vo2, QOL, and NYHA; reduced hospitalizations; patients preferred CRT Improvements in exercise capacity, functional status, and QOL

In group with QRS 120-150 msec, no improvement In group with QRS >150 msec, improvements in Vo2, AT, 6MWD, and QOL Improvements in NYHA, 6MWD, QOL, LVEF, ventricular volumes, mitral regurgitation, peak Vo2; reduced hospitalizations Improvements in QOL, NYHA, and clinical composite endpoints; CRT-D safe to use

Stopped early because of reduced all-cause mortality and hospitalization with CRT; reduced all-cause mortality with CRT-D Improvements in morbidity/mortality and cardiovascular hospitalization

Modified from Saxon LA, De Marco T, Prystowsky EN, et al, Executive Summary: Resynchronization Therapy for Heart Failure. Executive Consensus Conference, May 2002. http:// www.hrsonline.org/positionDocs/CRT_12_3.pdf/. AT, Anaerobic threshold; BiV, biventricular; CRT-D, CRT with defibrillator; echo, echocardiographic; HF, heart failure; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; 6MWD, 6-minute walk distance; NYHA, New York Heart Association functional class; QOL, quality of life; Vo2, oxygen uptake. *Accrual or accrual goals. †Primary endpoint.

282

TABLE

12-3 

SECTION 2  Clinical Concepts

Study Endpoints in Trials of CRT Devices

Measure Functional status Heart failure progression Heart failure outcome

Endpoints Quality of life (QOL) 6-minute walk distance Cardiopulmonary exercise test Left ventricular ejection fraction (LVEF), ventricular volume Mitral regurgitation Serum catecholamines, brain natriuretic peptide Heart rate variability Hospitalization Mortality

a more invasive procedure for LV stimulation. The echocardiographic substudy, however, as with the first European Pacing Therapies in Congestive Heart Failure (PATH-I) study, demonstrated improvement in several measures of response to CRT, comparable to levels seen in studies using transvenous LV stimulation for CRT.7,40,54 The VIGORCHF trial demonstrated a decrease in LV and left atrial volumes as well as improvements in LV outflow tract and aortic velocity time integrals and myocardial performance indices with just 12 weeks of CRT. The severity or grade of mitral regurgitation as well as mitral deceleration (a measure of improvement of diastolic LV function) also improved. In the two early U.S. trials that were the basis for attaining the initial approvals from the U.S. Food and Drug Administration (FDA) for CRT-defibrillator (CONTAK CD and MIRACLE-ICD; see later), patients with NYHA Class II were included, but FDA labeling was not requested for this patient subset and was granted only for patients with NYHA III and IV.8,57,58 Exclusion criteria included the presence of an implanted device and requirement for bradycardia pacing support or permanent AF. The early U.S. trials used parallel design; devices were implanted in all patients, who were then randomly assigned to “CRT on” or “CRT off ” status for 6 months. Two principal investigators at each enrolling center were designated in most trials, so the physician managing the medical therapies (heart failure) was blinded as to the treatment assignment, and the implanting physician (electrophysiologist) followed the device performance. The study endpoints in CRT trials have evolved over time. Although all trials have included safety and efficacy endpoints, the initial trials assessed only measures of heart failure functional status, LV systolic function (LVEF), and LV remodeling (LV end-systolic and diastolic dimensions). The later, larger studies targeted mortality and hospitalization endpoints (Table 12-3). The use of these multiple endpoint measures is standard for heart failure trials evaluating medical therapies and has highlighted the issue of defining “benefit” from CRT.1,6 One can define “response” as consisting only of symptom improvement, or one can require that all three measures of heart failure show benefit, as outlined in Table 12-3. To complicate the issue further, no 1 : 1 correlation seems to exist between these measures of response. Again, the CONTAK CD and MIRACLE-ICD studies enrolled some patients with NYHA Class II in addition to those with NYHA III and

Multisite Stimulation in Cardiomyopathy Studies The 2001-2002 European Multisite Stimulation in Cardiomyopathy (MUSTIC) studies provided the first long-term controlled trial data on the efficacy of CRT, delivered as BiV stimulation, for 3-month intervals, compared with normal sinus rhythm or continuous RV-based pacing in AF patients.3,56 Figure 12-2 illustrates the crossover study design of the MUSTIC and MUSTIC–Atrial Fibrillation studies. Although only 48 patients completed the two 3-month crossover study periods, all leads placed in the trial were transvenous, with no significant safety issues. Eligibility for patient enrollment included NYHA Class III with QRS longer than 150 msec. In patients with normal sinus rhythm, quality of life (QOL) score improved by 32%, 6-minute walk distance (6MWD) improved by 23%, and peak Vo2 improved by 8%. Although the study was not statistically powered to determine a reduction in rate of hospitalization, hospitalizations after CRT initiation decreased by two thirds.3 At the end of the crossover phase, patients (who were blinded to treatment) were asked to choose which 3-month period they preferred; 85% chose the pacing period during which they had been assigned to VDD, 10% had no preference, and 4% chose ODO (no pacing). Four patients had severe episodes of congestive heart failure exacerbation during the ODO pacing period. In the patients with permanent AF and continuous RV pacing, 37 of 59 who underwent CRT implantation completed both 3-month crossover phases and had documentation of 97% to 100% CRT delivery. Because of the significant number of dropouts (42%), the intention-to-treat analysis did not show a significant improvement with CRT. In the 37 patients with a complete data set and documentation of CRT, QOL measure did not improve, but 6MWD and peak Vo2 increased significantly, by 9% (P = .05) and 13% (P = .04), respectively.56 When the entire 6-month crossover phase is considered, 10 of 44 patients were hospitalized for heart failure decompensation during RV pacing, whereas only three were hospitalized for heart failure during the CRT period; 85% of patients preferred the CRT period. There was a trend toward a better QOL among patients with CRT (11% improvement; P = .09). Subsequent uncontrolled trials in patients with permanent AF and continuous RV pacing have shown a more robust improvement in these measures, as well as a reverse-remodeling response with CRT compared with RV pacing alone.60,61 The PAVE trial also showed improvement with CRT but did not require heart failure caused by systolic dysfunction for enrollment.62

Inactive pacing

Implantation

Baseline

IV functional status. In the NYHA II group, significant improvements in measures of functional status were not uniformly observed, although some patients experienced a positive reverse-remodeling response.57,58 This has been confirmed in the much larger REVERSE study, where CRT in patients with NYHA Class I/II heart failure resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes in patients with nonischemic cardiomyopathy.15 Clearly, CRT has a positive effect on decreasing LV size, and the subsequent MADITCRT study demonstrated that CRT favorably alters the natural history of heart failure by reducing hospitalization.14,59

CO1

CO2

Randomization Active pacing

4 weeks

2 weeks

12 weeks

12 weeks

Figure 12-2  Crossover study design of MUSTIC studies. Patients were randomly assigned to 3 months each of inactive pacing (ventricular, inhibited at basic rate of 40 bpm) and active pacing (atriobiventricular); CO1, end of crossover period 1; CO2, end of crossover period 2. (From Cazeau S, Leclercq C, Lavergne T, et al: Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873-880, 2001.)



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Pacing Therapies in Congestive Heart Failure The two Pacing Therapies in Congestive Heart Failure (PATH-I and PATH-II) European studies were groundbreaking in that chronic device programming was based on acute hemodynamic measures of cardiac performance. In addition, these same measures were used to optimize AV-delay programming.54,55 Begun in 1995 and completed in 1998, these trials enrolled patients with NYHA Class III or IV congestive heart failure, sinus rate higher than 55 beats per minute (bpm), and QRS duration longer than 120 msec. In PATH-I, patients were crossed-over between LV and BiV stimulation with a 1-month interval of no stimulation. A second study phase lasted 9 months and used the CRT mode that achieved what the follow-up physician determined was the most optimal mode. There were no differences in the acute or chronic response of patients whether programmed to LV or BiV CRT. Statistically significant improvements in peak Vo2 anaerobic threshold (24% improvement; P < = .001), 6MWD (25%; P < .001) and QOL (59%; P < .001) were observed at 3 months and 12 months of follow-up. Of 29 patients followed to 12 months, 21 improved from NYHA Class III or IV to Class I or II. Heart failure hospitalizations decreased from 76% in the year before implantation to 31% during the year after implantation. Importantly, LBBB was the type of conduction delay in more than 87% of patients; most CRT trials enroll up to 30% of patients with either intraventricular condition delay (IVCD) or RBBB.4-6,9 This difference may explain why LV stimulation in PATH-I resulted in only an equivalent response to BiV stimulation to achieve CRT, although the study was not statistically powered to demonstrate a difference between the two modalities, and the long-term data were pooled from both modes. The best that one can conclude is that in small numbers of patients who undergo hemodynamic optimization programming during implantation that shows equivalence between LV and BiV stimulation to achieve CRT, longterm symptom responses appear to be equivalent. Extending the observations from PATH-I, PATH-II evaluated LV-only CRT compared with no CRT in a 3-month crossover design.55 In all patients with LBBB (88% of subjects), LV pacing was identified as the optimal single-chamber pacing mode (compared with RV only) on the basis of immediate hemodynamic response, and AV delay timing was optimized in all patients. Patients were further divided by QRS duration according to whether the QRS was more than 120 msec but less than 150 msec (“short QRS”) or more than 150 msec (“long QRS”). Unfortunately, only 35 patients, slightly less than one half of all patients enrolled, completed both 3-month crossover intervals. Nonetheless, the study did demonstrate improvements in peak Vo2, anaerobic threshold, 6MWD, and QOL in the patients with long QRS. For example, 71% of the long-QRS group and 38% of the short-QRS group had an increase in the peak Vo2 of more than 1 mL/kg/min with active pacing. This was the first study to demonstrate that QRS duration predicts the magnitude of symptom response to CRT delivered as LV-only stimulation. Subgroup analysis of all but one of the larger U.S. long-term studies of BiV CRT also suggests that the magnitude of benefit may be greater in patients with longer QRS duration at baseline.5,8-10,57 The EARTH trial will compare chronic LV to BiV stimulation and RV stimulation and assess differences in symptoms and in echocardiographic and metabolic exercise test performance, according to stimulation mode in CRT candidates.63 Multicenter InSync Randomized Clinical Evaluation The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study was the only U.S. trial of CRT for heart failure that used a CRTpacemaker device only.5 The number of patients randomly allocated in U.S. clinical trials was much greater than those in the European trials until the CARE-HF trial. All 453 patients enrolled in the MIRACLE study underwent implantation of the CRT device and then random assignment to “CRT on” or “CRT off ” status for 6 months. Figure 12-3 illustrates the study design of the MIRACLE, MIRACLE-ICD, and CONTAK CD U.S. trials. Unlike the COMPANION trial, in which patients were randomly assigned after consent was obtained and before

CRT

CONTAK CD Implantation

Baseline 6MW, CPX

>30 days

6 months

CRT

No CRT

CRT

MIRACLE ICD Baseline 6MW

283

Implantation

Baseline CPX

0–7 days

6 months

CRT

No CRT

CRT

MIRACLE Baseline 6MW, CPX

Implantation

6 months

CRT

No CRT Figure 12-3  Study design of three U.S. trials. CONTAK CD Biventricular Pacing Study (CONTAK CD), Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD), and Multicenter InSync Randomized Clinical Evaluation (MIRACLE); 6MW, 6-mile walk distance; CPX, cardiopulmonary exercise test; CRT, cardiac resynchronization therapy.

device implantation, these earlier U.S. trials randomly assigned patients only after a successful CRT implant. The U.S. trials also employed strict protocol-mandated criteria on appropriate and stable heart failure medical regimen requirements before consent and device implantation. The primary endpoints, including 6MWD, QOL score, and NYHA functional class, were all favorably influenced by CRT, and the effects of CRT were apparent as early as 1 month after therapy initiation. Patients who underwent CRT showed 13% improvement in 6MWD, 13% improvement in QOL, about 1-mL/kg/min improvement in exercise capacity, and an increase in total exercise time of approximately 60 seconds. Unlike the European and acute hemodynamic studies, neither baseline QRS duration nor type of bundle branch block influenced response to CRT in the MIRACLE study. The secondary endpoints, Vo2 and LVEF, also improved with CRT, as did episodes of heart failure worsening, including heart failure hospitalizations. At 6 months, CRT was associated with decreased LV end-diastolic volume (LVEDV) and LV end-systolic volume, reduced LV mass, increased LVEF (+3.6%), decreased mitral regurgitation jet area (−2.5 cm2), and improvement in the clinical composite heart failure score. Improvements in LVEDV and LVEF were twofold greater in patients with nonischemic cardiomyopathy. CRT resulted in significant improvements in NYHA class and LVEF, regardless of age.64 CONTAK CD and Multicenter InSync ICD Randomized Clinical Evaluation Concurrent with the MIRACLE trial enrollment, two large-scale trials of CRT-defibrillator for patients with heart failure and primary or secondary indications for an ICD were also enrolling subjects, the Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLEICD) and the CONTAK CD Biventricular Pacing Study. Unlike the MIRACLE study, the 950 patients randomly assigned to different therapies in the CRT-D studies had primarily ischemic cardiomyopathy (61%-75%,) and about one half of the patients had a secondary indication for the ICD.8,57 In patients with NYHA Class III or IV status, both studies demonstrated improvements in functional measures of heart failure status. An ongoing debate concerns the impact of CRT and

284

SECTION 2  Clinical Concepts

reverse remodeling on ventricular arrhythmias. Neither study showed a difference in the incidence of treated episodes of ventricular tachycardia or ventricular fibrillation (VT/VF) with CRT on or off, indicating a neutral effect of CRT on the arrhythmia substrate early after device implantation. A subsequent analysis of the MIRACLE-ICD data indicated that patients with secondary ICD indications experienced more ICD therapies for VT, whereas those with primary ICD indications had more therapy for VF.65 The incidence of ICD therapy, as expected, was higher in those with secondary prevention indications. In CONTAK CD, the incidence of ICD therapy over the 6-month follow-up was 16% for both VT and VF. In contrast, in the InSync ICD Italian Registry, a significant reduction in ventricular arrhythmias and shock therapies was reported and correlated with the degree of ventricular remodeling at 12 months.66 Similar findings were seen in the InSync-III Marquis study, in which anatomic responders to CRT demonstrated fewer premature ventricular contractions (PVCs), runs of PVCs, and therapies for VT/VF.67 Improvements in LVEF and ventricular size and dimension and degree of mitral regurgitation were noted in the VIGOR-CHF, MIRACLE, MIRACLE-ICD, and CONTAK CD studies, all of which had core echocardiographic laboratories performing analysis, with excellent intraobserver and interobserver variability.7,40 As mentioned, even the patients with NYHA Class II benefited from CRT in terms of an echocardiographic response of reverse remodeling.16,57 These CRTrelated effects were independent of the use of β-blocker therapy.7 This finding suggests that CRT can exert beneficial effects on the remodeling process across a spectrum of heart failure severity, similar to that observed with angiotensin-converting enzyme (ACE) inhibitor therapy.1 A subsequent study of the effects of CRT on ventricular function, volume, and dimension has shown that the beneficial effects occur as early as 4 weeks and are sustained for a time even after CRT is suspended, indicating that CRT affects cardiac structure.68 Another measure of heart failure progression, level of plasma neurohormones, did not improve or worsen with CRT in the MIRACLEICD or MIRACLE study. This neutral effect may be a result of optimization of medical therapy with neurohormonal antagonists before device implantation or inadequate duration of follow-up.7

Comparison of Medical Therapy, Pacing, and Defibrillation on Heart Failure The Comparison of Medical Therapy, Pacing, and Defibrillation on Heart Failure (COMPANION) study was the first and only U.S. trial statistically powered to assess the impact of CRT on hospitalization and mortality endpoints.9,69 During COMPANION’s design, it was unclear whether ICD therapy in addition to CRT would reduce mortality in advanced heart failure compared with medical therapy. Therefore, the study randomly assigned patients to optimal medical (pharmacologic) therapy for heart failure (OPT), a CRT with pacemaker (CRT-P) alone, or a CRT with an ICD (CRT-D). The patients were assigned in a 1 : 2 : 2 ratio, respectively, to maximize the number of patients receiving devices. Statistical power was insufficient to compare CRT with CRT-D directly (both were compared with OPT), but the highest-order secondary endpoint was mortality. To enrich the anticipated event rate in the trial, patients also needed to have heart failure hospitalization in the previous year, but not in the month preceding enrollment, and to be receiving stable medical therapy at enrollment. Unlike the prior trials of CRT, patients were assigned for therapy and data were analyzed after they had provided informed consent, not after they had undergone a successful implantation. Figure 12-4 provides the design of the COMPANION study, and Table 12-4 lists the clinical characteristics of COMPANION patients. As with MIRACLE patients, and unlike those in the CRT-D studies, an equal proportion of patients in COMPANION had both ischemic and nonischemic etiologies for LV dysfunction. This was the first trial to enroll patients with advanced heart failure who were medically treated with “triple therapy,” consisting of ACE inhibitors, β-receptor blockers, and aldosterone antagonists. The primary study endpoint was a composite of all-cause hospitalization and mortality, and the secondary endpoint was mortality (1520 patients enrolled). Figure 12-5 shows the event-free survival curves for the primary and secondary endpoints and demonstrates the 20% 12-month reduction in death or hospitalization from any cause observed with both CRT and CRT-D devices compared with OPT. The risk of one of these events was 68% in OPT patients, attesting to the

Follow-up n = 1520

Follow-up

Follow-up

1

• OPT Baseline

Randomization Stratification

Implantation

Follow-up

Follow-up

Follow-up

Follow-up

Follow-up

2  • OPT • Resynchronization therapy Implantation

Follow-up

2  • OPT • Resynchronization therapy w/ICD backup <5 days

0

<2 working days

One week

One month

Quarterly

Time post-randomization Figure 12-4  Study design of COMPANION. Comparison of Medical Therapy, Pacing, and Defibrillation on Heart Failure study; ICD, implantable cardioverter-defibrillator; OPT, optimal pharmacologic therapy.



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

TABLE

12-4 

285

Clinical Characteristics of COMPANION Study Patients* Cardiac Resynchronization Therapy

Characteristic Age (yr) Male gender (%) NYHA III (%) Duration of heart failure (yr) LV ejection fraction LV end-diastolic dimension (mm) Heart rate (bpm) Blood pressure (mm Hg)   Systolic   Diastolic Distance walked in 6 min (m) QRS interval (ms) Ischemic cardiomyopathy (%) Diabetes (%) Bundle branch block (%)   Left   Right Pharmacologic Therapy (%) ACE inhibitor† ACE inhibitor or ARB† β-blocker Loop diuretic Spironolactone

Optimal Pharmacologic Therapy (N = 308) 68 69 82 3.6 0.22 67 72

Pacemaker (N = 617) 67 67 87 3.7 0.20 68 72

Pacemaker-Defibrillator (N = 595) 66 67 86 3.5 0.22 67 72

112 64 244 158 59 45

110 68 274 160 54 39

112 68 258 160 55 41

70 9

69 12

73 10

69 89 66 94 55

70 89 68 94 53

69 90 68 97 55

Modified from Bristow MR, Saxon LA, Boehmer J, et al: Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004. LV, Left ventricular; NYHA, New York Heart Association functional class. *Median values are given for continuous measures. There were no significant differences among the groups (n = 1520). †Patients who could not tolerate an angiotensin-converting enzyme (ACE) inhibitor received an angiotensin receptor blocker (ARB).

severity of heart failure in this population. Although CRT-P reduced mortality by 24%, this was not statistically significant (P = .06). CRT-D alone reduced mortality by 36% (P = .003) compared with OPT. Close inspection of the mortality curves shows that CRT survival parallels OPT survival until 6 months, when CRT shows benefit. In contrast, the CRT-D and OPT curves separate immediately. These observations suggest that the ICD portion of the CRT-D has an immediate effect to prevent sudden arrhythmic death, whereas the reductions in sudden death with CRT alone may be mediated through stabilization of heart failure status, which may be time dependent. Subsequent analysis showed that the reduced mortality with CRT-D resulted from a decrease in sudden cardiac death, and that the true reduction in hospitalizations resulted from a decrease in heart failure hospitalization, as adjudicated by an events committee.69,70 Subgroup analyses were remarkably consistent in demonstrating CRT benefit in all patient subgroups. There appeared to be equal benefit in women and men, in either ischemic or nonischemic etiologies of heart failure, regardless of LVEF greater or less than 20% and LV size greater or less than 67 mm. Those patients with longer QRS duration did appear to experience greater benefit with CRT, as did those with LBBB rather than RBBB or IVCD. Figure 12-6 provides the subgroup analysis from the COMPANION study, comparing CRT and CRT-D with OPT therapy for the primary and secondary endpoints. Any concern that the implantation of a CRT device may destabilize the usually very ill NYHA Class IV patient was addressed in a post hoc analysis of COMPANION.71 Although these devices did not impact significantly on heart failure deaths, both CRT and CRT-D significantly improved time to all-cause mortality and hospitalizations in the NYHA Class IV subset of patients. Time to sudden death was significantly reduced in the CRT-D group. The COMPANION data expand the role of CRT to achieve the three primary therapeutic goals in treating patients with heart failure: to improve symptoms, retard disease progression, and reduce rates of

hospitalization and mortality. There are two primary reasons for selecting a CRT-D over CRT-P alone. The COMPANION data support early sudden death protection with CRT-D, and the majority of patients with CRT indications also have ICD indications in singlechamber, primary prevention ICD trials.13,14 The 12-month and 24-month appropriate ICD therapy rate was 12% and 19%, respectively, higher than observed in the primary prevention ICD trials. Appropriate ICD therapy was predictive of risk of subsequent hospitalization and death, suggesting that sustained ventricular arrhythmias are a harbinger of worsening heart failure in CRT-D recipients.72 Cardiac Resynchronization-Heart Failure Study The Cardiac Resynchronization-Heart Failure (CARE-HF) study, enrolling 813 patients at 82 European centers, compared CRT only with optimal medical therapy.10 Over a mean follow-up of 29 months, CRT resulted in significant reductions in the primary composite endpoint of death or cardiovascular hospitalization. Reductions were also achieved in the secondary endpoint of mortality. Figure 12-7 illustrates the Kaplan-Meier curves for these endpoints. Comparing CARE-HF with COMPANION shows COMPANION patients to be a sicker group, perhaps because heart failure hospitalization was required in the year before enrollment.9 The 12-month mortality rate in the medical therapy group in CARE-HF was 12.6%, versus 19% in COMPANION. Only 38% of the patients in CARE-HF had coronary artery disease, compared with 56% in COMPANION; the mean LVEF was 25% in CARE-HF, compared with 21% in COMPANION; and a higher percentage of patients in COMPANION had NYHA Class IV status (16% vs. 6.5% in CARE-HF). Another issue is the positive effect of CRT on mortality in CARE-HF. The relative risk reduction with CRT in CARE-HF patients was equivalent to that of the COMPANION CRT-D patients (36%). The COMPANION CRT-P group’s 24% reduction in mortality was not statistically significant. These differences may be a result of the shorter duration of follow-up

286

SECTION 2  Clinical Concepts

A

B

Primary Endpoint

Secondary Endpoint

80 60 40 Pharmacologic therapy (216 events)

20 0

100

Pacemaker (414 events, P0.014) Pacemakerdefibrillator (390 events, P0.010)

Event-free Survival (%)

Event-free Survival (%)

100

0

16

6

1

36 25

14 8

3 0

80 Pharmacologic therapy (77 events)

70 60

Pacemaker (131 events, P0.059)

50

120 240 360 480 600 720 840 960 1080 Days after Randomization

No. at Risk Pharmacologic 308 176 115 72 46 24 therapy Pacemaker 617 384 294 228 146 73 Pacemaker595 385 283 217 128 61 defibrillator

Pacemaker-defibrillator (105 events, P0.003)

90

0

90 180 270 360 450 540 630 720 810 900 990 1080

Days after Randomization No. at Risk Pharmacologic 308 284 255 217 186 141 94 57 45 25 4 2 therapy 617 579 520 488 439 355 251 164 104 60 25 5 Pacemaker 595 555 517 470 420 331 219 148 95 47 21 1 Pacemakerdefibrillator

C

D

Death from or Hospitalization for Cardiovascular Causes

Death from or Hospitalization for Heart Failure 100

80 Pacemaker-defibrillator (312 events, P0.001)

60 40

Pharmacologic therapy (188 events)

20 0

0

Pacemaker (338 events, P0.002)

120 240 360 480 600 720 840 960 1080 Days after Randomization

No. at Risk Pharmacologic 308 199 134 91 56 29 therapy Pacemaker 617 431 349 282 194 102 Pacemaker595 425 341 274 167 89 defibrillator

20

8

2

51 45

22 20

5 3

Event-free Survival (%)

Event-free Survival (%)

100

Pacemaker-defibrillator (212 events, P0.001)

80 60 Pharmacologic therapy (145 events)

40 20 0

0

Pacemaker (237 events, P0.002)

120 240 360 480 600 720 840 960 1080 Days after Randomization

No. at Risk Pharmacologic 308 216 161 118 76 39 therapy Pacemaker 617 498 422 355 258 142 Pacemaker595 497 411 343 228 131 defibrillator

28

11

2

75 71

35 27

9 5

Figure 12-5  Kaplan-Meier estimates in COMPANION study. A, 12-month rates of death from or hospitalization for any cause—primary endpoint—were 68% in pharmacologic therapy group, 56% in group who received a pacemaker as part of CRT, and 56% in the group who received a pacemaker-defibrillator as part of CRT. B, 12-month rates of death from any cause—secondary endpoint—were 19% in pharmacologic group, 15% in pacemaker group, and 12% in pacemaker-defibrillator group. C, 12-month rates of death from or hospitalization for cardiovascular causes were 60% in pharmacologic , 45% in pacemaker, and 44% in pacemaker-defibrillator group. D, 12-month rates of death from or hospitalization for heart failure were 45% in pharmacologic, 31% in pacemaker, and 29% in pacemaker-defibrillator group. In pharmacologic therapy group, death from heart failure made up 24% of the events, hospitalization for heart failure 72% of events, and intravenous administration of inotropes or vasoactive drugs for more than 4 hours, 4% of events. P values are for comparison with optimal pharmacologic therapy (OPT). (From Bristow MR, Saxon LA, Boehmer J, et al: Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 21;350:2140-2150, 2004.)

in COMPANION; with longer follow-up, the value may have become significant. Another issue was the risk of sudden death in the CARE-HF patients given CRT; although only 8% of these patients were adjudicated as dying “suddenly,” these accounted for 37% of all deaths. COMPANION data indicate such deaths may have been prevented with a CRT-D device.69 The CRT-P patients in CARE-HF had a reduced risk of sudden death at extended follow-up of 37 months, supporting the concept that chronic stabilization of heart failure status reduces arrhythmias73,74 (Fig. 12-8). The CARE-HF trial answered several other important issues. CRT induces sustained LV reverse remodeling, with the most marked effects

in the first 3 to 9 months and continuing up to 29 months.75 The benefits of CRT in patients with and without an ischemic etiology were similar in relative terms.76 Before CARE-HF, follow-up beyond 12 months was available to far too few patients undergoing CRT. This is the first large trial to demonstrate benefit with respect to biomarker measurements as a surrogate of congestive heart failure severity with CRT. A nonsignificant decrease in N-terminal pro–brain natriuretic peptide (NT-BNP) was noted at 3 months, but by 18 months, there was a dramatic decrease of more than 1100 pg/mL (P = .0016). CARE-HF was the first large clinical trial to select patients on the basis of a wide QRS (>149 msec) or >120 msec and the presence of at least two of three markers of dyssynchrony: (1) aortic preejection delay



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

Variable

Hazard Ratio for Death from or Hospitalization for Any Cause

No. of Patients Pharmacologic Pacetherapy maker (n308) (n617)

Age 65 yr 65 yr Sex Male Female Cardiomyopathy Ischemic Nonischemic NYHA class III IV LVEF 20% 20% LVEDD 67 mm 67 mm QRS interval width 147 msec 148–168 msec 168 Bundle branch block Left Other Heart ratio 72 beats/min 72 beats/min Systolic BP 112 mm Hg 112 mm Hg Diastolic BP 68 mm Hg 68 mm Hg ACE inhibitor use No Yes β-blocker use No Yes Loop diuretic use No Yes Spironolactone use No Yes

Hazard Ratio for Death from or Hospitalization for Any Cause

287

Hazard Ratio for Death from Any Cause

Pacemakerdefibrillator (n595)

123 185

272 345

272 323

211 97

415 202

401 194

181 127

331 285

325 270

253 55

537 80

512 83

143 165

324 293

282 313

133 122

257 266

248 237

115 111 82

209 203 205

178 232 185

215 93

426 190

434 161

161 147

318 299

315 280

164 144

347 270

307 288

178 130

328 289

316 279

96 212

186 431

183 412

104 204

196 421

193 402

17 291

36 581

20 575

139 169

288 329

267 328 0.0

0.5 Pacemaker better

1.0

1.5 0.0

Pharmacologic therapy better

0.5 Pacemakerdefibrillator better

1.0

1.5 0.0

Pharmacologic therapy better

0.5

1.0

Pacemakerdefibrillator better

1.5

2.0

2.5

Pharmacologic therapy better

Figure 12-6  Patient characteristics and hazard ratios in COMPANION study. Hazard ratios and 95% confidence intervals for the primary endpoint (death from or hospitalization for any cause) and secondary endpoint (death from any cause) according to baseline characteristics of COMPANION patients. Echocardiographically determined values for left ventricular end-diastolic dimension (LVEDD) were not available for all patients. ACE, Angiotensin-converting enzyme; BP, blood pressure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association functional class. (From Bristow MR, Saxon LA, Boehmer J, et al: Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators: Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140-2150, 2004.)

greater than 140 msec, (2) interventricular mechanical delay more than 40 msec, and (3) delayed activation of the posterolateral LV wall, as judged by M-mode and pulsed-wave Doppler. The incremental benefit of a BiV defibrillator (CRT-D) over a BiV pacemaker (CRT-P) in patients with LV systolic dysfunction remains uncertain. The CRT-D device is more expensive than a CRT-P device

and has higher long-term costs because of a shorter battery life. Decision-analysis models suggest that the cost of both is within acceptable standards for QOL years, but that the CRT-P is associated with less costs than the CRT-D device.77-79 Appropriate ICD therapy in CRT patients predicts a much worse outcome, and the number needed to treat (NNT) analysis in COMPANION patients favors the placement of

288

SECTION 2  Clinical Concepts

Percentage of patients free of death from any cause or unplanned hospitalization for a major cardiovascular event

100

75 Cardiac resynchronization 50

Medical therapy

25

P <0.001

0

500

0

1000

1500

Days No. at risk Cardiac resynchronization Medical therapy

409

323

273

166

68

7

404

292

232

118

48

3

A 100

Percentage of patients free of death from any cause

Cardiac resynchronization 75

Medical therapy

50

25

P <0.002

0 0

500

1000

1500

Days No. at risk Cardiac resynchronization Medical therapy

409

376

351

213

89

8

404

365

321

192

71

5

B

the ICD with CRT therapy.72 Longer-term comparative clinical trials are needed to determine cost-effectiveness because the CRT-D costs are incurred at implant. Although sudden death appears to be reduced with long-term follow-up of CRT-P devices,73 sudden deaths certainly increase in CRT-P versus CRT-D recipients.74 None of the trials reported differences in the efficacy of CRT or CRT-D across patient subgroups, which are unlikely to be detected in underpowered post hoc analyses. Although the rate of sudden death is lower in patients receiving a defibrillator, one study found no difference in long-term survival in patients receiving CRT-P versus CRT-D.80 In the prospective multicenter MONA LISA cohort study of 198 patients with a CRT-P device for standard indications, prevalence of sustained VT was ascertained from stored intracardiac electrograms (EGMs); capture of EGMs was

Figure 12-7  Kaplan-Meier estimates in CAREHF study. A, Time to the primary endpoint of death from any cause or an unplanned hospitalization for a major cardiovascular event. B, Time to principal secondary outcome of death from any cause. (From Cleland JG, Daubert JC, Erdmann E, et al: Cardiac Resynchronization-Heart Failure [CARE-HF] Study Investigators: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005.)

triggered by a minimal number of programmed ventricular cycles at a minimal programmed cycle length.81 In all patients, devices were also programmed to facilitate the detection of sustained VT by bipolar and optimized ventricular sensing (spontaneous ventricular rate >150 bpm and >64 cycles). Within 1 year after implantation, mortality rate was 11.7%. Although the incidence of sustained VT was only 4.3%, these patients had a significantly higher risk of all-cause mortality and sudden cardiac death than those without sustained VT. This study highlights the value of remote monitoring to detect patients for urgent upgrade, although this is also associated with increased costs, and not all patients will have VT detected before a sudden fatal arrhythmia. Also, sustained episodes of VT could worsen heart failure symptom status and result in syncope.



289

12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators 1.00

1.00

CRT

CRT 0.75

Medical therapy Hazard ratio 0.55 (95% CI 0.37–0.82, P = 0.003)

.50

Survival

Survival

.75

.25

Hazard ratio 0.54 (95% CI 0.35–0.84, P = 0.006)

0.50

0.25 CRT = 38 HF deaths (9.3%) Medical therapy = 64 HF deaths (15.8%)

0 0

A

Medical therapy

400

800

1200

CRT = 32 sudden deaths (7.8%) Medical therapy = 54 sudden deaths (13.4%) 0.00

1600

Time (days)

0

400

800

B

1200

1600

Time (days)

Figure 12-8  Kaplan–Meier estimates in CARE-HF extension phase. CRT-P patients had reduced risk of sudden death at extended follow-up of 37 months. A, Time to death from worsening heart failure. B, Time to sudden death. (From Cleland JGF, Daubert JC, Erdmann E, et al: Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase] Eur Heart J 27:1928-1932, 2006.)

Two pivotal trials studied the effect of CRT in patients with mild heart failure, REVERSE and MADIT. Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study was the first randomized controlled trial (RCT) of CRT in NYHA Class II patients or in NYHA Class I patients with previous heart failure symptoms.59 Patients were randomized to CRT on or off, with a clinical composite endpoint scoring patients as improved, unchanged, or worsened; intergroup efficacy of CRT was limited to percent patients who worsened at 12 months, because asymptomatic Class I patients cannot improve their symptom status. The prospectively powered secondary endpoint was LV endsystolic volume index (LVESVI). The mean LVEF was 26.7%, mean QRS was 153 msec, and all patients were in sinus rhythm receiving OPT. A CRT-D was implanted in 83% of successfully implanted patients, with even distribution between ischemic and nonischemic arms. AV delay was optimized by echocardiography in all patients, regardless of randomization assignment, before the final programming. Although there was no significant difference in the primary endpoint between the two groups, the active CRT group benefited from reduced heart failure hospitalization and improved ventricular function, with a highly significant reduction in LVESVI59 (Fig. 12-9). The REVERSE European cohort of 287 patients had a longer follow-up over 24 months and were much younger with fewer comorbidities than the non-European sample. This cohort demonstrated a significant difference in primary endpoint between the two study groups, which became evident as early as 6 months and persisted for 24 months. A longer follow-up may have allowed the therapeutic effects of CRT to manifest in patients expected to have a slow progression of disease.15 Multi-Center Automatic Defibrillator Implantation Trial–CRT The Multi-Center Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) study was an RCT comparing CRT-D devices with RV-based ICDs in patients with QRS greater than 130 msec, ejection fraction (EF) of 30% or less, sinus rhythm, ischemic etiology (NYHA Class I or II) or nonischemic etiology (NYHA II only), and a guideline indication for an ICD.14 The primary endpoint was a composite of all-cause mortality and nonfatal

heart failure events (1820 patients enrolled). Over an average follow-up of 2.4 years, the CRT-D group had a 34% risk reduction in the primary endpoint. The trial was stopped early once the interim analysis identified the superiority of CRT-D (Fig. 12-10). The primary endpoint was driven almost entirely by a reduction in the risk of heart failure events, because the annual mortality rate was only 3% in each treatment group. The benefit was evident in patients with both ischemic and nonischemic cardiomyopathy. The outcome curves diverge within the first 2 months, suggesting an early benefit on heart failure hospitalization and other events requiring treatment. Interestingly, prespecified subgroup analysis showed that women derived a greater benefit from CRT-D independent of QRS duration. Patients with QRS of 150 msec or greater derived greater benefit, in keeping with previous trials. No benefit was observed among patients with right bundle branch block. Echocardiographic evaluation showed significant reductions in LV volumes and a mean improvement in EF of 11% at 1 year. Importantly, the results cannot be attributed to an increase in RV pacing–induced heart failure in the ICD group because

% of patients hospitalized for HF

PREVENTION OF HEART FAILURE EVENTS

15

P = 0.03

Hazard ratio = 0.47

10 CRT-OFF 5 CRT-ON 0 0

3

6

9

12

Months since randomization No. at risk CRT-OFF CRT-ON

191 419

187 415

181 411

176 409

119 251

Figure 12-9  Hazard ratios in REVERSE study. Time to first heart failure hospitalization in first 12 months in CRT-OFF and CRT-ON groups. (From Linde C, Abraham WT, Gold MR, et al: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol l52:1834-1843, 2008.)

290

SECTION 2  Clinical Concepts

Probability of survival free of heart failure

1.0

The significant improvement in mortality and heart failure hospitalization is a novel observation, as the MADIT-CRT study showed benefit only in heart failure hospitalization. The mean follow-up was longer in the RAFT study and this or other differences in the study populations not apparent from the clinical characteristics data may explain the improvement in mortality observed in RAFT and not in MADIT-CRT. The data from RAFT certainly lend support to the use of CRT in patients with less manifest symptoms of heart failure who have depressed ventricular function and QRS delay. A final important finding of the RAFT study is that the rate of adverse events within 30 days of device implantation was significantly higher in patients in the ICD-CRT group compared to the ICD group. These data indicate that even though LV coronary sinus vein lead implantation can be successfully achieved with current tools by the majority of implanting electrophysiologists, the procedure still carries significant incremental risk compared to a standard left-sided ICD implant. This is particularly important as, in practical terms, the patient populations most apt to increase as a result of the RAFT and MADIT-CRT studies are those undergoing ICD device change-outs with minimally symptomatic heart failure who have continuous RV pacing or native conduction delay.

0.9 CRT-ICD

0.8 0.7

ICD only

P <0.001

0.6 0.0 0

1

2

3

4

Years since randomization No. at risk (probability of survival) ICD only 731 621 (0.89) 379 (0.78) 173 (0.71) 43 (0.63) CRT-ICD 1089 985 (0.92) 651 (0.86) 279 (0.80) 58 (0.73) Figure 12-10  Kaplan-Meier estimates in MADIT-CRT. Probability of survival that is free of heart failure. (From Moss AJ, Hall WJ, Cannom DS, et al: MADIT-CRT Trial Investigators: Cardiac resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361:1329-1338, 2009.)

Procedural Safety and Left Ventricular Lead Performance

the demand pacing rate was programmed to 40 ppm. The FDA advisory panel has voted for approval on expansion of current CRT indications.82 Further evidence of the beneficial effects of CRT in patients with mild-to-moderate heart failure has recently been provided by the results of the RAFT study.83 In this trial, 1798 patients with NYHA class II or III heart failure, a QRS duration of 120 msec or more, and a left ventricular ejection fraction of 30% or less were randomly assigned to receive either an ICD alone or an ICD plus CRT. Both groups were on OPT and were followed for an average of 3 years. The primary end point was death from any cause or hospitalization for heart failure, whichever came first. There was a 25% risk reduction in the primary end point in favor of the ICD-CRT group with a similar significant risk reduction in the individual components of the primary end point.

TABLE

12-5 

In all the clinical trials subsequent to the PATH-I study and in patients enrolled early in the CONTAK CD study, LV lead placement was through a coronary sinus branch vein with an over-the-wire lead. In general, choice of lateral LV wall sites was based on trial results of short-term implants showing that the most robust hemodynamic response occurs at this site in patients with LBBB.48 Despite initial concerns about the additional risk of LV branch vein lead placement, particularly given the additional skills required and the extensive anatomic remodeling in advanced heart failure that makes access to the coronary sinus and its branch veins more challenging, the procedural safety and performance of LV leads have been very good (Table 12-5). A learning curve appears to be involved in CRT implantation, and CONTAK CD found that the threshold for attaining a higher than 95% rate of successful LV implantation was 15 cases.84

Procedure Safety and LV Lead Performance in Clinical CRT Trials

Parameter Subjects (N) Procedure length (hr) Successful Implants (%) First attempt Total Implantation Problems (%) Failure Coronary sinus trauma Deaths Other Late Complications (%) LV lead dislodgement or replacement Extracardiac stimulation Pocket infection Loss of capture Death Other Pacing Thresholds (volts @ 0.5 msec ±SD) At implantation Long term

MUSTIC 64

MIRACLE 528* 2.7*

CONTAK CD 289

MIRACLE-ICD 421 2.7

COMPANION† 1212

CARE-HF 409

90 92

NA NA*

87 NA

NA 88

NA 89§

86 95

8 NA 0 4.5

NA NA 0.7 —

13 2 0 15.2

12 4 0 38

11 3 0.08 —

5 2.4 — 1.5

13.6 12 3.4 0 0 3.4

6* 1.3* — 0.1 —

6.8 1.6 0 0 0 1.8

8.6 3 0 0 0 1.3

4 1.5 3.1 0.2 0.6 —

6 1.7 0.6 — 0.2 —

1.36 ±0.96

NA

NA

2.1 ±1

—

2.4 (3 mo)

NA

1.8 ±1.2 (13 mo)

1.5-1.7 (4189)‡ 1.7-2.3 (2187/8)‡ NA

2.4 ±1.8

—

MUSTIC, Multisite Stimulation in Cardiomyopathy; MIRACLE, Multicenter InSync Randomized Clinical Evaluation; CONTAK CD, CONTAK CD Biventricular Pacing Study; COMPANION, Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure; CARE-HF, Cardiac Resynchronization in Heart Failure; NA, not available. *Patients followed up only after successful implantation. †Cardiac resynchronization therapy with and without defibrillator treatment. ‡Model numbers in parentheses. §Successful in 87% of CRT-P and 91% of CRT-D.



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

The most common complication of LV lead placement is coronary sinus trauma, which occurs at a rate of 2% to 4%, although the incidence of true perforation resulting in cardiac tamponade is less than 1%. LV lead dislodgement requiring repositioning occurs in up to 8% of implants. Diaphragmatic stimulation requiring reoperation for lead repositioning occurs in 1% to 4% of patients, but this risk has been lowered with the introduction of bipolar LV leads.85 The reoperation rate for LV lead–related complications was similar in REVERSE (8%), CARE-HF (7%), and RAFT (6.9%).87 In MADIT-CRT the left ventricular lead required repositioning in 4% of patients. The long-term performance of several LV leads has been found to be safe and effective over time.88-90 Integrated bipolar RV defibrillator leads have a significantly lower incidence of RV anodal stimulation than dedicated bipolar RV defibrillator leads.91 The evolution of LV leads has driven the success of CRT. The high implant success rate (97%) seen in REVERSE undoubtedly represents an improvement in implantation techniques and lead technologies compared with earlier CRT studies. A new generation of smaller 4 French (4F) leads is currently in use, and further developments are anticipated with multipolar leads.92 The Quartet LV pacing lead features four pacing electrodes with up to 10 pacing configurations. Multiple vectors allow pacing around scar tissue and help overcome problems with high capture thresholds and diaphragmatic stimulation without the need for surgical repositioning of the lead.

Trials of Long-Term CRT in Special Populations Although the incidence of atrial fibrillation in patients with advanced heart failure is 30% or higher, the effects of CRT in this patient population have been poorly studied. One study compared the results of 25 months of CRT in 162 patients with permanent AF, including 48 patients who had His bundle ablation, with results in 511 patients in sinus rhythm. Only those in the His ablation subgroup were shown to benefit from symptomatic improvement, suggesting that the LV requires to be paced consistently for CRT to be successful.93 Post AV Nodal Ablation Evaluation The Post AV Nodal Ablation Evaluation (PAVE) study compared CRT with RV pacing in patients with permanent AF who were undergoing AV nodal ablation.62 Entry criteria for the study did not require patients to have symptomatic heart failure or systolic dysfunction. However, patients were required to have exercise limitation, defined as the inability to walk farther than 450 m during a 6MWD test, which was also the primary study endpoint. Peak Vo2 and QOL scores were assessed as secondary endpoints. A total of 252 patients were randomly assigned to either CRT or RV pacing; 205 patients (mean age 69 years, 64% male, 51% NYHA Class II, 32% NYHA III, 46% with LVEF < 0.45) completed 6 months of follow-up; 47 (19%) were withdrawn before completing follow-up, mostly from unsuccessful LV lead implantation (n = 21) or death (n = 16). Compared with RV pacing, which also produced improvements in the study endpoints, CRT resulted in greater 6MWD improvement (25.5 m), Vo2 increase (2 mL/kg/min), and QOL improvements. Improvements in LVEF were observed with CRT but not with RV pacing (P = .03). In patients with LVEF of 0.45 or less, the improvement in 6MWD in the CRT group was statistically significantly higher, by 41.0 m, than that in the RV pacing group (P = .04), and QOL measurements were higher as well. The magnitude of improvement was also more marked in patients with NYHA Class II or III in 6MWD. In all patients, symptoms and walk distance improved immediately after CRT and continued to improve throughout the 6-month follow-up. In patients with LVEF greater than 0.45 or NYHA Class I status, CRT had no advantage over RV pacing in QOL improvements. More subjects in the RV pacing group died, but the difference was not statistically significant (P = 0.16). We can conclude from this trial that CRT does provide greater improvement than RV pacing in the functional status of patients

291

undergoing AV nodal ablation if they have significant baseline limitation of exercise capacity. However, the need for His bundle ablation has been challenged in an observational study of 295 consecutive patients with NYHA Class III or IV heart failure, EF of 35% or less, and QRS of 120 msec or greater.94 Over follow-up of 6.8 years, no differences were found between patients in AF or sinus rhythm in any of the mortality or morbidity endpoints, even without AV junction ablation. The percentage of BiV pacing achieved in patients in AF was 87%. A very recent meta-analysis, which compared outcomes of CRT between heart failure patients with atrial fibrillation versus sinus rhythm shows that atrial fibrillation is associated with a lower likelihood of reverse remodeling and increased risk of clinical non-response and death compared to sinus rhythm.95 AV node ablation in selected patients with atrial fibrillation appeared to improve the rates of clinical response and survival. However, important differences exist between the device programming features for these two rhythms, and only a properly designed randomized trial can address the role of AV junction ablation in patients with permanent AF undergoing CRT. Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS Although CRT is clearly effective in patients with dyssynchrony from a wide QRS, more than one third of patients with a “narrow” QRS also display some degree of mechanical dyssynchrony. The Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS (RethinQ) trial has been the only trial to study the effect of CRT in patients with heart failure limited to a narrow QRS.96 Criteria for enrollment were ischemic or nonischemic cardiomyopathy with EF of 35% or less, NYHA Class III, QRS of 130 msec or less, and one of two echocardiographic measures of dyssynchrony: an opposing wall delay of 65 msec or longer on tissue Doppler imaging (TDI) or a septal-toposterior wall delay of 130 msec or greater on M-mode imaging. All RethinQ patients had a standard indication for an ICD and received a CRT device before being randomly assigned to the CRT group or the control group (no CRT). The majority (97%) of LV leads were implanted in a lateral position. In this randomized double-blind study of 172 patients, CRT did not significantly change the primary endpoint, which was exercise capacity. Secondary endpoints of QOL, NYHA functional class, and LV indices also showed little difference over a relatively short follow-up of 6 months. Nevertheless, the RethinQ study provided important data in patients with a QRS of 120 to 130 msec, a group not previously studied. Prespecified subgroup analysis showed a significant improvement in peak Vo2 and NYHA class in patients in the CRT arm with QRS of 120 msec or more. However, this did not translate into any difference in QOL score or 6MWD. When compared according to etiology of cardiomyopathy, there was a significant improvement in NYHA class and 6MWD in the subgroup of patients with a nonischemic classification in the CRT arm. However, no difference was seen in peak Vo2 and QOL scores. ESTEEM-CRT and Echo-CRT A smaller study, ESTEEM-CRT, used the standard deviation of time to peak velocity of 12 echocardiographic segments to select patients with mechanical dyssynchrony, but with a QRS of 120 msec or less. It also found no improvement in exercise performance or reverse remodeling over 6 months despite invasive dP/dtmax testing for AV optimization at implant.97 We can conclude that current echocardiographic criteria are unable to identify patients with mechanical but no electrical dyssynchrony who would benefit from CRT. Trials in progress include Echocardiography Guided Cardiac Resynchronization Therapy (Echo-CRT), an international trial enrolling patients with QRS of 130 msec or less and evidence of dyssynchrony, as assessed either by speckle tracking, radial strain, septal–posterior wall delay of 130 msec or longer or by color TDI with an opposing wall delay of 80 msec or greater. The primary endpoint will evaluate the effect of CRT on all-cause mortality or first hospitalization for worsening heart failure.98

292

SECTION 2  Clinical Concepts

Attempt/1 Attempt Type Elapsed Time Therapy Delivered

17J, Biphasic 00:01 mm:ss VF Shock 1

Pre-attempt EGM (10 sec max) Post-attempt EGM (10 sec max)

Initial Detection VF Zone Pre-attempt Avg A Rate 202 bpm Pre-attempt Avg V Rate 286 bpm

Post-attempt Avg A Rate Post-attempt Avg V Rate

25 mm/s

(AS) 813

3

25 mm/s

SVT 338

AF 290

AF 240 VF 233 0

AF 285

VF 205 PVC 400

VF 220

VF 203 V-Epsd

71 bpm 72 bpm

AF 288

AF SVT 280 338 VF VF VF VF 205 218 213 168 VF VF VF VF 215 205 215 215

AF 298

AF 260

SVT 333

SVT 310

[AS]

SVT AF AF SVT AS 323 263 268 353 603 VF VF VF VF VF VF - VT 138 205 145 188 178 273 145 328 VF VF VF VF VF VF -VF 140 280 175 155 135 343 98 205

AP 865 -1783 -1785

VP 858

V-Detct

R ATR PVP ATR

Chrg

Chrg

Shock

PVP

Figure 12-11  Concomitant conversion in RENEWAL-AVT. (1) Atrial features and therapies were programmed “on”; (2) atrial fibrillation (AF) induced and device allowed to detect AF; (3) ventricular fibrillation (VF) induced; (4) RENEWAL-3-AVT device (Guidant, Boston Scientific) allowed to detect arrhythmia and deliver therapy; (5) VF detected and therapy delivered during AF (ventricular detection takes precedence over atrial detection); (6) VF and AF converted with 17-J shock.

Pacing to Avoid Cardiac Enlargement The optimal pacing mode and site(s) for patients with normal LV systolic function remains uncertain. RV apical pacing has been associated with deleterious LV function in observational studies.99,100 The role of biventricular pacing in preventing adverse LV remodeling in patients with bradycardia and normal LVEF was recently reported. The Pacing to Avoid Cardiac Enlargement (PACE) trial randomly assigned 177 patients with a BiV pacemaker to receive BiV pacing or RV apical pacing.101 At 12 months, mean LVEF assessed by three-dimensional echocardiography was significantly lower in the RV pacing group, with an absolute difference of 7.4%, and LV end-systolic volume was significantly higher. There were no differences in heart failure hospitalization, functional capacity, or QOL between the two groups.

Trials Evaluating Device Features and Programming A number of ongoing or completed clinical trials have evaluated the use of CRT device features or programming options. Some features, such as atrial antitachycardia pacing and defibrillation, are available in an FDA-approved RV ICD and have been tested for safety and efficacy in a CRT device.20 In other cases, such as studies evaluating the usefulness of RV/LV offset programming for CRT, the feature is specific to a CRT device and intended to maximize response to therapy.102-104 RENEWAL Study In the multicenter RENEWAL 3 AVT clinical study of CRT-D in patients with AF, the safety and efficacy of a defibrillator capable of

advanced atrial therapies and diagnostics, including atrial defibrillation, was tested in a CRT device.20 In this single-arm study of 138 patients with paroxysmal or persistent AF in the year before enrollment, the delivery of atrial and ventricular antitachycardia therapies was not compromised by CRT delivery. Conversely, CRT did not impair the delivery of antitachycardia therapies. Figure 12-11 shows AF occurring in the presence of VF; both atrial and ventricular diagnostics and therapies were programmed “on.” The device correctly sensed both AF and VF and prioritized treatment of VF with a 17-J shock, which converted the rhythm to atrially paced CRT. DECREASE-HF and Rhythm-II-ICD Two trials have investigated if an optimal RV and LV pacing sequence yields the best global cardiac performance in CRT recipients. The Device Evaluation of CONTAK RENEWAL-2 and EASYTRAK-2: Assessment of Safety and Effectiveness in Heart Failure (DECREASEHF) was the first prospective randomized trial comparing LV only or interventricular (VV) offset against simultaneous BiV stimulation to achieve CRT.102 306 patients (NYHA III or IV heart failure, LVEF ≤35%, QRS ≥150 msec) were randomized to three arms in a 1 : 1 : 1 ratio. To ensure ventricular pacing, programming of the AV delay was performed via the Expert Ease device feature, which uses QRS duration, lead location, and the patient’s native AV interval to determine the optimal programmed atrioventricular delay, as measured from intracardiac electrograms. In patients randomized to sequential BiV pacing, the VV timing was programmed with LV activation preceding RV activation by 20 to 80 msec. Echocardiographic assessments were performed at baseline, 3 months, and 6 months to determine the effects



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

293

Figure 12-12  Impact of Doppler echo optimization on hemodynamics in CRT. Upper panel, Pulsed-wave Doppler–derived mitral inflow pattern before and after AV optimization. Lower panel, Corresponding waveform at LV outflow tract.

of the method of CRT delivery on cardiac function. All groups had a significant reduction in LV volume and an improvement of LVEF (median increase of 6.7%) with a trend toward greater improvement with simultaneous BiV pacing. The multicenter, single blind, randomized Resynchronization for the Hemodynamic Treatment for Heart Failure Management II–ICD (RHYTHM-II-ICD) trial compared the effects of optimized VV delay programming to simultaneous BiV stimulation on clinical outcomes.103 A post hoc analysis studied ventricular remodeling based on paired echocardiographic recordings made over 6-month follow-up.104 Significant improvements in functional status and LV indices were seen in both study groups, but optimization of the VV delay conferred no incremental benefit compared with simultaneous BiV stimulation. These results suggest that individual optimization and programming of VV settings is necessary. Further data will be available in the Evaluation of Resynchronization Therapy in Heart Failure (EARTH) study, which is comparing LV pacing with BiV pacing with a primary endpoint of total exercise duration at a submaximal workload at 12 months.105 Currently, VV timing offset is offered in two FDA-approved CRT devices.106 The data in support of this method of CRT delivery come from a MIRACLE-ICD substudy. ATRIOVENTRICULAR OPTIMIZATION STUDIES The issue of AV delay programming has not been systematically evaluated in large clinical trials of long-term CRT. Uncontrolled data on short-term and long-term therapies based largely on echocardiographic assessment of mitral inflow and forward output have shown that for most subjects, AV delay programming during atrial sensing is optimal at 100 to 130 msec, although exceptions exist.46 One report demonstrated that altering programming in implanted CRT devices from atrially sensed VDD stimulation to DDD stimulation actually worsened intraventricular LV synchrony and curtailed LV filling and worsened the myocardial performance index, a measure of systolic and diastolic function.107-108 These effects are most likely caused by delay in intra-atrial conduction times. Compared to atrial sensing, pacing from a long-term implanted right atrial lead results in delayed left atrial

activation which, in turn, reduces LV filling time. This important observation suggests that echocardiographic evaluation and repeated AV delay optimization may be indicated in patients with CRT devices who require atrial rate support, to ensure that CRT efficacy is not compromised (Fig. 12-12). This hypothesis was tested in a prospective multicenter double-blind study using the QuickOpt method in FREEDOM (A Frequent Optimization Study using the QuickOpt Method), which compared frequent (every 3 months) AV/PV and VV delay optimization with a single empirical or optimized setting.109 The primary outcome was a heart failure clinical composite score at 12 months. 1647 patients were randomized in a 1 : 1 fashion and stratified by etiology of cardiomyopathy. The majority of patients were in NYHA Class III and received a primary prevention CRT-D device. There was no significant treatment difference in the primary or secondary endpoint between the 2 groups or in the prespecified subgroup analysis based on etiology. Although to date no randomized study has demonstrated the need for regular adjustment, the Clinical Evaluation of Advanced Resynchronization (CLEAR) study was proof of principle that optimization of pacemaker settings by means of a sensor that measures peak endocardial acceleration can reduce the rate of CRT nonresponders.110 Several small studies have previously demonstrated improved clinical outcomes with echocardiographically guided optimization of the AV delay compared with an empirically set AV delay.111,112 The SMARTAV trial, which was recently reported, randomized 980 patients in a 1 : 1: 1 ratio to a fixed empiric AV delay (120 msec), echocardiographically optimized AV delay or AV delay optimized using SmartDelay, an electrogram based algorithm113. The primary endpoint was left ventricular end-systolic volume. Secondary end points included NYHA class, quality of life score, 6-minute walk distance, left ventricular enddiastolic volume and LVEF. The inclusion criteria for CRT-D were as in previous trials and, following randomization, patients underwent echocardiographic imaging at 3 and 6 months. In contrast to the FREEDOM trial, AV delay optimization was performed after 3 months of follow up in the SD arm only. At 6 months, the change in LVESV for the SD arm was no different than either the echo or fixed arms. No significant differences were noted in any of the secondary structural or

294

SECTION 2  Clinical Concepts

functional end points by optimization group. We can conclude from these trials that the routine use of AV optimization does not offer any advantage over nominal settings but still has a role to play in managing patients who are non-responders. The magnitude of BiV pacing that confers the optimal clinical benefit was reported in a post hoc analysis of mortality and heart failure hospitalization in 1812 patients undergoing CRT in two trials: CRT RENEWAL and REFLEx. Subjects were grouped according to percent BiV pacing quartiles. The greatest magnitude of benefit occurred with greater than 92% pacing.114 Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke particularly in patients with congestive heart failure caused by LV systolic dysfunction. Because these arrhythmias may occur intermittently, initiation of prophylactic anticoagulation is frequently delayed until patients are symptomatic or ECG evidence is obtained. The IMPACT study is a multicenter randomized trial designed to test the hypothesis that oral anticoagulant therapy guided by episodes of atrial high rate detected and stored by a CRT device improves clinical outcomes, by reducing the combined rate of stroke, systemic embolism, and major bleeding, compared with conventional management in CRT recipients.115

Screening Echocardiography and LV Lead Position for CRT Response Depending on how “response” is defined, the major clinical trials of CRT indicate that the magnitude of response to CRT is clinically significant for a variety of endpoints, but that a symptomatic improvement in functional endpoints in not seen in all CRT recipients. Table 12-6 summarizes the data from RCTs. Together, the data indicate that depending on the endpoint measure, up to 30% of patients may not receive at least one of the potential benefits of CRT. A leading contributor to CRT response is believed to be intraventricular dyssynchrony, and investigators have focused on measures of mechanical dyssynchrony to improve the rate of response to therapy.116-119 However, no study has demonstrated that screening for mechanical dyssynchrony either predicts outcome or is superior in patient selection to QRS or electrical delay. Echocardiography, because it is noninvasive, is the most widely used method for short-term and long-term assessments of both baseline mechanical dyssynchrony and response to therapy. Also, the advent of tissue Doppler ultrasound methods has led to a host of measures that assess regional and particularly intraventricular dyssynchrony.116-117 Up to 50% of patients without QRS delay who have depressed LVEF and symptomatic heart failure also have mechanical dyssynchrony.120-121 Further, uncontrolled trials indicate that these patients demonstrate response to CRT that is similar in magnitude to that in patients with wide QRS delay.121,122 Despite being in use for 10 years, however, there

TABLE

12-6 

Magnitude of Response to CRT in Randomized Controlled Trials (RCTs)*

Outline Measure Functional Functional class improvement (% improving one NYHA class) Quality-of-life score improvement 6-minute walk distance improvement (m) Peak Vo2 improvement (mL/kg/min) Heart Failure Progression LV ejection fraction LV end-systolic volume index (mL/m2) LV end-diastolic dimension index (mm/m2) Heart Failure Outcome (%) Relative risk reduction in heart failure hospitalization/mortality Relative risk reduction in cardiovascular hospitalization/mortality

Magnitude Summary 62 to 85 −18 to −24 25 to 46 0.8 to 2 0.03 to 0.11 −3 to −7 −3 to −6 34 to 52 36

NYHA, New York Heart Association functional class (I-IV); Vo2, oxygen uptake. *Data from references 2 to ; 3-month to 3-year follow-up.

TABLE

12-7 

Interobserver and Intraobserver Variability in PROSPECT

Echo Measure LVESV LPEI SPWMD Ts-SD Ts-peak (basal)

Intraobserver CV (%) 3.8 3.7 24.3 11.4 15.8

Interobserver CV (%) 14.5 6.5 72.1 33.7 31.9

Interobserver K Coefficient* NA 0.67 0.35 0.15 0.25

From Chung ES, Leon AR, Tavazzi L, et al: Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation 117:2608-2616, 2008. CV, Coefficient of variability; LPEI, left ventricular preejection interval; LVESV, left ventricular end-systolic volume; SPWMD, septal-posterior wall motion delay; Ts-SD, standard deviation of time from QRS to peak velocity for 12 LV segments; Ts-peak (basal), maximum difference of time to peak velocity for 6 segments. *Based on binary predictor variable that indicates if echocardiographic measure is above or below the cutoff.

are no published acquisition standards for assessing mechanical dyssynchrony by TDI or strain rate imaging. It is also not clear if patients with QRS delay but without echocardiographic evidence of mechanical dyssynchrony show response to CRT. Nonetheless, these various echocardiographic measures provide an elegant method for assessing mechanical dyssynchrony and resynchronization and offer important ancillary information. Based on current data, however, measures of mechanical dyssynchrony cannot be used to identify CRT candidates, and there are no multicenter trial data to indicate that findings of mechanical dyssynchrony on echocardiography can predict either clinical or reverse-remodeling response to CRT. Echocardiographic measures of dyssynchrony can be valuable in identifying ventricular regions that are scarred and may be used to customize programming, particularly in patients who are not feeling better or not doing more after CRT implant.116-122 Predictors of Response to CRT The Predictors of Response to CRT (PROSPECT) trial was the first prospective multicenter study that evaluated 12 common echocardiographic parameters of mechanical dyssynchrony using both conventional and TDI-based methods.123 The study sought to determine if measures of dyssynchrony were correlated with a positive CRT response, using a validated clinical composite score and a measure of reverse remodeling consisting of 15% or more reduction in LV endsystolic volume (LVESV) at 6 months. Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications. Three core echocardiography laboratories were used, and all centers received detailed training on echocardiographic acquisition. There was no correlation between clinical or reverse-remodeling response and the 12 dyssynchrony measures. Despite training at all core laboratories, poor intraobserver and interobserver reproducibility and quality of echocardiograms precluded evaluation of many studies (Table 12-7). Thus, at present, QRS duration remains the only prospectively validated parameter for selecting patients who would benefit from CRT. There is no uniform definition of response to CRT. Most trials have used either a clinical response based on distance walked in 6 minutes or improvement in NYHA functional class over time or an echocardiographic response based on changes in EF or LVESV. Agreement among these response criteria has failed the test of scrutiny. Recently, agreement among 15 response criteria selected from the 26 most-cited publications on predicting response to CRT was assessed in 426 patients from PROSPECT.124 Seven criteria were based on echocardiography, seven on clinical measures, and one was based on a combination of both. The level of agreement not caused by chance among these 15 criteria was poor in 75% and strong in only 4% of cases. The level of agreement between echocardiographic and clinical response criteria was particularly poor and almost equal to the level of agreement predicted by chance.



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

TABLE

12-8 

295

Recent Controlled Trials of Cardiac Resynchronization Therapy (CRT)

Study Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) (Multicenter) Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) (Multicenter)

Type (Duration) Assessment of 12 echo measures of LV mechanical dyssynchrony to predict response (6 months) Randomized controlled trial of CRT compared to optimal medical therapy in mild heart failure (12 months)

Multicenter Automatic Defibrillator Implantation Trial–CRT (MADIT-CRT) (Multicenter)

Prospective randomized (3 : 2) controlled trial of CRT-D vs. ICD alone (Mean follow-up: 2.4 years)

Pacing to Avoid Cardiac Enlargement (PACE) (Asia)

Comparison of biventricular pacing with RV apical pacing (12 months)

Resynchronization/ Defibrillation for Ambulatory Heart Failure Trial (Multicenter)

Prospective randomized (1 : 1) controlled trial of CRT-D vs ICD; mean follow-up 40 months

Enrollment (Pub) Dates 2008

2008

2004-2008 (2009)

2009

2003-2009 (2010)

Inclusion Criteria Standard CRT indication with NYHA III or IV, LVEF ≤35%, and QRS ≥130 msec

Endpoints Clinical composite score and ≥15% reduction in LVESV

N 498

Results No single measure found to predict response to CRT

NYHA I or II QRS ≥120 msec LVEF ≤40% LVEDD ≥55 mm Standard CRT indication

Clinical composite (CC) response, LVESVI, NYHA, QOL

610

NYHA I or II LVEF ≤0.3 QRS ≥130 msec Sinus rhythm, ICD indication, ischemic and nonischemic Standard pacing indication, normal LVEF

All-cause mortality or nonfatal heart failure event (predefined), echo indices

1820

No difference in CC response, but CRT on group had greater improvement in LVESVI and delayed time to first hospitalization Trial stopped early due to reduced all-cause mortality or heart failure events with CRT compared with ICD

LVEF, LVESV, LV dyssynchrony, MR, diastolic function, functional class, QOL All-cause mortality or hospitalization for heart failure

177

NYHA Class II or III, LVEF ≤0.3, QRS ≥120 msec (or paced ≥200 msec), ICD indication, ischemic and nonischemic

1798

RV apical pacing group had lower mean LVEF and higher LVESV CRT-D group had significantly reduced mortality or heart failure events compared to ICD group, but more adverse events noted

CRT-D, CRT with defibrillator; echo, echocardiographic; ICD, implantable cardioverter-defibrillator; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVESV(I), left ventricular end-systolic volume (index); MR, mitral regurgitation; N, number of patients enrolled; NYHA, New York Heart Association functional class; QOL, quality of life; RV, right ventricular.

Despite early acute studies suggesting that LV coronary sinus branch vein position is essential to achieving optimal CRT response,46 the influence of LV lead position on chronic outcomes such as mortality and hospitalization seems minimal. In an analysis of lead position in patients enrolled in COMPANION, LV lead position did not influence the major event-driven outcomes of mortality and hospitalization or impact clinical response.125 A similar conclusion was drawn by a Danish retrospective review of 567 consecutive patients treated with CRT over 10 years.126 A presumed “optimal” LV lead position between 2 and 5 o’clock in the short axis circumference and basal or middle ventricle in the long axis did not correlate with a lower mortality or better clinical response. These findings argue against rejecting a coronary sinus branch vein that achieves stable LV pacing only because it is not in a lateral or posterolateral position. Similarly, there seems little justification for proceeding to a thoracotomy implant if a nonlateral branch vein can be identified that results in stable LV pacing. Table 12-8 summarizes recent controlled CRT trials.

Future Populations for Cardiac Resynchronization Therapy In general, the new randomized clinical trials of CRT are attempting to build on observations made in previous studies to identify additional patients with heart failure who may benefit from CRT. These studies are targeting those scheduled to undergo implantation or who already have an implanted device because of heart failure and who have RV pacing–induced LBBB.99 Because of the potential for worsening of heart failure from RV pacing–induced dyssynchrony, as well as the findings of uncontrolled studies that “upgrading” RV devices to CRT devices in patients with heart failure improves symptoms and ventricular function, upgrading of RV devices is a common practice in experienced CRT implantation centers and meets Class IIa guidelines but falls outside FDA labeling.60,61 There is currently no randomized trial evaluating CRT in this setting.

Conventional versus Multisite Pacing for Bradyarrhythmia Therapy A CRT device may also have a role in ameliorating pacing-induced dyssynchrony in that group of patients who have depressed ventricular function and a guideline indication for pacing. The Conventional versus Multisite Pacing for Bradyarrhythmia Therapy (COMBAT) study compared biventricular pacing (BiVP) with right ventricular apical pacing (RVP) in patients with LV dysfunction and AV block.127 This prospective, multicenter, randomized double-blind crossover study enrolled 60 patients with LVEF of 40% or less, receiving optimal medical therapy, in NYHA Class II to IV, and with AV block resulting in a Class I indication for pacing. All patients had a BiV pacemaker implanted and were then randomized to receive either RVP-BiVP-RVP or BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated for the primary endpoints of QOL and NYHA functional class. Secondary endpoints included 6MWT, Vo2max, mortality, and echocardiographic indices. Over a mean follow-up of 17.5 months, BiVP was associated with significant improvements in QOL, NYHA class, LVEF, and LVESV compared with RVP. However, the effects of pacing mode on 6MWT and Vo2max were not significantly different in COMBAT, which included a relatively large proportion of patients with Chagas cardiomyopathy. BLOCK-HF and BioPace Studies The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) study is evaluating the role of CRT in patients with depressed LVEF (≤0.45) and AV block in whom a pacemaker is indicated. The study is assessing whether CRT limits the clinical progression of heart failure compared with DDD RV-based pacing. The primary composite endpoint consists of mortality, morbidity, and cardiac function.128 The Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) study is randomizing 1200 patients with conventional bradycardia indication to RV or BiVP with

296

SECTION 2  Clinical Concepts

or without AV synchrony, depending on atrial rhythm and regardless of underlying EF. The primary endpoint is total mortality.129

Managing Heart Failure with CRT Devices: Additional Device Features A number of device features offer more comprehensive and frequent assessment in the management of patients with advanced heart failure who have a CRT device. Assessment of clinical status before an acute exacerbation of heart failure requiring urgent care is a therapeutic goal and adds both clinical benefit and economic value to CRT-Ds.130 Features predictive of worsening heart failure, such as heart rate variability, are already present in some CRT devices.131 Also, CRT reduced minimum heart rate and increased standard deviation (SD) of the R-R interval. A deterioration of these measures may predict worsening heart failure before it is clinically apparent. Further, these measures can be obtained remotely from the device at frequent intervals. In one study, continuous heart rate variability, as measured by SD of 5-minute median atrial-atrial intervals sensed by the CRT device, was associated with mortality and hospitalization risk.132 Another available feature is thoracic impedance monitoring, measured between the RV lead and the pulse generator. Acute decreases in intrathoracic impedance may reflect increased fluid retention indicative of worsening heart failure. The role of thoracic impedance changes in CRT recipients was systematically analyzed in a study of 532 heart failure patients. An audible alert decreased the rate of combined death and heart failure hospitalization, with a low rate of undetected events.133 The FAST trial demonstrated that impedance measures were superior to weight changes in CRT-D recipients for predicting heart failure exacerbations.134 However, false-positive readings can be observed in up to 75% of patients with impedance changes. These measures, however, whether used alone or combined with other measures (e.g., symptoms or arrhythmia burden), particularly if collected remotely, hold promise for the long-term management of CRT recipients, who face a high risk of worsening heart failure despite the device.70 The relationship between atrial tachyarrhythmias and fluid overload has been retrospectively analyzed in 59 ambulatory patients with LV systolic dysfunction and OptiVol index–capable devices.135 Tachyarrhythmias were not only more prevalent in patients with worsening pulmonary congestion episodes but also preceded 43% of these episodes. Widely available since 2006 for CRT-Ds, remote monitoring allows daily surveillance of device function and patient status.21,22 Such systems, using telephone or radiofrequency (RF) communication, allow the physician to monitor device function with the patient at home and provide secure access to the Internet for frequent review of device data. The opportunity for better patient management with “virtual” patient encounters is currently being studied, with reports indicating earlier detection of device failure and better management of tachyarrhythmias and heart failure.136,137 This is likely to translate into greater patient safety and enhanced patient and clinician satisfaction. In addition, other aspects of the patient’s condition, such as weight and blood pressure, can be added to the remote transmission to provide a broader view of the patient’s clinical status for all physicians involved in treating the CRT patient. The impact of the magnitude of RV pacing on mortality was analyzed in the ALTITUDE study using data from more than 100,000 patients in the Boston Scientific LATITUDE remote-monitoring system.138 The mean implant duration was 38 ±20 months. Compared to the RV pacing group, with more than 5% pacing, the group with less than 5% pacing was associated with 43% lower mortality. These results confirm those of the DAVID trial.99 Another prospectively defined question addressed in ALTITUDE was the impact of continuous versus more intermittent biventricular pacing on mortality. The percentage of BiVP meaningfully influenced mortality. Median and mean BiVP was 98% and 93%, respectively, in this real-world setting. Mortality was inversely related to the percentage of BiVP, with an optimal cutoff of 97%; lower BiVP was associated with worse mortality outcomes. This

suggests that efforts to optimize the percentage of BiVP, such as AV nodal ablation, are worthwhile. Similar analysis of data, which can reveal programming strategies that reduce inappropriate ICD shocks, points to the power of remote-monitoring systems. Long-term survival in CRT-D patients followed remotely appears superior to those followed in clinic, according to a recent report of over 40,000 CRT recipients.139 This is most likely a result of increased patient engagement and early diagnosis of arrhythmias (e.g., AF) or worsening heart failure. Currently, a stand-alone device that may be incorporated into a CRT system, the implantable hemodynamic monitor, measures pulmonary artery pressures and provides a reliable surrogate for pulmonary artery diastolic pressure both at rest and with activity.140 The Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial enrolled 274 patients from 40 U.S. centers with NYHA Class III/IV status and at least one heart failure hospitalization within 6 months while undergoing optimal medical therapy. The primary endpoint was the rate of combined heart failure hospitalizations, emergency department visits, and urgent visits. The trial showed that access to these measurements may aid in the longterm management of patients with heart failure.19 The concept of adding CRT or defibrillator capability to a cardiac restraint or support device is also being investigated.141 The Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients (HOMEOSTASIS) Study Group recently reported on the outcomes in 40 patients in NYHA Class III or IV heart failure who, irrespective of LVEF, had been implanted with an investigational left atrial (LA) pressure monitor.23 After an initial blinded phase of 3 months, patients received individualized therapy instructions guided by LA pressures on a handheld module. Over median follow-up of 25 months, there was a significant reduction in mean daily LA pressure, which translated to a better event-free survival than in the observation period. However, this small, nonrandomized feasibility study limits the conclusions about the safety and clinical effectiveness of this strategy. The LA pressure monitor is being evaluated in the multicenter Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy (LAPTOP-HF) trial and will be implanted alone or with a CRT or ICD device.142 Other techniques delivering electrical impulses to the heart to treat heart failure are in development. Cardiac contractility modulation (CCM) signals deliver high-current impulses from a lead to the heart during the absolute refractory period and do not elicit a new action potential. In a subgroup of the patients with wide QRS, CCM signals were also applied simultaneously with BiV pacing; the effects of CRT and CCM on acute contractile performance, as quantified by dP/dtmax, were additive in most patients.3 The initial experiences with long-term CCM signal applications were obtained in patients with NYHA Class III symptoms and QRS duration of 120 msec or less.143,144 To date, however, completed studies of CCM are nonrandomized, are nonblinded (therefore subject to placebo effect), and have small sample sizes. In a recent European, randomized double-blind study (FIX-CHF-4) of CCM in patients with symptomatic heart failure, patients with EF of 35% or less who were in NYHA Class II or III received a CCM pulse generator and (based on design of MUSTIC) completed two 3-month crossover study periods.145 Although a strong placebo effect was seen in the first 12-week period, there was a significant difference in peak Vo2 and QOL scores between groups at 24 weeks. A further study (FIX-HF-5) now completed in the United States is testing the safety and efficacy of CCM as a treatment for heart failure.142 If these studies show CCM treatment in patients with normal QRS duration to be as safe and effective as CRT in patients with prolonged QRS, a new, easily deployable treatment would be available to patients with otherwise untreatable symptoms. Future studies could also evaluate whether CCM is effective in patients with wide QRS unresponsive to CRT, and if combining CRT with CCM is more effective than CRT alone. Testing these hypotheses would be facilitated by development of a single device that incorporates pacing, antitachycardia therapies, and CCM. Incorporation of microelectromechanical systems (MEMS) technology into LV leads themselves is another area of interest. Development



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

of short-term and long-term leads with nanotechnology would allow assessment of acute hemodynamic and regional cardiac performance.146

Conclusion Since FDA approval in 2001, cardiac resynchronization devices have gained an established role in the treatment of patients with advanced heart failure caused by systolic dysfunction in association with QRS delay. Patients not only feel better and can do more with CRT, but they

297

also live longer, with less frequent hospitalization. Studies have conclusively demonstrated the benefit of CRT in patients at earlier stages of heart failure and are now focusing on extending the benefits to patients with, or about to receive, right ventricular pacing devices. Other leadbased technologies capable of diagnosing or treating heart failure may be incorporated into future CRT devices. Expanding the flexibility and usefulness of information obtained from the device can also advance the treatment of heart failure in CRT recipients, and we are just beginning to appreciate the potential of the CRT device to provide immediate and ancillary data about the status of heart failure disease in a particular patient.

REFERENCES 1. Jessup M, Abraham WT, Casey DE, et al: 2009 Focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119(14):1977-2016, 2009. 2. Hunt SA, Abraham WT, Chin M, et al: ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure), developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation, endorsed by the Heart Rhythm Society. Circulation 112(12):e154-e235, 2005. 3. Cazeau S, Leclercq C, Lavergne T, et al: Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344(24):873880, 2001. 4. Saxon LA, Boehmer JP, Hummel J, et al: The VIGOR CHF and VENTAK CHF Investigators. Biventricular pacing in patients with congestive heart failure: two prospective randomized trials. Am J Cardiol 83(5B):120D-123D, 1999. 5. Abraham WT, Fisher WG, Smith AL, et al: MIRACLE Study Group. Cardiac resynchronization in chronic heart failure. N Engl J Med 346(24):1845-1853, 2002. 6. Saxon LA, Ellenbogen KA: Resynchronization therapy for the treatment of heart failure. Circulation 108(9):1044-1048, 2003. 7. St John Sutton MG, Plappert T, Abraham WT, et al: Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study Group: Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 107(15):1985-1990, 2003. 8. Young JB, Abraham WT, Smith AL, et al: Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure. The MIRACLE ICD Trial. JAMA 289(20):2685-2694, 2003. 9. Bristow MR, Saxon LA, Boehmer J, et al: Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350(21):2140-2150, 2004. 10. Cleland JG, Daubert JC, Erdmann E, et al: Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352(15):1539-1549, 2005. 11. Hammill SC, Kremers MS, Kadish AH, et al: National ICD Registry Annual Report. 2008 Review of the ICD Registry’s third year, expansion to include lead data and pediatric ICD procedures, and role for measuring performance. Heart Rhythm 6(9):1397-1401, 2009. 12. Moss AJ, Zareba W, Hall WJ, et al: The Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 346(12):877-883, 2002. 13. Bardy GH, Lee KL, Mark DB, et al: Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352(3):225-237, 2005. 14. Moss AJ, Hall WJ, Cannom DS, et al: MADIT-CRT Trial Investigators. Cardiac resynchronization therapy for the prevention of heart failure events. N Engl J Med 361(14):1329-1338, 2009. 15. Daubert C, Gold MR, Abraham WT, et al; Reverse Study Group: Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol 54(20):1837-1846, 2009.

16. St John Sutton M, Ghio S, Plappert T, et al: Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association Class I/II heart failure. Circulation 120(19):1858-1865, 2009. 17. Curtis AB, Yancy CW, Albert NM, et al: Cardiac resynchronization therapy utilization for heart failure: findings from IMPROVE HF. Am Heart J 158(6):956-964, 2009. 18. Mann DL, Acker MA, Jessup M, et al: Acorn Trial Principal Investigators and Study Coordinators. Clinical evaluation of the CorCap Cardiac Support Device in patients with dilated cardiomyopathy. Ann Thorac Surg 84(4):1226-1235, 2007. 19. Bourge RC, Abraham WT, Adamson PB, et al: COMPASS-HF Study Group. Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 51(11):1073-1079, 2008. 20. Saxon LA, Greenfield RA, Crandall BG, et al: Results of the multicenter RENEWAL 3 AVT clinical study of cardiac resynchronization defibrillator therapy in patients with paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 17(5):520-525, 2006. 21. Medtronic CareLink Network. http://www.medtronic.com/ carelink/. 22. Guidant Corporation. LATITUDE Patient Management. https:// www.latitude.guidant.com/. 23. Ritzema J, Troughton R, Melton I, et al: Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients (HOMEOSTASIS) Study Group. Physician-directed patient selfmanagement of left atrial pressure in advanced chronic heart failure. Circulation 121(9):1086-1095, 2010. 24. Schocken DD, Benjamin EJ, Fonarow GC, et al: Prevention of heart failure: a scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation 117(19):2544-2565, 2008. 25. Fang J, Mensah GA, Croft JB, Keenan NL: Heart failure–related hospitalization in the U.S., 1979 to 2004. J Am Coll Cardiol 52(6):428-434, 2008. 26. Lloyd-Jones D, Adams R, Carnethon M, et al: Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3):480-486, 2009. 27. Liao L, Allen LA, Whellan DJ: Economic burden of heart failure in the elderly. Pharmacoeconomics 26(6):447-462, 2008. 28. http://www.cdc.gov/dhdsp/library/pdfs/fs_heart_failure.pdf. 29. Cohn JN, Goldstein SO, Greenberg BH, et al: A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 339(25):1810-1816, 1998. 30. Pitt B, Zannad F, Remme WJ, et al: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341(10):709-717, 1999. 31. Silvet H, Amin J, Padmanabhan S, et al: Prognostic implications of increased QRS duration in patients with moderate and severe left ventricular systolic dysfunction. Am J Cardiol 88(2):182-185, A6, 2001. 32. Baldasseroni S, Opasich C, Gorini M, et al: Left bundle branch block is associated with increased 1-year sudden death and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian Network on Congestive Heart Failure. Am Heart J 143(3):398-405, 2002. 33. Stephenson K, Skali H, McMurray JJ, et al: Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: the VALIANT experience. Heart Rhythm 4(3):308-313, 2007. 34. Hawkins NM, Wang D, McMurray JJ, et al: CHARM Investigators and Committees. Prevalence and prognostic impact of bundle branch block in patients with heart failure: evidence from the CHARM programme. Eur J Heart Fail 9(5):510-517, 2007. 35. Tabrizi F, Englund A, Rosenqvist M, et al: Influence of left bundle branch block on long-term mortality in a population with heart failure. Eur Heart J 28(20):2449-2455, 2007.

36. Clark AL, Goode K, Cleland JG: The prevalence and incidence of left bundle branch block in ambulant patients with chronic heart failure. Eur J Heart Fail 10(7):696-702, 2008. 37. Horwich T, Lee SJ, Saxon L: Usefulness of QRS prolongation in predicting risk of inducible monomorphic ventricular tachycardia in patients referred for electrophysiologic studies. Am J Cardiol 92(7):804-809, 2003. 38. Steendijk P, Tulner SA, Schreuder JJ, et al: Quantification of left ventricular mechanical dyssynchrony by conductance catheter in heart failure patients. Am J Physiol Heart Circ Physiol 286(2):H723-H730, 2004. 39. Kass DA, Chen CH, Curry C, et al: Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 99(12):1567-1573, 1999. 40. Saxon LA, De Marco T, Schafer J, et al: VIGOR-CHF Investigators. Effects of chronic biventricular stimulation for resynchronization on echocardiographic measures of remodeling. Circulation 105(11):1304-1310, 2002. 41. Leclercq C, Faris O, Tunin R, et al: Systolic improvement and mechanical resynchronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block. Circulation 106(14):1760-1763, 2002. 42. Fantoni C, Kawabata M, Massaro R, et al: Right and left ventricular activation sequence in patients with heart failure and right bundle branch block: a detailed analysis using three-dimensional non-fluoroscopic electroanatomic mapping system. J Cardiovasc Electrophysiol 16(2):112-119, 2005. 43. Saxon LA: If only rights were really lefts. J Cardiovasc Electrophysiol 16(7):120-121, 2005. 44. Aiba T, Hesketh GG, Barth AS, et al: Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy. Circulation 119(9):1220-1230, 2009. 45. Blanc JJ, Etienne Y, Gilard M, et al: Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 96(10):3273-3277, 1997. 46. Auricchio A, Stellbrink C, Block M, et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 99(23):2993-3001, 1999. 47. Nelson GS, Berger RD, Fetics BJ, et al: Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundlebranch block. Circulation 102(25):3053-3059, 2000. 48. Butter C, Auricchio A, Stellbrink C, et al: Pacing Therapy for Chronic Heart Failure II Study Group. Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation 104(25):3026-3029, 2001. 49. Hay I, Melenovsky V, Fetics BJ, et al: Short-term effects of rightleft heart sequential cardiac resynchronization in patients with heart failure, chronic atrial fibrillation, and atrioventricular nodal block. Circulation 110(22):3404-3410, 2004. 50. Nelson GS, Curry CW, Wyman BT, et al: Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation 101(23):2703-2709, 2000. 51. Derval N, Steendijk P, Gula LJ, et al: Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites. J Am Coll Cardiol 55(6):566-575, 2010. 52. Bertini M, Marsan NA, Delgado V, et al: Effects of cardiac resynchronization therapy on left ventricular twist. J Am Coll Cardiol 54(14):1317-1325, 2009. 53. Bank AJ, Kaufman CL, Kelly AS, et al: Results of the Prospective Minnesota Study of ECHO/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study. J Card Fail 15(5):401-409, 2009. 54. Auricchio A, Stellbrink C, Sack S, et al: Pacing Therapies in Congestive Heart Failure (PATH-CHF) Study Group. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol 39(12):2026-2033, 2002. 55. Auricchio A, Stellbrink C, Butter C, et al: Pacing Therapies in Congestive Heart Failure II Study Group, Guidant Heart Failure Research Group. Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients

298

SECTION 2  Clinical Concepts

stratified by severity of ventricular conduction delay. J Am Coll Cardiol 42(12):2125-2157, 2003. 56. Linde C, Braunschweig F, Gadler F, et al: Long-term improvements in quality of life by biventricular pacing in patients with chronic heart failure: results from the Multisite Stimulation in Cardiomyopathy study (MUSTIC). Am J Cardiol 91(9):10901095, 2003. 57. Higgins SL, Hummel JD, Niazi IK, et al: Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. J Am Coll Cardiol 42(8):1454-1459, 2003. 58. Abraham WT, Young JB, Leon AR, et al: Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic heart failure. Circulation 110(18):2864-2868, 2004. 59. Linde C, Abraham WT, Gold MR, et al: Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol l52(23):1834-1843, 2008. 60. Baker CM, Christopher TJ, Smith PF, et al: Addition of a left ventricular lead to conventional pacing systems in patients with congestive heart failure: feasibility, safety, and early results in 60 consecutive patients. Pacing Clin Electrophysiol 25(8):1166-1671, 2002. 61. Horwich T, Foster E, De Marco T, et al: Effects of resynchronization therapy on cardiac function in pacemaker patients “upgraded” to biventricular devices. J Cardiovasc Electrophysiol 15(11):1284-1289, 2004. 62. Doshi RN, Daoud EG, Fellows C, et al: Left ventricular–based cardiac stimulation Post AV Nodal Ablation Evaluation (the PAVE study). J Cardiovasc Electrophysiol 16(11):1160-1165, 2005. 63. http://clinicaltrials.gov/ct2/show/NCT00900549. 64. Kron J, Aranda JM, Jr, Miles WM. et al: Benefit of cardiac resynchronization in elderly patients: results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials. J Interv Card Electrophysiol 25(2):91-96, 2009. 65. Wilkoff BL, Hess M, Young J, Abraham WT: Differences in tachyarrhythmia detection and implantable cardioverter defibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 15(9):1002-1009, 2004. 66. Di Biase L, Gasparini M, Lunati M, et al: Antiarrhythmic effect of reverse ventricular remodeling induced by cardiac resynchronization therapy: the InSync ICD (Implantable CardioverterDefibrillator) Italian Registry. J Am Coll Cardiol 52 (18):1442-1449, 2008. 67. Markowitz SM, Lewen JM, Wiggenhorn CJ, et al: Relationship of reverse anatomical remodeling and ventricular arrhythmias after cardiac resynchronization. J Cardiovasc Electrophysiol 20(3):293-298, 2009. 68. Yu CM, Chau E, Sanderson JE, et al: Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 105(4):438-445, 2002. 69. Carson P, Anand I, O’Connor C, et al: Mode of death in advanced heart failure. The Comparison of Medical, Pacing, and Defibrillation Therapies in Heart Failure (COMPANION) trial. J Am Coll Cardiol 46(12):2329-2334, 2005. 70. Anand IS, Carson P, Galle E, et al: Cardiac resynchronization therapy reduces the risk of hospitalizations in patients with advanced heart failure: results from the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial. Circulation 24:119(7):969-977, 2009. 71. Lindenfeld J, Feldman AM, Saxon L, et al: Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association Class IV heart failure. Circulation 115(2):204-212, 2007. 72. Saxon LA, Bristow MR, Boehmer J, et al: Predictors of sudden cardiac death and appropriate shock in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial. Circulation 114(45):2766-2772, 2006. 73. Cleland JGF, Daubert JC, Erdmann E, et al: Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CAREHF) trial extension phase]. Eur Heart J 27(16):1928-1932, 2006. 74. Saxon LA: More is better with cardiac resynchronization therapy—but is it enough? Eur Heart J 27(16):1891-1892, 2006. 75. Ghio S, Freemantle N, Scelsi L, et al: Long-term left ventricular reverse remodeling with cardiac resynchronization therapy: results from the CARE-HF trial. Eur J Heart Fail 11(5):480-488, 2009. 76. Wikstrom G, Blomström-Lundqvist C, Andren B, et al: CAREHF Study Investigators. The effects of aetiology on outcome in patients treated with cardiac resynchronization therapy in the CARE-HF trial. Eur Heart J 30(7):782-788, 2009. 77. Yao G, Freemantle N, Calvert MJ, et al: The long-term costeffectiveness of cardiac resynchronization therapy with or without an implantable cardioverter-defibrillator. Eur Heart J 28(1):42-51, 2007. 78. Feldman AM, de Lissovoy G, Bristow MR, et al: Cost-effectiveness of cardiac resynchronization therapy in the Comparison of

Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial. J Am Coll Cardiol 46(12):2311-2321, 2005. 79. Fox M, Anderson R, Dean J, et al: The clinical effectiveness and cost-effectiveness of cardiac resynchronization (biventricular pacing) for heart failure: systematic review and economic model. In Health Technology Assessment, 2007. http://www.ncchta.org/ fullmono/mon1147.pdf. 80. Stabile G, Solimene F, Bertaglia E, et al: Long-term outcomes of CRT-PM versus CRT-D recipients. Pacing Clin Electrophysiol 32(Suppl 1):141-145, 2009. 81. Boveda S, Marijon E, Jacob S, et al: Incidence and prognostic significance of sustained ventricular tachycardias in heart failure patients implanted with biventricular pacemakers without a back-up defibrillator: results from the prospective, multicentre, MONA LISA cohort study. Eur Heart J 30(10):1237-1244, 2009. 82. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/PMAApprovals/ ucm230212.htm 83. Tang AS, Wells GA, Talajic M, et al: Cardiac resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363(25):2385-2395, 2010. 84. Higgins S, Giudici M, Hummel J, et al: Procedure time and success rates for the placement of a coronary venous lead designed for left ventricular pacing [abstract]. J Am Coll Cardiol 39:77A, 2002. 85. Saxon LA, Bristow MR, DeMarco T, Krueger SK: Procedural outcomes and device performance in the COMPANION trial of resynchronization therapy for heart failure. Circulation 110(17):SIII-443, 2004. 86. Tang AS, Wells GA, Talajic M, et al: Cardiac resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363(25):2385-2395, 2010. 87. Gras D, Böcker D, Lunati M, et al: Implantation of cardiac resynchronization therapy systems in the CARE-HF trial: procedural success rate and safety. Europace 9(7):516-522, 2007. 88. http://www.accessdata.fda.gov/cdrh_docs/pdf/P010012b.pdf. 89. Johnson WB, Abraham WT, Young JB, et al: InSync Registry Investigators. Long-term performance of the attain Model 4193 left ventricular lead. Pacing Clin Electrophysiol 32(9):1111-1116, 2009. 90. Epstein AE, Baker JH, 2nd, Beau SL, et al: Performance of the St. Jude Medical Riata leads. Heart Rhythm 6(2):204-209, 2009. 91. Freedman RA, Petrakian A, Boyce K, et al: Performance of dedicated versus integrated bipolar defibrillator leads with CRTdefibrillators: results from a Prospective Multicenter Study. Pacing Clin Electrophysiol 2(2):157-165, 2009. 92. http://clinicaltrials.gov/ct2/show/NCT00964938. 93. Gasparini M, Auricchio A, Regoli F, et al: Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 48(4):734-743, 2006. 94. Khadjooi K, Foley PW, Chalil S, et al: Long-term effects of cardiac resynchronization therapy in patients with atrial fibrillation. Heart 94:879-883, 2008. 95. Wilton SB, Leung AA, Ghali WA, et al: Outcomes of cardiac resynchronization therapy in patients with versus without atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm 2011, doi:10.1016/j.hrthm.2011.02.014. 96. Beshai JF, Grimm RA, Nagueh SF, et al; RethinQ Study Investigators: Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 357(24):2461-2471, 2007. 97. Leon AR, Niazi I, Herrman K, et al: Chronic evaluation of CRT in narrow QRS patients with mechanical dyssynchrony from a multicenter study: ESTEEM-CRT. Heart Rhythm 5(5S):23-24, 2008. 98. http://clinical trials.gov/ct2/show/NCT00683696. 99. Wilkoff BL, Cook JR, Epstein AE, et al: DAVID Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial. JAMA 288(24):3115-3123, 2002. 100. Thambo JB, Bordachar P, Garrigue S, et al: Detrimental ventricular remodelling in patients with congenital complete heart block and chronic right ventricular apical pacing. Circulation 110(25):3766-3772, 2004. 101. Yu CM, Chan JY, Zhang Q, et al: Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 361(22):2123-2134, 2009. 102. Rao RK, Kumar UN, Schafer J, et al: Reduced ventricular volumes and improved systolic function with cardiac resynchronization therapy: a randomized trial comparing simultaneous biventricular pacing, sequential biventricular pacing, and left ventricular pacing. Circulation 115(16):2136-2144, 2007. 103. Boriani G, Müller CP, Seidl KH, et al: Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. The Resynchronization for the HemodYnamic Treatment for Heart Failure Management II implantable cardioverter defibrillator (RHYTHM-II-ICD) study. Am Heart J 151(5):1050-1058, 2006. 104. Boriani G, Biffi M, Müller CP, et al: A prospective randomized evaluation of VV delay optimization in CRT-D recipients: echocardiographic observations from the RHYTHM-II-ICD study. Pacing Clin Electrophysiol 32(10 Suppl 1):120-125, 2009.

105. http://clinicaltrials.gov/ct2/show/NCT00901212. 106. US Food and Drug Administration, Center for Devices and Radiological Health. Premarket Approval (PMA) Database. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/ pma.cfm. 107. Bernheim A, Ammann P, Sticherling C, et al: Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing. J Am Coll Cardiol 45(9):1482-1487, 2005. 108. Tei C, Ling LH, Hodge DO, et al: New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. J Cardiol 26(6):357-366, 1995. 109. Abraham WT, Gras DS: Randomized Clinical Trial to Assess the Safety and Efficacy of Frequent Optimization of Cardiac Resynchronization Therapy using the QuickOpt Method (FREEDOM) Trial Results. Presented at Late breaking Clinical Trials, Heart Rhythm Society Annual Scientific Sessions May 2010. 110. Ritter P, Nägele H, Lunati M, et al: Clinical benefit of cardiac resynchronization therapy in patients optimized by Sonr or standard methods: final results from the CLEAR study. Europace 12(Suppl 1):50, 2010. 111. Sawhney NS, Waggoner AD, Garhwal S, et al: Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy. Heart Rhythm 1(5):562-567, 2004. 112. Morales MA, Startari U, Panchetti L, et al: Atrioventricular delay optimization by Doppler-derived left ventricular dP/dt improves 6-month outcome of resynchronized patients. Pacing Clin Electrophysiol 29(6):564-568, 2006. 113. Ellenbogen KA, Gold MR, Meyer TE, et al: Primary results from the SmartDelay determined AV optimization: A comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial: A randomized trial comparing empirical, echocardiography-guided and algorithmic atrioventricular delay programming in cardiac resynchronization therapy. DOI: 10.1161/CIRCULATIONAHA.110992552 Accessed on 11/21/2010. 114. Koplan BA, Kaplan AJ, Weiner S, et al: Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J Am Coll Cardiol 53(4):355-360, 2009. 115. Ip J, Waldo AL, Lip GY, et al: Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: rationale, design, and clinical characteristics of the initially enrolled cohort The IMPACT study. Am Heart J 158(3):364-370, 2009. 116. Bax JJ, Ansalone G, Breithardt OA, et al: Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical use? A critical appraisal. J Am Coll Cardiol 44(1):1-9, 2004. 117. Ansalone G, Giannantoni P, Ricci R, et al: Doppler myocardial imaging in patients with heart failure receiving biventricular pacing treatment. Am Heart J 142(5):881-886, 2001. 118. Sogaard P, Egeblad H, Pedersen AK, et al: Sequential versus simultaneous biventricular resynchronization for severe heart failure: evaluation by tissue Doppler imaging. Circulation 106(16):2078-2084, 2002. 119. Sogaard P, Egeblad H, Kim WY, et al: Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 40(4):723-730, 2002. 120. Yu CM, Lin H, Zhang Q, Sanderson JE: High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration. Heart 89(1):54-60, 2003. 121. Achilli A, Sassara M, Ficili S, et al: Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and “narrow” QRS. J Am Coll Cardiol 42(12):21172124, 2003. 122. Gasparini M, Mantica M, Galimberti P, et al: Beneficial effects of biventricular pacing in patients with a “narrow” QRS. Pacing Clin Electrophysiol 26(1 Pt 2):169-174, 2003. 123. Chung ES, Leon AR, Tavazzi L, et al: Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation 117(20):26082616, 2008. 124. Fornwalt BK, Sprague WW, BeDell P, et al: Agreement is poor among current criteria used to define response to cardiac resynchronization therapy. Circulation 121(18):1985-1991, 2010. 125. Saxon LA, Olshansky B, Volosin K, et al: Influence of left ventricular lead location on outcomes in the COMPANION study. J Cardiovasc Electrophysiol 20(7):769-772, 2009. 126. Kronborg MB, Albertsen AE, Nielsen JC, Mortensen PT: Longterm clinical outcome and left ventricular lead position in cardiac resynchronization therapy. Europace 11(9):1177-1182, 2009. 127. Filho MM, De Siqueira SF, Costa R, et al: Conventional versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study. J Cardiac Fail 16(4):293-300, 2010. 128. Curtis AB, Adamson PB, Chung E, et al: Biventricular versus right ventricular pacing in patients with AV block (BLOCK HF): clinical study design and rationale. J Cardiovasc Electrophysiol 18(9):965-971, 2007. 129. Funck RC, Blanc JJ, Mueller HH, et al: Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and



12  Clinical Trials of Cardiac Resynchronization Therapy: Pacemakers and Defibrillators

endpoints of the Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) study. Europace 8(8):629-635, 2006. 130. Saxon LA: Improvement in heart rate turbulence as a measure of response to beta-blocker therapy for heart failure. J Cardiovasc Electrophysiol 15(7):757-758, 2004. 131. Medtronic. InSync Sentry CRT-D Device. http:// www.medtronic.com/for-healthcare-professionals/productstherapies/cardiac-rhythm/cardiac-resynchronization-therapydevices/historical-crt-devices/index.htm. 132. Adamson PB, Smith AL, Abraham WT, et al: Continuous autonomic assessment in patients with symptomatic heart failure: prognostic value of heart rate variability measured by an implanted cardiac resynchronization device. Circulation 110(16):2389-2394, 2004. 133. Catanzariti D, Lunati M, Landolina M, et al: Italian Clinical Service OptiVol-CRT Group. Monitoring intrathoracic impedance with an implantable defibrillator reduces hospitalizations in patients with heart failure. Pacing Clin Electrophysiol 32(3):363-370, 2009. 134. O’Connor CM, Koch WJ, Mann DL: Highlights of the 2009 Scientific Sessions of the Heart Failure Society of America. J Card Fail 16(1):2-8, 2010.

135. Jhanjee R, Templeton GA, Sattiraju S, et al: Relationship of paroxysmal atrial tachyarrhythmias to volume overload: assessment by implanted transpulmonary impedance monitoring. Circ Arrhythm Electrophysiol 2(5):488-494, 2009. 136. Santini M, Ricci RP, Lunati M, et al: Remote monitoring of patients with biventricular defibrillators through the CareLink system improves clinical management of arrhythmias and heart failure episodes. J Interv Card Electrophysiol 24(1):53-61, 2009. 137. Hauck M, Bauer A, Voss F, et al: “Home monitoring” for early detection of implantable cardioverter-defibrillator failure: a single-center prospective observational study. Clin Res Cardiol 98(1):19-24, 2009. 138. Hayes DL, Boehmer JP, Day J, et al: Right ventricular pacing impacts mortality in a large cohort of ICD recipients. Heart Rhythm 6(5 Suppl 1):75, 2009. 139. Saxon LA, Hayes DL, Gilliam FR, et al: Long-term outcome after ICD and CRT implantation and influence of remote device follow-up: the ALTITUDE survival study. Circulation 122(23):2359-2367, 2010. 140. Braunschweig F, Linde C, Adamson PB, et al: Continuous central hemodynamic measurements during the six-minute walk test and daily life in patients with chronic heart failure. Eur J Heart Fail 11(6):594-601, 2009.

299

141. Starling RC, Jessup M, Oh JK, et al: Sustained benefits of the CorCap Cardiac Support Device on left ventricular remodeling: three year follow-up results from the Acorn clinical trial. Ann Thorac Surg 84(4):1236-1242, 2007. 142. http:// www.clinicaltrials.gov. 143. Pappone C, Rosanio S, Burkhoff D, et al: Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 90(12):13071313, 2002. 144. Pappone C, Augello G, Rosanio S, et al: First human chronic experience with cardiac contractility modulation by nonexcitatory electrical currents for treating systolic heart failure: Midterm safety and efficacy results from a multicenter study. J Cardiovasc Electrophysiol 15(4):418-427, 2004. 145. Borggrefe MM, Lawo T, Butter C, et al: Randomized, doubleblind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. Eur Heart J 29(8):1019-1028, 2008. 146. MEMS and Nanotechnology Clearinghouse. What is MEMS technology? http://www.memsnet.org/mems/what-is.html.

13  13

Pacing for Sinus Node Disease ANNE M. GILLIS

Sinus node disease (SND) is the most common indication for a

cardiac pacing system.1 SND increases exponentially with age, affecting 1 of every 600 cardiac patients older than 65. SND is characterized by electrophysiologic abnormalities of both the sinus node and the atria. These electrophysiologic abnormalities include disturbances of impulse generation and exit from the sinus node to atrial tissue, impaired impulse transmission within the atria and specialized cardiac conduction system, failure of subsidiary pacemaker activity, and paroxysmal or chronic atrial tachycardias, including atrial fibrillation.2,3 The electrocardiographic manifestations of SND include (1) sinus bradycardia, (2) sinus pauses or sinus arrest, (3) sinoatrial exit block, (4) atrial tachycardia, (5) atrial fibrillation (initially paroxysmal), and (6) sinus node chronotropic incompetence.2,3 Bradyarrhythmias alternating with paroxysmal atrial flutter or fibrillation are common in SND. The natural history of SND includes recurrent syncope, heart failure, stroke, and atrial fibrillation.

Pathophysiology and Diagnosis CELLULAR ELECTROPHYSIOLOGY The sinoatrial node is a heterogeneous tissue with multiple cell types and a complex structure.3,4 The action potential governing pacemaking usually arises in the center of the sinoatrial node and propagates into the surrounding muscle of the right atrium. A variety of ionic currents contribute to normal sinus node automaticity (Fig. 13-1). These include If, a hyperpolarization-activated inward current, and the L- and T- type calcium currents (ICaL, ICaT). At present, debate remains over which of these currents is dominantly responsible for sinus node automaticity.5 There is limited or no measurable sodium current (INa) in the center of the node, but it is measurable in the periphery.3,4 INa may be responsible for activating peripheral cells. Outward currents that govern sinus node automaticity include the sodium-potassium (Na+,K+) pump, the delayed rectifier current (IKr), and the potassium channel activated by the muscarinic receptor, IKACh. The sodiumcalcium exchanger and sarcoplasmic reticulum (SR)–mediated calcium ion (Ca2+) release also influence sinus node automaticity. Abnormalities of one or more of these ionic currents may contribute to sinus node dysfunction. During aging, connexin 43 (Cx43) disappears from the sinus node, which may contribute to abnormalities of conduction within the sinus node.3,6 The molecular architecture of the human sinus node has recently been described.4 A complex and heterogeneous expression of ion channels is present within the sinus node compared to a paranodal region within the terminal crest and right atrial (RA) tissue. There is a lower expression of Nav1.5, Kv4.3, Kv1.5, HERG, Kir2.1, Kir6.2, the cardiac ryanodine receptor, the SR calcium pump, connexin 40 (Cx40), and Cx43 messenger ribonucleic acid (mRNA), but a higher expression of Cav1.3, Cav3.1, hyperpolarization-activated cyclic nucleotide–gated channel genes (HCN1, HCN4) mRNA in the sinus node compared to RA tissue (Figs. 13-2 and 13-3). Similar differences in expression of the corresponding ion channel proteins are observed in the sinus node compared to RA tissue. The expression pattern of many ion channels in the paranodal area is intermediate between that of the sinus node and right atrium, although greater expression of Kv4.2, Kir6.1, minK-related peptides, and other potassium channels (TASK1, SK2) is observed in the paranodal area than in the sinus node or atrial tissue. Estimating conductance of the key ionic

300

currents based on a percentage of the mRNA levels expressed in the sinus node, then incorporating these in a mathematical model of human atrial action potential, successfully produced a model of pacemaking.4 Abnormalities of one or more ionic channels, transporters, or receptors that are inherited or that develop under pathophysiologic states, including aging or atrial fibrillation (AF), likely contribute to the substrate for SND.3 Knockout of various ion channels (Nav1.5, sodium channel β2-subunit, Cav1.3, Cav3.1, HCN2, HCN4, ankyrin-B) and gapjunction subunits (Cx40) in transgenic mice result in a SND phenotype characterized by bradycardia, sinus dysrhythmia and sinus node exit block.3-7 Mutations of the HCN4 gene have been associated with reduced membrane expression and decreased If currents in conjunction with abnormalities of sinus node dysfunction.8-10 In an experimental model of heart failure, decreases in the intrinsic sinus rate have been observed in association with significant decreases in If.11 Mutations of the alpha subunit of the sodium channel that causes one form of the long QT syndrome have also been associated with SND.12-14 Such mutations may lead to the presence of a persistent inward current and a negative shift in voltage-dependence of inactivation that either separately or in combination may cause a reduction in the sinus rate. Congenital SND that is characterized by bradycardia progressing to atrial inexcitability has also been associated with mutations of the α-subunit of the sodium channel that cause loss of function or significant impairments in channel gating (inactivation), resulting in reduced myocardial excitability.15 SND has also been linked to mutations in ankyrin-B, a protein important in the regulation of ion channel function.16,17 Knockout of HERG1 B, the gene that encodes IKr, in mice has also been associated with episodic sinus bradycardia.18 Mutations of the KCNQ1 gene that encodes the KvLQT1 potassium channel are also associated with SND.19 Thus, decrease or loss of IKr or IKs in the long QT syndrome may contribute to SND in that setting. Maternal antibodies may contribute to sinus node dysfunction in the setting of congenital complete heart block by inhibition of ICaL and ICaT.20 Knockout of ICaL in transgenic mice has been associated with SND.3,21,22 Some experimental models of ventricular hypertrophy and heart failure have been reported in association with sinus node dysfunction and AF.23-27 Because SND is age dependent, changes in sinus node function may be secondary to changes in ion channels or gap junctions. Loss of INa in the periphery of the sinus node and decreased expression of Cx43 have been reported in animal models of aging and may explain abnormalities of sinus node function.3 Thus, the causes of SND are likely multifactorial. CLINICAL ELECTROPHYSIOLOGY In normal hearts, the sinus node complex displays a dynamic range of activation sites along the posterolateral right atrium.28 There are multiple origins of sinus activation and exit sites to the atria, providing evidence of multicentricity of the sinus node complex. Electroanatomic mapping has demonstrated that preferential pathways of conduction exist between the sinus node and the exit of sinus activity to the atria. In SND, the sinus node complex more often is unicentric and localized to the low crista terminalis.29,30 Electroanatomic mapping in patients with SND has also demonstrated significant increases in atrial refractory periods at all RA sites, increased atrial conduction times along the lateral right atrium and coronary sinus, and greater number



13  Pacing for Sinus Node Disease Block of ICa,L

301

Block of If Control

Csº

Control

mV

0 20 mV

–25 Nifedipine –50

A

100 ms

B

–75

INaCa

Block of ICaT It

Control Ni2+ ICa,L

HCN4

NCX1

ICa2+

3Na+

Ca2+ SR

Ca,1,3

ICa,T

0 mV INa

ERG

Ca3

Na,1,1 Na,1,5

KJQT1

IKr

IKs

C

D Inhibition of SR Ca2+ release

Block of INa

2 µM Control ryanodine

100 nM Control TTX 30 µM TTx +40 0 mV

mV

+20 0 –20 20 mV

–40

200 ms

–60

E

F 200 ms

Figure 13-1  Pacemaking mechanisms. A, Block of L-type calcium current (ICa,L) by 2 µmol/L of nifedipine abolishes action potential; data from rabbit sinus node tissue. B, Block of If by 1 mmol/L Cs+ slows pacemaking; isolated rabbit sinus node cell. C, Block of ICa,T by 40 µmol/L Ni2+ slows pacemaking; isolated rabbit sinus node cell. D, Summary of ionic currents and ion channels in pacemaking. E, Block of highly TTX-sensitive INa (possibly carried by Nav1.1) and poorly TTX-sensitive INa (presumably carried by Nav1.5) by low and high doses of TTX slows pacemaking; isolated mouse sinus node cell. F, “Block” of Ca2+ release from the sarcoplasmic reticulum (SR) by ryanodine slows pacemaking; isolated guinea pig sinus node cell. TTX, TTx. (From Dobrzynski H, Boyett MR, Anderson RH: New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation 115:1921-1932, 2007.)

and duration of double potentials along the crista terminalis29 (Fig. 13-4).29 Significant regional conduction slowing with double potentials and fractionation associated with areas of low voltage and electrical silence has also been observed in the right atrium. The slow conduction may be caused by increased fibrosis in the atria, although other determinants of conduction velocity (e.g., INa or connexin expression) have not been studied in patients with SND. Areas of low voltage/scarring in the right atrium can be widespread, progressive, and severe. Similar changes are seen in conditions of chronic atrial stretch and increasing

age.30 The mechanism of these changes in patients with SND is unclear. These results indicate not only that there is disease of the sinus node, but that the atrial electrophysiologic abnormalities also extend to the RA myocardium. Patients with congestive heart failure (CHF) manifest significant sinus node remodeling, characterized by anatomic and structural changes along the crista terminalis, and a reduction in functional sinus node reserve.31,32 Compared to age-matched controls, patients with CHF have greater prolongation of the intrinsic sinus cycle length, more prolonged sinus node recovery time, caudal origin of sinus activity,

Tbx3

120

*

80

** * **

40

** *

0

C

* 0.1

* *

0

a 0.004 * ** *

**

*

250 200

100 50 * *

Relative abundance of mRNA

20

*

**

80

** *

0

* *

Cav3.1 8

12 10

* *

8 6 4 2 0

0

G

15 10 5 * * *

a 0.029 a 0.023 * * * * * ** * *

0

K

* * * * *

100

* *

80

*

* * ** *

no de Pa ra no da la re a R ig ht at riu m

0

nu s

Si

nu s

J

no de Pa ra no da la re a R ig ht at riu m

0

* *

a <0.001 ** * *

a <0.001 *

Si

15

5

2

* * * *

HCN4 a <0.001 b <0.001 c 0.021 *

20

a <0.001 **

*

HCN2

20

* *

4

I

HCN1

10

*

6

a <0.001 a <0.001 * * * * ** * ** * *

H

25

* *

F

*

** *

** *

40

* **

Cav1.3

* * *

a 0.002 * * * * *

*

14

120

*

40 * *

Cav1.2

140

**

*

E

180

*

60

150

0

D

a 0.002 b 0.002 c 0.015

80

60

a <0.001 *

* *

40

* * *

20

a 0.001 * * *

*

0

L

um

0.2

a <0.001 b 0.024 c 0.046 *

300

ea

* *

Navβ1

Nav1.5

ar

0.3

**

0

de

a 0.004 *

0.4

c 0.034 * ** **

* *

no da l

Relative abundance of mRNA

0.5

a 0.002

0.2

**

B Nav1.4

Relative abundance of mRNA

a 0.001 c 0.02

tri

A

*

*

0.4

ht a

**

0

0.6

ig

100

**

0.8

no

200

* * * *

*

Pa ra

* * **

300

160

nu s

400

R

a 0.005 **

Nav1.2

Si

Relative abundance of mRNA

ANP

Figure 13-2  Relative abundance of mRNA in sinus node. A to L, Measurements by quantitative polymerase chain reaction for cell-type markers (ANP, Tbx3) and Na+, Ca2+, and HCN channel subunits. Mean ± SEM values are shown (n = 6). a and b, Significantly different from sinus node (SN; a) or paranodal area (PN; b; 1-way ANOVA); c, significantly different from PN (paired-t test). Individual data for all six subjects are indicated by asterisks. (From Chandler NJ, Greener ID, Tellez JO, et al: Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation 119:1562-1575, 2009.)



13  Pacing for Sinus Node Disease

303

HCN4 Endocardium

Sinus node

Epicardium

2 mm Paranodal area

Sinus node

Right atrium

60

*

Signal intensity (arbitrary units)

50 40

*

*

30 20 10

um tri R ig ht a

da la re a ra no

Pa

50 µm

Si nu

s

no de

0

Figure 13-3  Expression of HCN4 protein in sinus node, paranodal area, and right atrium. Top, Low-power montage of immunolabeling of HCN4 (green signal); white dashed line highlights sinus node. Middle and bottom, High-power images of immunolabeling of HCN4 in cell membrane (green signal) in three tissues; graph shows intensity of HCN4 labeling in sinus node, paranodal area, and right atrium; mean ± SEM (n = 4). *Significantly different (P < .05) from sinus node (one-way ANOVA). (From Chandler NJ, Greener ID, Tellez JO, et al: Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation 119:1562-1575, 2009.)

304

SECTION 2  Clinical Concepts

Bipolar voltage map Control

SVC

SND

CS

CS

Scar IVC Mean RA bipolar voltage 0.68 mV

IVC Mean RA bipolar voltage 2.1 mV

A

SVC

SND Control

4.5 *

Bipolar voltage amplitude (mV)

4.0

*

3.5 3.0

* p <0.01 *

*

*

HSRA

LSRA

*

2.5 2.0 1.5 1.0 0.5 0.0

B

HLRA

LLRA

HPRA

prolongation of sinoatrial conduction time, greater number and duration of fractionated electrograms or double potentials along the crista terminalis, loss of voltage amplitude along the crista, and abnormal and circuitous propagation of the sinus impulse. In addition, atrial refractoriness and regional conduction times are prolonged, and these changes may contribute to the propensity to AF in this setting.32 Experimental and clinical data suggest that both AF and atrial flutter cause adverse remodeling of the sinus node.33-39 Sinus node activation in patients with persistent atrial flutter is characterized by more caudal activation, slower conduction time along preferential pathways, and modest shifts within the functional pacemaker complex. Prolonged sinus pauses after paroxysms of AF may result from depression of sinus node function that is eliminated by curative ablation of AF.38 Sinus node recovery times are prolonged immediately following successful cardioversion and shorten over time.39 In an experimental model of atrial tachyarrhythmias, downregulation of HCN2, HCN3, and minK subunit expression along with the corresponding currents If and IKs has been reported.40 These changes were associated with abnormalities of sinus node function, whereas the L- and T-type calcium units and

LPRA

Figure 13-4  A, Bipolar voltage mapping in a patient with sinus node disease (SND) (right) and age-matched control (left). Both atria are oriented such that posterior right atrium (RA) is en face. Areas of electrical silence (scar) are demonstrated in gray. Note patient with SND demonstrates significantly greater number of points with double potentials (DP blue dots) and fractioned electrograms (FS red dots). SVC, IVC, Superior, inferior vena cava; CS, coronary sinus. B, Regional bipolar voltage; HSRA, high septal right atrium; LSRA, low septal RA; HLRA, high lateral RA; LLRA, low lateral RA; HPRA, high posterior RA; LPRA, low posterior RA. (From Sanders P, Morton JB, Kistler PM et al: Electrophysiological and electroanatomic characterization of the atria in sinus node disease: evidence of diffuse atrial remodeling. Circulation 109:1514-1522, 2004.)

Cx43 were unaffected. These data suggest that changes in If and IKs contribute to the abnormalities of sinus node function associated with AF. The long-term loss of atrioventricular (AV) synchrony induced by VVI pacing is also associated with atrial electrical remodeling, characterized by nonuniform prolongation of atrial refractoriness and prolonged atrial conduction and sinus node recovery times.33 These electrophysiologic changes are reversible after restoration of AV synchrony with DDD pacing. Together, the changes in atrial and sinus node electrophysiology may contribute to the higher incidence of AF observed in patients treated with VVI pacing versus AV sequential pacing. The cellular mechanisms resulting in the association between sinus node dysfunction and atrial tachyarrhythmias (tachycardia) at present remain unknown. CLINICAL PRESENTATION The most common symptoms for which patients with SND seek medical attention include presyncope, syncope, palpitations, decreased



13  Pacing for Sinus Node Disease

TABLE

13-1 

Symptoms of Sinus Node Disease

Type Major

Symptoms Syncope Presyncope Fatigue Decreased exercise tolerance Palpitations Confusion Memory loss

Less specific

exercise tolerance, and fatigue2,3 (Table 13-1). Symptoms are usually intermittent and may be of variable duration. Many patients with electrocardiographic evidence of sinus node disease may be asymptomatic. Symptoms secondary to systemic thromboembolism may also be observed. Syncope may be secondary to profound sinus bradycardia, asystole, or atrial tachycardias. Syncope may occur without warning or may be heralded by dizziness or palpitations. The physical examination is frequently unremarkable, although sinus bradycardia or AF should raise suspicion of SND. However, sinus bradycardia is frequently observed in normal, healthy individuals of all age ranges. Clinical correlation with symptoms is important.

305

Syncope occurred in 23%, symptomatic heart failure in 17%, permanent AF in 11%, and symptomatic paroxysmal atrial tachyarrhythmias in 6%. The rates of cardiovascular events were 35%, 49%, and 63% after 1, 2, and 4 years, respectively. Older age and associated left ventricular dysfunction were independent predictors of cardiovascular events. The rate of syncope was 16%, 31%, and 31% after 1, 2, and 4 years, respectively. Although a favorable outcome was observed in 43% of patients, the cohort studied was small and duration of follow-up relatively short. In a cohort of 213 patients with symptomatic SND treated with atrial pacing, the incidence of permanent AF during follow-up was 1.4% per year.45 The risk of developing AF increased substantially in patients age 70 or older at pacemaker implantation. The risk of highgrade AV block was 1.8%/yr and was much greater in patients with complete bundle branch block or bifascicular block (35%) than in patients without such conduction disturbances (6%). Survival rates in this population were similar to those of a matched general population (97% at 1 year, 89% at 5 years, 72% at 10 years). Retrospective data also support the conclusion that survival in patients with SND treated with pacemaker therapy is similar to a general matched population.46

Clinical Outcomes in Sinus Node Disease

DIAGNOSIS

PACING AND SURVIVAL

Table 13-2 summarizes the diagnostic tools presently available for SND. Because of the intermittent nature of this syndrome, the diagnosis is often time-consuming and frustrating. The sensitivity of both noninvasive tests and invasive electrophysiologic studies to identify SND as a potential cause of syncope are low (4%-16%).2 Implantable loop recorders have increased the likelihood of diagnosing bradycardia as the cause of syncope in patients with SND, and this approach in select patients is more cost-effective than a strategy of serial noninvasive studies followed by invasive studies.41-43

A number of retrospective studies47 and one prospective study48 have reported that atrial-based pacing compared to ventricular pacing is associated with improved survival in patients with symptomatic bradycardia secondary to SND. Andersen et al.48 randomized 225 patients (mean age 76 years) with sinus node dysfunction, normal AV conduction, and a normal QRS complex to AAI or VVI pacing. Over a mean of 5.5 years of follow-up, fewer cardiac deaths occurred in the atrial pacing group (19%) compared to the ventricular pacing group (34%; P = .0065). The annual mortality rate was 3% in the atrial versus 6.4% in the ventricular pacing group. However, these results have not been confirmed in three larger clinical trials. The Pacemaker Selection in the Elderly (PASE) trial randomized 407 patients age 65 and older to receive a dual-chamber pacemaker programmed to either the DDDR or the VVIR mode.49 Overall mortality was similar in the two pacing groups. Of the 175 patients with SND as the primary indication for pacing in this study, overall mortality was slightly higher in the VVIR group (8.8%/yr) than the DDDR group (5.2%/yr; P = .09). The Canadian Trial of Physiologic Pacing (CTOPP) randomized 2568 patients from a general pacemaker population, 42% with SND as an indication for pacing but without permanent AF, to receive a ventricular (1474) or atrial-based (1094) pacemaker.50 Over a mean follow-up of 3.1 years, overall mortality was similar in both groups (6.3%/yr in physiologic vs. 6.6%/yr in ventricular pacing group; P = 0.92). Since the effects of atrial pacing for prevention of AF were delayed in the CTOPP population, and similar observations were reported by Danish investigators,48 the follow-up in CTOPP was extended. Over 6.4 years, the primary composite outcome of cardiovascular death or stroke occurred at 6.1%/year in patients assigned to ventricular pacing and 5.5%/year in those assigned to physiologic pacing.51 The relative risk reduction was 8.1% with physiologic pacing (95% CI = −6.5 to 20.7; P = 0.26). The Mode Selection Trial (MOST) investigators randomized 2010 patients with SND to rate-modulated ventricular or dual-chamber pacing.52 Over a mean follow-up of 2.76 years, annual mortality was similar in both groups: 7.1% in the physiologic versus 7.4% in the ventricular pacing group (P = 0.65) (Fig. 13-5). A pooled analysis of five randomized trials did not show a significant reduction in mortality (hazard ratio [HR] = 0.95; 95% CI = 0.87 to 1.03) associated with atrial or dual-chamber pacing versus ventricular pacing.53 In a population-based cohort of 8777 patients with SND treated with AAI or DDD pacemakers, a slight increase in all-cause

NATURAL HISTORY The course of SND is unpredictable; periods of symptomatic sinus node dysfunction may be separated by long periods of normal function.2 SND is believed to evolve over 10 to 15 years, commencing with an asymptomatic phase and ultimately progressing to complete failure of sinus node activity and the emergence of subsidiary pacemaker escape rhythms or the development of chronic AF. Menozzi et al.44 performed a prospective study in 35 untreated patients with SND.44 These subjects had a mean sinus rate at rest of 50 beats per minute or less (≤50 bpm) and/or intermittent sinoatrial block, as well as symptoms attributable to SND. The patients were followed for up to 4 years (mean, 17 ± 15 months). During follow-up, 57% of patients experienced at least one cardiovascular event that required treatment.

TABLE

13-2 

Diagnostic Evaluation of Sinus Node Function

Diagnostic Mode Electrocardiogram (ECG) Exercise treadmill testing Autonomic testing Invasive electrophysiologic assessment

Device/Measurement 12-lead ECG, including carotid sinus massage Ambulatory electrocardiographic monitoring Event recorders (patient activated or auto triggered) Implantable loop recorder

Tilt-table testing Pharmacologic interventions Sinus node recover time (SNRT) Sinoatrial conduction time (SACT) Sinus node effective refractory period (SNERP) Direct recording of sinoatrial electrogram Effect of autonomic blockade on SNRT, SACT, SNERP

306

SECTION 2  Clinical Concepts

V. rate during atrial arrhythmias

Atrial arrhythmias Duration VP VS

% of V. beats 50 40 30 20 10 0 <

80

100

120

140

160

180

200

>

Ventricular rate (bpm)

24 hr 12 hr 4 hr 1 hr 10 min 1 min <1 min

Count

= >72 hr – <72 hr – <24 hr – <12 hr – <4 hr – <1 hr – <10 min

Cardiac compass: 06/29/09 to 12/21/09 Atrial arrhythmia trend: 25 days with >4 hours AT/AF (hours/day) 24 20 16 12 8 4 0 06/29

07/29

08/28

A Feb 2009 Apr 2009 P = Program I = Interrogate _ = Remote

I

AT/AF total hours/day

V rate during AT/AF (bpm) max/day avg/day

09/27 Date (mm/dd)

0 6 5 10 16 19 73 93 222

10/27

11/26

12/26

Jun 2009 Aug 2009 Oct 2009 Dec 2009 Feb 2010

I

P

I

P

24 20 16 12 8 4 0

>200 150 100 <50

% Pacing/day Atrial Ventricular

Avg. V rate (bpm) Day Night

B

100 75 50 25 0 >120 100 80 60 <40

Figure 13-5  Examples of information during AT/AF stored in pacemaker diagnostics. A, Histogram showing ventricular rate during atrial fibrillation (AF); distribution of AF by duration; date and duration of individual episodes of AF. Note the histograms of ventricular rate during atrial tachycardia (AT)/AF demonstrate suboptimal rate control. B, Cardiac Compass showing time course of paroxysmal AF, including more persistent episodes. Note overall reasonable rate control during episodes of AF.

mortality (HR = 1.12; CI = 1.00 to 1.25), was seen among DDD patients compared to AAI patients.54 PACING AND ATRIAL FIBRILLATION Paroxysmal AF, atrial flutter, and atrial tachycardia (AT) occur frequently in SND.55 AT/AF detection and data storage features are now present in most dual-chamber pacemakers, facilitating the diagnosis and treatment of AF.55-61 Some devices have special algorithms developed specifically for the prevention and management of atrial tachyarrhythmias.58-61

Detection of Atrial Fibrillation Accurate detection of atrial tachyarrhythmias, including atrial flutter and AF, by implantable devices with advanced AT management features is important for several reasons. Accurate detection ensures the appropriateness of automatic mode switching and of atrial antitachycardia pacing (ATP) for atrial flutter. Many implantable devices provide a wide range of diagnostic data, including the frequency of AT/AF, time of onset and duration of episodes, quantity of AT/AF (burden expressed as % of day or hours/day), ventricular rate control during AF, and symptomatic events56-58 (see Fig. 13-5). Such information may be



13  Pacing for Sinus Node Disease 100

TABLE

Survival free of hospitalization (%)

13-3 

Factors Influencing Device Detection of AT/AF

Sensing Undersensing

75

Factors Low atrial EGM in sinus rhythm Atrial EGM in blanking period Programmed atrial rate Programmed AT/AF duration Programmed atrial sensitivity Programmed atrial blanking period Far-field R-wave (FFRW) detection

No VHR

50

307

Oversensing

AT/AF, Atrial tachycardia/fibrillation; EGM, electrogram.

VHR 25

AT/AF detection because some sites (e.g., near coronary sinus os, within RA appendage) are associated with a high incidence of far-field R-wave (FFRW) oversensing that may be inappropriately classified as AF. Figure 13-7 shows an example of inappropriate classification caused by FFRW oversensing. Interelectrode lead spacing (e.g., 5 mm) may also minimize FFRW sensing. Attention to these issues promotes high sensitivity and specificity of AT/AF detection.72 Applying these parameters, sensitivity of AT/AF detection was 97% for sustained episodes of 5 minutes or longer.73 Some devices have incorporated newer detection algorithms that include pattern recognition to facilitate detection of AT/AF and minimize inappropriate detection caused by FFRW oversensing.72,73 Such algorithms have high sensitivity (>95%) and specificity for AT/AF detection.72-75

0 0

6

12

18

24

30

Months Figure 13-6  Survival free from hospitalization for cardiovascular symptoms. Patients who experienced ventricular high-rate (VHR) events predominantly from AF with a rapid ventricular response (blue line) were more likely to be hospitalized than patients without VHR episodes (purple line; Logrank P = .001). (From Willems R, Morck ML, Exner DV, et al: Ventricular high-rate episodes in pacemaker diagnostics identify a high-risk subgroup of patients with tachy-brady syndrome. Heart Rhythm 1:414-421, 2004.)

Pacing Mode in Prevention of Atrial Fibrillation Several prospective randomized clinical trials have reported that atrial or dual-chamber pacing prevents paroxysmal and permanent AF in patients with symptomatic bradycardia as the primary indication for cardiac pacing. Danish investigators reported a 46% relative risk reduction for the development of AF in the atrial pacing group (P = .012).48 The CTOPP study reported an 18% risk reduction in the development of AF (P = .05) in patients randomized to atrial-based versus ventricular pacing.50,76 This effect was sustained over longer-term follow-up (20% risk reduction at 6 years; P = .009).51 Patients with a structurally normal heart were most likely to derive benefit from atrial-based pacing.76 Although a retrospective subgroup analysis in CTOPP suggested that pacemaker-dependent patients were most likely to benefit from physiologic pacing for prevention of AF, this effect was not confirmed over long-term follow-up.51 The PASE investigators reported a 32% reduction in AF in patients with SND as the primary indication for pacing who were randomized to the dual-chamber pacing mode versus the ventricular pacing mode (P = .06).49 MOST reported a 21% relative risk reduction in the development of AF (P = .008) and a 56% relative risk reduction in the development of permanent AF (P < .001) in patients randomized to dual-chamber versus ventricular pacing52 (Fig. 13-8). Table 13-4 summarizes the results of these clinical trials. In contrast, the United Kingdom Pacing and Cardiovascular Events (UKPACE) trial investigators, who randomized 2021 patients age 70 and older with high-grade AV block to dual-chamber or ventricular pacing, did

valuable for managing antiarrhythmic drug therapy62-64 and when considering the need for antithrombotic therapy.65,66 Patients with AF associated with episodes of rapid ventricular rates are more likely to experience hospitalization for cardiovascular events63 (Fig. 13-6). Identification of such episodes by an implanted cardiac device can prompt changes in antiarrhythmic drug therapy. With advances in remote monitoring of pacemakers and implantable defibrillators, early detection of AT may facilitate earlier medical intervention.67 Many recent clinical device trials have used devicebased indices of arrhythmia recurrence, frequency, and burden as surrogates for clinical endpoints.56 Although measures of AT/AF burden in devices is quite accurate, counts of AT/AF frequency are less accurate because of variations in device-based criteria for detection, termination, and redetection, as well as intermittent atrial undersensing during AT/AF episodes.68,69 Some investigators report comparatively low values for appropriate AT/AF episode detection using early-generation pacemaker modeswitching and detection algorithms.70 Table 13-3 summarizes factors influencing AT/AF underdetection or overdetection. It is important that pacemakers be programmed to optimize detection of AT/AF, with careful attention to the atrial sensitivity and post–ventriculoatrial blanking period. Atrial undersensing from inappropriate noise reversion has been described when high atrial sensing levels are programmed.71 Atrial lead position is an important factor for appropriate TABLE

13-4 

Randomized Trials of Physiologic Pacing and Impact on Atrial Fibrillation (AF)

Parameter Number Age (yr) Pacing indication Follow-up (yr) Pacing modes AF risk (%/yr) RR reduction (%) P value

Danish AAI vs. VVI48 225 71 ± 17 SND-AAI 5.5 AAI vs. VVI 4.1 vs. 6.6 46 0.012

CTOPP50 2568 73 ± 10 All pacemaker patients 3.1 Physiologic vs. VVIR 5.3 vs. 6.3 18 0.05

Extended CTOPP51 2568 73 ± 10 All pacemaker patients 6.4 Physiologic vs. VVIR 4.5 vs. 5.7 20 0.009

DDDR-l, Long atrioventricular delay; DDDR-s, short atrioventricular delay; RR, relative risk.

MOST52 2050 74 (67-80) SND 2.7 DDDR vs. VVIR 7.9 vs. 10.0 21 0.008

Danish AAI vs. DDD125 177 74 ± 9 SND-AAI 2.9 AAI vs. DDDR-s vs. DDDR-l 2.4 vs. 8.3 vs. 6.2 73 0.02

308

SECTION 2  Clinical Concepts

GR suspended for 20 sec

AT/AF onset

EGM suspended for 1 min 30 sec

AT/AF detection

Figure 13-7  Example of false-positive detection of atrial tachycardia (AT) resulting from far-field R-wave oversensing. AF, Atrial fibrillation; EGM, electrogram.

not observe a benefit of dual-chamber pacing for AF.77 These data suggest that the primary benefit of dual-chamber pacing for prevention of AF occurs in patients with SND. In the CTOPP population, the number needed to treat (NNT) to prevent any AF over 10 years (ideal longevity of dual-chamber pacemaker) was nine patients.58 In the MOST population, NNT to prevent permanent AF in patients with SND over 3 years was nine patients. The cost differential of dual-chamber pacing compared with ventricular pacing in CTOPP was $2500.78 The additional cost of dual-chamber pacing is approximately $1/day. AF is frequently unrecognized in the pacemaker population; anticoagulation is often underutilized; and class I-III antiarrhythmic drug therapy for prevention of AF may be proarrhythmic. Accordingly, atrial or dual-chamber pacing may be a cost-effective therapy to prevent a condition that causes substantial

morbidity.78,79 However, to date, no study has shown that prevention of AF in this patient population translates into a substantial clinical benefit, whether improved quality of life or functional capacity or reduced hospitalization or health care utilization. Pacing Algorithms in Prevention of Atrial Fibrillation Over the past decade, a number of clinical studies have evaluated the role of atrial pacing algorithms for prevention of atrial fibrillation.58,59,80 Initial studies investigated the efficacy of atrial overdrive pacing achieved by programming a higher base pacing rate on suppression of AF.81,82 Subsequently, selective pacing algorithms were designed to target the triggers and substrate for AF, including continuous pacing rather than fixed-rate atrial overdrive, algorithms to prevent pauses after atrial premature beats or exercise, transient overdrive pacing after



13  Pacing for Sinus Node Disease HOSPITALIZATION FOR HEART FAILURE, STROKE, OR DEATH

PRIMARY ENDPOINT 0.50

0.50 P0.48 Adjusted P0.32

0.40

Ventricular pacing

0.30 0.25 0.20

0.35 0.30 0.25

Dual-chamber pacing

0.20 0.15

Dual-chamber pacing

0.15

P0.23 Adjusted P0.05

0.40 Event rate

0.35 Event rate

Ventricular pacing

0.45

0.45

0.10

0.10

0.05

0.05 0.00

0.00 0

6

12 18 24 30 36 42 48 54 60

Months No. at Risk Ventricular 996 934 897 813 678 557 431 320 218 125 39 pacing Dual-chamber 1014 963 930 833 693 555 431 328 214 120 28 pacing

0

6

Months

ATRIAL FIBRILLATION

0.50 0.45 0.40 0.30 0.25 Ventricular pacing

0.20 0.15 0.10

Dual-chamber pacing

0.05 0.00 0

6

12 18 24 30 36 42 48 54 60 Months

No. at Risk Ventricular 996 890 855 766 637 516 402 300 200 116 36 pacing Dual-chamber 1014 932 894 801 658 528 406 307 191 106 27 pacing

Event rate

P0.13 Adjusted P0.02

0.35

12 18 24 30 36 42 48 54 60

No. at Risk Ventricular 996 880 839 752 624 504 388 287 193 110 35 pacing Dual-chamber 1014 926 889 793 649 518 394 297 188 105 26 pacing

HOSPITALIZATION FOR HEART FAILURE

Event rate

309

0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00

P0.008 Adjusted P0.004

Ventricular pacing

Dual-chamber pacing

0

6

12 18 24 30 36 42 48 54 60 Months

No. at Risk Ventricular 996 815 761 668 542 432 333 242 162 92 27 pacing Dual-chamber 1014 852 795 700 572 444 341 248 148 77 20 pacing

Figure 13-8  Rates of clinical events according to the mode of pacing in the MOST trial. (From Lamas GA, Lee KL, Sweeney MO, et al: Mode Selection Trial in Sinus Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus node dysfunction. N Engl J Med 346:1854-1862, 2002.)

detection of premature atrial contractions (PACs) or after termination of an episode of AF, and atrial ATP for termination of atrial flutter that transitions into AF.58,60,61 Although small studies suggested promise of one or more of these algorithms for suppression of AF, larger randomized clinical trials have failed to demonstrate a major benefit of these therapies for prevention of AF compared to control groups with fixedrate or rate-responsive pacing. To test the hypothesis that atrial pacing might prevent paroxysmal AF in patients without symptomatic bradycardia as a primary indication for pacing, the Atrial Pacing Peri-Ablation for the Prevention of AF (PA3) study randomized 97 patients with frequent paroxysmal AF being considered for AV junction ablation to a trial of atrial pacing versus no pacing.81 The time to first recurrence of AF and total AF burden documented over 3-month follow-up were similar in the atrial

pacing group (1.9 days; 95% CI = 0.8 to 4.6) compared to the no pacing group (4.2 days; 95% CI = 1.8 to 9.5; P = NS). In Phase II the PA3 trial tested the hypothesis that atrial pacing versus AV synchrony would prevent AF.82 After AV junction ablation, 76 patients were randomized to DDDR versus VDD pacing. The time to first recurrence of sustained AF and total AF burden over time were similar in the DDDR (0.37 day; 95% CI = 0.1 to 1.3) and the VDD (0.5 day; 95% CI, 0.2 to 1.7; P = NS) pacing groups. Furthermore, AF burden increased progressively over time, and 42% of the study population had developed permanent AF within 1 year after ablation. Patients maintained on constant antiarrhythmic drug therapy throughout the PA3 study developed significant increases in AF burden and were more likely to develop permanent AF very early after AV junction ablation than patients with deferred ablation.83

310

SECTION 2  Clinical Concepts

Mode-switch duration (hr)

Symptomatic AF burden (%)

The dynamic atrial overdrive (DAO) pacing algorithm was evaluated in the Atrial Dynamic Overdrive Pacing Trial (ADOPT).84 Investigators randomized 399 patients with SND and paroxysmal AF to a trial of DDDR pacing versus DDDR pacing plus the overdrive atrial pacing algorithm. Patients were followed at 1, 3, and 6 months after pacemaker insertion. The primary study outcome was symptomatic AF burden, defined as percentage of days in symptomatic AF. Both groups experienced a substantial reduction in symptomatic AF over time. In addition, a modest but statistically significant reduction was found in symptomatic AF associated with the DAO algorithm during follow-up (Fig. 13-9, upper panel). However, the absolute risk reduction diminished over time: 1.25% at 1 month versus 0.36% at 6 months. Moreover, overall AF burden calculated from the mode-switch diagnostics was similar between the two groups and indeed, increased over time, suggesting that the overdrive pacing algorithm had no effect on total AF burden over time (Fig. 13-9, lower panel). Other studies have not demonstrated a significant impact of DAO pacing for prevention of AF. The Atrial Septal Pacing Clinical Efficacy Trial (ASPECT) randomized 298 patients with paroxysmal AF and associated symptomatic bradycardia to conventional DDDR pacing or DDDR pacing plus three additional atrial pacing algorithms specifically designed for prevention of AF at atrial-septal or right atrial appendage pacing sites.85 After 3 months of treatment, patients were crossed-over to the alternate pacing strategy and followed for an additional 3 months. AF burden, determined from the diagnostic counters (in pacemaker measured as % time in AF) was the primary study outcome. The three AF prevention algorithms (atrial pacing preference, atrial rate stabilization, and “post mode switch overdrive” pacing) did not reduce AF burden or AF frequency despite suppression of atrial premature beat frequency (Fig. 13-10). The AFTherapy Study randomized 372 patients with drug-refractory paroxysmal AF to dual-chamber pacing programmed to single-rate or rate-responsive pacing at lower rates of either 70 or 85 bpm or to a control group with single-rate pacing at 40 bpm.60 In the subsequent preventive pacing phase, patients were randomized to pacing at a lower rate of 70 bpm with or without programming of four preventive pacing algorithms. The primary endpoint was AF burden, with secondary endpoints of time to first AF episode and averaged sinus rhythm duration. Substantial data were excluded from the analysis because of

6

Overdrive pacing OFF Overdrive pacing ON

4.44% 4

atrial-sensing issues, predominantly oversensing, resulting in inappropriate classification of events as AF. In the conventional pacing phase, no significant differences in AF burden were found between the various lower rates and the control group or between single-rate and rateresponsive pacing. In the second phase, patients receiving preventive pacing therapies had a similar AF burden (median, 0 hr/day) compared with patients receiving conventional pacing (0.18 hr/day; P = 0.47). In the Study of Atrial Fibrillation Reduction (SAFARI) trial, 240 patients with qualifying AF 4 months after pacemaker implantation were randomized to a suite of six pacing prevention therapies programmed on or off and followed for 6 months.61 A modest but statistically significant decrease in AF burden (median, 0.08 hr/day) was seen in the group randomized to AF prevention therapies on versus no change in AF burden in off group. Patients with a high baseline burden of AF (>1.44 hr/day) randomized to prevention therapies on experienced a significant reduction in AF burden (median, 1.38 hr/day), versus an increase in AF burden of 0.31 hr/day in the subgroup with high baseline AF burden randomized to therapies off. A study based on characteristics preceding onset of AF derived from pacemaker diagnostic data analyzed whether subgroups of patients benefited from pace prevention therapies. During a 3-month diagnostic phase with conventional pacing, Lewalter et al.86 identified a substrate group (>70% of AF episodes preceded by <2 PACs before AF onset) and a trigger group (those with ≤70% of AF episodes with <2 PACs before AF onset). In the trigger group, pacing algorithms were programmed to avoid or prevent atrial premature beats, and in the substrate group, continuous atrial overdrive pacing was enabled. In the trigger group (n = 73), AF burden was reduced 28% (median AF burden: 2.06 hr/day during monitoring vs. 1.49 hr/day with pacing therapies “on” (P = .03) in association with reduced atrial premature beat frequency. AF burden was unchanged in the substrate group (median AF burden: 1.82 hr/day during monitoring vs. 2.38 hr/day with overdrive pacing “on” (P = 0.12). Thus, individualizing AF pace prevention algorithms based on individual AF onset characteristics may be beneficial in some patients. Based on all the available data from studies conducted over the past decade, selective atrial prevention pacing algorithms have not substantially reduced the AF burden or significantly impacted clinical

3.19%

2.63% 1.93%

2

1.73%

1.37%

0 1 month

3 months

6 months

1 month

3 months

6 months

1800 1600 1400 1200 1000 800 600 400 200 0 Time following randomization

Figure 13-9  Upper panel, Time spent in symptomatic atrial fibrillation (AF) at 1-, 3-, and 6-month follow-up in 399 patients randomized to DDDR pacing with dynamic atrial overdrive (DAO) programmed ON (purple bar) or OFF (blue bar). Lower panel, AF burden estimated from the mode switch duration counters retrieved by pacemaker interrogation at 1-, 3-, and 6-month follow-up in 399 patients randomized to DDDR pacing with dynamic atrial overdrive (DAO) programmed ON (purple bar) or OFF (blue bar). (Data from Carlson MD, Ip J, Messenger J, et al: ADOPT Investigators. A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). J Am Coll Cardiol 42:627-633, 2003.)

13  Pacing for Sinus Node Disease 125

250

100

200

75

150

50

100

25

50

0

Pacing Algorithms in Termination of Atrial Fibrillation Episodes of atrial tachycardia and atrial flutter occur frequently in patients with AF, and AT or atrial flutter often transition between episodes of AF.73,74,87,88 Figure 13-11 illustrates an example of AF that organizes into atrial flutter and is then effectively terminated by atrial ATP therapy, which has been incorporated into some pacemakers and implantable defibrillators. Efficacy of atrial ATP for termination of AT and atrial flutter ranges from 30% to 54%.87,89-93 In select individuals, atrial ATP therapy reduces AT/AF burden over time.60,90,93 The hypothesis that successful pace termination of AT or atrial flutter would prevent AF over time was tested in the Atrial Therapy Efficacy and Safety Trial (ATTEST).89 In a parallel design, 370 patients received a Medtronic AT 500 and were randomized to DDDR pacing or DDDR pacing with atrial ATP therapies and atrial pace prevention therapies programmed on. Over 3-month follow-up, 15,000 episodes of AT were treated by atrial ATP therapies, with device-classified efficacy of 41%. However, AF frequency and AF burden were not reduced by the delivery of prevention therapies or atrial ATP therapies (Fig. 13-12). Friedman et al.94 randomized 405 patients with a history of AF and an implantable cardioverter-defibrillator (ICD, for standard indications) to atrial prevention and termination therapies on (n = 199) or off (n = 206). Patients were followed for 7 months. The mean AT/AF burden was 4.3 ± 20.0 hr/month in patients with AT/AF prevention

0 Septal

Nonseptal

Septal

AF prevention ON

Nonseptal

AF prevention OFF

Figure 13-10  Atrial fibrillation (AF) frequency (left bars) and AF burden (right bars) in 298 patients randomized to septal pacing or nonseptal pacing and crossover to trials of three atrial pacing algorithms for prevention of AF (AF Prevention Rx). AF frequency and burden were similar at both pacing sites. The pacing prevention therapies did not reduce AF frequency or burden. Data are median (lines) and 25th and 75th percentiles (lower and upper border of boxes). (Data from Padeletti L, Purerfellner H, Adler SW, et al: Worldwide ASPECT Investigators. Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia. J Cardiovasc Electrophysiol 14:1189-1195, 2003.)

7 5 0

A P

V P

7 5 0

F D

V P

2 1 0

F D

2 1 0

8 6 0

F D

2 2 0

F D

A P

V P

7 5 0

2 2 0

V P

F D

7 5 0

2 2 0

F D

8 6 0

2 1 0

F D

2 2 0

7 5 0

A P

F D

2 3 0

V P

F D

2 1 0

F D

8 6 0

2 1 0

F D

V P

7 5 0

2 1 0

7 5 0

A P

V P

7 5 0

F D

2 1 0

V P

A S

311

outcomes secondary to AF. Accordingly, programming such therapies cannot be routinely recommended. If such therapies are programmed “on,” their efficacy should be reevaulated over time. AF burden (hr/day)

AF frequency (episodes/day)



1 9 0

A P

7 5 0

1 1 1 2 8 7 6 8 0 0 0 0 A A A A P P P P

1170

4 5 0

2 1 1 1 1 1 1 1 1 1 1 1 0 7 7 6 5 5 7 6 6 5 3 4 0 0 0 0 0 0 0 0 0 0 0 0 A F F F F F F F F F F F F S S S S S S S S S S S S S

V P

7 5 0

2 0 0

1 1 8 8 0 0 F F F S S S

T D

V S

7 5 0

V P

8 4 0

V S

V P

7 5 0

8 6 0

A P

8 2 0

V P

7 5 0

V P

A P

8 6 0

V P

First Rx Figure 13-11  Example of atrial fibrillation (AF) organizing into atrial flutter. Panels display atrial electrogram (EGM) and annotated markers indicating how pacemaker classifies each atrial and ventricular event, as well as cycle length (in msec) between each interval. The initial rhythm is AF (upper panel), which subsequently organizes into atrial flutter (cycle length 210 msec). The atrial flutter is terminated by a ramp atrial antitachycardia pacing (ATP) therapy restoring atrial-paced rhythm. The marker channel notations indicate how the device classifies each beat. Interbeat intervals are also shown (in msec). AP, Atrial-paced event; AR, atrial event sensed in atrial refractory period; FS, AF-sensed event; TD, tachycardia detected; TS, tachycardia-sensed event; VP, ventricular-paced event.

SECTION 2  Clinical Concepts

p0.20

5 4

1.0 3 2 0.5 1

ATP enabled

4 Median burden (hr/day)

p0.65

Low ATP efficacy High ATP efficacy

2

p <0.001 0 –6

0

0 Atrial therapies ON

Atrial therapies OFF

Figure 13-12  Left, Atrial fibrillation (AF) frequency in patients randomized to atrial antitachycardia pacing (ATP) therapy and three AF pace prevention therapies ON (purple) or OFF (blue) in ATTEST trial. Patients were followed for 3 months. Data are box plots with 25th and 75th percentiles at the bottom and top borders; median data shown by horizontal lines. Right, AF burden over 3 months of follow-up in the two treatment groups. (Data from Lee MA, Weachter R, Pollak S, et al; ATTEST Investigators: The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency: results of a randomized trial in patients with bradycardia and atrial tachyarrhythmias. J Am Coll Cardiol 41:1926-1932, 2003.)

and termination therapies on versus 9.0 ± 50.0 hr/month in the off group (P = 0.11). Several factors may explain the discrepancy between the reported high atrial ATP efficacy for AT termination and the failure to demonstrate a significant reduction in AT/AF burden.57 Device-classified efficacy may be exaggerated because of spontaneous termination of many episodes of AT.74 Indeed, in ATTEST89 and GEM-III-AT clinical evaluation,74 approximately half of episodes classified as AT/AF lasted less than 10 minutes. By design, these devices define ATP “efficacy” if sinus or atrial paced rhythm occurs before redetection of AT/AF. Although the redetection time is usually less than 1 minute, these devices could allow up to 3 minutes from the last delivered ATP therapy for redetection to occur. Using a more conservative definition of efficacy— termination of AT or AF within 20 seconds of delivery of atrial ATP therapy—atrial ATP efficacy is lower than previously reported, terminating only 26% of all atrial tachyarrhythmias and 32% of AT episodes. These observations have led to changes in detection algorithms in newer devices. The incorporation of 50-Hz burst pacing algorithms into atrial defibrillators has not been shown to terminate AF.74 In the studies evaluating atrial ATP efficacy for AF prevention, not all patients were maintained on class I-III antiarrhythmic therapy, which may be important in facilitating ATP therapy and preventing early recurrence of AT/AF.95,96 Some episodes of AT are not reentrant, and some episodes classified as “AT” may have been AF that could not be pace-terminated.97 Certain patients do benefit from atrial ATP therapy for prevention of AF62,93 (see Fig. 13-11). Patients with high atrial ATP efficacy for termination of AT (>60% of all treated episodes effectively terminated) experience a significant reduction in AF burden98 (Fig. 13-13). As many as 30% of patients with SND and paroxysmal AF may benefit from atrial ATP therapy. Also, more aggressive programming of atrial ATP therapy than using the nominal values in these devices may increase therapy efficacy.99 Most studies comparing AF pacing algorithms in AF prevention have conducted relatively short-term follow-up. Comparing atrial ATP therapy, we combined atrial ATP and atrial pace prevention algorithms to conventional DDDR pacing for prevention of AF over 3 years of follow-up in 71 patients with AT/AF after pacemaker insertion.100 AT/ AF burden remained stable over 3 years in the DDDR and ATP and

–3

0

3

6

9

12

Time (months) Figure 13-13  Median AT/AF burden (hours/day) measured over time before and after activation of atrial antitachycardia pacing (ATP) therapy in the high ATP efficacy (blue squares) and low ATP efficacy (purple circles) groups. AT/AF burden decreased significantly over time (P < .001) in the high ATP efficacy group. (From Gillis AM, Koehler J, Morck M, et al: High atrial antitachycardia pacing therapy efficacy is associated with a reduction in atrial tachyarrhythmia burden in a subset of patients with sinus node dysfunction and paroxysmal atrial fibrillation. Heart Rhythm 2:791-796, 2005.)

prevention groups, but increased significantly over time in the ATP group (Fig. 13-14). Patients not receiving class I-III antiarrhythmic therapy were more likely to experience an increase in AT/AF burden over time. Furthermore, atrial ATP is not always effective and in some patients could be proarrhythmic. Therefore, again, if atrial ATP therapies are programmed on, their effectiveness needs to be reevaluated over time. Site-Specific Atrial Pacing for Atrial Fibrillation Prevention Clinical and experimental studies have demonstrated that septal pacing, dual-site RA pacing, and biatrial pacing reduce total atrial p <0.0005 p <0.002 24 20 AT/AF burden (hr/d)

AF Frequency (median episodes/mo)

1.5

AF Burden (median hr/mo)

312

16 12 8 4 0 BL 1

2 3 yr

BL 1

2 3 yr

BL 1

2 3 yr

Figure 13-14  Median AT/AF burden at baseline (BL) and 1, 2, and 3 years of follow-up in patients randomized to DDDR pacing, DDDR plus atrial ATP, or DDDR plus atrial antitachycardia pacing (ATP) and prevention therapies. AT/AF burden increased significantly at 3 years compared with baseline and 1-year follow-up. Data are box plots with 25th and 75th percentiles at the bottom and top borders; median data shown by horizontal lines. (Modified from Gillis AM, Morck M, Exner DV, et al: Impact of atrial antitachycardia pacing and atrial pace prevention therapies on atrial fibrillation burden over long-term follow-up. Europace 11:1041-1047, 2009.)



13  Pacing for Sinus Node Disease AP

313

LAO

Figure 13-15  Chest radiographs showing atrial lead positioned on right atrial septum near Bachmann bundle. (Courtesy Ken E. Ellenbogen.)

conduction times and dispersion of atrial refractoriness.101-103 In the cardiac surgery population, randomized trials report that RA, dual-site RA, and biatrial pacing prevent postoperative AF.104 In the pacemaker population, several clinical trials have evaluated the efficacy of selective atrial pacing sites for AF prevention. Patients randomized to pacing at the interatrial septum (Bachmann bundle) were less likely to develop permanent AF (47%) than those randomized to pacing in RA appendage (75%; P < .05).105 Figure 13-15 shows chest x-ray images of the atrial lead location in the septum at the Bachmann bundle. In a small series of patients, Padaletti et al.106 reported a significant reduction in AF frequency and AF burden in patients randomized to pacing near the triangle of Koch compared to those paced in the RA appendage. However, other studies have not confirmed these benefits.85,107 In the largest randomized trial conducted to date comparing RA appendage pacing to atrial-septal pacing, a significant reduction in AF frequency or AF burden was not observed over short-term follow-up in the two groups85 (see Fig. 13-10). Dual-site RA pacing, RA appendage and coronary sinus os, lead locations have been reported to confer a modest benefit for AF prevention compared to RA appendage pacing alone.108 The benefit of dual-site RA pacing was greatest in patients treated with antiarrhythmic drugs. Biatrial pacing has been reported to prevent paroxysmal AF and development of permanent AF in patients with marked intra-atrial conduction delays,109 perhaps secondary to atrial hemodynamic benefits associated with biatrial pacing.110 At present, the role of selective atrial lead site for prevention of AF in the pacemaker population remains uncertain.111 A hybrid approach, including aggressive antiarrhythmic therapy combined with dual-site RA pacing and RA linear ablation, has been reported to provide effective AF rhythm control in select patients.112 Nevertheless, a single-site atrial lead location would be preferable given the added expense and complexity of additional leads. Small studies incorporating AF pace prevention algorithms with septal or dual-site pacing locations also have not been shown to prevent AF.113-115 The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is currently evaluating whether low atrial-septal pacing compared to RA appendage pacing with or without atrial overdrive pacing will suppress AF116 (NCT 00419640). A total enrollment of 380 patients with a follow-up of at least 3 years is planned. The primary endpoint is the development of persistent AF. A similar trial in progress, RESPECT (CT 00289289), is also evaluating atrial pacing from the septum versus RA appendage (enrollment >400 patients),

with the primary endpoint of symptom frequency and secondary endpoint of need for cardioversion. PACING AND STROKE Thromboembolism secondary to AF occurs in SND. In the Danish study, thromboembolic events were significantly less likely to occur in the atrial (12%; 2.1%/yr) than in the ventricular (23%; 4.3%/yr) pacing group (P = .023).48 In the Danish study, use of anticoagulation therapy was minimal. However, the larger clinical trials failed to show a benefit of atrial pacing for prevention of cerebrovascular accident (CVA, stoke). In CTOPP, annual incidence of stroke was similar in the atrial (1.0%) and the ventricular (1.1%) pacing groups.50,51 In MOST, annual CVA incidence was similar in the dual-chamber (1.5%) and the ventricular (1.8%) pacing groups.52,117 The failure to show a benefit of reducing stroke by preventing AF in these larger trials may be caused by other factors. The etiology of stroke in an elderly pacemaker population is multifactorial, not only secondary to emboli originating in the left atrium because of AF.118 Furthermore, the impact of randomized clinical trials of anticoagulation for prevention of stroke may have led to increased use of antithrombotic therapy in pacemaker patients with AF. In MOST, 72% of patients were receiving antiplatelet therapy or warfarin. A pooled analysis of the five largest randomized trials comparing atrial to ventricular pacing did demonstrate a significant reduction in stroke with atrial pacing (HR = 0.81; CI = 0.67 to 0.99; P = 0.038), which was similar among patients with SND and AV block.53 Relationship Between Stroke Risk and Atrial Fibrillation Burden/Duration Analysis from clinical trials suggests that patients with intermittent AF are at similar risk for stroke as those with persistent or permanent AF. Analysis of AF data retrieved from device telemetry in several cohort studies suggested that longer-lasting AT/AF events were associated with an increased risk of arterial thromboembolism.65,66 Importantly, in a significant number of pacemaker patients, relapse of AF lasting more than 48 hours occurred in the absence of symptoms.119 Data from 725 patients with pacemakers capable of monitoring AT/ AF burden showed that AT/AF lasting 24 hours or longer conferred a threefold increased risk of systemic thromboembolism compared with patients with no AT/AF or with AT/AF episodes lasting less than 24 hours.65

314

SECTION 2  Clinical Concepts

The TRENDS study designed a prospective observational cohort to assess the relationship between low levels of AF burden and the risk of stroke.66 Patients with one or more risk factors for stroke and a pacemaker or ICD that monitored AT/AF daily were followed for a mean of 1.4 years. AT/AF burden was defined as the longest total AT/AF duration on any given day during a 30-day window. The varying exposure was updated daily and related to the development of systemic thromboembolism during follow-up. The annualized thromboembolic risk during follow-up of 2486 patients was 1.1% for zero AT/AF burden and 1.1% for low and 2.4% for high burden subsets. These data suggest that systemic thromboembolism is a quantitative function of AT/AF burden, and that AT/AF burden longer than 5.5 hours on any day of the 30 days appeared to double the risk of systemic thromboembolism. The TRENDS data did not allow the investigators to define a safe AT/AF burden threshold that confers a risk no greater than that of patients with zero AF burden. The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) is a multicenter cohort follow-up study in elderly hypertensive patients with a recently implanted pacemaker and no prior history of AF.120 The study tests the hypothesis that AT/AF detected by pacemaker diagnostics during follow-up predicts an increased risk of CVA and other vascular events, with results expected soon. Preliminary results were presented in November 2010 at the American Heart Association Meeting. ASSERT showed that device-detected atrial tachyarrhythmias were associated with an increased risk of stroke and systemic embolism (2.5x). PACING AND PACEMAKER SYNDROME The pacemaker syndrome consists of a constellation of signs and symptoms that result from the loss of AV synchrony during ventricular pacing2,121 (Table 13-5). The definition and diagnostic criteria of pacemaker syndrome vary, but symptoms include fatigue, dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, orthostatic hypotension, and syncope. In the MOST study, pacemaker syndrome was prospectively defined as (1) new or worsened dyspnea, orthopnea, elevated jugular venous pressure, rales, and edema, with ventriculoatrial conduction during ventricular pacing, or (2) symptoms of dizziness, weakness, presyncope or syncope, and reduced systolic blood pressure (>20 mm Hg) during VVIR pacing compared with atrial pacing or sinus rhythm.52,121 The incidence of pacemaker syndrome was 13.8% at 6 months, 16.0% at 1 year, 17.7% at 2 years, 19.0% at 3 years, and 19.7% at 4 years. Univariate predictors of pacemaker syndrome were a higher percentage of ventricular paced beats, a higher programmed lower pacemaker rate, and a slower underlying sinus heart rate. However, only a higher percentage of paced beats was an independent predictor of developing pacemaker syndrome. Quality of life (using various metrics) decreased with the diagnosis of pacemaker syndrome and improved after the pacemaker was reprogrammed to a physiologic mode.121 In the PASE study, of the 204 patients randomized to VVIR, 26% crossed over to DDDR for intolerance to ventricular pacing.49 The Danish study reported a 2% incidence of pacemaker TABLE

13-5  Degree Mild

Moderate

Severe

Symptoms of Pacemaker Syndrome Symptoms Venous pulsation in neck Fatigue Weakness Palpitations Fullness in chest Dizziness Dyspnea Chest pain Jaw pain Confusion Syncope Presyncope

syndrome;48 in CTOPP it was 2.7% at 3 years.50 The incidence of pacemaker syndrome was likely underestimated in these latter two trials, because treatment would have required a surgical intervention. Pacemaker syndrome possibly was overestimated in the MOST and PASE studies, because it was simple to cross patients over to the DDDR pacing mode.121 PACING AND CONGESTIVE HEART FAILURE In the Danish study, New York Heart Association (NYHA) functional class and diuretic use were significantly higher during follow-up in the ventricular than in the atrial pacing group 48. In CTOPP, the annual incidence of hospitalization for CHF was similar in the ventricular (3.5%) and atrial (3.1%) pacing groups (relative risk reduction, 7.9%; 95% CI = −18.5 to 28.3%; P = 0.52).50 In MOST the annual incidence of hospitalization for CHF was similar in patients receiving dualchamber (3.7%) or ventricular (4.4%) pacing (HR = 0.82; 95% CI = 0.63 to 1.06; P = 0.13).52 During follow-up, patients receiving dualchamber pacing had a lower heart failure score than patients receiving ventricular pacing (average points/ follow-up visit: ventricular, 1.75; dual chamber, 1.49; P < .001). PACING AND QUALITY OF LIFE Dual-chamber pacing is associated with improved physiologic parameters, including cardiac output, exercise capacity, and exercise oxygen consumption (Vo2), compared with ventricular pacing.118 However, none of the large clinical trials conducted to date has demonstrated substantial improvements in quality of life (QOL) measures associated with atrial-based pacing compared to ventricular pacing.122 The PASE study did not demonstrate an improvement in QOL measures in patients treated with dual-chamber pacing compared to ventricular pacing, although there was a modest improvement in some SF-36 scales at 3 months of follow-up in the subgroup with SND.49 In MOST, dual-chamber pacing resulted in a small but measurable increase in QOL compared with ventricular pacing.52 In MOST, AF development after pacemaker insertion did not appear to be a major QOL determinant. In CTOPP, QOL improved after pacemaker implantation in both atrial pacing and ventricular pacing groups, but no significant healthrelated QOL difference was observed.122 ADEPT did not observe an improvement in QOL measures associated with rate-adaptive pacing in patients with chronotropic incompetence.123 Thus, atrial-based pacing may confer some modest improvements in quality of life in patients with SND, particularly the group at risk for pacemaker syndrome.49

Potential Detrimental Effects of Ventricular Pacing Although some randomized trials studying pacing mode selection for patients with sinus node disease have reported no clinical benefit of DDDR pacing over VVIR pacing, post hoc analyses from MOST have reported an association between a high percentage of right ventricular (RV) apical pacing and worse clinical outcomes, including an increased risk for AF and heart failure hospitalization.124 This raises concern that the beneficial effects of maintaining AV synchrony may have been mitigated by the deleterious effects of RV apical pacing. RISK OF ATRIAL FIBRILLATION The MOST investigators reported that ventricular pacing adversely influenced the development of AF, independent of AV synchrony.124 Patients programmed to DDDR were more likely to be paced in the ventricle (90%) than patients programmed to VVIR (58%; P = .001). Patients more frequently paced in the ventricle were more likely to develop AF. The risk of developing AF increased approximately 1% for each 1% increase in ventricular pacing (Fig. 13-16). Nielsen et al.125



13  Pacing for Sinus Node Disease

315

HEART FAILURE 7 Risk of HFH relative to VVIR patient with cum % VP = 0

Risk of HFH relative to DDDR patient with cum % VP = 0

7 6 5 4 3 2 1 0

6 5 4 3 2 1 0

0

20

A

40

60

80

100

0

20

B

Cum % VP

40

60

80

100

80

100

Cum % VP

ATRIAL FIBRILLATION 4 Risk of AF relative to VVIR patient with cum % VP = 0

Risk of AF relative to DDDR patient with cum % VP = 0

4

3

2

1

0

3

2

1

0 0

20

C

40

60

80

100

Cum % VP

0

D

20

40

60

Cum % VP

Figure 13-16  Relation of event risk to cumulative percent ventricular pacing (cum % VP) as estimated by Cox models with linear spline functions. Dashed lines represent 95% confidence intervals for point-by-point estimates of the hazard ratio for a 1% change in cum % VP. A, DDDR mode, heart failure hospitalization (HFH); B, VVIR mode, HFH; C, DDDR mode, atrial fibrillation (AF); D, VVIR mode, AF. (From Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Mode Selection Trial Investigators. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 107:2932-2937, 2003.)

also reported adverse effects of AV sequential pacing compared to atrial pacing on the development of AF. They randomized 177 patients with sick sinus syndrome to AAIR pacing, DDDR pacing with a short (≤150 msec) or a long (300 msec) AV interval. AF during follow-up was significantly less common in the AAIR group (7.4%) than either the DDDR-short (23.3%) or the DDDR-long (17.5%) AV delay group (P = 0.03).126 The impact of ventricular pacing after AV junction ablation on AF burden was evaluated in patients participating in the PA3 study who remained on stable antiarrhythmic drug therapy throughout follow-up.82 Before ablation, AF burden was 3.0 ± 1.2 hr/day and increased to 10.4 ± 2.2 and 11.8 ± 2.3 hr/day in the two follow-up periods (P < .05). These data suggest that the proarrhythmic effect of ventricular pacing occurs rapidly in patients with AF. RISK OF HEART FAILURE In MOST, ventricular pacing more than 40% of the time in the DDDR group was associated with a 2.6-fold risk of hospitalization for CHF, whereas pacing more than 80% in VVIR was associated with a 2.5-fold risk of hospitalization124 (see Fig. 13-16). The DAVID trial randomized 506 patients who had received a dual-chamber ICD to dual-chamber rate-responsive pacing at 70 bpm or ventricular backup pacing at

40 bpm.127 Only 12% of this study population had severely symptomatic heart failure. The primary study outcome measure, death or hospitalization for new or worsened heart failure, was lower in the ventricular paced group compared to the dual-chamber paced group (relative hazard 1.61, range 1.06-2.44; P ≤ .03). The rate of hospitalization at 1 year for CHF was 13.3% in the ventricular group versus 22.6% in the dual-chamber group. Patients with left ventricular (LV) dysfunction who were more frequently paced in the ventricle were more likely to experience an adverse outcome.128 Patients with DDDR RV pacing greater than 40% had worse outcomes than the VVI backup group. The Pacing to Avoid Cardiac Enlargement (PACE) study was designed to test the hypothesis that atrial-synchronized biventricular pacing (BiVP) is superior to RV apical pacing in preserving LV systolic function and avoiding adverse LV remodeling in patients with a normal left ventricular ejection fraction (LVEF) and standard indications for pacing.129 Patients (177) in whom a biventricular pacemaker had been successfully implanted were randomly assigned to receive BiVP (89) or RV apical pacing (88). More than 40% of the study population had SND as the primary indication for pacing. The primary endpoints were LVEF and left ventricular end-systolic volume (LFESV). At 12 months, mean LVEF was significantly lower in the RV pacing group than the BiVP group (54.8 ± 9.1% vs. 62.2 ± 7.0%; P < .001) and LVESV was

316

TABLE

13-6 

SECTION 2  Clinical Concepts

Effects of Right Ventricular (RV) Apical Pacing

Functional Change Ventricular electrical activation delays Myocardial perfusion defects Left ventricular (LV) remodeling

Effects Interventricular dyssynchrony Intraventricular dyssynchrony Asymmetrical hypertrophy Fibrosis Ventricular dilatation Functional mitral regurgitation ↓LV ejection fraction ↑Filling pressures ↑LV strain

Left atrial (LA) remodeling

significantly higher in the RV group than the BiVP group (35.7 ± 16.3 mL vs. 27.6 ± 10.4 mL; P < .001). There were no differences in hospital admissions for heart failure during follow-up between the two groups. Although interesting, the data do not generally apply to the population with SND. By study design, short AV intervals were programmed, which forced a high proportion of RV apical pacing. The abnormal effects of RV apical pacing have been attributed to the abnormal electrical and mechanical activation pattern of the ventricles.130 Table 13-6 summarizes adverse effects of RV apical pacing on electrical and mechanical function, including changes in cardiac metabolism and perfusion, remodeling, and hemodynamics. Myocardial perfusion defects may be present in up to 65% of patients after long-term RV apical pacing and are mainly located near the pacing site. RV pacing may also result in structural changes and LV remodeling, including mitochondrial variations and degenerative fibrosis. Changes in LV wall thickness, LV remodeling, functional mitral regurgitation, and left atrial remodeling may occur during RV apical pacing. Hemodynamic properties and global mechanical function may be affected by the abnormal electrical and mechanical activation of the left ventricle. Pacing at the RV apex may result in a decrease in cardiac output and may alter LV filling properties. Changes in myocardial strain and timing of regional strain have been reported in an animal model of cardiac pacing. Prinzen et al.131 reported a significant decrease in strain in the regions close to the pacing site and an increase in myocardial strain in remote regions. The timing of peak regional strain considered to be “mechanical dyssynchrony” is also altered during pacing. Together, these changes may contribute to decreased LV systolic function, decreased functional capacity, and ultimately progression to symptomatic heart failure. Functional mitral regurgitation may lead to adverse atrial electrical remodeling, creating a substrate for AF. Figure 13-17 illustrates a conceptual model of the potential detrimental effects of RV apical pacing. ALGORITHMS TO MINIMIZE VENTRICULAR PACING Based on the concern about the potential adverse consequences of frequent RV apical pacing, algorithms have been introduced to minimize ventricular pacing, including search AV hysteresis, managed ventricular pacing (MVP), and AAIsafeR mode.132-139 These algorithms substantially reduced the amount of ventricular pacing, from 90% to 1% in select patient populations, including those with SND.132-136

30 minutes later; it will progressively double, up to 16 hours, if the subsequent AV conduction check does not uncover intrinsic AV conduction. If 10 consecutive AV conduction failures occur at 16 hours, the algorithm will disable, and the device will revert to the DDD mode. In search AV hysteresis, the maximum sensed AV interval shortens when the atrial rate exceeds 80 bpm and is 150 msec at 120 bpm or higher. Managed Ventricular Pacing The MVP algorithm operates in the AAIR mode, with backup DDDR pacing if AV conduction fails.132-134 In the AAIR mode, if AV conduction fails for one beat, a ventricular backup pacing stimulus is delivered 80 msec after the next atrial beat to avoid long pauses (Fig. 13-18). If AV conduction fails for two of four successive atrial sensed or paced events, the device switches to the DDDR mode. Automatic conduction checks are then performed by the inhibition of one ventricular paced event. The first conduction check occurs 1 minute after switching to the DDDR mode. If intrinsic AV conduction occurs, the algorithm reverts to the AAIR mode. The interval for conduction checks progressively doubles (2, 4, 8 minutes) up to 16 hours; checks then occur every 16 hours. The MVP mode does not automatically disable. AAIsafeR Mode The AAIsafeR mode operates in the AAIR mode and switches to the DDDR mode when certain criteria are met.136-138 Mode switching from AAIR to DDDR occurs if at least seven intervals between atrial paced or sensed events and ventricular sensed events exceed a predefined limit (programmable between 350 and 450 msec; AV block I criterion). If 3 of 12 sensed or paced atrial events are not followed by a ventricular sensed event, mode switching from AAIR to DDDR occurs (AV block II criterion). Two consecutive atrial events without consecutive ventricular sensed events results in mode switching (AV block III criterion). To avoid prolonged pauses, DDDR pacing occurs if a programmable duration of ventricular asystole is detected (programmable between 2 and 4 seconds) independent of the relationship between atrial and ventricular events. These pacing algorithms have substantially reduced the percent ventricular pacing in both patients with SND and those with intermittent AV block, although the magnitude of benefit is less than in patients with SND133-136 (Fig. 13-19). Importantly, many patients with AV block Deleterious effects of VVI pacing

Ventricular dyssynchrony

Retrograde conduction/ valvular regurgitation

Myocardial dysfunction

Atrial stretch/ atrial electrical remodeling

Search AV Hysteresis Search AV hysteresis operates in the DDDR, DDIR, DVIR, or VDD modes.134,135 A programmable maximum AV offset or extension is applied to the programmed sensed and paced AV intervals. The maximum operational AV intervals can range from 40 to 600 msec based on the programmed AV intervals and the maximum increase in AV interval programmed. Search AV mode continuously adapts the operating AV interval to a value slightly longer than the AV conduction time (≈30 msec). If 8 of 16 ventricular paced events occur at maximum sensed or paced AV intervals, these intervals will return to the programmed values. A conduction check is then automatically performed

Atrial fibrillation

Thromboembolism

CHF

Death Figure 13-17  Potential mechanisms of the deleterious effects of ventricular pacing. CHF, Congestive heart failure.



13  Pacing for Sinus Node Disease

N

1

N

P

P

P

P

317

N

25 mm/sec 10 mm/mV 2 25 mm/sec 10 mm/mV

P

P

P

P

P

P

P

P

1 25 mm/sec 10 mm/mV 2 25 mm/sec 10 mm/mV Figure 13-18  Examples of rhythm strips during operation of managed ventricular pacing mode. Upper panel, Sinus rhythm with first-degree AV block and intraventricular conduction delay. While operating in AAI/R mode, AV conduction fails after an atrial-paced event and is followed by a ventricular rescue pacing stimulus delivered 80 msec after the next programmed atrial beat, so that long pauses are avoided. Lower panel, AAI pacing with marked first-degree AV block followed by AV conduction failure. Ventricular rescue pacing stimulus is delivered 80 msec after the next programmed atrial beat and is followed by resumption of marked first-degree AV block.

as the primary indication for pacing experience intermittent AV block, and intrinsic AV conduction is preserved much of the time.133-135 Thus, these algorithms should be considered for patients with intermittent AV block. Clinical Outcomes The Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) trial tested the hypothesis that a strategy of minimizing ventricular pacing would reduce the risk of persistent AF better than conventional dual-chamber pacing.139 Patients with SND (n = 1065), intact AV conduction, and a normal QRS interval were randomized to conventional DDDR pacing or

DDDR pacing with algorithms to minimize ventricular pacing (search AV or MVP) programmed “on.” The AV interval was programmed between 120 and 180 msec for patients randomized to conventional DDDR pacing. Patients were followed for 1.7 ± 1.0 years, when the study was stopped because it had met the primary outcome. The median percent ventricular pacing was lower in the group assigned to minimal ventricular pacing (9.1%) compared to the conventional DDDR group (99%). The percent atrial pacing was similar in both groups. During follow-up, persistent AF developed in 68 of 535 patients assigned to conventional DDDR pacing (12.7%) versus 40 of 530 in the group assigned to minimal ventricular pacing (7.9%; P = .004 by log rank test). A 40% reduction in the relative risk of developing AV BLOCK

100

100

90

90

80

80

% Ventricular pacing

% Ventricular pacing

SND

70 60 50 40 30

70 60 50 40 30

20

20

10

10

0 DDDR

MVP

0 DDDR

MVP

Figure 13-19  Reduction in proportion of ventricular pacing using the managed ventricular pacing (MVP) mode compared to the DDD/R mode based on indication for pacing. Both patient subgroups showed a significant reduction in percent ventricular pacing in the MVP mode. Left, Patients with sinus node disease (SND). Right, Patients with atrioventricular (AV) block. (Modified from Gillis AM, Pürerfellner H, Israel CW, et al. Medtronic Enrhythm Clinical Study Investigators: Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Pacing Clin Electrophysiol 29:697-705, 2006.)

318

SECTION 2  Clinical Concepts

% Ventricular pacing

100 80

pointes VT have been reported in pacemaker patients attributed to prolonged pauses secondary to programming in the MVP mode.143,144 Based on these observations, the MVP mode should not be considered in patients with long QT syndrome or those with permanent complete heart block.

MVP Search AV

60

Treatment of Sinus Node Disease 40

PACING MODALITIES

20 0 No AVB

1AVB

2AVB

E3AVB

P3AVB

Figure 13-20  Differences in percent ventricular pacing in the managed ventricular pacing (MVP) compared to the search AV hysteresis mode; AVB, Atrioventricular block; 1, first-degree; 2, second-degree; E3, episode third-degree; P3, persistent third degree third-degree. (Data from Pürerfellner H, Brandt J, Israel C, et al: Comparison of two strategies to reduce ventricular pacing in pacemaker patients. Pacing Clin Electrophysiol 31:167-176, 2008.)

persistent AF was seen with the strategy of minimizing ventricular pacing. No differences in mortality, hospitalization for heart failure, or cardioversion for AF were observed between the two groups. Although this study supports a strategy of minimizing ventricular pacing for prevention of AF, the magnitude of benefit has been overestimated by the study design. Most centers programming “conventional” DDDR pacing would select longer AV delays (usually >200 msec). The study design actually imposed a higher degree of ventricular pacing in the DDDR mode than would be traditionally expected with individualized programming of AV delays in pacemaker follow-up programs. Is One Mode for Minimizing Ventricular Pacing Superior? Clinical studies report that MVP mode offers greater reduction in the percent ventricular pacing than search AV mode, except for patients with permanent AV block.134,135 Figure 13-20 shows ventricular pacing in MVP versus search AV mode in 322 patients followed for 1 month. MVP was associated with a significant reduction in percent ventricular pacing for all categories of AV conduction except permanent AV block. Whether such differences translate into improved clinical outcomes remains unknown. Complications and Clinical Nuances Overall, these algorithms have been reported to be safe and well tolerated.132-139 However, depending on device programming, prolonged AV delays of up to 600 msec may occur. These long AV delays cannot be considered physiologic and may result in pacemaker syndrome, with atrial contraction occurring early in diastole.140 This may be particularly detrimental for patients with heart failure or mitral regurgitation. Examples of varying AV delays and pauses followed by backup ventricular pacing associated with MVP mode are shown in Figure 13-18. Although the MVP mode relies primarily on atrial pacing, timing cycles are based on ventricular intervals. In the case of a ventricular premature beat, noncompetitive atrial pacing will extend the ventriculoatrial (VA) interval, resulting in an extension of the next atrial pacing interval.141 This results in atrial pacing rates below the programmed lower rate limit. Abrupt changes in ventricular cycle length (short-long-short) sequences have been reported to facilitate ventricular tachyarrhythmia onset in patients with implantable defibrillators. Such short-long-short sequences may be observed with the MVP mode and may constitute a form of ventricular proarrhythmia142 (Fig. 13-21). Short-long-short sequences may also be observed with traditional DDDR programming preceding VT. Cases of torsade de

Table 13-7 shows the indications for pacing in the patient with SND.145 Although none of the large, randomized clinical trials have shown a survival benefit of atrial-based pacing, dual-chamber pacemakers are often implanted in North America.1 Atrial or dual-chamber pacing may be considered in patients with SND for prevention of AF and pacemaker syndrome.48,145 However, prevention of AF in this population has not been demonstrated to reduce stroke or mortality. Figure 13-22 shows a decision tree on pacing mode selection for patients with SND.146 It is important to remember that many patients with SND have intrinsic AV conduction and do not require ventricular pacing most of the time. Consequently, considering strategies that minimize ventricular pacing, such as AAIR pacing when clinically indicated, programming long AV delays to minimize ventricular pacing, using algorithms to minimize RV apical pacing, or even backup ventricular pacing at a low rate, may be sufficient for most patients with SND. Backup ventricular pacing may be effective for the patient with infrequent pauses and normal chronotropic response. In patients with an implantable defibrillator, AAI pacing showed no advantage over backup VVI pacing.147 AAIR Pacing As many as 20% of patients with symptomatic SND are potential candidates for AAIR pacing systems.1,48 A rate-adaptive pulse generator should be considered because of the high incidence of chronotropic incompetence in patients with SND.146 Although this is the most economical approach to providing atrial pacing in this population, AAIR mode is used for less than 1% of implants in North America.1 Concerns about progression of AV block and the development of chronic AF likely explain the low utilization of AAIR in SND patients. However, these concerns appear to be unfounded if patients are carefully selected.148,149 The risk of progression to AV block is less than 1% per year if patients have normal AV conduction and no intraventricular conduction delays on the surface electrocardiogram (ECG) at implant. The likelihood of developing permanent AF is small (<1.5 %/yr) if patients are under age 70 at implant, have no history of paroxysmal AF,148,149 and show no evidence of marked intra-atrial conduction delays.150 Table 13-8 lists the contraindications to AAIR pacing. Given the concerns that dual-chamber pacing may result in unnecessary ventricular pacing that promotes the development of AF and CHF, higher TABLE

13-7  Class I

IIa

IIb III

Indications for Pacing in Sinus Node Disease Indications Sinus node dysfunction with documented symptomatic bradycardia, including sinus pauses Symptomatic chronotropic incompetence Symptomatic sinus bradycardia secondary to required drug therapy Sinus node dysfunction with heart rate <40 bpm without a clear association between symptoms and documented bradycardia Syncope of unknown origin when evidence of sinus node dysfunction discovered or provoked during electrophysiologic study Minimally symptomatic, with heart rate <40 bpm while awake Sinus node dysfunction in asymptomatic patients Symptoms suggestive of bradycardia clearly documented in absence of bradycardia Symptomatic bradycardia secondary to nonessential drug therapy

Class I: General consensus that pacing is indicated; Class II: divergence of opinion on need for pacing; Class III: general consensus that pacing is not indicated.



13  Pacing for Sinus Node Disease

319

Chart speed: 25.0 mm/sec

EGM1: Atip to Aring

(1 mV)

EGM2: Vtip to Vring

(10 mV) 6 1 0

A–A (ms) Markers

V S

V–V (ms)

8 6 0

A R

9 6 0

6 1 0

8 4 0

A R

6 1 0

A P

V S

A P 6 1 0

8 3 0

A S

6 2 0

6 2 0

A P

V S

6 2 0

A S

V S

A P

A S

T T T T T T T T T T T T T T T 3 F 3 F 3 F 3 F 3 F 3 F 3 F 2P 2 P2 P2 P2 P 2 P2 P2 P 0 0 0 0 0 1 0 4 4 4 4 4 4 4 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

4 6 0

5 1 0

6 1 0

A P

V S

6 2 0

8 4 0

6 2 0

6 2 0

A P

V S

6 3 0

A P V S

8 4 0

6 1 0

A P

V S

6 1 0

6 5 0

VV SP

6 1 0

A P

6 1 0

V S

6 3 0

V S

6 0 0

V S

6 3 0

A P 6 4 0

V S

114

A P V P 3 7 0

1040

6 3 0

A P

6 2 0

A P

V S

6 2 0

6 2 0

A P

6 2 0

A P

6 3 0

A P 6 4 0

V S

V S

A P 6 3 0

FVT FVT Rx 1 burst Figure 13-21  Example of ventricular tachycardia (VT) onset following a pause during AAI pacing with MVP programmed “on.” Data are retrieved from interrogation of an ICD AV conduction failure during atrial pacing (AP) results in a 1040-msec pause. This is followed by a ventricular premature beat that initiates VT. The VT is successfully pace-terminated.

Pacing in SND

LVEF <0.35

Normal LV

Normal AV conduction

Abnormal AV conduction

Normal AV conduction

Abnormal AV conduction

AAI

Backup VVI or DDD – MRVP features

AAI

DDD – MRVP features Consider septal pacing or CRT

Chronotropic incompetence AAIR

Chronotropic incompetence

MRVP– minimize RV pacing

DDDR–MVRP features

Chronotropic incompetence AAIR

Chronotropic incompetence DDDR – MVRP features

Figure 13-22  Selection of “physiologic pacing” mode for patients with sinus node disease (SND). AAI, Atrial pacing; AAIR, atrial rate-adaptive pacing; AV, atrioventricular; DDD, dual-chamber pacing; DDDR, dual-chamber rate-adaptive pacing; MRVP, minimize right ventricular pacing; VVI, ventricular pacing. (Modified from Gillis AM: Redefining physiologic pacing: lessons learned from recent clinical trials. Heart Rhythm 3:1371, 2006.)

320

TABLE

13-8 

SECTION 2  Clinical Concepts

Contraindications to AAI/AAIR Pacing

Type Absolute

Relative

Contraindications AV block documented except during sleep AV block during carotid sinus massage P-R interval >220 msec IVCD on electrocardiogram Age >70 yr Wenckebach block during atrial pacing <120 bpm His-ventricular (HV) interval >75 msec Infra-His block during atrial pacing

AV, Atrioventricular; IVCD, intraventricular conduction delay.

utilization of AAIR pacing should be considered in patients with SND. A cost-effectiveness analysis performed in the MOST population showed that during the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject, at an incremental cost-effectiveness ratio of $53,000 per quality-adjusted year of life gained. This cost could be further reduced by increasing the use of AAIR over DDDR pacing in select patients.79 Rate-Adaptive Pacing Chronotropic incompetence is common in SND, and rate-adaptive pacing is beneficial in select patients. ADEPT evaluated whether dualchamber rate-modulated pacing, compared with dual-chamber pacing alone, improved QOL in 872 patients with documented chronotropic incompetence.123 At 6 months, patients randomized to DDDR had a higher peak exercise heart rate (113.3 ± 19.6 bpm) than those randomized to DDD (101.1 ± 21.1 bpm; P < .0001). However, at 1 year, there were no significant differences between groups randomized to DDD versus DDDR with respect to specific activity scale or the secondary QOL endpoints. Alternate Ventricular Pacing Sites There has been some debate about the optimal ventricular pacing site for minimizing the risk of heart failure or AF in patients receiving

dual-chamber pacemakers.151 However, it is important to remember that the vast majority of patients with SND have intrinsic AV conduction the vast majority of the time. Accordingly, strategies to minimize ventricular pacing whenever possible should be pursued, including the judicious use of AAI pacing, optimal use of AV search hysteresis, and use of algorithms that switch from AAI to DDD pacing when atrial conduction fails.146 Clinical studies have demonstrated that the amount of ventricular pacing can be substantially reduced with these newer pacing algorithms, even in patients with AV block as the primary indication for pacing.132-138 No data to date suggest that biventricular pacing prevents heart failure in patients without significant systolic dysfunction.152 Right ventricular outflow tract and high RV septal pacing sites may be associated with shorter ventricular activation times and less ventricular dyssynchrony than RV apical pacing.151,153,154 However, no large clinical trials have shown that any of these pacing sites are superior to the traditional RV apical pacing site. Clinical trials evaluating alternate RV pacing sites are in progress. BIOLOGIC PACEMAKERS Advances in the development of biologic pacemakers are underway, and progress in this field has recently been reviewed.155 Suppression of Kir2.1 channels has unmasked latent pacemaker activity in ventricular cells. Overexpression of HCN2 channels has elicited ectopic pacemaker activity in a canine model. Subepicardial injection of HCN2-overexpressing human mesenchymal stem cells into canine left ventricle induced spontaneous rhythms in animals with chronic AV block. In this model, the pacemaking activity required 10 to 12 days to become stable, then persisted for at least 6 weeks. In contrast to the direct cell injection approaches, fusion technology allows implantation of biologic pacemakers at a specific site. Cardiac stem cells may be viable candidates for biologic pacemakers, and work in this field is underway. Although this field is evolving rapidly, much works needs to be done before biologic pacemakers become reality (see Chapter 7).

REFERENCES 1. Mond HG, Irwin M, Morillo C, Ector H: The world survey of cardiac pacing and cardioverter-defibrillators: calendar year 2001. Pacing Clin Electrophysiol 27:955-964, 2004. 2. Gillis AM: Pacing for sinus node disease: indications, techniques and clinical trials. In Ellenbogen KA, Kay GW, Wilkoff BL, editors: Clinical cardiac pacing and defibrillation, ed 3, Philadelphia, 2007, Saunders, pp 407-427. 3. Dobrzynski H, Boyett MR, Anderson RH: New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation 115:1921-1932, 2007. 4. Chandler NJ, Greener ID, Tellez JO, et al: Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation 119:1562-1575, 2009. 5. Verkerk AO, van Ginneken AC, Wilders R: Pacemaker activity of the human sinoatrial node: role of the hyperpolarizationactivated current, If. Int J Cardiol 132:318-336, 2009. 6. Jones SA, Lancaster MK, Boyett MR: Aging-related changes of connexins and conduction within the sinoatrial node. J Physiol 560 Pt 2:429-437, 2004. 7. Ludwig A, Herrmann S, Hoesl E, Stieber J: Mouse models for studying pacemaker channel function and sinus node arrhythmia. Prog Biophys Mol Biol 98:179-185, 2008. 8. Schulze-Bahr E, Neu A, Friederich P, et al: Pacemaker channel dysfunction in a patient with sinus node disease. J Clin Invest 111:1537-1545, 2003. 9. Stieber J, Hofmann F, Ludwig A: Pacemaker channels and sinus node arrhythmia. Trends Cardiovasc Med 14:23-28, 2004. 10. Ueda K, Nakamura K, Hayashi T, et al: Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J Biol Chem 279:27194-27198, 2004. 11. Verkerk AO, Wilders R, Coronel R, et al: Ionic remodeling of sinoatrial node cells by heart failure. Circulation 108:760-766, 2003. 12. Veldkamp MW, Wilders R, Baartscheer A, et al: Contribution of sodium channel mutations to bradycardia and sinus node dysfunction in LQT3 families. Circ Res 92:976-983, 2003. 13. Ruan Y, Liu N, Priori SG: Sodium channel mutations and arrhythmias. Nat Rev Cardiol 6:337-348, 2009. 14. Lei M, Huang CL, Zhang Y: Genetic Na+ channelopathies and sinus node dysfunction. Prog Biophys Mol Biol 98:171-178, 2008.

15. Benson DW, Wang DW, Dyment M, et al: Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest 112:1019-1028, 2003. 16. Hund TJ, Mohler PJ: Ankyrin-based targeting pathway regulates human sinoatrial node automaticity. Channels (Austin) 2:404406, 2008. 17. Le Scouarnec S, Bhasin N, Vieyres C, et al: Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci USA 105:15617-15622, 2008. 18. Lees-Miller JP, Guo J, Somers JR, et al: Selective knockout of mouse ERG1 B potassium channel eliminates IKr in adult ventricular myocytes and elicits episodes of abrupt sinus bradycardia. Mol Cell Biol 23:1856-1862, 2003. 19. Demolombe S, Lande G, Charpentier F, et al: Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I. Phenotypic characterisation. Cardiovasc Res 50:314-327, 2001. 20. Hu K, Qu Y, Yue Y, Boutjdir M: Functional basis of sinus bradycardia in congenital heart block. Circ Res 94:e32-e38, 2004. 21. Platzer J, Engel J, Schrott-Fischer A, et al: Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102:89-97, 2000. 22. Zhang Z, Xu Y, Song H, et al: Functional Roles of Ca(v)1, 3 (α1D) calcium channel in sinoatrial nodes: insight gained using genetargeted null mutant mice. Circ Res 90:981-987, 2002. 23. Gillis AM, Kavanagh KM, Mathison HJ, et al: Heart block in mice overexpressing calcineurin but not NF-AT3. Cardiovasc Res 64:488-495, 2004. 24. Opthof T, Coronel R, Rademaker HM, et al: Changes in sinus node function in a rabbit model of heart failure with ventricular arrhythmias and sudden death. Circulation 101:2975-2980, 2000. 25. Hong CS, Cho MC, Kwak YG, et al: Cardiac remodeling and atrial fibrillation in transgenic mice overexpressing junctin. FASEB J 16:1310-1312, 2002. 26. Du Y, Huang X, Wang T, et al: Downregulation of neuronal sodium channel subunits Nav1, 1 and Nav1, 6 in the sinoatrial node from volume-overloaded heart failure rat. Pflugers Arch 454:451-459, 2007. 27. Zicha S, Fernández-Velasco M, Lonardo G, et al: Sinus node dysfunction and hyperpolarization-activated (HCN) channel

subunit remodeling in a canine heart failure model. Cardiovasc Res 66:472-481, 2005. 28. Stiles MK, Brooks AG, Roberts-Thomson KC, et al: High-density mapping of the sinus node in humans: role of preferential pathways and the effect of remodeling. J Cardiovasc Electrophysiol 21:532-539, 2010. 29. Sanders P, Morton JB, Kistler PM, et al: Electrophysiological and electroanatomic characterization of the atria in sinus node disease: evidence of diffuse atrial remodeling. Circulation 109:1514-1522, 2004. 30. Kistler PM, Sanders P, Fynn SP, et al: Electrophysiologic and electroanatomic changes in the human atrium associated with age. J Am Coll Cardiol 44:109-116, 2004. 31. Sanders P, Kistler PM, Morton JB, et al: Remodeling of sinus node function in patients with congestive heart failure: reduction in sinus node reserve. Circulation 110:897-903, 2004. 32. Sanders P, Morton JB, Davidson NC, et al: Electrical remodeling of the atria in congestive heart failure: electrophysiological and electroanatomic mapping in humans. Circulation 108:14611468, 2003. 33. Sparks PB, Mond HG, Vohra JK, et al: Electrical remodeling of the atria following loss of atrioventricular synchrony: a longterm study in humans. Circulation 100:1894-1900, 1999. 34. Sparks PB, Jayaprakash S, Vohra JK, Kalman JM: Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter. Circulation 102:1807-1813, 2000. 35. Kalman JM, Sparks PB: Electrical remodeling of the atria as a consequence of atrial stretch. J Cardiovasc Electrophysiol 12:5155, 2001. 36. Manios EG, Kanoupakis EM, Mavrakis HE, et al: Sinus pacemaker function after cardioversion of chronic atrial fibrillation: is sinus node remodeling related with recurrence? J Cardiovasc Electrophysiol 12:800-806, 2001. 37. Hadian D, Zipes DP, Olgin JE, Miller JM: Short-term rapid atrial pacing produces electrical remodeling of sinus node function in humans. J Cardiovasc Electrophysiol 13:584-586, 2002. 38. Hocini M, Sanders P, Deisenhofer I, et al: Reverse remodeling of sinus node function after catheter ablation of atrial fibrillation in patients with prolonged sinus pauses. Circulation 108:11721175, 2003.



13  Pacing for Sinus Node Disease 39. Raitt MH, Kusumoto W, Giraud G, McAnulty JH: Reversal of electrical remodeling after cardioversion of persistent atrial fibrillation. J Cardiovasc Electrophysiol 15:507-512, 2004. 40. Yeh YH, Burstein B, Qi XY, et al: Funny current downregulation and sinus node dysfunction associated with atrial tachyarrhythmia: a molecular basis for tachycardia-bradycardia syndrome. Circulation 119:1576-1585, 2009. 41. Krahn AD, Klein GJ, Yee R, Skanes AC: Randomized Assessment of Syncope Trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 104:46-51, 2001. 42. Krahn AD, Klein GJ, Yee R, et al: Cost implications of testing strategy in patients with syncope: Randomized Assessment of Syncope Trial. J Am Coll Cardiol 42:495-501, 2003. 43. Solano A, Menozzi C, Maggi R, et al: Incidence, diagnostic yield and safety of the implantable loop-recorder to detect the mechanism of syncope in patients with and without structural heart disease. Eur Heart J 25:1116-1119, 2004. 44. Menozzi C, Brignole M, Alboni P et al: The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome. Am J Cardiol 82:1205-1209, 1998. 45. Brandt J, Anderson H, Fahraeus T, Schuller H: Natural history of sinus node disease treated with atrial pacing in 213 patients: implications for selection of stimulation mode. J Am Coll Cardiol 20:633-639, 1992. 46. Jahangir A, Shen WK, Neubauer SA, et al: Relation between mode of pacing and long-term survival in the very elderly. J Am Coll Cardiol 33:1208-1216, 1999. 47. Connolly SJ, Kerr C, Gent M, Yusuf S: Dual-chamber versus ventricular pacing: critical appraisal of current data. Circulation 94:578-583, 1996. 48. Andersen HR, Nielsen JC, Thomsen PEB, et al: Long-term follow-up of patients from a randomized trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 350:12101216, 1997. 49. Lamas GA, Orav EJ, Stambler BS, et al: Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators. N Engl J Med 338:1097-1104, 1998. 50. Connolly SJ, Kerr CR, Gent M, et al: CTOPP Investigators. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiological Pacing. N Engl J Med 342:1385-1391, 2000. 51. Kerr CR, Connolly SJ, Abdollah H, et al: Canadian Trial of Physiological Pacing: effects of physiological pacing during long-term follow-up. Circulation 109:357-362, 2004. 52. Lamas GA, Lee KL, Sweeney MO, et al: Mode Selection Trial in Sinus Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus node dysfunction. N Engl J Med 346:1854-1862, 2002. 53. Healey JS, Toff WD, Lamas GA, et al: Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation 114:11-17, 2006. 54. Fored CM, Granath F, Gadler F, et al: Atrial vs. dual-chamber cardiac pacing in sinus node disease: a register-based cohort study. Europace 10:825-831, 2008. 55. Gillis AM, Morck M: Atrial fibrillation after DDDR pacemaker implantation. J Cardiovasc Electrophysiol 13:542-547, 2002. 56. Gillis AM: Rhythm control in atrial fibrillation: endpoints for device-based trials. Heart Rhythm 1:B52-B57, 2004. 57. Gillis AM: Pacing to prevent atrial fibrillation. Cardiol Clin 18:25-36, 2000. 58. Gillis AM: Clinical trials of pacing for maintenance of sinus rhythm. J Interv Card Electrophysiol 10 Suppl 1:55-62, 2004. 59. Ellenbogen KA: Pacing therapy for prevention of atrial fibrillation. Heart Rhythm 4 Suppl 3:84-87, 2007. 60. Camm AJ, Sulke N, Edvardsson N, et al: AFTherapy Investigators. Conventional and dedicated atrial overdrive pacing for the prevention of paroxysmal atrial fibrillation: the AFTherapy study. Europace 9:1110-1118, 2007. 61. Gold MR, Adler S, Fauchier L, et al: SAFARI Investigators. Impact of atrial prevention pacing on atrial fibrillation burden: primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial. Heart Rhythm 6:295-301, 2009. 62. Gillis AM, Morck M, Fitts S: Antitachycardia pacing therapies and arrhythmia monitoring diagnostics for the treatment of atrial fibrillation. Can J Cardiol 18:992-995, 2002. 63. Willems R, Morck ML, Exner DV, et al: Ventricular high-rate episodes in pacemaker diagnostics identify a high-risk subgroup of patients with tachy-brady syndrome. Heart Rhythm 1:414421, 2004. 64. Boriani G, Padeletti L, Santini M, et al: Rate control in patients with pacemaker affected by brady-tachy form of sick sinus syndrome. Heart J 154:193-200, 2007. 65. Capucci A, Santini M, Padeletti L, et al: Italian AT500 Registry Investigators. Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. J Am Coll Cardiol 46:1913-1920, 2005. 66. Glotzer TV, Daoud EG, Wyse DG, et al: The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol 2:474-480, 2009. 67. Ricci RP, Morichelli L, Santini M: Remote control of implanted devices through home monitoring technology improves

detection and clinical management of atrial fibrillation. Europace 11:54-61, 2009. 68. De Simone A, Senatore G, Turco P, et al: Specificity of atrial mode switching in detecting atrial fibrillation episodes: roles of length and contiguity. Pacing Clin Electrophysiol. 28 Suppl 1:4749, 2005. 69. Van Hemel NM, van de Bos AA, Koïstinen J, Fast JH: Verification of pacemaker automatic mode switching for the detection of atrial fibrillation and atrial tachycardia with Holter recording. Europace 8:950-961, 2006. 70. Passman RS, Weinberg KM, Freher M, et al: Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias. J Cardiovasc Electrophysiol 15:773-777, 2004. 71. Kolb C, Halbfass P, Zrenner B, Schmitt C: Paradoxical atrial undersensing due to inappropriate atrial noise reversion of atrial fibrillation in dual-chamber pacemakers. J Cardiovasc Electrophysiol 16:696-700, 2005. 72. Purerfellner H, Gillis AM, Holbrook R, Hettrick DA: Accuracy of atrial tachyarrhythmia detection in implantable devices with arrhythmia therapies. Pacing Clin Electrophysiol 27:983-992, 2004. 73. Fitts SM, Hill MR, Mehra R, Gillis AM: High rate atrial tachyarrhythmia detections in implantable pulse generators: low incidence of false-positive detections. The PA3 Clinical Trial Investigators. Pacing Clin Electrophysiol 23:1080-1086, 2000. 74. Gillis AM, Unterberg-Buchwald C, Schmidinger H, et al: GEM III AT Worldwide Investigators. Safety and efficacy of advanced atrial pacing therapies for atrial tachyarrhythmias in patients with a new implantable dual-chamber cardioverter-defibrillator. J Am Coll Cardiol 40:1653-1659, 2002. 75. Kouakam C, Kacet S, Hazard JR, et al: Ventak AV Investigators. Performance of a dual-chamber implantable defibrillator algorithm for discrimination of ventricular from supraventricular tachycardia. Europace 6:32-42, 2004. 76. Skanes AC, Krahn AD, Yee R, et al: Canadian Trial of Physiologic Pacing. Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. CTOPP Investigators. J Am Coll Cardiol 38:167-172, 2001. 77. Toff WD, Camm AJ, Skehan JD: United Kingdom Pacing and Cardiovascular Events Trial Investigators. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med 353:145-155, 2005. 78. Gillis AM, Kerr CR: Whither physiologic pacing? Implications of CTOPP. PACE 23(8):1193-1196, 2000. 79. Rinfret S, Cohen DJ, Lamas GA, et al: Cost-effectiveness of dualchamber pacing compared with ventricular pacing for sinus node dysfunction. Circulation 111:165-172, 2005. 80. Gillis AM: Selective pacing algorithms for prevention of atrial fibrillation: the final chapter? Heart Rhythm 6:295-301, 2009. 81. Gillis AM, Wyse DG, Connolly SJ, et al: Atrial pacing periablation for prevention of paroxysmal atrial fibrillation. Circulation 99:2553-2558, 1999. 82. Gillis AM, Connolly SJ, Lacombe P, et al: PA3 Investigators. A randomized crossover comparison of DDDR versus VDD pacing post-AV node ablation for prevention of atrial fibrillation. Circulation 102:736-741, 2000. 83. Willems R, Wyse DG, Gillis AM: Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) Study Investigators. Total AV nodal ablation increases atrial fibrillation burden in patients with paroxysmal AF despite continuation of antiarrhythmic drug therapy. J Cardiovasc Electrophysiol 14:1296-1301, 2003. 84. Carlson MD, Ip J, Messenger J, et al: ADOPT Investigators. A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). J Am Coll Cardiol 42:627-633, 2003. 85. Padeletti L, Purerfellner H, Adler SW, et al: Worldwide ASPECT Investigators. Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia. J Cardiovasc Electrophysiol 14:1189-1195, 2003. 86. Lewalter T, Yang A, Pfeiffer D, et al: Individualized selection of pacing algorithms for the prevention of recurrent atrial fibrillation: Results from the VIP registry. Pacing Clin Electrophysiol 29:124-134, 2006. 87. Israel CW, Hugl B, Unterberg C, et al: Pace-termination and pacing for prevention of atrial tachyarrhythmias: results from a multicenter study with an implantable device for atrial therapy. J Cardiovasc Electrophysiol 12:1121-1128, 2001. 88. Israel CW, Ehrlich JR, Gronefeld G, et al: Prevalence, characteristics and clinical implications of regular atrial tachyarrhythmias in patients with atrial fibrillation: insights from a study using a new implantable device. J Am Coll Cardiol 38:355-363, 2001. 89. Lee MA, Weachter R, Pollak S, et al: ATTEST Investigators. The effect of atrial pacing therapies on atrial tachyarrhythmia burden and frequency: results of a randomized trial in patients with bradycardia and atrial tachyarrhythmias. J Am Coll Cardiol 41:1926-1932, 2003. 90. Friedman PA, Dijkman B, Warman EN, et al: Atrial therapies reduce atrial arrhythmia burden in defibrillator patients. Circulation 104:1023-1028, 2001. 91. Adler SW, 2nd, Wolpert C, Warman EN, et al: Efficacy of pacing therapies for treating atrial tachyarrhythmias in patients with ventricular arrhythmias receiving a dual-chamber implantable cardioverter defibrillator. Circulation 104:887-892, 2001. 92. Stephenson EA, Casavant D, Tuzi J, et al: ATTEST Investigators. Efficacy of atrial antitachycardia pacing using the Medtronic AT500 pacemaker in patients with congenital heart disease. Am J Cardiol 92:871-876, 2003.

321

93. Israel CW, Gronefeld G, Li YG, Hohnloser SH: Usefulness of atrial pacing for prevention and termination of atrial tachyarrhythmias in a patient with persistent atrial fibrillation. Pacing Clin Electrophysiol 25:1527-1529, 2002. 94. Friedman PA, Ip JH, Jazayeri M, et al: RID-AF Investigators. The impact of atrial prevention and termination therapies on atrial tachyarrhythmia burden in patients receiving a dual-chamber defibrillator for ventricular arrhythmias. J Interv Card Electrophysiol 10:103-110, 2004. 95. Camm AJ, Savelieva I: Rationale and patient selection for “hybrid” drug and device therapy in atrial and ventricular arrhythmias. J Interv Card Electrophysiol 9:207-214, 2003. 96. Murgatroyd FD: “Pills and pulses”: hybrid therapy for atrial fibrillation. J Cardiovasc Electrophysiol 13:S40-S46, 2002. 97. Konings KT, Kirchhof CJ, Smeets JR, et al: High-density mapping of electrically induced atrial fibrillation in humans. Circulation 89:1665-1680, 1994. 98. Gillis AM, Koehler J, Morck M, et al: High atrial antitachycardia pacing therapy efficacy is associated with a reduction in atrial tachyarrhythmia burden in a subset of patients with sinus node dysfunction and paroxysmal atrial fibrillation. Heart Rhythm 2:791-796, 2005. 99. Hugl B, Israel CW, Unterberg C, et al: AT500 Verification Study Investigators. Incremental programming of atrial antitachycardia pacing therapies in bradycardia-indicated patients: effects on therapy efficacy and atrial tachyarrhythmia burden. Europace 5:403-409, 2003. 100. Gillis AM, Morck M, Exner DV, et al: Impact of atrial antitachycardia pacing and atrial pace prevention therapies on atrial fibrillation burden over long-term follow-up. Europace 11:10411047, 2009. 101. Yu WC, Chen SA, Tai CT, et al: Effects of different atrial pacing modes on atrial electrophysiology: implicating the mechanism of biatrial pacing in prevention of atrial fibrillation. Circulation 96:2992-2996, 1997. 102. Prakash A, Delfaut P, Krol RB, Saksena S: Regional right and left atrial activation patterns during single- and dual-site atrial pacing in patients with atrial fibrillation. Am J Cardiol 82:11971204, 1998. 103. Papageorgiou P, Anselme F, Kirchhof CJ, et al: Coronary sinus pacing prevents induction of atrial fibrillation. Circulation 96:1893-1898, 1997. 104. Crystal E, Connolly SJ, Sleik K, et al: Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation 106:75-80, 2002. 105. Bailin SJ, Adler S, Giudici M: Prevention of chronic atrial fibrillation by pacing in the region of Bachmann’s bundle: results of a multicenter randomized trial. J Cardiovasc Electrophysiol 12:912-917, 2001. 106. Padeletti L, Porciani MC, Michelucci A, et al: Interatrial septum pacing: a new approach to prevent recurrent atrial fibrillation. J Interv Card Electrophysiol 3:35-43, 1999. 107. Hermida JS, Kubala M, Lescure FX, et al: Atrial septal pacing to prevent atrial fibrillation in patients with sinus node dysfunction: results of a randomized controlled study. Am Heart J 148:312-317, 2004. 108. Saksena S, Prakash A, Ziegler P, et al: Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy. J Am Coll Cardiol 40:1140-1150, 2002. 109. D’Allonnes GR, Pavin D, Leclercq C, et al: Long-term effects of biatrial synchronous pacing to prevent drug-refractory atrial tachyarrhythmia: a nine-year experience. J Cardiovasc Electrophysiol 11:1081-1091, 2000. 110. Doi A, Takagi M, Toda I, et al: Acute haemodynamic benefits of biatrial atrioventricular sequential pacing: comparison with single atrial atrioventricular sequential pacing. Heart 90:411418, 2004. 111. Gammage MD, Marsh AM: Randomized trials for selective site pacing: do we know where we are going? Pacing Clin Electrophysiol 27:878-882, 2004. 112. Madan N, Saksena S: Long-term rhythm control of drugrefractory atrial fibrillation with “hybrid therapy” incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation. Am J Cardiol 93:569-575, 2004. 113. Hermida JS, Kubala M, Lescure FX, et al: Atrial septal pacing to prevent atrial fibrillation in patients with sinus node dysfunction: results of a randomized controlled study. Am Heart J 148:312-317, 2004. 114. De Simone A, Senatore G, Donnici G, et al: Dynamic and dualsite atrial pacing in the prevention of atrial fibrillation: The STimolazione Atrial DInamica Multisito (STADIM) Study. Pacing Clin Electrophysiol 30 Suppl 1:71-74, 2007. 115. Spitzer SG, Wacker P, Gazarek S, et al: PASTA Study Group. Primary prevention of atrial fibrillation: does the atrial lead position influence the incidence of atrial arrhythmias in patients with sinus node dysfunction? Results from the PASTA Trial. Pacing Clin Electrophysiol 32:1553-1561, 2009. 116. Lau CP, Wang CC, Ngarmukos T, et al: SAFE Study Steering Committee for SAFE Study Group. A prospective randomized study to assess the efficacy of rate and site of atrial pacing on long-term development of atrial fibrillation. J Cardiovasc Electrophysiol 20:1020-1025, 2009. 117. Greenspon AJ, Hart RG, Dawson D, et al: MOST Study Investigators. Predictors of stroke in patients paced for sick sinus syndrome. J Am Coll Cardiol 43:1617-1622, 2004.

322

SECTION 2  Clinical Concepts

118. Lamas GA, Ellenbogen KA: Evidence base for pacemaker mode selection: from physiology to randomized trials. Circulation 109:443-451, 2004. 119. Israel CW, Grönefeld G, Ehrlich JR, et al: Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. J Am Coll Cardiol 43:47-52, 2004. 120. Hohnloser SH, Capucci A, Fain E, et al: ASSERT Investigators and Committees. ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial (ASSERT). Am Heart J 152:442447, 2006. 121. Link MS, Hellkamp AS, Estes NA, 3rd, et al: MOST Study Investigators. High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST). J Am Coll Cardiol 43:20662071, 2004. 122. Newman D, Lau C, Tang AS, et al: CTOPP Investigators. Effect of pacing mode on health-related quality of life in the Canadian Trial of Physiologic Pacing. Am Heart J 145:430-437, 2003. 123. Lamas GA, Knight JD, Sweeney MO, et al: Impact of ratemodulated pacing on quality of life and exercise capacity: evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT). Heart Rhythm 4:1125-1132, 2007. 124. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Mode Selection Trial Investigators. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 107:2932-2937, 2003. 125. Nielsen JC, Kristensen L, Andersen HR, et al: A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 42:614-623, 2003. 126. Kristensen L, Nielsen JC, Mortensen PT, et al: Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome. Heart 90:661-666, 2004. 127. Wilkoff BL, Cook JR, Epstein AE, et al: DAVID Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. 128. Sharma AD, Rizo-Patron C, Hallstrom AP, et al: DAVID Investigators. Percent right ventricular pacing predicts outcomes in the DAVID trial. Heart Rhythm 2:830-834, 2005. 129. Yu CM, Chan JY, Zhang Q, et al: Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 361:2123-2134, 2009.

130. Tops LF, Schalij MJ, Bax JJ: The effects of right ventricular apical pacing on ventricular function and dyssynchrony implications for therapy. J Am Coll Cardiol 54:764-776, 2009. 131. Prinzen FW, Hunter WC, Wyman BT, McVeigh ER: Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol 33:1735-1742, 1999. 132. Sweeney MO, Ellenbogen KA, Casavant D, et al: Multicenter prospective randomized safety and efficacy study of a new atrialbased managed ventricular pacing mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol 16:811-817, 2005. 133. Gillis AM, Pürerfellner H, Israel CW, et al: Medtronic Enrhythm Clinical Study Investigators. Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Pacing Clin Electrophysiol 29:697-705, 2006. 134. Pürerfellner H, Brandt J, Israel C, et al: Comparison of two strategies to reduce ventricular pacing in pacemaker patients. Pacing Clin Electrophysiol 31:167-176, 2008. 135. Murakami Y, Tsuboi N, Inden Y, et al: Difference in percentage of ventricular pacing between two algorithms for minimizing ventricular pacing: results of the IDEAL RVP (Identify the Best Algorithm for Reducing Unnecessary Right Ventricular Pacing) study. Europace 12:96-102, 2010. 136. Savouré A, Fröhlig G, Galley D, et al: A new dual-chamber pacing mode to minimize ventricular pacing. Pacing Clin Electrophysiol 28 Suppl 1:43-46, 2005. 137. Pioger G, Leny G, Nitzsché R, Ripart A: AAIsafeR limits ventricular pacing in unselected patients. Pacing Clin Electrophysiol 30 Suppl 1:S66-S70, 2007. 138. Xue-Jun R, Zhihong H, Ye W, et al: Clinical comparison between a new dual-chamber pacing mode-AAIsafeR and DDD mode. Am J Med Sci 339:145-147, 2010. 139. Sweeney MO, Bank AJ, Nsah E, et al: Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) Trial. Minimizing ventricular pacing to reduce atrial fibrillation in sinus node disease. N Engl J Med 357:1000-1008, 2007. 140. Pascale P, Pruvot E, Graf D: Pacemaker syndrome during managed ventricular pacing mode: what is the mechanism? J Cardiovasc Electrophysiol 20:574-576, 2009. 141. Cheng A, Calkins H, Berger RD: Managed ventricular pacing below the lower rate limit: is it simply caused by ventricularbased pacing? Heart Rhythm 6:1240-1241, 2009. 142. Sweeney MO, Ruetz LL, Belk P, et al: Bradycardia pacing-induced short-long-short sequences at the onset of ventricular tachyarrhythmias: a possible mechanism of proarrhythmia? J Am Coll Cardiol 50:614-622, 2007.

143. Vavasis C, Slotwiner DJ, Goldner BG, Cheung JW: Frequent recurrent polymorphic ventricular tachycardia during sleep due to managed ventricular pacing. Pacing Clin Electrophysiol 33:641-644, 2010. 144. Van Mechelen R, Schoonderwoerd R: Risk of managed ventricular pacing in a patient with heart block. Heart Rhythm 3:13841385, 2006. 145. Epstein AE, Dimarco JP, Ellenbogen KA, et al: American College of Cardiology/American Heart Association Task Force on Practice; American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 guidelines for DeviceBased Therapy of Cardiac Rhythm Abnormalities: executive summary. Heart Rhythm 5:934-955, 2008. 146. Gillis AM: Redefining physiologic pacing: lessons learned from recent clinical trials. Heart Rhythm 3:1367-1372, 2006. 147. Wilkoff BL, Kudenchuk PJ, Buxton AE, et al: DAVID-II Investigators. DAVID (Dual Chamber and VVI Implantable Defibrillator) II trial. J Am Coll Cardiol 53:872-880, 2009. 148. Kristensen L, Nielsen JC, Pedersen AK, et al: AV block and changes in pacing mode during long-term follow-up of 399 consecutive patients with sick sinus syndrome treated with an AAI/AAIR pacemaker. Pacing Clin Electrophysiol 24:358-365, 2001. 149. Andersen HR, Nielsen JC, Thomsen PE, et al: Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome. Circulation 98:1315-1321, 1998. 150. De Sisti A, Leclercq JF, Stiubei M, et al: P-wave duration and morphology predict atrial fibrillation recurrence in patients with sinus node dysfunction and atrial-based pacemaker. Pacing Clin Electrophysiol 25:1546-1554, 2002. 151. Gillis AM, Chung MK: Pacing the right ventricle: to pace or not to pace. Heart Rhythm 2:201-206, 2005. 152. Daoud E, Doshi R, Fellows C, et al: Ablate and pace with cardiac resynchronization therapy for patients with reduced ejection fraction: sub-analysis of PAVE study. Heart Rhythm 1:s59, 2004. 153. Stambler BS, Ellenbogen K, Zhang X, et al: ROVA Investigators. Right ventricular outflow versus apical pacing in pacemaker patients with congestive heart failure and atrial fibrillation. J Cardiovasc Electrophysiol 14:1180-1186, 2003. 154. Victor F, Mabo P, Mansour H, et al: A randomized comparison of permanent septal versus apical right ventricular pacing: short-term results. J Cardiovasc Electrophysiol 17:238-242, 2006. 155. Cho HC, Marbán E: Biological therapies for cardiac arrhythmias: can genes and cells replace drugs and devices? Circ Res 106:674-685, 2010.

14  14

Pacing for Atrioventricular Conduction System Disease BRUCE S. STAMBLER  |  KENNETH A. ELLENBOGEN

Anatomy The sinus (or sinoatrial, SA) node lies near the junction of the superior vena cava and the right atrium. The sinus node is supplied by the sinus nodal artery, which originates from the proximal few centimeters of the right coronary artery (RCA) in about 55% of human subjects and from the proximal few centimeters of the left circumflex (LCx) artery in the remainder1-3 (Fig. 14-1). The atrioventricular (AV) node lies directly above the insertion of the septal leaflet of the tricuspid valve and just beneath the right atrial (RA) endocardium.3 The atrioventricular junction is a structure encompassing the AV node with its posterior, septal, and left atrial (LA) approaches, as well as the His bundle and its bifurcation. The AV node is a small, subendocardial structure located within the interatrial septum, at the distal convergence of the preferential internodal conduction pathways that course through the atria from the sinus node.1 As with the SA node, the AV node has extensive autonomic innervation and an abundant blood supply. The AV node consists of three regions— the transitional cell zone, compact node, and penetrating bundle— distinguished by functional and histologic differences (Fig. 14-2). The transitional cell zone, which consists of cells constituting the atrial approaches to the compact AV node, has the highest rate of spontaneous diastolic depolarization. The compact node is composed of groups of cells that have extensions into the central fibrous body and the anulus of the mitral and tricuspid valves. These cells appear to be the site of most of the conduction delay through the AV node.4 The penetrating bundle consists of cells that lead directly into the His bundle and its branching portion. Only the proximal two thirds of the AV node are supplied by the AV nodal artery;3 the distal segment of the AV node has a dual blood supply in 80% of human hearts from the same AV nodal artery and the left anterior descending (LAD) artery. In 90% of patients, the AV nodal artery originates from the RCA. During acute myocardial infarction (AMI), conduction disturbances in the AV node are usually the consequence of an occlusion proximal to the origin of the AV nodal artery. Therefore, the conduction abnormalities are usually associated with inferior AMI. The AV nodal tissue merges with the His bundle, which runs through the inferior portion of the membranous interventricular septum and then, in most cases, continues along the left side of the crest of the muscular interventricular septum. The His bundle usually receives a dual blood supply from both the AV nodal artery and branches of the LAD artery.5 Unlike the SA and AV nodes, the bundle of His and Purkinje system have relatively little autonomic innervation. The right bundle branch (RBB) originates from the His bundle. It is a narrow structure that crosses to the right side of the interventricular septum and extends along the right ventricular (RV) endocardial surface to the region of the anterolateral papillary muscle of the right ventricle, where it divides to supply the papillary muscle, the parietal RV surface, and the lower part of the RV surface.5 The proximal portion of the RBB is supplied by branches from the AV nodal artery or the LAD artery, whereas the more distal portion is supplied mainly by branches of the LAD artery.

The left bundle branch (LBB) is anatomically much less discrete than the RBB. The LBB may divide immediately as it originates from the bundle of His or may continue for 1 to 2 cm as a broad band before dividing.3,5 The LBB fibers spread out over the left ventricle in a fanlike manner, a “cascading waterfall,” with many subendocardial interconnections that resemble a syncytium rather than two, anatomically discrete, distinct branches or fascicles.5 As originally proposed by Rosenbaum,6 however, it is clinically useful to consider the LBB as dividing into an anterior branch or fascicle and a larger and broader posterior branch or fascicle, both of which radiate toward the anterior and posterior papillary muscles of the left ventricle, respectively. The LBB and its anterior fascicle have a blood supply similar to that of the proximal portion of the RBB; the left posterior fascicle is supplied by branches of the AV nodal artery, the posterior descending artery, and the circumflex coronary artery.

Diagnosis of Atrioventricular Conduction Disturbances ELECTROCARDIOGRAPHY First-degree atrioventricular (AV) block usually is caused by conduction delay within the AV node. Much less frequently, first-degree AV block is caused by intra-atrial or infra-Hisian conduction delay.7 Localization of the site of second-degree AV block to the AV node or HisPurkinje system can be obtained by His bundle recording during invasive electrophysiologic testing, but in most cases, careful analysis of the electrocardiogram (ECG) and the effect of various pharmacologic agents on the block will suffice.8 Adherence to precise definitions of second-degree AV block, particularly in cases of 2 : 1 AV block and suspected type II AV block, is critical to avoiding diagnostic errors that could result in potentially unnecessary permanent pacemaker implantation.9 Furthermore, type I and type II designations refer only to ECG patterns and not to the anatomic site of block. Classic type I (Wenckebach) second-degree AV block has three characteristics: (1) progressive P-R interval prolongation before the nonconducted beat, (2) progressive decrease in the increment of P-R interval prolongation, and (3) progressive decrease in the R-R interval, parallel to the progressive decrease in the increment of change in the P-R interval.10 All patterns of type I second-degree AV block not having this pattern are called “atypical” patterns, although in actuality, they may occur more often than the classic variety11 (Fig. 14-3). As a general rule, type I second-degree AV block with a narrow QRS complex is almost always caused by delay within the AV node. Delay within the His bundle (intra-Hisian block), however, is a rare cause of type I second-degree AV block with a narrow QRS and requires an electrophysiologic study for definitive diagnosis. Intra-Hisian block should be suspected in a patient with a narrow QRS if type I seconddegree AV block is provoked by exercise. In contrast, type I AV nodal block at rest improves with exercise. When type I second-degree AV block is associated with concomitant bundle branch block (BBB), the site of delay or block is in the His-Purkinje system (infranodal) in up to 60% to 70% of cases.10

323

324

SECTION 2  Clinical Concepts

definition of type II block (i.e., a single block beat), it does suggest that the anatomic site of AV block is infranodal, and that permanent pacing is indicated. On the other hand, Wenckebach periodicity before the development of high-grade AV block suggests an AV nodal site. Lange et al.12 reported on their experience with a large number of patients with transient second-degree AV block and narrow QRS

SAN His bundle

LCx LAD

AVN Ventricular septum

Post. div. of LBB

Tricuspid valve

PDA

RBB

Ant. div. of LBB

Figure 14-1  Diagrammatic representation of the conduction system and its blood supply. Ant. div., Anterior division; AVN, atrioventricular node; LAD, left anterior descending artery; LBB, left bundle branch; LCx, left circumflex artery; PDA, posterior descending artery; Post. div., posterior division; RBB, right bundle branch; SAN, sinoatrial node. (From de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, Davis.)

Type II second-degree AV block is defined as a single nonconducted sinus P wave associated with fixed P-R intervals before and after the blocked beat (Fig. 14-4). The sinus rate must be stable (i.e., constant P-P intervals), and there must be at least two consecutive conducted P waves to determine the P-R interval, which can be either normal or prolonged. Type II second-degree AV block should not be diagnosed in the case of a nonconducted atrial premature beat or if there is simultaneous sinus slowing and AV nodal block (e.g., hypervagotonia). Type I block with relatively long Wenckebach sequences and small increases in AV nodal conduction time may be confused with type II AV block but should not be classified as such (even though the site of block may be either AV nodal or infranodal in such cases). Type II second-degree AV block is most often encountered when the QRS complex is prolonged (in about 70% of cases) and is localized within the His-Purkinje system; in contrast, type II AV block with a narrow QRS is within the His bundle (i.e., intra-Hisian). Sudden AV block of more than one impulse with stable sinus rhythm and 1 : 1 AV conduction with constant P-R and P-P intervals before and after the block has been labeled “advanced AV block,” “paroxysmal AV block,” and “type II AV block.” Although this rhythm does not conform to the strict

Figure 14-2  A, Section through the crest of the muscular ventricular septum of the human heart, oriented in attitudinally correct fashion, shows the insulated nature of the branching atrioventricular bundle and the left bundle branch. B, Section (trichrome stain) from a human child’s heart shows the region of the atrioventricular (AV) node. The cells of the compact node are joined to the atrial myocardial cells through short regions of transitional cells. The node itself is part of the atrial wall, with no fibrous sheath interposed between the histologically specialized tissues and the working atrial myocardium. C, Illustration scanned from Tawara’s monograph of 1906, reoriented to anatomically correct position and relabeled. It shows the axis of conduction tissue (orange), extending from the atria myocardium (yellow), penetrating the insulating plane (red) and branching on crest of the muscular ventricular septum (also yellow). Compare with A and B. (From Anderson RH, Ho SY, Becker AE: Anatomy of the human atrioventricular junctions revisited. Anat Rec 260:81, 2000.)

Atrioventricular membranes

Branching atrioventricular bundle

Left bundle branch

A

Atrial myocardial cells Transitional cells

B

Compact AV node

Central fibrous body Right bundle branch

Compact atrioventricular node

Penetrating bundle

C

Branching bundle

Left bundle branch



325

14  Pacing for Atrioventricular Conduction System Disease

1 2 3 V1 HRA HBE T

Lead II (continuous) 0.19 A A

A

650 240H 40

v

A

660

A

v A 230H

A

740

240H

40

v

780

A

A

200H 300 msec

40

v

0.74

0.20

.18

.18

Figure 14-4  Type II second-degree atrioventricular (AV) block showing repeating episodes of block. Note that the P-R interval is constant both before and after the nonconducted P wave, and that there is associated bundle branch block.

complexes detected on ambulatory Holter monitoring. The researchers emphasized the many ways in which second-degree AV block can be manifested. Classic, type I AV block with progressive PR prolongation to more than 40 msec during at least three beats before the blocked P waves was seen in only 50% of patients. Another pattern observed was a subtler Wenckebach periodicity with minor PR prolongation of 20 to 40 msec before a blocked P wave in 29% of patients. A third pattern, seen in 8% of patients and termed pseudo–Mobitz type II AV block, demonstrated nearly constant P-R intervals before the blocked P wave, followed by PR shortening on the subsequent conducted beat (see Fig. 14-3). Classic Mobitz type II second-degree AV block, with constant P-R intervals for at least three beats before the blocked P wave, followed by the same P-R interval after the blocked P wave, was seen in 4% of patients (see Fig. 14-4). A mixed, type I Wenckebach and pseudo– Mobitz type II AV block was seen in 6% of all patients. Of patients showing periods of pseudo–Mobitz type II block, 44% also demonstrated classic Wenckebach conduction patterns at some time.12

0.97

0.16 0.19

0.20

0.20

0.20

0.20

0.78

0.80

0.83

0.92

0.94

1.00

0.50

0.20

1.04

0.20

1.06

0.20

0.85

1.02

0.28

0.96

0.20

0.97

0.94

0.21

0.94

0.18

0.84

0.88

Figure 14-5  Rhythm strip demonstrating vagally mediated seconddegree atrioventricular (AV) block. Note the progressive slowing of the heart rate before the first episode of AV block, although no change in P-R interval can be discerned. During the second episode of block, both sinus slowing and P-R interval prolongation occur, confirming the presence of type I second-degree AV block.

Slowing of the sinus cycle length often preceded the blocked P wave in both classic and pseudo–Mobitz type II AV blocks (Fig. 14-5). Diagnosis of the site of AV block may be problematic with 2 : 1 atrioventricular block, which should not be classified as type I or type II block. The anatomic site in 2 : 1 AV block can be in the AV node or His-Purkinje system (Fig. 14-6). The most likely site of AV block can often be determined by noting the company that the 2 : 1 AV block keeps. When 2 : 1 AV block is associated with a wide QRS complex, the block is in the His-Purkinje system in 80% and the AV node in 20% of cases (Fig. 14-7). A long P-R interval (>0.30 second) on conducted beats during 2 : 1 AV block with a narrow QRS complex suggests an AV nodal site, whereas a normal P-R interval favors intra-Hisian block. In general, the response of the block, particularly 2 : 1 AV block, to pharmacologic agents may help to determine the site. Atropine generally improves AV conduction in patients with AV nodal block; however, atropine is expected to worsen conduction in patients with block localized to the His-Purkinje system, because of its effect on increasing sinus rates without improving His-Purkinje conduction (Fig. 14-8). Carotid sinus stimulation is expected to worsen block localized to the AV node, whereas it either has no effect or improves conduction in

1540

1

0.20

0.74

0.20

0.84

.18

0.20

40

Figure 14-3  Atypical or uncommon type I second-degree atrioventricular (AV) block in the AV node. Surface leads I (1), II (2), III (3), and V1 are displayed with intracardiac electrograms recorded from the high right atrium (HRA), His bundle (HBE), and right ventricular apex (RV). There is little alteration in the A-H interval before the fourth atrial complex not conducting to the ventricle. The true nature of this arrhythmia is revealed by the first-conducted P wave (A, atrial electrogram) after the pause, which is associated with substantial shortening of the A-H interval from 230 to 240 msec to 200 msec. (From Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3, Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109.)

.18

0.19

A

1550

2 3 V1 A

775 A V H HBE 290 HRA

T

A A

785

A

785 A V H 270

A A

765

A

785 A V H 270

A A 500 msec

Figure 14-6  Spontaneous 2 : 1 (high-grade) atrioventricular (AV) block localized to the AV node. Surface leads I (1), II (2), III (3), and V1 are displayed with intracardiac electrograms recorded from the high right atrium (HRA), His bundle (HBE), and right ventricular apex (RV). Alternate atrial depolarizations (A) are not followed by either a His bundle or a ventricular depolarization. On the basis of a surface electrocardiogram, the finding of 2 : 1 AV block with a narrow QRS is compatible with a block at either the AV node or an infra-Hisian bundle site. The intracardiac recordings localize the site of block to the AV node. (From Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3. Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109.)

326

SECTION 2  Clinical Concepts

I II III V1 HBE

A H

AH

A H

AH

A H

AH

RV Figure 14-7  Intracardiac tracing of 2 : 1 second-degree atrioventricular (AV) block located in the His-Purkinje system. Sinus rhythm with left bundle branch block is present. Surface leads I, II, III, and V1 are displayed with intracardiac electrograms recorded from the high right atrium, His bundle (HBE), and right ventricular apex (RV). The A-H intervals are constant, but every other atrial complex fails to activate the ventricle even though each atrial depolarization is followed by a His bundle deflection. This finding shows that the site of AV block is within the His-Purkinje system. (From Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3, Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109.)

describe these AV conduction disturbances on the ECG is misleading, because the site of block in such cases may be located in the AV node or His-Purkinje system.9 The P-R interval does not identify patients who have prolonged H-V intervals in such cases. Up to 50% of patients with bifascicular block and prolonged P-R intervals have prolongation of the A-H interval (i.e., AV nodal conduction time).14 Trifascicular block should be used only to refer to alternating RBBB and LBBB, RBBB with a prolonged H-V interval (regardless of the presence or absence of left anterior or posterior fascicular block), and LBBB with a prolonged H-V interval. In addition, the term can be used in a patient with second- or third-degree AV block in the His-Purkinje system with (a) permanent block in all three fascicles, (b) permanent block in two fascicles with intermittent conduction in the third, (c) permanent block in one fascicle with intermittent block in the other two fascicles, or (d) intermittent block in all three fascicles. Thus, according to its Control

4021 I II

patients with His-Purkinje system disease by causing sinus node slowing. The effect of any given drug, however, may be difficult to predict because its effect on the sinus node may be greater than its effect on the AV node. For example, atropine may improve AV node conduction, but if atropine causes excessive SA node acceleration, AV conduction may improve marginally or not at all. The response to infusion of isoproterenol is less clear. Isoproterenol may improve conduction disorders localized in the AV node as well as occasionally in the His-Purkinje system. The diagnosis of complete heart block (CHB) rests on demonstration of complete dissociation between atrial and ventricular activation. Care must be taken to distinguish transient AV dissociation caused by competing atrial and junctional or ventricular rhythms with similar rates (so-called isorhythmic AV dissociation). If sufficiently long monitoring strips are available, intermittent conduction of appropriately timed atrial events is seen. Temporary atrial pacing can be performed to accelerate the atrial rate to overdrive the competing junctional or ventricular arrhythmia, demonstrating intact AV conduction. In the presence of atrial fibrillation (AF), CHB can be inferred when the ventricular rate becomes regular rather than the typical, irregular ventricular response (Fig. 14-9). Digoxin toxicity may be the cause of heart block with AF, and this and other drug toxicity should be ruled out before one assumes that structural AV conduction disease is present. In patients with chronic AF, regular R-R intervals may occasionally be caused by “concealed” sinus rhythm (i.e., no evidence of atrial activity because of very-low-amplitude P waves) and not heart block or digitalis intoxication.13 The escape rhythm in CHB may be generated by the AV junction, His bundle, bundle branches, or distal conduction system. Rarely, the underlying rhythm arises from the ventricular myocardium or, for all practical purposes, is absent. The site of AV block is important in that it determines to a great extent the rate and reliability of the underlying escape rhythm. The site of origin of the escape rhythm in cases of advanced AV block is more important than the escape rate itself.7 For example, in heart block associated with inferior AMI or congenital CHB, the escape rhythm is usually generated by the AV junction, and permanent pacing may not be required. Nevertheless, it is worth emphasizing that symptomatic AV block requires pacing regardless of the site, morphology, or rate of the escape rhythm. Trifascicular block is present when bifascicular block is associated with HV prolongation. However, trifascicular block also is often applied loosely to the electrocardiographic patterns of bifascicular block—right bundle branch block (RBBB) plus left anterior hemiblock, RBBB plus left posterior hemiblock, or left bundle branch block (LBBB)—plus first-degree AV block. Using “trifascicular block” to

III V1 HRA

A

A H

HBE

1175 AH 100 HV 70

A

Atropine 1 mg

H

IV

V1

HRA

A

H

V

770 AH 60 HV 80

A

H

V

HBE

B Atropine 1.5 mg IV V1 A HBE

C

RV

H

AA 550 AH 75 A H

AH

AH 75 HV 75

1100

Figure 14-8  His-Purkinje atrioventricular block after atropineinduced increase in sinus rate. Surface leads I, II, III, and V1 are displayed with intracardiac electrograms recorded from the high right atrium (HRA), His bundle (HBE), and right ventricular apex (RV). A, Sinus rhythm at a cycle length of 1175 msec with 1 : 1 AV conduction. Left bundle branch block is present, and the H-V interval is slightly prolonged, to 70 msec. B, After injection of 1 mg of atropine, the sinus rate speeds up to 770 msec and the H-V interval increases to 80 msec, but 1 : 1 AV conduction is still present. The A-H interval shortens despite the faster sinus rate, because of the direct effect of atropine on AV nodal conduction. C, After injection of 1.5 mg of atropine, the sinus cycle length decreases further to 550 msec, and 2 : 1 AV block occurs below the His bundle. Atropine worsens AV conduction in this patient, not through a direct drug effect, but because the atropine-induced improvement in AV nodal conduction stresses the already-abnormal His-Purkinje system. (From Miles WM, Klein LS: Sinus nodal dysfunction and atrioventricular conduction disturbances. In Naccarelli GV: Cardiac arrhythmias: a practical approach. Mt Kisco, NY, 1991, Futura, pp 243-282.)



14  Pacing for Atrioventricular Conduction System Disease

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 14-9  Twelve-lead electrocardiogram from a patient with recent aortic valve surgery and atrial fibrillation treated with digoxin. Surface leads I, II, III, and V1 are displayed with intracardiac electrograms recorded from the high right atrium, His bundle, and right ventricular apex. The QRS complexes are narrow and occur at a regular rate of 56 bpm, illustrating complete heart block with a junctional escape rhythm in the setting of atrial fibrillation. Despite discontinuation of digoxin, complete heart block persisted in this patient.

strict definition, when interpreting an ECG in the absence of a His bundle recording, trifascicular block should be applied only to the patterns of alternating RBBB and LBBB or RBBB with intermittent left anterior and posterior hemiblocks. These situations are class I indications for permanent pacing, even in asymptomatic individuals. ELECTROPHYSIOLOGIC STUDY Invasive electrophysiologic study (EPS; e.g., His bundle recording) is a useful means of evaluating AV conduction in patients who have symptoms and in whom the need for permanent pacing is not obvious (Fig. 14-10). Electrophysiologic studies (strictly for evaluation of the conduction system and site of block) are not required in patients with symptomatic high-grade or complete AV block recorded on surface ECGs, ambulatory Holter monitoring, or transtelephonic recordings. The need for permanent pacing has already been established in these patients (class I indication). However, EPS may be indicated in patients with high-grade AV block if another arrhythmia is suspected or is a likely cause of symptoms. For example, even if high-grade AV block is I II III V1 HRA Mp Md RV Figure 14-10  Surface leads I, II, III, and V1 reveal sinus rhythm with 2 : 1 AV conduction, marked P-R interval prolongation during conducted beats, and right bundle branch block. Intracardiac electrograms from the high right atrium (HRA), proximal and distal poles of the His bundle catheter (Mp and Md, respectively), and the right ventricle (RV) are shown. The distal pole of the His bundle catheter registers a His bundle potential, which can be seen as a discrete sharp potential between the atrial and the ventricular electrograms on that channel. During nonconducted atrial complexes, spontaneous infra-Hisian block is apparent because the His bundle potential (arrow) is not followed by a ventricular electrogram.

327

documented on spontaneous recordings, ventricular tachycardia may still be the cause of syncope in patients with extensive AMI. In patients with alternating BBB, EPS almost invariably demonstrates a high degree of His-Purkinje system disease. These patients typically have very long H-V intervals and are at very high risk of progression to CHB in a short time. Pacing in these patients is indicated on clinical grounds, and EPS may not be necessary.7 Electrophysiologic studies are also not indicated in patients whose symptoms are shown not to be associated with a conduction abnormality or block. In addition, patients without symptoms who have intermittent AV block associated with sinus slowing, gradual PR prolongation before a nonconducted P wave, and a narrow QRS complex should not undergo EPS, given the benign prognosis of these findings. The incidence of progression of bifascicular block to CHB is variable, ranging from 2% to 6% per year. The method of patient selection affects this incidence, with patients who have asymptomatic bifascicular block progressing to CHB at a rate of 2% per year, and patients with symptoms (e.g., syncope or presyncope) progressing at a rate closer to 6% per year.15 Many of these studies emphasize the high mortality associated with bundle branch block (BBB) and bifascicular block. It is worth emphasizing that the mortality associated with the presence of structural heart disease predominantly reflects death resulting from AMI, heart failure, or ventricular tachyarrhythmias rather than bradyarrhythmias. Three large studies of patients with chronic BBB have been performed to assess the role of His bundle conduction (e.g., H-V interval) measurements in predicting progression to CHB. The measurement of the H-V interval represents the conduction time through the His bundle and bundle branches until ventricular activation begins. Because these studies included both asymptomatic and symptomatic patients, care must be taken to ensure that similar patient populations are compared for proper interpretation of these results. Dhingra et al.15 prospectively followed 517 patients with BBB and measured the time required for progression to second- and third-degree block. Only 13% of patients presented with syncope; the others had no symptoms. The cumulative 7-year incidence of progression to AV block was 10% in the group with a normal H-V interval and 20% in the group with H-V interval prolongation. The cumulative mortality rate at 7 years was 48% in patients with a normal H-V interval and 66% in patients with a prolonged H-V interval. This study emphasized that despite the high mortality associated with the presence of bifascicular block, there is only a low rate of progression to more advanced AV block. McAnulty et al.16 studied 554 patients with “high-risk” BBB, defined as LBBB, RBBB and left-axis or right-axis deviation, RBBB with alternating left- and right-axis deviation, or alternating RBBB and LBBB. The cumulative incidence of AV block, either type II second-degree or CHB, was 4.9%, or 1% per year, in patients with a prolonged H-V interval and 1.9% in patients with a normal H-V interval (difference not significant). H-V interval prolongation did not predict a higher risk of development of CHB. After entry into the study, 8.5% of patients experienced syncope. The incidence of complete AV block was 17% in patients with syncope versus 2% in patients without a history of syncope. Scheinman et al.17 studied 401 patients with chronic BBB for about 30 months. This study, in contrast to the Dhingra15 and McAnulty16 studies, primarily included patients with symptoms referred for EPS. About 40% of the patients in the Scheinman study had a history of syncope.17 In patients with an H-V interval of more than 70 msec, the incidence of progression to spontaneous second- or third-degree AV block was 12%. The incidence of complete AV block was 25% for those with an H-V interval of 100 msec or greater. The yearly incidence of spontaneous AV block was 3% in those with a normal H-V interval and 3.5% in those with a prolonged H-V interval. These findings therefore suggest a relationship between a prolonged H-V interval and development of CHB during the ensuing years in patients with intraventricular conduction disturbances. It also seems that the risk varies directly with the extent of HV prolongation.

328

SECTION 2  Clinical Concepts

Symptomatic patients with syncope or presyncope are at much higher risk than asymptomatic patients. The overall risk of CHB in an unselected, symptom-free group of patients with chronic BBB is low (<6%/yr). Current recommendations are not to perform EPS in patients with asymptomatic BBB.18 A number of studies evaluated the clinical usefulness of EPS in patients with BBB and syncope. Electrophysiologic studies were performed before the current era of ICD implantation in patients with syncope and advanced structural heart disease. In one study, 112 patients with chronic BBB and syncope or near-syncope underwent EPS.19 A normal result predicted a good long-term prognosis. About 25% of patients had significant conduction system disorder, underwent pacemaker implantation, and experienced recurrence of symptoms at a rate of only 6%. In the study reported by Morady et al.,20 28% of patients (7 of 32) had sustained, induced monomorphic ventricular tachycardia (VT), whereas about 20% had conduction disturbances at EPS. Six of the seven patients who received pacemakers had no recurrent symptoms. Thus, electrophysiologic studies may be useful in patients with BBB or bifascicular block and syncope for several reasons. First, negative EPS results may identify a group of patients at low risk for cardiac events, especially in the absence of advanced structural heart disease. Induction of sustained VT during EPS identifies patients at risk for life-threatening ventricular arrhythmias who require ICDs. Programmed ventricular stimulation in patients with BBB and syncope may induce bundle branch reentrant VT, which may be readily cured with radiofrequency catheter ablation. Also, EPS identifies patients with advanced conduction system disease (e.g., prolonged H-V interval with BBB) who need pacemakers. The clinical trials that established the role of the ICD for both primary and secondary prevention of sudden death, as well as for cardiac resynchronization therapy, have significantly affected the management of patients with BBB and syncope. Current guidelines recommend ICD implantation in patients with syncope of undetermined etiology in the setting of advanced structural heart disease, because these patients are likely to have an arrhythmic cause of syncope. Thus, if LV dysfunction is present (left ventricular ejection fraction [LVEF] ≤35%-40%) in patients with BBB and syncope, ICD implantation is indicated, and many centers may choose not to perform EPS in these patients. Electrophysiologic studies may still be considered in patients with syncope or near-syncope and BBB with no, minimal, or mild structural heart disease (LVEF >40%). IDENTIFYING PATIENTS AT RISK FOR AV BLOCK In patients with symptomatic BBB or bifascicular block, EPS with measurement of H-V intervals has been used for several decades. A “markedly prolonged” H-V interval (≥100 msec) is predictive of development of symptomatic heart block. As noted earlier, Scheinman et al.17 demonstrated that an H-V interval of 100 msec or longer identified a group of patients who had a 25% risk of development of heart block over a mean follow-up of 22 months. According to current guidelines published by the American College of Cardiology (ACC), American Heart Association (AHA) Task Force on Practice Guidelines, and North American Society for Pacing and Electrophysiology (NASPE), an H-V interval of 100 msec or longer in an asymptomatic patient documented as an incidental finding on EPS is a class IIa indication for permanent implantation of a pacemaker.21 Although the finding of a markedly prolonged H-V interval is quite specific, it is very insensitive because H-V intervals of 100 msec or longer are uncommon. Atrial pacing to stress the His-Purkinje system may provide additional information to identify patients at risk of spontaneous AV block. Healthy subjects do not experience second- or third-degree infraHisian block during atrial pacing when the atrial rate is gradually increased, as would occur spontaneously. Certain pacing protocols with abrupt onset of pacing at rapid rates are more likely to induce infra-Hisian block, even in healthy subjects, but even this finding is

rare at pacing rates below 150 beats per minute (bpm) in healthy individuals. Because AV nodal dysfunction is frequently seen in patients with significant His-Purkinje system disease, AV nodal block may occur at lower pacing rates than those necessary to demonstrate infraHisian block. This “protective” effect of AV nodal dysfunction during resting states may lead to the incorrect conclusion that significant HisPurkinje disease is not present. However, a second trial of atrial pacing after administration of atropine or isoproterenol to facilitate AV nodal conduction may demonstrate infra-Hisian block. Dhingra et al.22 reported a 50% rate of progression to type II or complete AV block in patients in whom block develops distal to the His bundle at paced rates of less than 150 bpm. In a later study, Petrac et al.23 evaluated 192 patients with chronic BBB and syncope, of whom 18 (9%) had incremental atrial pacing–induced infra-Hisian second-degree AV block at a paced rate of 150 bpm or less (mean pacing rate, 112 ±10 bpm). During a mean follow-up of 68 ±35 months, 14 of the 18 patients (78%) demonstrated spontaneous second- or third-degree AV block, confirming that this abnormal finding identifies a subgroup at a high risk for development of heart block. As with an H-V interval of 100 msec or less, however, His-Purkinje block during incremental atrial pacing at physiologic rates is uncommon in patients with BBB and syncope. According to current guidelines, if atrial pacing–induced infra-Hisian block that is “not physiologic” is demonstrated as an incidental finding on EPS, permanent pacing is recommended (class IIa indication).21 Provocative drug tests have been suggested as another means of evaluating the distal conduction system24 (Fig. 14-11). Pharmacologic stress testing may be considered in patients with BBB and syncope who have a baseline H-V interval of 70 msec or higher (but <100 msec) and no infra-Hisian block demonstrated. Data describing the experience with intravenous type Ia (procainamide, ajmaline, disopyramide) or type Ic (flecainide) antiarrhythmic drugs are limited.15,25-27 Only intravenous procainamide is available in the United States. Administration of these agents may result in a marked increase in the H-V interval (>15-20 msec), an H-V interval greater than 100 msec, or precipitation of spontaneous type II second- or third-degree AV block, all of which may indicate a higher risk for development of CHB. Intravenous disopyramide has the potential benefit of facilitating AV nodal conduction by its anticholinergic properties while accentuating underlying infraHisian disease through its membrane-stabilizing effects.26 Tonkin et al.27 administered procainamide at a dose of up to 10 mg/kg to 42 patients with BBB and syncope and produced intermittent second- or third-degree His-Purkinje block or H-V prolongation to more than 15 msec during sinus rhythm in 11 patients (26%).28 However, only 2 of the 11 patients (18%) with a positive result had documented highgrade AV block during 38 months of follow-up, and three of five asymptomatic control patients with BBB (60%) had a positive procainamide challenge test result. Other studies of class I antiarrhythmic drug testing to stress the His-Purkinje system likewise have limited patient numbers, lack adequate control groups or follow-up, and seem to indicate that pharmacologic testing has low predictive value. Current permanent pacing guidelines do not include a recommendation regarding the need for permanent pacing on the basis of results of pharmacologic stress testing of the His-Purkinje system. Electrophysiologic testing has recognized limitations for identifying patients with significant AV nodal or His-Purkinje dysfunction. Although finding an abnormality on EPS may be helpful, its sensitivity is low and cannot be used alone to exclude a significant AV conduction disturbance. In a small study by Fujimura et al.,29 13 patients with documented symptomatic transient second- or third-degree AV block referred for implantation of a permanent pacemaker underwent AV conduction testing at pacemaker insertion. These tests included facilitation of AV nodal conduction with atropine and pharmacologic stress of His-Purkinje conduction with low doses of procainamide. Surprisingly, only 2 of the 13 patients showed significant abnormalities in the AV conduction system (inducible infra-Hisian block in both cases) during EPS, yielding a sensitivity of 15.4%. Two other patients had moderately prolonged H-V intervals, although much shorter than



14  Pacing for Atrioventricular Conduction System Disease

symptom is recurrent Stokes-Adams attacks (Adams-Stokes syncope) or documented episodes of polymorphic ventricular tachycardia. Patients with long P-R intervals may have symptoms suggestive of pacemaker syndrome and may demonstrate resolution of symptoms with institution of dual-chamber pacing. It is important to emphasize that symptoms can be subtle or nonspecific in some patients or may be of sufficiently long duration that a high index of suspicion is warranted. Some clinicians recommend temporary pacing to document improvement of symptoms or reversal of long-standing problems, but the usefulness of this intervention has not been demonstrated in prospective studies.

I II III V1 RA RA RV HBE1

FIRST-DEGREE AV BLOCK

HBE2 HV60 msec

HBE3

A

I II III V1 RA RA RV HBE1 HBE2 HBE3

B

329

AH

V

AH

HV110 msec

Figure 14-11  A, Electrophysiologic testing in the baseline state in a patient with syncope reveals a left bundle branch block pattern during sinus rhythm. There is 1 : 1 atrioventricular (AV) conduction with an H-V interval of 60 msec. B, After a loading dose of procainamide, 2 : 1 AV conduction develops. The first and third atrial activations are conducted to the ventricles with an H-V interval of 110 msec. The third and fourth atrial activations conduct through the AV node to generate a His bundle potential without subsequent ventricular activation. Thus, this test illustrates spontaneous infra-Hisian block induced by procainamide. HBE1, HBE2, and HBE3 are proximal, middle, and distal His bundle catheter recordings, respectively; RA, right atrial recordings; RV, right ventricular recording.

100 msec. If these two patients are included in the diagnostic data, the sensitivity of EPS is increased to 46%, raising important questions about EPS sensitivity for identifying patients at risk for symptomatic AV block.

Classification, Epidemiology, and Natural History of Atrioventricular Conduction Disturbances Atrioventricular block can be classified clinically on the basis of electrocardiographic findings, anatomic site of block, onset, extent of severity, clinical presentation, underlying etiology, or associated conditions. Each of these classifications provides insight into the basis and management of these clinical disorders. Patients who present with symptomatic first-, second-, or thirddegree AV block may complain of syncope, dizziness, decreased energy, palpitations, or recurrent presyncope or dizziness. Other symptoms, which primarily reflect inadequate cardiac output or tissue perfusion, are fatigue, angina, and congestive heart failure. The most severe

The prognosis and natural history in patients with primary first-degree AV block and moderate PR prolongation traditionally has been thought of as being benign. Progression to CHB over time occurred in about 4% of patients in the Mymin et al.30 study, which involved only young, male U.S. Air Force pilots. Most of the patients (66%) had only mild to moderate PR prolongation, to about 0.22 to 0.23 second. In the great majority of subjects, the P-R interval remained within a narrow range, changing by less than 0.04 second. More recently, a Framingham Heart Study report challenged the long-held belief that first-degree AV block has a benign prognosis.31 In this large, community-based sample with long-term follow-up, patients with first-degree AV block (PR > 200 msec) at baseline were at substantially increased risk of future atrial fibrillation (about twofold) and pacemaker implantation (about threefold) and a moderately increased risk of all-cause mortality, compared with individuals without first-degree AV block. Patients with “markedly prolonged” P-R interval may or may not be symptomatic at rest, but may demonstrate a pseudo–pacemaker syndrome caused by AV dyssynchrony, particularly during exertion. These events are more likely to become symptomatic during exercise, because the P-R interval may not shorten appropriately as the R-R interval decreases. Zornosa et al.32 described PR prolongation after radiofrequency ablation resulting from injury of the fast–AV nodal pathway in patients with AV nodal reentry. Symptoms caused by long P-R intervals resolved after DDD pacing was performed. Kim et al.33 also described a patient with intermittent failure of fast-pathway conduction who experienced lightheadedness, weakness, and chest fullness when the P-R interval suddenly shifted from between 160 and 180 msec to 360 msec; this patient’s condition improved after pacing. Implantation of permanent pacemakers is reasonable in patients with first-degree AV block with symptoms similar to those of pacemaker syndrome or hemodynamic compromise (class IIa indication).21 Previous versions of the ACC/AHA/NASPE guidelines required documentation of alleviation of symptoms with temporary AV pacing before permanent pacing. However, this requirement was removed in the 2002 revision of the guidelines, in part because a temporary AV pacing study may not demonstrate symptomatic improvement at rest and is often impractical to perform during exercise. Thus, it is reasonable to institute permanent pacing in symptomatic patients with extremely long P-R intervals (≥0.30 sec) that do not shorten during exercise. Permanent pacemaker implantation may also benefit patients with left ventricular (LV) systolic dysfunction, congestive heart failure, and marked first-degree AV block (>0.30 sec) in whom a shorter A-V interval results in hemodynamic improvement. An acute study in patients with first-degree AV block suggested that systolic performance measured using a Doppler echocardiography–derived aortic flow timevelocity integral improved after institution of DDD pacing at a rate of 70 bpm if the intrinsic AV conduction time (A-R interval) was longer than 0.27 second.34 The optimal AV delay in this study was 159 ± 22 msec, which is consistent with most other studies, in that the optimal AV delay is about 150 msec at rest. However, given the need for frequent ventricular pacing support to optimize the A-V interval in these patients, atrio-biventricular pacing is likely to be the optimal long-term pacing mode in these patients with LV systolic dysfunction and heart failure.

330

SECTION 2  Clinical Concepts

SECOND-DEGREE AV BLOCK Controversy surrounds the prognosis and need for permanent pacing in patients with chronic type I second-degree AV block in the presence of a narrow QRS complex. Some consider this condition benign only in young people or athletes without organic heart disease. The natural history of 56 patients with chronic type I second-degree AV block, some of whom were younger than 35 or were well-trained athletes, was described in 1981 by Strasberg et al.35 They concluded that progression to CHB is relatively uncommon in this patient population, and that this finding carries a benign prognosis in the absence of structural heart disease. In 1985, however, Shaw et al.36 suggested that patients with type I second-degree AV block have a worse prognosis than ageand gender-matched individuals, unless the patients already had permanently implanted pacemakers. The 214 patients with chronic second-degree AV block (mean age, 72) were divided into three groups—type I block (77), type II block (86), and 2 : 1 or 3 : 1 block (51)—and monitored over a 14-year period. The 3-year and 5-year survival rates were similarly poor, regardless of the type of AV block. Patients with type I block without BBB fared no better than those with type II block. Patients with type I second-degree AV block who received permanent pacemakers had survival similar to that of an age- and gender-matched control population. In 1991 the British Pacing and Electrophysiology Group (BPEG) suggested that pacing should be considered in adults in whom type I second-degree AV block occurs during much of the day or night, regardless of the presence or absence of symptoms.37 In 2004, Shaw et al.38 reported again on the prognosis of patients with type I seconddegree AV block and once again concluded that type I second-degree AV block is not a benign condition in patients 45 years or older. The majority of their patients with type I second-degree AV block who were 45 years or older progressed to higher-degree AV block, experienced symptomatic bradycardia, or died prematurely if they did not receive pacemakers. These investigators recommended pacemaker implantation in patients with type I second-degree AV block even in the absence of symptoms or structural heart disease, except in those younger than 45. According to current ACC/AHA/NASPE guidelines, however, permanent pacemaker implantation in asymptomatic type I seconddegree AV block that is at the supra-His (AV node) level or is not known to be intra-Hisian or infra-Hisian is considered insupportable by current evidence (class III indication). It seems prudent, on the basis of available data, at least to monitor closely any elderly patient with asymptomatic type I AV block or 2 : 1 AV block with narrow QRS complexes, because these electrocardiographic abnormalities may be markers for progressive conduction system disease. The natural history of asymptomatic type II second-degree AV block initially was addressed in a University of Illinois study reported in 1974 that found most patients experienced symptoms within a relatively short period.39 In 1985, Shaw et al.36 reported that 86 patients (mean age, 74) monitored between 1968 and 1982 with chronic Mobitz type II second-degree heart block had a 5-year survival rate of 61%. The 5-year survival of those who underwent permanent pacemaker implantation was significantly better than those who did not. These observations form the basis for recommendations to institute permanent pacing in all patients with type II second-degree AV block, regardless of symptoms (class IIa indication with a narrow QRS; class I recommendation with a wide QRS).21 COMPLETE HEART BLOCK The natural history of spontaneously developing asymptomatic CHB in adult life predates pacemaker therapy.40-42 Currently, almost all adult patients with CHB eventually have symptoms and undergo pacemaker placement. Several studies in the 1960s emphasized the poor prognosis of patients with CHB. The 1-year survival rate of patients who experienced Stokes-Adams attacks caused by CHB and who did not receive pacing was only 50% to 75%, significantly less than that of a genderand age-matched control population.41 The “best” prognosis was in

Figure 14-12  Rhythm strip of high-grade atrioventricular (AV) block. The baseline rhythm is sinus tachycardia, in which the P wave occurs simultaneously with the T wave. After the fifth QRS complex, there is an abrupt, or paroxysmal, onset of AV block with four consecutive P waves that do not conduct to the ventricles. The sixth QRS complex probably represents a junctional escape rhythm followed by three conducted complexes and then a longer episode of high-grade AV block. Before both episodes of high-grade AV block, there is no obvious P-R interval prolongation, nor is there slowing of the sinus rate to suggest hypervagotonia as a cause of this patient’s block.

patients with an idiopathic or unknown cause of CHB. At least 33% of deaths were related to CHB and Stokes-Adams attacks. These differences in survival persisted even after 15 years of follow-up and appear to be related to the considerably higher incidence of sudden death.42 Some debate whether the presence of syncope is associated with a worse prognosis in patients with documented CHB. The prognosis for transient CHB was poor as well, with 36% 1-year mortality reported in at least one 1970s study.41 Whether this poor prognosis applies now to patients with transient CHB who have not received pacing is unknown. Edhag and Swahn41,42 reported in the 1960s and 1970s on the longterm prognosis of 248 patients with high-grade AV block, most of whom had complete heart block, with a mean 6.5 years of follow-up. The mean age at pacemaker implantation was 66, and the 1-year survival of patients who received pacemakers was 86%, versus 95% for an age- and gender-matched group of Swedish patients. After the first year, survival in the patients with pacemakers was similar to that in the general population. Edhag42 compared survival in different age groups, found no difference in survival between elderly patients with heart block who underwent permanent pacing and the age- and gendermatched general population. In contrast, younger patients with heart block had an increased mortality even after pacing than controls. This higher mortality likely is a reflection of the underlying structural heart disease responsible for high-grade AV block. Complete heart block can be described as acute or chronic depending on its onset. Acute AV block associated with myocardial ischemia is rare but may occur and result in transient AV block. High-grade AV block is strictly defined as 3 : 1, 4 : 1, or higher AV ratios in which AV synchrony is intermittently present. As in complete AV block, highgrade AV block may be localized anywhere in the conduction system (Fig. 14-12). In some patients, high-grade AV block may be present at multiple levels in the conduction system. Generically, “high-grade AV block” has been used to describe any form of AV block that suggests an increased risk for CHB or symptomatic bradycardia. This typically includes type II second-degree block, 2 : 1 AV block, strictly defined high-grade AV block, and CHB. The generic use of high-grade AV block is best avoided, because the multiple forms of AV block included have variable pathogeneses and prognoses that blur the clinical usefulness of the term. PAROXYSMAL AV BLOCK Paroxysmal AV block is defined as the sudden occurrence, during a period of 1 : 1 AV conduction, of a block of sequential atrial impulses resulting in a transient total interruption of AV conduction.43-45 It is thus the onset of a paroxysm of high-grade AV block associated with a period of ventricular asystole before conduction returns or a subsidiary pacemaker escapes. Paroxysmal AV block may occur in a variety of clinical conditions but has been described most often in association with vagal reactions, such as during vomiting, coughing, or swallowing, after urination, or with abdominal pain, carotid sinus massage,



coronary angiography, or head-up tilt-table testing. Patients with neurally mediated syncopal syndromes may have transient heart block, typically with associated sinus slowing. On the other hand, paroxysmal AV block also may occur in patients with severe, distal conduction disease. This may manifest as tachycardia-dependent AV block in the His-Purkinje system (as also called phase 3 or voltage-dependent block) during or after exertion; with the abrupt onset of bradycardia or after a pause (phase 4 block); and in type II second-degree AV block. Paroxysmal AV block in these patients (not related to vagal AV block) is a marker for His-Purkinje disease, with an unpredictable escape mechanism. Permanent pacemaker implantation in these patients (with the possible exception of block mediated by acute myocardial ischemia) is almost always indicated.45 One report described the clinical experience in 20 patients (mean age, 63 + 14 years) with paroxysmal AV block seen at a single institution over a 12-year period.46 Paroxysmal AV block in these patients was related to a vagal reaction, AV-blocking drugs, or distal conduction disease. The AV block in these patients lasted from 2.2 to 36 seconds. Fifteen patients experienced syncope, and one patient had bradycardiainduced polymorphic VT that required electrical cardioversion. About one-half the patients had structural heart disease and a wide QRS duration. Complete AV block can be classified as congenital or acquired. In patients with acquired complete AV block, the site of block is localized distal to the His bundle in about 70% to 90% of patients, to the His bundle in 15% to 20%, and within the AV node in 16% to 25%.7 In patients with congenital complete AV block, the escape rhythm is more often found in the proximal His bundle or AV node. BUNDLE BRANCH BLOCK Most patients with chronic BBB or bifascicular block have underlying structural heart disease (prevalence, 50%-80%).15-17,19 Historically, it was believed that progression from chronic bifascicular block to trifascicular block was common. Retrospective studies in patients with chronic bifascicular block suggested that the risk of progression to complete AV block was 5% to 10% per year. In the early 1980s, the results of several large prospective studies questioned assumptions about the incidence and clinical implications of the progression of conduction system disease in this patient population. Prospective studies of groups of symptom-free patients with bifascicular block who were found to have prolonged H-V intervals on EPS showed that such patients are at increased risk for CHB, but that the absolute risk remains very low, about 1% to 2% per year.15,17 McAnulty et al.16 found that the risk for development of CHB was 5% in 5 years. A prolonged H-V interval was associated with higher values for both total cardiovascular mortality and sudden death. Prolonged H-V interval is likely associated with more extensive structural heart disease. Furthermore, these studies demonstrated that in the absence of symptoms, routine His bundle recordings are of limited usefulness in patients with bifascicular block. Asymptomatic individuals with chronic BBB need no further evaluation than an occasional ECG. On the other hand, patients with syncope and bifascicular block represent a different clinical problem. If a thorough clinical evaluation, including a history, physical examination, and ECG, do not uncover a cause of syncope, EPS may be useful.19,20 Linzer et al.47 found that the presence of first-degree AV block or BBB increased the odds ratio of finding abnormalities suggesting risk of bradyarrhythmia (predominantly heart block) by three- to eightfold during EPS in patients with unexplained syncope (Table 14-1). Electrophysiologic studies may uncover other causes of syncope, such as sinus node dysfunction, rapid supraventricular tachycardias, and inducible monomorphic ventricular tachycardia. In some studies, monomorphic VT was inducible in at least 30% of patients with BBB and syncope.19,20 A minority of patients are found to have a markedly prolonged H-V interval, abnormal or fragmented His bundle electrogram, or block distal to the His bundle with atrial pacing, suggesting the need for implantation of a permanent pacemaker.

14  Pacing for Atrioventricular Conduction System Disease

TABLE

14-1 

331

Odds Ratio for Abnormality on Electrophysiologic Testing in Patients with Syncope

Clinical Variables Age Duration (months) Gender (male) Organic heart disease Sudden loss of consciousness Left ventricular ejection fraction Electrocardiogram Bundle branch block Sinus bradycardia First-degree heart block Premature ventricular contractions Holter Monitoring Sinus bradycardia Sinus pause Mobitz I atrioventricular block Premature ventricular contractions

Multivariable 1.01 1.00 1.76 1.53 1.93 0.99

95% Confidence Interval for Multivariable 0.99-1.03 0.98-1.02 0.79-3.93 0.71-3.33 0.89-4.16 0.93-1.06

2.97* 3.47* 7.89† 1.47

1.23-7.21 1.12-10.71 2.12-29.31 0.37-5.82

0.68 1.04 0.63 0.87

0.21-2.23 0.26-4.23 0.06-6.33 0.35-2.13

Modified from Linzer M, Prystowsky EN, Divine GW, et al: Predicting the outcomes of electrophysiologic studies of patients with unexplained syncope: preliminary validation of a derived model. J Gen Intern Med 6:113, 1991. *P <.05. †P <.001.

CONGENITAL AV BLOCK Congenital CHB traditionally was diagnosed in the first month after birth in a child in whom a slow heart rate was detected and certain infectious etiologies rarely seen today, such as diphtheria, rheumatic fever, and congenital syphilis, were excluded.48,49 Currently, with fetal echocardiography, many cases are diagnosed in utero and, if associated with structural heart disease, are associated with a high rate of fetal death. The incidence of congenital CHB is estimated to be 1 in 15,000 to 22,000 live births. More than one half of fetuses found to have congenital CHB have structural heart disease, including congenitally corrected transposition of the great arteries, and often have a poor prognosis in infancy. When congenital CHB is detected in utero in a child with a structurally normal heart, the condition is frequently associated with intrauterine exposure to maternal autoantibodies to Ro and La (i.e., neonatal lupus); this situation has a better prognosis than when congenital heart disease is present. The development of AV block in a child with a structurally normal heart is uncommon but should not be confused with congenital CHB. Childhood-onset heart block often is presumed to be caused by viral myocarditis. In patients with congenital CHB, the mean resting heart rate is between 40 and 60 bpm, but decreases with age. Although controversial in the past, the indications for permanent pacemaker implantation in young patients with congenital CHB have evolved on the basis of improved understanding of the natural history of the disease. Current guidelines indicate that permanent pacemaker implantation should be performed for congenital CHB patients with a wide QRS escape, complex ventricular ectopy, ventricular dysfunction, a ventricular rate less than 55 bpm, or congenital heart disease and a ventricular rate less than 70 bpm (class I indications).21 Permanent pacemaker implantation may also be considered for patients after the first year of life with an average heart rate less than 50 bpm, abrupt pauses in heartbeat that are two or three times the basic cycle length, or associated with exercise intolerance caused by chronotropic incompetence (class IIa indications). In asymptomatic children or adolescents with an acceptable rate, a narrow QRS complex, and normal ventricular function, a permanent pacemaker also may be considered (class IIb). Pacemaker implantation in asymptomatic patients with congenital CHB is associated with improved long-term survival and prevention of syncope. However, it must be recognized that ventricular dysfunction caused by right ventricular (RV) pacing–associated dyssynchrony may occur years or

332

SECTION 2  Clinical Concepts

decades after pacemaker implantation. A 2004 study demonstrated that long-term transvenous RV apical pacing was associated with deleterious LV remodeling and reduced exercise capacity after 10 ±3 years of follow-up in patients with congenital CHB.50 Therefore, these patients require periodic evaluation of ventricular function after pacemaker implantation. In addition, alternative ventricular pacing sites, including RV septum and left ventricle, have been proposed in patients with congenital CHB, who may require many decades of ventricular pacing but have not been definitively defined. Ventricular dysfunction in this setting may result from myocardial autoimmune disease in association with RV pacing–induced ventricular dyssynchrony. Interestingly, a recent study suggests that the natural history of patients with isolated congenital CHB who require pacing depends on their antibody status.51 Antinuclear antibody (ANA) status was a predictor for the development of heart failure and death. Long-term RV pacing was not associated with development of congestive heart failure, deterioration in ventricular function, or reduced survival in congenital AV block patients without ANAs. INHERITED CONDUCTION SYSTEM DISEASES Inherited causes of AV conduction disturbances have been increasingly recognized and better understood over the last decade. The genetics of conduction disease represents an exciting new development in our understanding of the AV conduction system.52,53 Although at present no clear role exists for genetic testing in most forms of conduction system disease, knowledge is still limited in this area. Animal models have provided insights by elucidating molecular genetic causes of AV block. Many of the identified cases of inherited AV conduction disease previously would have been classified as idiopathic or having an unknown cause. Although inheritance makes no obvious contribution to most human conduction disease, familial clustering in cases of “idiopathic” conduction system degeneration is consistent with a hereditary basis. Some cases with familiar clustering have an autosomal dominant pattern of inheritance and associated congenital heart malformations and cardiomyopathy. However, inherited conduction system disease is not a single entity caused by a single gene mutation. Inherited conduction system disease may be associated with congenital heart diseases, neuromuscular disorders, and cardiomyopathies. Inherited conduction diseases include developmental transcription factor mutations, cardiac ion channelopathies, and mutations in genes regulating energy metabolism, gap junctions, and structural proteins. Mutations in genes encoding cytoskeletal and nuclear membrane proteins are involved in the muscular dystrophies, including myotonic dystrophy, Emery-Dreifuss muscular dystrophy, and limb-girdle muscular dystrophy type 1B. All these neuromuscular disorders may be associated with cardiac conduction defects. Myotonic dystrophy is the most common form of muscular dystrophy. This autosomal dominant inherited disorder is caused by an expansion of cytosine-thymineguanine repeat on chromosome 19.54 High-degree AV block and BBB are the most common conduction system defects.55 A mouse knockout model of the myotonic dystrophy protein kinase displays first-, second-, and third-degree AV block.56 The mechanism of AV nodal pathology is thought to be caused by alterations in the activation kinetics or amplitude of the ICa,L current. Mutations in the gene encoding for the inner nuclear membrane protein lamin A/C (LMNA) cause Emery-Dreifuss muscular dystrophy with conduction system defects.57 Progressive conduction disease is present in virtually all cases and leads to the need for permanent pacing. LMNA also is implicated in a variety of other diseases including Hutchinson-Gilford syndrome, mandibuloacral dysplasia, CharcotMarie-Tooth disease–type atypical Werner’s syndrome, and the Dunnigan type familial partial lipodystrophy, most of which also are associated with cardiac conduction system defects.53 Lamin A/C is necessary for the structural integrity of the nucleus; in the presence of LMNA mutation, myocardial cells exposed to mechanical stress undergo cell damage. LMNA mutations also are associated with dilated cardiomyopathy, with AV conduction defects referred to as “laminopathy.”58

Otomo et al.59 described a large Japanese family with 21 of 224 members affected by this genetic defect, which manifests clinically as progressive AV block, dilated cardiomyopathy, heart failure, and sudden death. EPS in affected individuals demonstrated AV nodal dysfunction (marked prolongation of A-H interval) and normal HV and QRS durations. Histologic evaluation of postmortem heart specimens from affected members showed preferential degeneration, with replacement by fibrofatty tissue of the AV nodal region. Patients may die suddenly at a young age. Of note, there may be a gender difference in the severity of the cardiac phenotypes seen in lamin A/C disease. Males often have significant cardiac disease, with moderate or severe LV dysfunction developing in the first two to three decades of life, whereas females with the same mutations are more likely to have progressive conduction disease, with less severe LV dysfunction. Mutations in the cardiac-specific sodium channel gene (SCN5A) have been associated with progressive cardiac conduction system disease.60 Interestingly, SCN5A mutations can produce a variety of other phenotypes, including Brugada syndrome, congenital type 3 long QT syndrome (LQTS), idiopathic ventricular fibrillation, congenital sick sinus syndrome, atrial fibrillation, and dilated cardiomyopathy. An overlap syndrome involving a mutation in the cardiac sodium channel is associated with conduction system disease along with LQTS and Brugada syndrome.61,62 Homozygous mutations in the SCN5A gene can cause a highly lethal combination of LQTS and 2 : 1 AV block in infants.63 SCN5A mutations reduce cardiac sodium current, resulting in decreased action potential upstroke velocity and slowed impulse propagation, mainly in fast-conducting sodium channel–dependent conduction tissue. SCN5A mutation carriers often have long P waves and prolonged P-R and QRS intervals with normal A-H and prolonged H-V intervals, indicative of infra-Hisian delays.64 At present, at least 11 SCN5A mutations seem to be causally related to inherited cardiac conduction system disease.64-69 A novel SCN5A mutation involving a heterozygous single-nucleotide mutation resulted in an amino acid substitution (A1180V) in a three-generation Chinese family.69 The mutation causes a negative shift of voltage-dependent inactivation of the cardiac sodium channels with slower recovery, leading to a ratedependent sodium current reduction and a moderate increase in late sodium current. The A1180V mutation was associated with familial, progressive, adult-onset AV block in the third decade of life that preceded the subsequent development of dilated cardiomyopathy. Interestingly, early signs of the sodium channel defect in unaffected carriers of the pedigree were detected in the ECG manifested by QRS widening at high heart rates and QTc prolongation at rest. This suggests a possible opportunity for early diagnosis of the mutation before development of a clinically significant conduction system defect or cardiomyopathy, even in the absence of a genetic test. Defects in potassium channel genes may be a molecular basis for some inherited AV conduction disturbances in humans. The LQT7 syndrome, or Andersen-Tawil syndrome, is caused by mutations in the KCNJ2 encoding an inward rectifier potassium channel, Kir2.1, and is another cardiac ion channelopathy associated with conduction system disorders.70 Andersen-Tawil patients may present with conduction abnormalities, such as AV block, BBB, or intraventricular conduction delay. This syndrome is characterized by potassium-sensitive periodic paralysis, ventricular arrhythmias, and dysmorphic features. A molecular defect in KCNQ1, the pore-forming α-subunit of the IKS potassium channel, also may be a causative mutation responsible for AV conduction disease.71 An S140G mutation in KCNQ1 has been genetically linked in a Chinese family to atrial fibrillation and to a slow ventricular response in AF as a manifestation of AV conduction disease. Thirteen of 16 AF patients in the family with the KCNQ1 S140G mutation had a slow ventricular response in AF, with mean heart rate less than 60 bpm in the absence of AV nodal–blocking medications. In addition, a transgenic mouse model with myocardium-specific expression of the human KCNQ1 S140G mutation manifested frequent episodes of first-, second-, advanced-, or third-degree AV block. Several mutations in genes encoding proteins that regulate septation of the heart have been associated with conduction system disease. In



addition to conduction disease, this phenotype includes atrial or ventricular septal defects. The Nkx2.5 homeobox gene is critically involved in development of the cardiac conduction system.72-74 Loss-of-function mutations in the homeobox transcription factor Nkx2.5 cause a loss of DNA-binding activity of this gene. These mutations are associated with progressive AV node dysfunction and other diffuse conduction system abnormalities. Studies in Nkx2.5-deficient mice have shown that Nkx2.5 insufficiency perturbs the conduction system during development, resulting in hypoplasia of the AV node, His bundle, and Purkinje system. Mutations in the T-box transcription factor Tbx5, which similarly is an important early regulator of cardiac development, cause Holt-Oram syndrome.75 This syndrome is manifested by congenital heart disease (usually secundum-type atrial septal defects) associated with progressive AV block and upper-limb deformities.76 Less often, Holt-Oram patients have structurally normal hearts and clinically manifest with only AV block and subtle hand malformations. Another transcription factor associated with conduction system defects is HF-1b, an SP1related transcription factor preferentially expressed in the cardiac conduction system and ventricular myocytes.77 Mice deficient for HF-1b are prone to sudden death and have AV block. Downregulation of the gapjunction protein connexin 40 (Cx40) has been hypothesized as a unifying genetic mechanism responsible for the AV conduction defects in Nkx2.5, Tbx5, and HF-1b transcription factor mutations.53 Mutations in the PRKAG2 gene, which encodes for a regulatory subunit of adenosine monophosphate (AMP)–activated protein kinase involved in intracellular energy metabolism, are found in association with a familial form of the Wolff-Parkinson-White (WPW) syndrome.78 However, high-grade AV block is the dominant clinical rhythm disturbance associated with this genetic defect.79 PRKAG2 gene mutations are characterized by pseudohypertrophy of the left and right ventricles caused by glycogen deposition in cardiac muscle. Ventricular preexcitation is thought to be caused by anulus fibrosis disruption and glycogen deposition, distinct from the muscular-appearing bypass tracts observed in typical WPW syndrome. Index of suspicion for PRKAG2 disease should be raised when massive LV wall thickening (>30 mm) is present in association with high-grade AV block. A mouse model carrying a mutation responsible for the human disease has been generated.80 Many of the metabolic storage disorders that have a genetic basis, including Pompe disease, Anderson-Fabry disease, and Danon disease, are associated with cardiac involvement that includes prominent AV conduction disturbances.81 These diseases may also display abnormal electrical AV connections similar to the ventricular preexcitation seen in PRKAG2 disease. Mitochondrial disorders comprise a group of diverse genetic diseases, with cardiac conduction defects reported in 10% to 40% of the patients with these disorders.82 Kearns-Sayre syndrome (ophthalmoplegia plus), which involves large mitochondrial DNA deletions, consists of the triad of complete AV block, chronic progressive external ophthalmoplegia, and pigmentary degeneration of the retina.83 It can present with AV block and dilated cardiomyopathy, along with muscle weakness, central nervous system dysfunction, and endocrinopathies. The conduction defects typically involve the distal His bundle, bundle branches, and infranodal conduction. The accelerated and unpredictable rate of progression to complete AV block, together with an associated mortality of up to 20%, should lead to routine evaluation of patients with Kearns-Sayre syndrome for AV conduction disturbances and electrocardiographic screening of family members. Current guidelines advocate pacemaker implantation in patients with Kearns-Sayre syndrome with ECG changes indicative of conduction defects, with or without symptoms, because of the unpredictable progression of AV conduction disease in this syndrome (see Tables 14-3 and 14-4). ACQUIRED CAUSES OF AV BLOCK Acquired AV block may be secondary to a number of causes of generalized myocardial scarring (Table 14-2). These causes include atherosclerosis, dilated cardiomyopathy, hypertension, infiltrative

14  Pacing for Atrioventricular Conduction System Disease

TABLE

14-2 

333

Causes of Acquired Atrioventricular (AV) Block

Category Idiopathic fibrodegenerative diseases Ischemic heart diseases Nonischemic cardiomyopathies Cardiac surgery

Ablation

Trauma Infections

Neuromuscular diseases

Infiltrative diseases

Neoplastic diseases Connective tissue diseases

Drugs

Miscellaneous causes

Specific Causes Lev’s disease Lenègre’s disease Myocardial infarction Ischemic cardiomyopathy Myocarditis Idiopathic dilated cardiomyopathies Hypertensive heart disease Coronary artery bypass Aortic, mitral, or tricuspid valve replacement/repair Ventricular septal defect repair Congenital heart disease repair Septal myomectomy His bundle ablation Ablation of septal accessory connections Ablation of slow or fast AV nodal pathway for AV nodal reentrant tachycardia Catheter-based septal ablation for hypertrophic cardiomyopathy Chest trauma Endocarditis Chagas’ disease Lyme disease Acute rheumatic fever Other: bacterial, viral, rickettsial, fungal Myotonic dystrophy Fascioscapulohumeral dystrophy Other muscular dystrophies Kearns-Sayre syndrome Friedreich’s ataxia Amyloidosis Sarcoidosis Hemochromatosis Carcinoid Postradiation therapy Primary and metastatic tumors Rheumatoid arthritis Systemic lupus erythematosus Systemic scleroderma Ankylosing spondylitis Others β-Adrenergic blockers Calcium channel antagonists Digoxin and other cardiac glycosides (e.g., oleandrin) Amiodarone Procainamide, flecainide Adenosine Chemotherapeutic agents (arsenic trioxide) Antimalarials (chloroquine) Tricyclic antidepressants Phenothiazines Donepezil Exercise Vagal mediation (hypervagotonia, neurocardiac, vasovagal) Temporal lobe epilepsy Hyperkalemia

cardiomyopathies, inflammatory disorders, and infectious diseases. In most cases the specific etiology is clinically unknown and, with few exceptions (e.g., Lyme disease, endocarditis, sarcoidosis), is relatively unimportant from a therapeutic point of view. The most common cause of chronic acquired AV block is related to aging of the cardiac cytoskeleton. An entity known as idiopathic bilateral bundle branch fibrosis, or Lev’s disease, is characterized by slowly progressive replacement of specialized conduction tissue by fibrosis, resulting in progressive fascicular block and BBB. Lev84 proposed that damage to the proximal LBB and adjacent main bundle or main bundle alone is the result of an aging process exaggerated by hypertension and arteriosclerosis of the blood vessels supplying the conduction system. Another variant of idiopathic conduction system disorder is Lenègre’s disease, which occurs in younger patients and is characterized by loss of

334

SECTION 2  Clinical Concepts

conduction tissue, predominantly in the peripheral parts of the bundle branch.85 As noted, some cases previously classified as “idiopathic” conduction disease, especially when there is familial clustering, may have a genetic cause for the conduction disease. Patients with sick sinus syndrome are known to be at risk for concomitant symptomatic heart block.86 The block may be caused by progressive fibrodegenerative disease extending from the sinus node region to the AV conduction system. The relative frequency of this association varies between studies. Rosenqvist and Obel87 pooled the data from 28 published studies and reported a mean incidence for development of second- or third-degree AV block of 0.6% per year (range, 0-4.5%/yr) in patients in whom permanent atrial pacemakers have been implanted for symptomatic sinus node dysfunction. The total prevalence of second- or third-degree AV block was 2.1% (range, 0-11%). In a retrospective review of 1395 patients with sick sinus syndrome monitored for a mean of 34 months, Sutton and Kenny88 estimated that the annual incidence for development of conduction system diseases was 3%; such conduction diseases included significant first-degree AV block, BBB, HV prolongation, and a low Wenckebach heart rate. Thus, AV conduction system disease occurs relatively frequently in patients with sinus node dysfunction. Similarly, sinus node dysfunction, particularly chronotropic incompetence, may occur frequently in patients with acquired CHB. Complete AV block may occur after cardiac surgical or interventional catheter-based procedures. CHB occurs more often (3%-6% incidence) after replacement of aortic, mitral, or tricuspid valves, given the proximity of their anuli to the AV junction, than after isolated coronary artery bypass graft (CABG) surgery, in which the incidence is less than 1% to 2%.89,90 CHB is often seen after surgical procedures to repair ventricular septal defects, tetralogy of Fallot, AV canal defects, or subvalvular aortic stenosis.91,92 Heart block is also a potential complication of septal myomectomy and catheter-based septal ablation to relieve LV outflow tract obstruction in hypertrophic cardiomyopathy.93,94 The incidence of heart block requiring permanent pacing after alcohol septal ablation varies from 10% to 33%. Baerman et al.95 investigated the time course of conduction defects after bypass surgery. Surgical technique consisted of cold, hyperkalemic cardioplegia, and conduction defects resolved partially or completely in 50% of patients. Patients with conduction defects generally had longer cardiopulmonary bypass times, longer aortic cross-clamp times, and more vessels requiring bypass. In three of the four patients with CHB, the heart block eventually resolved after discharge and implantation of a permanent pacemaker. Reasons for conduction abnormalities after cardiac surgery include ischemic injury to the conduction system, direct surgical manipulation or trauma to conduction tissue, traumatic disruption of the distal conduction system, edema, dissecting hematomas, and alterations in conduction caused by cardioplegia. Surgery for correction of valvular heart disease often leads to conduction defects. After discontinuation of cardiopulmonary bypass, a variety of cardiac rhythm disturbances may be seen, including sinus arrest, junctional rhythm, BBB, AV block, and sinus bradycardia. Many of these rhythm disturbances are transient, resolving within 5 to 7 days. Transient BBB is quite common, occurring in 4% to 35% of patients and generally resolving within 12 to 24 hours.89 In one study, newly acquired, persistent BBB developed in 15.6% of patients after aortic valve replacement and was associated with a higher adverse event rate.96 The investigators recommended that prophylactic implantation of a pacemaker be considered soon after surgery in patients who demonstrate persistent BBB. Conduction disturbances are particularly common both in patients with aortic valve disease and after aortic valve replacement, with 5% to 30% of patients experiencing some conduction abnormality after valve replacement. Most of these abnormalities are transient; however, chronic CHB may occur. Postoperative AV block that is not expected to resolve after cardiac surgery is a class I indication for permanent pacing. The incidence of conduction disorders requiring permanent pacing in patients after aortic valve replacement is 3% to 6%.97

Intraoperative heart block does not predict the need for permanent pacing.98 One study found that risk factors for irreversible AV block requiring permanent pacemaker implantation after aortic valve replacement were previous aortic regurgitation, myocardial infarction, pulmonary hypertension, and postoperative electrolyte imbalance.97 In another study, Koplan et al.99 developed and validated a preoperative risk score to predict the need for permanent pacing after cardiac valve surgery, using a large database of surgical patients at a single institution (1992–2002). Preoperative predictors of the need for permanent pacing after cardiac valve surgery were age over 70, previous valve surgery, multivalve surgery (especially tricuspid), preoperative BBB (especially RBBB), and first-degree AV block. The incidence of permanent pacemaker implantation ranged from 25% in high-risk patients to 3.6% in low-risk patients, with risk based on preoperative variables. Glikson et al.100 showed that postoperative complete AV block was the most important predictor of subsequent pacemaker dependency. They recommended earlier decisions on the timing of permanent pacemaker implantation, by the sixth postoperative day in patients with a wide QRS escape rhythm, and by the ninth day in patients with a narrow QRS rhythm. In most institutions, permanent pacing would be instituted earlier, probably by the fourth to sixth postoperative day. Persistent heart block occurs infrequently (0.5%-2% of patients) after radiofrequency catheter ablation (RFA) of septal accessory pathways or the slow AV nodal pathway in patients with AV nodal reentrant tachycardia.101 Transient, intraprocedural AV block during ablation performed close to the AV septum does not necessarily indicate that permanent pacemaker implantation is required. Ablation of the fast pathway in AV nodal reentrant tachycardia in the anterior septum is associated with a higher risk of transient AV block than RFA of the slow pathway in the posterior septum. In more than 500 patients, transient second- or third-degree AV block was seen in 20% during fast-pathway ablation, in 2.3% during slow-pathway ablation, and in 42% during combined fast-and-slow pathway attempted ablation.102 Within 7 days after RFA, however, persistent AV block was seen in 3.4%, 0.2%, and 0% of patients in these groups, respectively. Late occurrence of unexpected heart block after RFA of AV nodal reentry (using a posterior approach) or posteroseptal accessory pathways is rare (<0.5% incidence) and often resolves after a few weeks.103 In patients who experience this rare RFA complication, prolonged clinical observation and monitoring rather than immediate pacemaker implantation is a reasonable approach. The risk for development of heart block may decrease with the use of cryoablation for the treatment of AV nodal reentry and accessory pathways near the AV node. A higher incidence of heart block (1%-10% of patients) was observed when patients underwent surgical ablation for the WPW syndrome, especially when the accessory pathway was in an anteroseptal, intermediate septal, or posteroseptal location, or after surgical modification of the AV node for treatment of AV nodal reentrant tachycardia.104 Radiofrequency catheter ablation is used to create permanent complete AV block in patients with paroxysmal and chronic atrial tachyarrhythmias (most frequently AF). This treatment option is reserved for the small group of patients in whom AV node–blocking drugs cannot control the heart rate or who are intolerant, unwilling, or unable to take drugs to maintain sinus rhythm or control the ventricular response during AF. In most studies, RFA of the AV junction can be accomplished in more than 90% of patients with a right-sided approach through placement of an ablation catheter across the tricuspid valve and recording of a His bundle potential or, less frequently, by placement of the catheter in the left ventricle on the septum underneath the noncoronary cusp of the aortic valve to record a His bundle potential. Radiofrequency ablation of the AV junction should be performed only in patients with a previously implanted permanent pacemaker or at permanent pacemaker implantation (class I indication for pacing). There are no studies to assess outcome without permanent pacing after catheter RFA of the AV junction. Radiofrequency current ablation of the AV junction usually results in a junctional escape rhythm of 40 to 50 bpm. In one study, about 65% of patients had an escape rhythm



with an average rate of 39 bpm, with a new RBBB in 24%, a new LBBB in 6%, and an idioventricular rhythm in 19%.105 Several studies have shown AV junction ablation with pacemaker therapy to be highly effective at controlling symptoms and to result in improved quality of life in patients with paroxysmal and chronic AF. In patients with depressed LV function, significant improvements in ventricular function are measured after ablation and pacing in 20% to 40% of patients in some series.105,106 Currently, many patients with depressed LV function who undergo AV junction ablation receive devices with biventricular pacing capabilities. Atrioventricular nodal modification is a catheter ablation procedure designed to impair but not fully destroy AV nodal conduction in patients with rapid ventricular rates during AF.107 Radiofrequency energy is delivered in and around the slow AV nodal pathway in the posterior septum in an attempt to leave conduction intact over the fast AV nodal pathway. At present, however, AV nodal modification has fallen out of favor and is performed infrequently in patients with AF. In some patients, AV nodal modification results in a slower ventricular response during AF and possibly avoids permanent pacemaker placement, but in other patients, there is an unpredictable decrease in the ventricular rate. Patients who undergo AV nodal modification may remain symptomatic because of recurrent rapid AV conduction or the irregularity of the ventricular response during AF and may subsequently require complete AV nodal ablation. A bimodal RR histogram during AF has been suggested as indicative of dual–AV nodal physiology and may be a predictor of successful outcome after AV nodal modification.108 However, the risk of sudden death or syncope from unexpected, late CHB is a significant concern with this procedure. The rate of inadvertent AV block during the procedure may be as high as 25%.108 The incidence of long-term AV block is quite variable as well as controversial, with estimates for late development of CHB ranging from 0% to more than 20% in different series.109 In patients with blunt or penetrating chest trauma, a variety of conduction disturbances, including AV block, have been reported, but appear to be rare complications of this type of injury.110,111 The reported conduction abnormalities after chest trauma consist of BBB and varying degrees of AV block, including CHB. The most common abnormality is RBBB, followed by first-degree AV block, and the least common is CHB. Most AV conduction defects after traumatic chest injury are transient and resolve early. A few cases of persistent heart block requiring permanent pacemaker implantation have been described. Delayed development of complete AV block has been seen, occurring 15 to 30 days after injury, suggesting that patients with blunt chest trauma should be monitored for late complications. The severity of injury does not always correlate with the development of posttraumatic complications, including conduction disorders. The mechanism of conduction defects in this setting may be related to ischemia and infarction of the conduction system. Complete heart block has been described in various infectious diseases, including bacterial, viral, fungal, protozoan, and rickettsial infections. Heart block may occur with endocarditis and may be either transient or permanent. In most infectious diseases, heart block is transient and resolves with treatment of the underlying infection. In some cases, transient heart block may recur, and permanent pacing is required. This is particularly true in patients with entities such as endocarditis, in which a valve ring abscess may erode into the con­ duction system, and in patients with infections such as Chagas’ disease.112-115 AV block occurs in up to 25% of patients with endocarditis complicated by perivalvular abscess, with the aortic valve involved much more than the mitral valve. Lyme disease is the most common cause of reversible AV block in younger patients. This systemic illness, first described in 1975, was characterized later as an infection caused by a spirochete, Borrelia burgdorferi, which is transmitted to humans by a tick bite. This illness is often characterized by a rash, erythema chronicum migrans, which is followed by cardiac and neurologic abnormalities and then, in some cases, by arthritis.116 Cardiac involvement may occur in 8% to 10% of Lyme disease patients, is generally transient, and may consist of a

14  Pacing for Atrioventricular Conduction System Disease

335

myocarditis or a myopericarditis.117 Varying degrees of AV block are a common manifestation of carditis, occurring in about 75% of patients. More than 50% of Lyme patients with AV block have symptomatic high-grade or complete AV block that requires temporary pacing. Most often, the site of block is localized to the AV node, although occasional cases have been reported in which the site of block is intra-Hisian or infra-Hisian.118,119 Continuous cardiac monitoring is recommended in all patients with second-degree AV block and a prolonged P-R interval of more than 0.30 second, because of the risk for development of complete AV block. CHB generally resolves within 1 to 2 weeks. Recurrent AV block has not been reported. Rarely, some patients may have symptomatic AV block as the sole manifestation of Lyme disease.120 Permanent pacing is rarely required except for persistent CHB, which is uncommon. Two important axioms worth repeating are that (1) heart block associated with infectious disease usually resolves with appropriate and prompt antibiotic treatment, and (2) conduction disease is rarely the only manifesting feature of an infectious illness. Heart block may occur rarely after radiation therapy or chemotherapy. Heart block may occur after radiation therapy if radiation is directed at the mediastinum, as for Hodgkin’s and some non-Hodgkin’s lymphomas.121 Radiation therapy may induce fibrosis of the cardiac conduction system, as well as the atrial and ventricular myocardium, and may accelerate coronary atherosclerosis. Rarely, tumors, including mesothelioma of the AV node, cardiac lymphoma, and metastatic disease to the heart from breast, lung, or skin cancer, may involve the conduction system.122 AV block has been reported as a rare complication of chemotherapeutic agents (e.g., arsenic trioxide treatment for leukemia). In general, however, it is unusual for toxicity to antineoplastic drugs, such as doxorubicin, to result in damage to the cardiac conduction system. Certain neuromuscular diseases may give rise to progressive and insidiously developing cardiac conduction system disease. The disorders include Duchenne’s muscular dystrophy, fascioscapulohumeral muscular dystrophy, X-linked muscular dystrophy, myasthenia gravis, myotonic dystrophy, and Friedreich’s ataxia.123 Abnormalities of conduction manifest as infranodal conduction disturbances resulting in fascicular block or CHB. This has been noted particularly in KearnsSayre syndrome (progressive external ophthalmoplegia with pigmentary retinopathy), Guillain-Barré syndrome, myotonic muscular dystrophy, slowly progressive X-linked Becker’s muscular dystrophy, and fascioscapulohumeral muscular dystrophy. Myotonic muscular dystrophy and Kearns-Sayre syndrome are both associated with a high incidence of conduction system disease that frequently is rapidly progressive and cannot be predicted by the ECG or isolated His bundle recordings. His-Purkinje disease can culminate in fatal Stokes-Adams attacks unless anticipated by insertion of a pacemaker. In a study of 49 patients with myotonic dystrophy (46 ±9 years old) and an H-V interval of 70 msec or longer, high-grade paroxysmal AV block was recorded after pacemaker implantation in 47% of patients who had had no known bradycardia on entry into the study.124 The researchers concluded that prophylactic implantation of permanent pacing should be considered in patients with myotonic dystrophy and prolonged H-V interval (≥70 msec) even without bradycardia-related symptoms. Waiting for the development of complete AV block in patients with neuromuscular diseases may expose them to significant risk of sudden death or syncope related to AV block. Permanent pacing should be considered early in the course of neuromuscular disease and should be offered to the asymptomatic patient once any conduction abnormality is noted. A recent study found that “severe” ECG abnormalities (rhythm other than sinus, QRS >120 msec, P-R interval >240 msec, or secondor third-degree AV block) and clinical diagnosis of atrial tachyarrhythmia are independent predictors, with moderate sensitivity, of sudden death in patients with myotonic dystrophy type 1.125 Heart block may occur with amyloid and other infiltrative diseases, including hemochromatosis, porphyria, oxalosis, Refsum’s disease, carcinoid, Hand-Schüller-Christian disease, and sarcoidosis.126 Cardiac sarcoidosis should be considered in the differential diagnosis in a young patient (20-40 years old) presenting with CHB.127 Cardiac

336

SECTION 2  Clinical Concepts

manifestations of sarcoidosis are present in at least 25% of patients with systemic sarcoidosis and can include CHB (~30%), ventricular tachyarrhythmias, intracardiac masses, ventricular aneurysms, and dilated cardiomyopathy.128-130 However, only 40% to 50% of patients with cardiac sarcoidosis at autopsy had clinical evidence of myocardial involvement during their lifetime.130 Newer modalities such as magnetic resonance imaging (MRI) may be helpful in the diagnosis of cardiac sarcoid, which can be difficult because of the lack of definitive criteria and the nonspecific clinical manifestations.131 Cardiac sarcoidosis is associated with noncaseating granulomas that tend to involve the conduction system with varying degrees of AV conduction block. The majority of patients with sarcoid heart disease have extracardiac involvement that manifests either clinically or on biopsy. Other organ systems involved in sarcoid include the lymph nodes, skin, eyes, and the nervous, musculoskeletal, renal, and endocrine systems. Isolated cardiac involvement in sarcoidosis is less common and usually precedes future systemic sarcoidosis. Although there are no large randomized trials or prospective registries of patients with cardiac sarcoidosis, the available literature indicates that cardiac sarcoidosis with heart block, ventricular arrhythmias, or LV dysfunction is associated with a poor prognosis and an increased risk of sudden death.132 Myocardial involvement in sarcoid accounts for up to 13% to 25% of deaths from sarcoidosis. In Japan, sarcoid heart disease is more common, accounting for up to 85% of mortality from sarcoidosis.127 AV block may resolve after long-term treatment with corticosteroids, alone or in combination with other immunosuppressive therapy.133 However, heart block in patients with sarcoid heart disease generally warrants a permanent pacemaker, even if AV conduction block reverses transiently, because of possible disease progression. An ICD should be considered in patients with sarcoidosis undergoing device implantation for AV block, because of the risk of ventricular tachyarrhythmias and sudden death.21 However, definitive clinical data are not available to stratify risk of sudden cardiac death among patients with cardiac sarcoidosis. Thus, decisions regarding ICD implantation must be individualized. Connective tissue disorders giving rise to conduction system disease include periarteritis nodosa, rheumatoid arthritis, polymyositis, mixed connective tissue disorders, Reiter’s syndrome, ulcerative colitis, scleroderma, Takayasu’s arteritis, systemic lupus erythematosus, and ankylosing spondylitis.134,135 In one study of 50 consecutive patients with scleroderma, EPS demonstrated conduction abnormalities in up to 50% of patients, suggesting a much higher level of cardiac involvement in patients than readily apparent clinically. However, CHB is uncommon.136 Most patients with AV conduction disorders have other clinical manifestations of the connective tissue disease. AV block has been reported as a rare complication of antimalarial therapy used to treat systemic autoimmune diseases (e.g., chloroquine for rheumatoid arthritis or systemic lupus erythematosus). Exercise-induced transient AV block is a relatively rare condition that is usually caused by a block in the His-Purkinje system137,138 (Fig. 14-13). The incidence of exercise-induced AV block during treadmill exercise testing is between 0.1% and 0.5%.139 Donzeau et al.140 reported 14 symptomatic patients with exercise-induced AV block, in nine of whom block was localized to an infranodal site. Other studies have confirmed that exercise-induced AV block is primarily infraHisian.141,142 In these studies, about 25% to 75% of patients had underlying BBB. Several reports of patients with cardiac asystole after exertion have demonstrated postexercise sinus arrest with ventricular asystole.143 Some researchers proposed that transient ischemia of the conduction system is a mechanism of exercise-induced AV block in patients with severe RCA lesions and chronic infranodal conduction disturbances.139 A case of pseudo–AV block during exercise was caused by His bundle parasystole.144 Permanent pacing is recommended in patients with exercise-induced AV block, even in the asymptomatic state, because of the high incidence of symptomatic AV block. Drug-induced bradycardia is a common and important clinical problem.145 Many common drugs, including β-adrenergic blockers, calcium channel antagonists, digoxin, class I and III antiarrhythmic

Lead II at rest

Lead II after 2 min. of exercise

Figure 14-13  Tracings from patient with syncope and frequent 2 : 1 atrioventricular (AV) block with incomplete right bundle branch block. Upper tracing, Lead II rhythm strip; sinus rate of 97 bpm. Periods of 3 : 2 AV conduction were not available to determine whether the patient’s 2 : 1 AV conduction was caused by type I or type II AV block. Lower tracing, Rhythm strip obtained 2 minutes into treadmill testing shows 3 : 1 AV conduction with an increase in heart rate to 142 bpm. The development of high-grade AV block despite exercise-induced increases in sympathetic tone and decrease in parasympathetic tone suggests infra- or intra-Hisian block and the need for permanent pacing.

drugs, tricyclic antidepressants, phenothiazines, lithium, and donepezil (a cholinesterase inhibitor used to treat Alzheimer’s disease), can cause AV conduction disturbances. In patients presenting with drug-induced AV block, drug therapy can be stopped entirely, reduced in dosage, or continued if there is no acceptable alternative. In the last case, if druginduced AV block results in symptomatic bradycardia, permanent pacemaker implantation is recommended (class I indication). On the other hand, if the AV block is caused by drug toxicity, is expected to resolve, and is unlikely to recur, pacemaker implantation is generally considered unnecessary, according to current guidelines. However, if AV block occurs in the setting of drug use or toxicity, and the block is expected to recur even after the drug is withdrawn, pacemaker implantation may be considered (class IIb indication).21 Supporting this guideline recommendation, Zeltser et al.146 suggest that in the majority of patients presenting with presumed druginduced AV block, discontinuation of the offending medications does not obviate the need for pacemaker implantation. In this study, AV block persisted after drug discontinuation in most patients. Furthermore, even if AV block resolved when drugs were discontinued, patients remained at risk of recurrent AV block in the absence of offending drugs. Among a consecutive series of 169 mostly elderly patients with structural heart disease presenting with second- or third-degree AV block not related to AMI, vasovagal syncope, digitalis toxicity, or RFA, 92 patients (54%) had drug-induced AV block while receiving β-blockers and/or verapamil or diltiazem. Drug therapy was discontinued in 79 patients; in 32 (41%), AV block resolved within 48 hours. However, in 18 (56%) of the 32 patients with drug-induced AV block who experienced spontaneous resolution of AV block after drug discontinuation, AV block recurred. Ten of these patients had syncope during the subsequent 3 weeks of follow-up without drug therapy. On the basis of this experience, the researchers estimated that the medications caused only 8% of all cases of AV block and only 15% of occurrences of AV block in patients receiving medications. Vagally mediated AV block infrequently requires a permanent pacemaker, especially in the absence of recurrent syncope or profound asystole. AV block may occur in the setting of increased vagal tone in response to various stimuli, such as carotid sinus hypersensitivity, coughing, swallowing, and visceral distention.147-149 Because vagally mediated AV block often occurs in young, otherwise healthy patients, especially during sleep, it must be differentiated from type II seconddegree AV block, because the latter patients require implantation of a permanent pacemaker.150 In most cases, vagally induced AV block occurs at the level of the AV node and is associated with a narrow QRS complex.151 As a general rule, vagally mediated AV nodal block shows obvious heart rate slowing, even if only slight, before the onset of block, because of the concomitant effect of increased vagal tone on the sinus node (Fig. 14-14). Rarely, vagal stimulation may precipitate phase IV or bradycardia-mediated block in the His-Purkinje system.43



14  Pacing for Atrioventricular Conduction System Disease

830

890

840

910

1040

1000

970

920

920

890

337

890

Figure 14-14  Rhythm strip from a 44-year-old man with asymptomatic paroxysmal high-grade atrioventricular (AV) block, but without structural heart disease. Tracing shows sudden, transient total interruption of AV conduction with ventricular asystole. The AV block is preceded by 1 : 1 AV conduction with a narrow QRS complex and is associated with concomitant prolongation in the sinus cycle length (indicated by the numbers in msec). These findings are consistent with vagally induced AV block at the level of the AV node and usually do not require permanent pacing.

Indications for Permanent Pacing in Chronic Atrioventricular Block Historically, chronic or acquired AV block with syncope was the first indication for cardiac pacing. Intermittent or chronic high-grade AV block still accounts for a large but varying number of permanent pacemaker implantations, depending on the series. The proportion of pacing related to AV block without atrial fibrillation, according to world and U.S. surveys, ranged from 21% to 54% of pacemakers in 1997.152,153 Despite published guidelines, permanent pacemaker implantation continues to be underused in patients with CHB. From 1996 to 2001, there were 165,541 patients admitted to U.S. hospitals with a primary diagnosis of complete heart block. Only 74% to 83% of patients with a primary diagnosis of CHB received permanent pacemakers before hospital discharge.154 Furthermore, African-Americans and ethnic minorities were significantly less likely (68% and 60% implantation rates, respectively) than white patients (80% implantation rate) to receive pacemakers for CHB. In 1984 a subcommittee of the ACC/AHA Task Force on Assessment of Cardiovascular Procedures formulated a set of guidelines for the indications for permanent pacing.155 These guidelines were revised in 1991, 1998, 2002, and 2008 based on major new studies that have advanced knowledge in this area, as well as new developments in the technology of devices to treat bradyarrhythmias.21,156,157 Tables 14-3 and 14-4 list permanent pacing indications for acquired AV block and chronic bifascicular and trifascicular block in the 2008 ACC/AHA/ NASPE revised guidelines.21

TABLE

14-3  Class I

Class IIa

Class IIb

Class III

Indications for pacemaker implantation are categorized into three classes as follows: Class I: Conditions for which there is evidence or general agreement that pacemaker implantation is useful and effective, and that the benefits greatly exceed the risks. There is general agreement among physicians that a permanent pacemaker should be implanted. This implies that the condition is chronic or recurrent but not caused by drug toxicity, acute myocardial ischemia or infarction, or electrolyte imbalance. Class II: Conditions for which cardiac pacemakers are generally found acceptable or necessary, but there is some divergence of opinion. In a class IIa indication, the weight of evidence and opinion is in favor of the usefulness and efficacy of implantation, and therefore it is reasonable to perform the implantation. In a class IIb indication, the usefulness or efficacy is less well established by evidence and opinion, but pacemaker implantation may be considered. Class III: Conditions for which adequate benefit from permanent pacemakers is considered insupportable by current evidence and for which there is general agreement that a pacemaker is not indicated and may be harmful. Recommendations supported by studies based on data derived from multiple randomized controlled clinical trials (RCTs) with large numbers of patients are ranked at level of evidence A; those based on a limited number of trials involving smaller numbers of patients or from well-designed data analyses of nonrandomized studies or observational data registries are ranked at level of evidence B; and those based on expert consensus and years of clinical experience are ranked at level of evidence C.

Indications for Permanent Pacing for Acquired Atrioventricular (AV) Block in Adults Third-degree and advanced second-degree AV blocks at any anatomic level, associated with any one of the following conditions: Bradycardia with symptoms (including heart failure) or ventricular arrhythmias presumed to result from AV block (level of evidence: C) Arrhythmias and other medical conditions that require drug therapy that results in symptomatic bradycardia (level of evidence: C) Documented periods of asystole ≥3 seconds or any escape rate <40 bpm with an escape rhythm that is below the AV node in awake, symptom-free patients in sinus rhythm (levels of evidence: C) Documented periods of atrial fibrillation and bradycardia with 1 or more pauses of at least 5 seconds or longer in awake, symptom-free patients (levels of evidence: C) After catheter ablation of the AV junction (levels of evidence: C) Postoperative AV block that is not expected to resolve after cardiac surgery (level of evidence: C) Neuromuscular diseases with AV block, such as myotonic muscular dystrophy, Kearns-Sayre syndrome, Erb’s (limb-girdle) dystrophy, and peroneal muscular atrophy with or without symptoms (level of evidence: B) Second-degree AV block with associated symptomatic bradycardia regardless of the type or site of block (level of evidence: B) Asymptomatic persistent third-degree AV block at any anatomic site with average awake ventricular rates of 40 bpm or faster if cardiomegaly or left ventricular dysfunction is present or if the site of block is below the AV node (level of evidence: B) Second- or third-degree AV block during exercise in the absence of myocardial ischemia (level of evidence: C) Persistent third-degree AV block with an escape rate >40 bpm in asymptomatic adult patients without cardiomegaly (level of evidence: C) Asymptomatic second-degree AV block at intra- or infra-His levels found at electrophysiologic study (level of evidence: B) First- or second-degree AV block with symptoms similar to those of pacemaker syndrome or hemodynamic compromise (level of evidence: B) Asymptomatic type II second-degree AV block with narrow QRS; when type II second-degree AV block occurs with a wide QRS, including isolated right bundle branch block, pacing becomes a class I recommendation (level of evidence: B) Neuromuscular diseases, such as myotonic muscular dystrophy, Erb’s (limb-girdle) dystrophy, and peroneal muscular atrophy, with any degree of AV block (including first-degree AV block), with or without symptoms, because there may be unpredictable progression of AV conduction disease (level of evidence: B) AV block in the setting of drug use or drug toxicity when block is expected to recur even after drug is withdrawn (level of evidence: B) Asymptomatic first-degree AV block (level of evidence: B) Asymptomatic type I second-degree AV block at supra-Hisian (AV node) level, or that which is not known to be intra- or infra-Hisian (level of evidence: C) AV block expected to resolve and unlikely to recur (e.g., drug toxicity, Lyme disease, or transient increases in vagal tone or during hypoxia in sleep apnea syndrome in the absence of symptoms) (level of evidence: B)

338

TABLE

14-4  Class I

Class IIa

Class IIb

Class III

SECTION 2  Clinical Concepts

Indications for Permanent Pacing in Chronic Bifascicular Block Advanced second-degree AV block or intermittent third-degree AV block (level of evidence: B) Type II second-degree AV block (level of evidence: B) Alternating bundle branch block (level of evidence: C) Syncope not demonstrated to be caused by AV block when other likely causes have been excluded, specifically ventricular tachycardia (level of evidence: B) Incidental finding at EPS of extremely prolonged H-V interval (≥100 msec) in a symptom-free patient (level of evidence: B) Incidental finding at EPS of pacing-induced infra-Hisian block that is not physiologic (level of evidence: B) Neuromuscular diseases, such as myotonic muscular dystrophy, Erb’s (limb-girdle) dystrophy, and peroneal muscular atrophy with bifascicular block or any fascicular block, with or without symptoms (level of evidence: C) Fascicular block without AV block or symptoms (level of evidence: B). Fascicular block with first-degree AV block without symptoms (level of evidence: B)

AV, Atrioventricular; EPS, electrophysiologic study.

Acute Myocardial Infarction Prior to the era of reperfusion therapy for AMI, AV block occurred in 12% to 25% of all patients with AMI; first-degree AV block occurred in 2% to 12%, second-degree block in 3% to 10%, and third-degree block in 3% to 7%.158-160 It is unclear whether thrombolytic therapy has altered the overall incidence of AV conduction defects in patients with AMI.161-163 In one study, use of a thrombolytic agent was associated with a higher rate of occurrence of complete AV block (odds ratio = 1.44) but a tendency toward a lower rate of occurrence of BBB (odds ratio = 0.68).162 Another study suggested that thrombolytic therapy was associated with a tendency toward a lower rate of third-degree AV block in anterior AMI but a higher rate in inferior AMI.163 Among 6657 patients admitted with AMI between 1990 and 1992 and included in the Trandolapril Cardiac Evaluation (TRACE) randomized trial in Denmark, 340 (5.1%) experienced third-degree AV block during their hospitalization.163 The incidence of third-degree AV block was higher among patients with inferior AMI (193 of 2061; 9.4%) than among those with anterior AMI (44 of 1747; 2.5%).163 Likewise, in pooled data from 75,993 patients with ST-segment elevation AMI treated with thrombolytic therapy, 5251 patients (6.9%) had second- or thirddegree AV block. AV block occurred in 9.8% of those with inferior AMI and in 3.2% of those with anterior AMI.164 The onset of AV block usually occurs 2 to 3 days after the infarction but has a range of a few hours to 10 days. The mean duration is usually 2 to 3 days, and range of duration is 12 hours to 16 days. In one large study, third-degree AV block occurred within 48 hours of symptom onset in 81% of patients, with a trend toward later onset of thirddegree AV block in anterior rather than inferior AMI.164 Clinicopathologic studies indicate that there is a relationship between the anatomic location of an AMI and involvement of the conduction system.165 The development of AV and intraventricular blocks during anterior AMI is related to the extent of the ischemic/ infarcted area. AV block in patients with inferior AMI more often results from vagal reflexes or local metabolites occurring early within the AV node in a transient fashion. Mechanisms proposed for AV block in the presence of inferior AMI include Bezold-Jarisch reflex, reversible ischemia or injury of the conduction system, local accumulation of adenosine or its metabolites, and local AV nodal hyperkalemia. Stimulation of the Bezold-Jarisch reflex causes an abnormally increased output of vagal nerve traffic; it is initiated by ischemia of the afferent nerves in the area of the inferoposterior left ventricle. Reperfusion of the RCA with thrombolytic agents is a strong stimulus for the BezoldJarisch reflex.166,167 Despite this, the Second Thrombolysis in Myocardial Infarction (TIMI II) study did not show an increase in AV block in patients with inferior AMI who received thrombolytic therapy and had a patent infarct-related artery.168

In inferior or posterior AMI, obstruction of the RCA produces reversible ischemia of the AV node. In patients who experienced AV block after inferior AMI, pathologic studies demonstrated little or no necrosis, structural damage, or histologic degenerative changes in the conduction system in most cases.165,169 However, Bilbao et al.170 identified a subgroup of patients with fatal inferior or posterior AMI and AV block who had necrosis of the prenodal atrial myocardial fibers. These necrotic fibers were absent in patients without AV block. Clinically, the transient nature of the AV block supports the concept that injury to the AV node is reversible.171 The anatomic data reported by Bassan et al.158 support the concept that the blood supply of the AV node is dual. In their prospective study, 11 of 51 patients who survived an inferior AMI had some degree of transient AV block, and about 90% of the patients with AV block had simultaneous obstruction of the RCA (or left coronary artery [LCA] when it was dominant) and the proximal segment of the LAD artery. Moreover, patients with inferior AMI and LAD artery obstruction had a sixfold higher risk for development of AV block than those without LAD artery obstruction. However, the TIMI-II data do not support this finding; in study patients with inferior AMI and AV block, the incidence of disease in the LAD was low and was similar to that in patients with inferior AMI without AV block.168 The Thrombolysis and Angioplasty in Acute Myocardial Infarction (TAMI) study group also showed no increase in incidence of LAD disease in patients with inferior AMI and complete AV block.172 Local accumulation of endogenous adenosine or its metabolites also has been suggested to play a mechanistic role in AV block occurring as an early complication of inferior AMI.173 Several case reports or small series have suggested that aminophylline, a competitive adenosine antagonist, reverses atropine-resistant AV block in patients with inferior AMI.174 Current practice guidelines for management of ST-segment-elevation AMI, however, recommend against giving aminophylline to treat bradyarrhythmias because it increases myocardial oxygen demand and is arrhythmogenic.175 A higher level of potassium was found in the lymph draining from the infarcted inferior and posterior cardiac walls of dogs after experimental RCA occlusion, suggesting that local AV nodal hyperkalemia may play a role in the development of AV block in the presence of inferior AMI.176 Sugiura et al.177 found that serum potassium value was an independent predictor of the occurrence of fascicular blocks in anteroseptal AMI. Anterior or anteroseptal AMI results from obstruction of the LAD artery. Occurrence of AV block and BBB in patients with anterior AMI is usually the result of necrosis of the septum and the conduction system below the AV node and reflects more extensive and permanent myocardial damage with severe LV dysfunction.169,178,179 However, Wilber et al.180 described two patients with anterior AMI and complete AV block in whom 1 : 1 conduction returned within minutes after late reperfusion (>40 hours) with angioplasty. Their experience suggests that reversible ischemia rather than necrosis of the conduction system occurs in some patients. Some experimental studies in dogs with anterior AMI suggest that extensive but reversible ischemia of the infranodal conduction tissue occurs, as evidenced by recovery from complete AV block. Several clinical studies also report that most patients with anterior AMI and high-grade AV block who are discharged from the hospital show late recovery of 1 : 1 AV conduction.181-185 AV BLOCK WITHOUT BUNDLE BRANCH BLOCK Incidence In a series of 684 consecutive patients with AMI admitted to the Los Angeles County-University of Southern California Medical Center (LAC-USCMC) Coronary Care Unit (CCU) between 1966 and 1970, 110 had AV block (16%); 79 of 110 patients (72%) with AV block did not have BBB.186 The total percentages of patients who had first-, second-, or third-degree AV block at some time were 6%, 7%, and 4%, respectively (Table 14-5).



14  Pacing for Atrioventricular Conduction System Disease

TABLE

14-5 

Atrioventricular Block (AVB) in Acute Myocardial Infarction (AMI) without Bundle Branch Block*

Incidence First-degree AVB Second-degree AVB Third-degree AVB Site of infarction Inferior Anterior Combined Progression First-degree AVB to second-or third-degree AVB Second-degree AVB to third-degree AVB Outcome Hospital mortality Return to 1 : 1 conduction in survivors

12% (79/684 patients) 6% (44/684 patients) 7% (50/684 patients) 4% (29/684 patients) 79% 18% 6% 59% 36% 29% 95%

Modified from de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, FA Davis, pp 191-207. *Data from 684 consecutive patients with AMI at Los Angeles County-University of Southern California Medical Center (LAC-USCMC), Los Angeles.

Site of Infarction Atrioventricular block is more often associated with inferior infarction, and in those who experience second- and third-degree blocks, inferior AMI is present two to four times more frequently than anterior AMI. The site of block in inferior infarction is above the His bundle in about 90% of patients, whereas in anterior infarction, the conduction abnormality is usually localized below the His bundle in the distal conducting system.187 In the LAC-USCMC series, of the 79 patients with AV block who did not have BBB, 60 (76%) had an inferior infarction, 14 (18%) an anterior infarction, and 5 (6%) a combined infarction (Table 14-6). Progression of AV Block In patients with inferior AMI, progression of AV block typically occurs in stages, whereas in those with anterior AMI, it may occur in stages, or third-degree AV block or ventricular asystole may develop suddenly171 (Fig. 14-15). Outcome Atrioventricular block complicating AMI is associated with a high mortality rate (24%-48%), two to three times that for AMI without AV block (9%-16%). Even with thrombolytic therapy and primary percutaneous coronary interventions, if AV block occurs in the setting of AMI, mortality remains high, especially in anterior MI.168,172,188,189 This poor prognosis generally reflects the larger ischemic/infarcted region associated with development of AV block in the setting of AMI. Although AV block that occurs during inferior AMI predicts a higher risk of in-hospital death, it may be less predictive of long-term mortality in patients who survive to hospital discharge.168,172 Before the reperfusion era, Tans et al.160 reported that in patients with inferior AMI, TABLE

14-6 

339

Atrioventricular Block in Anterior and Inferior-Posterior Acute Myocardial Infarction (AMI)

Feature Pathophysiology Site of block Frequency Progression to complete AV block Intraventricular conduction defect Escape focus Escape rate (per minute) Prognosis

Anterior AMI Extensive necrosis of septum Infranodal Less frequent Sudden

Inferior-Posterior AMI Reversible ischemia, injury of conduction system Intranodal Two to four times more frequent Gradual

Common

Rare

Ventricular 20-40 High mortality

Junctional 40-60 Lower mortality

Figure 14-15  Lead II rhythm strip shows sudden ventricular asystole in a patient with acute myocardial infarction complicated by right bundle branch block and left-axis deviation. (From de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, Davis.)

those with high-grade AV block and no severe pump failure had a higher in-hospital mortality rate (17%) than those without high-grade AV block (9%).160 The major cause of death in patients who have AV block in the setting of AMI is pump failure.190 In the LAC-USCMC series, the hospital mortality rate was 29% (32 of 110 patients); 29 of the 32 deaths (91%) were caused by pump failure. Survival, therefore, is greatly influenced by the severity of the hemodynamic disturbance and is less dependent on the degree of heart block. Death is related primarily to extensive myocardial damage, but in an important minority of patients, it can be attributed to sudden ventricular asystole or severe bradycardia. AV BLOCK WITH BUNDLE BRANCH BLOCK Prior to the widespread use of thrombolytic therapy, BBB was present during hospitalization in 8% to 18% of patients with AMI.191-196 The presence of a persistent intraventricular conduction defect during the hospitalization increases the risk of high-grade AV block as well as other complications and is associated with poor survival in patients with AMI. In patients receiving thrombolytic therapy, the incidence of persistent intraventricular conduction defects appearing during the hospitalization is reduced to about 4% to 9%.161-163,197 However, the adverse risk associated with intraventricular conduction defects (except for isolated left anterior hemiblock) has persisted even in the modern era of AMI reperfusion therapy. In an older series of 2779 patients with AMI admitted from 1966 to 1977 to the LAC-USCMC CCU, 257 (9%) had BBB186 (Table 14-7). Of the 257 patients, 83 (32%) had LBBB, 80 (31%) had RBBB, 72 (28%) had RBBB plus left-axis deviation, 21 (9%) had RBBB plus right-axis deviation, and one had alternating BBB. The conduction abnormality was “new” in 60%; that is, the BBB developed during the infarction and was documented by serial ECGs or was present on admission and was not seen on previous ECGs or reverted to normal conduction later as documented by serial ECGs. When the site of infarction was not obscured by the BBB in the LAC-USCMC series, the block was associated with anterior AMI about three times as often as with inferior AMI. Progression of AV Block In the LAC-USCMC series conducted before the thrombolytic era, progression of AV block occurred in 75 of the 257 patients (29%) with AMI and BBB (see Table 14-7). Of the 28 patients with AV block and BBB who initially had a normal P-R interval, 13 (46%) experienced first-degree AV block. Nine of the 13 (69%) remained in first-degree block, two (15%) progressed to second-degree block type II only, one (8%) had type II second-degree block that progressed to third-degree AV block, and one had thirddegree block without first having second-degree block. Six patients had type II second-degree block without initially having first-degree AV block, four of whom (67%) went on to have third-degree AV block.

340

TABLE

14-7 

SECTION 2  Clinical Concepts

Bundle Branch Block (BBB) in Acute Myocardial Infarction (AMI)

Incidence Left BBB Right BBB Right BBB + LAD obstruction Right BBB + RAD obstruction Onset of BBB New Old Site of Infarction Inferior Anterior Combined Indeterminate Nontransmural Incidence of AVB First degree Second degree Third degree Progression of AVB First-degree AVB to second- or third-degree AVB Second-degree AVB to third-degree AVB Progression to high-grade AVB Bilateral BBB + first-degree AVB New bilateral BBB + first-degree AVB First-degree AVB New BBB + first-degree AVB Bilateral BBB New BBB New bilateral BBB Outcome Hospital mortality Return to 1 : 1 conduction in survivors

9%: (257/2779 patients)* 32% (83/257 patients) 31% (80/257 patients) 28% (72/257 patients) 9% (21/257 patients) 60% 40% 21% 52% 4% 18% 5% 29% (75/257 patients) 10% (25/257 patients) 5% (13/257 patients) 14% (37/257 patients) 32% 46% 18% (46/257 patients) 50% 43% 30% 29% 18% 16% 15% 20% 89%

Modified from de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, FA Davis, pp 191-207. *Data from 2779 AMI patients seen from October 1966 to March 1977 at Los Angeles County-University of Southern California Medical Center (LAC-USCMC), Los Angeles. AVB, Atrioventricular block; LAD, left anterior descending artery; RAD, right anterior descending artery.

Of the total 41 patients who had first-degree AV block and BBB, 13 (32%) progressed to high-grade block. Twenty-eight (68%) were admitted in first-degree AV block. Sixteen of the 28 (57%) remained in first-degree block; three (11%) progressed to type II second-degree AV block, one of whom went on to third-degree block; five (18%) progressed to type I second-degree block, two of whom went on to third-degree block; and four (14%) patients had third-degree block without initially having second-degree AV block. Of the total 24 patients who had second-degree AV block and BBB, 11 (46%) progressed to third-degree block. Six had second-degree AV block on admission; of these, type II block occurred in four, one of whom progressed to third-degree block, and type I occurred in two, one of whom progressed to third-degree block. There were 37 patients with third-degree AV block and BBB, 13 (35%) of whom were admitted in third-degree block. Of the 24 who progressed to third-degree block, 11 (46%) had demonstrated seconddegree block; 7 of the 11 had type II second-degree block. Consistent with the LAC-USCMC series, AV block occurred in other studies in about one third of patients with AMI and BBB.186,198-201 Two large studies from the 1970s and 1980s developed a data bank on patients with BBB in association with MI: a collaborative multicenter study involving five centers185 and a study conducted at LACUSCMC.186 Both studies have limitations because (1) the data were obtained retrospectively and (2) at the time, no guidelines existed pertaining to pacemaker insertion, which was performed at the physician’s discretion in all cases. Thus, although these studies are unable to provide definitive answers about the natural history of BBB in association with AMI, they nevertheless do offer valuable clinical information. In the multicenter study reported by Hindman et al.,185 high-grade AV block (third- or second-degree block with a type II pattern) occurred in 55 of 432 patients (22%). To determine which patients

were at considerable risk for development of high-grade AV block while hospitalized with AMI, several variables were analyzed. Combinations of the three following ECG findings identified high-risk patients: (1) first-degree AV block, (2) bilateral BBB (if both bundle branches were involved [e.g., RBBB plus left- or right-axis deviation] or alternating RBBB and LBBB), and (3) “new” BBB. The absence of all variables or the presence of only one of the three defined variables was associated with a lower risk (10%-13%) for development of highgrade AV block during hospitalization. The risk was moderate for patients with first-degree AV block with either new BBB or bilateral BBB (19%-20%), and highest (31%-38%) for new bilateral BBB regardless of the P-R interval (Fig. 14-16). In the LAC-USCMC study, high-grade AV block occurred in 46 of 257 patients (18%). The absence of all three variables (first-degree AV block, bilateral BBB, and new BBB) or the presence of either bilateral BBB or new BBB or new bilateral BBB was associated with the lowest risk (10%-18%) for development of high-grade AV block during hospitalization with AMI.186 The risk was moderate for first-degree AV block with or without new BBB (29%-30%) and highest (50%) for bilateral BBB plus first-degree AV block, regardless of whether the BBB was old or new (Fig. 14-17). Despite some differences in the findings between the two studies, both studies found that the following subgroups of patients were at highest risk for high-grade AV block: (1) those with new bilateral BBB plus first-degree AV block (risks, 38%185 and 43%186), (2) those with bilateral BBB plus first-degree AV block (risks, 20% and 50%, respectively), and (3) new BBB plus first-degree AV block (risks, 19% and 29%, respectively). Subgroups in whom the findings of the two studies show different risks can be considered to be at moderate risk for highgrade AV block. These subgroups include patients with (1) new bilateral BBB (risks, 31% and 15%, respectively) (Fig. 14-18), (2) first-degree AV block (risks, 13% and 30%, respectively), and (3) bilateral BBB (risks, 10% and 18%, respectively). The remaining subgroups of patients with AMI and BBB can be considered to be at lowest risk (≤10%) for development of high-grade AV block. The database assembled by the Multicenter Investigation of the Limitation of Infarct Size (MILIS) was used to develop a simplified method of predicting the occurrence of CHB. Data from 698 patients with proven MI were analyzed, and the presence or absence of ECG abnormalities of AV or intraventricular conduction was determined for each patient. Risk factors for development of CHB were as follows: first-degree AV block, Mobitz type I AV block, Mobitz type II AV block,

None of variables L 9%

1° AVB 13% L

20% M 38%

Bilateral BBB 10%

H

19%

31% H

M

L

“New” BBB 11% L Figure 14-16  Venn diagram for 432 patients in multicenter study, depicting the risk for high-grade atrioventricular block (AVB) in patients with acute myocardial infarction and bundle branch block (BBB). (From Hindman MC, Wagner GS, JaRo M, et al: The clinical significance of bundle branch block complicating acute myocardial infarction. 2. Indications for temporary and permanent pacemakers. Circulation 58:689, 1978. Copyright 1978 American Heart Association.)



14  Pacing for Atrioventricular Conduction System Disease

pacing should be individualized according to the patient-related risk factors and the available personnel and equipment at each institution.

None of variables L 10%

1° AVB 30% M

Outcome 50% H 43%

Bilateral BBB 18%

H

29%

L

15% L

M “New” BBB 16% L

Figure 14-17  Venn diagram for 257 patients in the Los Angeles County–University of Southern California Medical Center (LAC-USCMC) study, depicting the risk for high-grade atrioventricular block (AVB) in patients with acute myocardial infarction and bundle branch block (BBB). (From de Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease. Philadelphia, 1983, Davis.)

left anterior hemiblock, left posterior hemiblock, RBBB, and LBBB. A risk score for the development of CHB was devised that consisted of the sum of each patient’s individual risk factors. Incidences of CHB of 1.2%, 7.8%, 25%, and 36% were associated with risk scores of 0, 1, 2, and 3 or more, respectively (Fig. 14-19). The risk score was subsequently tested on the published results of six studies for a combined total of 2151 patients.202 The limitations of this scoring system include the lack of differentiation between newly appearing and old BBB, a factor that has been shown to be of predictive value. It is likely that consideration of such factors would further improve the accuracy of the scoring system, but it would also add to its complexity. Another criticism of the scoring system is that it would assign a risk score of only 1 to a patient with isolated Mobitz type II AV block, a disorder usually believed to be highly predictive of progression to CHB. Isolated Mobitz type II AV block is, however, relatively rare. It must be recognized that the algorithms and clinical databases used to estimate the risk for occurrence of CHB in the setting of AMI were developed in the prethrombolytic era, and thus must be interpreted cautiously when applied to the modern post-AMI patient population. The availability of transcutaneous pacing and early primary percutaneous coronary interventions has had an important effect on the clinical management of these patients with AMI in the current era. The actual clinical decision whether to institute prophylactic temporary

A

341

The short-term and long-term mortality and sudden death rates are higher in patients with AMI and BBB (25%-50%) than in those without BBB (15%).160,191,195,203 The one exception is the isolated finding of left anterior fascicular block in patients with AMI, which appears not to carry an unfavorable prognosis. When the infarction is extensive and produces diffuse conduction system abnormalities progressing to high-grade AV block, it is also extensive enough to damage a large amount of myocardial muscle. Therefore, affected patients often die from pump failure and from ventricular tachyarrhythmias, and the adverse prognosis is not necessarily caused by development of highgrade AV block. Nevertheless, some of these patients do not die from heart failure or ventricular arrhythmias, and in these patients, the conduction abnormality may be contributory and can be the major cause of death if prophylactic pacing is not undertaken. In some patients, sudden third-degree AV block or asystole is abrupt and fatal if untreated. It is interesting that in the LAC-USCMC study, 75% of patients with BBB and AMI had either no heart failure or, at worst, mild heart failure.186 These results as well as those of Hindman et al.185 showed that high-grade AV block influenced hospital mortality independent of pump failure. IMPACT OF THROMBOLYTIC THERAPY Several prospective trials involving thrombolytic therapy of AMI provide data pertaining to the effect of such therapy on the development of high-grade (second- or third-degree) AV block and BBB.168,172 Clemmensen et al.172 examined the effect of thrombolytic therapy and adjunctive angioplasty as a treatment strategy for AMI (TAMI trial) after inferior AMI. In all patients, treatment was initiated with thrombolytic agents within 6 hours of symptom onset. There were 373 patients with an inferior AMI, of whom 50 (13%) had complete AV block; 54% of these patients had complete AV block on admission. In all but two patients, the block was manifest within 72 hours of onset of symptoms. The duration of block was less than 1 hour in 25% and less than 12 hours in 15%; the median duration of block was 2.5 hours. There was no difference in the rate of infarct vessel patency between those with and those without AV block (90% and 91%, respectively). A precipitating clinical event—vessel reperfusion, performance of percutaneous transluminal coronary angioplasty (PTCA)—or vessel reocclusion was identifiable in 38% of cases of complete AV block. At the predischarge angiogram, the vessel patency rate was 11% lower in the group with AV block than in the group without block (71% vs. 82%, respectively). Those in whom AV block developed showed a decrease in LVEF between the early postthrombolytic angiogram and the

I

aVR

V1

V4

I

aVR

V1

V4

II

aVL

V2

V5

II

aVL

V2

V5

III

aVF

V3

V6

III

aVF

V3

V6

B

Figure 14-18  A and B, Electrocardiograms of a patient with anterior acute myocardial infarction and development of “new” bilateral bundle branch block (BBB)—left BBB and right BBB with right-axis deviation. This patient had sudden ventricular asystole.

342

SECTION 2  Clinical Concepts

Duke data MILIS Prior data 25

0 0

1

2

3

CHB risk score Figure 14-19  Comparison of the incidence of complete heart block (CHB) predicted by the CHB risk score method (purple bars), the observed incidence of CHB in the Duke University myocardial infarction database (blue bars), and the observed incidence of CHB or CHB and Mobitz II atrioventricular (AV) block in six reported studies (red bars). MILIS, Multicenter Investigation of the Limitation of Infarct Size. (From Lamas GA, Muller JE, Turi AG, et al: A simplified method to predict occurrence of complete heart block during acute myocardial infarction. Am J Cardiol 57:1213, 1986.)

predischarge angiogram. Also, those who experienced AV block had higher in-hospital mortality, 10 of 50 (20%) versus 12 of 323 (4%; P < .001). When age, LVEF in the acute phase, number of diseased vessels, and grade of blood flow through the culprit lesion were entered into a multivariate model, the development of complete AV block still contributed significantly to the risk for in-hospital death. After a median follow-up period of 22 months, mortality rates for patients with and without AV block were equivalent (2%). These data suggest that, compared with the prethrombolytic era, use of thrombolytics and angioplasty has altered neither the incidence of complete AV block nor the associated greater ventricular dysfunction or in-hospital mortality of patients with inferior AMI. In another study of 1786 patients with inferior AMI who received recombinant tissue-type plasminogen activator (rt-PA) within 4 hours of symptom onset, high-grade (second- or third-degree) AV block developed in 214 (12%) (TIMI-II trial).168 Of the group who had AV block, 113 (6.3% of total, or 52% of those who ever had AV block) had this finding on admission. The remaining 101 patients (5.7%) experienced heart block during the 24 hours after treatment with thrombolytics. Patients who already had high-grade AV block before receiving thrombolytic therapy tended to be older and had a higher prevalence of cardiogenic shock than those without heart block. Nevertheless, the presence of heart block did not carry a higher 21-day mortality rate independent of other variables, such as shock, and the 1-year mortality rate was similar to that in the group without heart block. Patients in this study were randomly assigned to coronary arteriography 18 to 48 hours after admission. Among those who had heart block after admission, the infarct-related artery was less frequently patent than in those without heart block (28 of 39 [72%] vs. 611 of 723 [84.5%]; P = .04]). The RCA was the infarct-related artery more often in patients who had heart block than in those who did not (36 of 69 [92.3%] vs. 542 of 723 [75.1%], respectively; P = .04). Among patients without heart block at hospital admission, death occurred within 48 hours in 4 of 9 patients (44%) with new heart block and in 8 of 68 (12%) without new heart block at 24 hours. The 21-day mortality rate was higher in the group with AV block than in the group without block (10 of 101 [9.9%] vs. 35 of 1572 [2.2%], respectively; P < .001), as was the 1-year mortality rate (15 of 101 [14.9%] vs. 65 of 1572 [4.2%], respectively; P = .001). A temporary pacemaker was inserted in about one third of patients who had heart block on admission and in almost 30% of patients who experienced heart block after institution of thrombolytic therapy, whereas only 6.5% of patients without heart block received temporary pacemakers. None of the patients who had heart block on admission

or who experienced heart block later received permanent pacemakers, but four patients without heart block at 24 hours went on to receive permanent pacemakers. Heart block was not listed as a primary or contributing cause of death in any patient. The data from these two studies of thrombolytic therapy suggest that aggressive treatment with thrombolytic agents or thrombolytic therapy plus angioplasty is not associated with a lower incidence of high-grade or complete AV block in patients with inferior AMI than was seen in the prethrombolytic era; the incidence remains about 10% to 13%, with about one half of cases appearing as new AV block during hospitalization. The infarct-related vessel is more often the RCA, and there is a lower vessel patency rate after thrombolysis among patients in whom AV block complicates inferior AMI. In-hospital and early posthospitalization mortality rates are higher in patients with block than in those without AV block, among patients treated with thrombolytics, with or without angioplasty. It has not been clear, however, that patients with acute AV block continue to be at greater risk of death over the long term if they survive the initial hospitalization. A study that pooled data from four large RCTs involving 70,000 patients with AMI treated with thrombolytic therapy evaluated the short- and longterm mortality rates associated with second- and third-degree AV blocks.164 Compared with patients with AMI and no AV block, patients with AMI and AV block were more than three times more likely to die within 30 days and 1.5 times more likely to die during 1 year of follow-up. The higher short- and long-term mortality rates were observed in the setting of inferior as well as anterior AMI (Fig. 14-20). The presumption remains, as before the era of thrombolytic therapy, that the presence or development of AV block is associated with a higher mortality because it tends to indicate the presence of more extensive infarction or injury. In trials conducted with thrombolytic therapy in AMI, BBB is reported present on admission in up to 2% to 4% of patients.202 In the first Global Utilization of Streptokinase and Tissue-Type Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial, among 26,003 North American patients, 420 (1.6%) had left (n = 131) or right (n = 289) BBB on admission ECG.204 Interestingly, reversion of BBB occurred in 24% of patients during hospitalization and was associated with a 50% relative risk reduction in 30-day mortality, from 20% to 10%. Prognosis for patients who recovered normal intraventricular conduction (i.e., transient BBB) was similar to that for patients who

50 45 40 Mortality (%)

Risk of endpoint (%)

50

35 30 25 20 15 10 5 0 30 days

6 months

All with AVB All without AVB Anterior MI with AVB

1 year

Anterior MI without AVB Inferior MI with AVB Inferior MI without AVB

Figure 14-20  Unadjusted mortality rates in patients with and without atrioventricular block (AVB). MI, Myocardial infarction. (From Meine TJ, Al-Khatib SM, Alexander JH, et al: Incidence, predictors, and outcomes of high-degree atrioventricular block complicating acute myocardial infarction treated with thrombolytic therapy. Am Heart J 149:670, 2005.)



never had BBB. Another study examined the significance of RBBB in AMI in the prethrombolytic era and compared it with the incidence and prognostic significance of new RBBB in the thrombolytic era.205 In a multicenter prospective study of 1238 patients with 1-year follow-up, a higher rate of new and transient RBBB and lower rate of bifascicular block were found in patients receiving thrombolytic therapy. The overall prognostic implications of RBBB, however, were unchanged and included a higher rate of heart failure, greater chance of needing a permanent pacemaker, and a higher 1-year mortality rate.205 BUNDLE BRANCH BLOCK AFTER RECOVERY The subset of patients with persistent BBB and transient high-grade AV block during AMI are at increased risk of late mortality.185,206,207 It is now recognized that most of these deaths are sudden and result from ventricular tachyarrhythmias. In a previous era, however, controversy surrounded whether these patients were at high risk for sudden death from a bradyarrhythmia.183,201,208-210 Some investigators suggested that patients with persistent BBB plus transient AV block during the acute infarction had a higher risk of dying suddenly as a result of CHB. They attempted to identify the subset of patients at highest risk of late sudden death due to AV block in order to maximize the therapeutic benefit of permanently implanting a pacemaker. The multicenter study by Hindman et al.185 supported the previous reports by Atkins206 and Ritter,207 who found that the subset of patients with chronic BBB and transient high-grade AV block during AMI were at increased risk of late sudden death. These data showed that patients who did not receive pacing had a higher incidence of sudden death or recurrent high-grade AV block during follow-up (65%) than those who were given permanent pacing (10%), suggesting that implantation of a permanent pacemaker protected against sudden death in these patients. Waugh et al.211 likewise recommended permanent pacemaker therapy to prevent syncope or sudden death in another group of highrisk patients, those with bilateral BBB plus transient high-grade AV block (type II progression). Other studies from the same era, however, questioned whether these patients are at high risk for sudden death from a bradyarrhythmia.183,203,208-210 For example, Nimetz et al.201 reported that late sudden death occurred in 4 of 13 (31%) survivors with BBB and second- or third-degree AV block and in 14 of 41 (34%) survivors without AV block. Ginks et al.183 found that of patients with anterior AMI complicated by CHB with return to normal sinus rhythm but with persistent BBB, 4 of 14 hospital survivors (29%) with anterior MI, persistent BBB, and transient AV block died, and 2 of 4 (50%) with permanent pacemakers died during a follow-up period averaging 49 months. In a study by Murphy et al.209 of patients surviving AMI complicated by BBB, none of the deaths resulted from heart block, even in patients with transient AV block during the AMI. Lie et al.210 reported on a group of 47 patients who had survived anterior infarction complicated by BBB and who were kept for 6 weeks in the monitoring area; 17 of the 47 patients (36%) sustained late ventricular fibrillation. Likewise, the Birmingham Trial of permanent pacing in patients with persistent intraventricular defects after AMI showed no significant difference in survival between patients with and without heart block during up to 5 years of follow-up.212 Finally, in a prospective long-term study, Talwar et al.213 monitored 18 patients with anterior AMI, intraventricular defects, and transient complete AV block for a mean of 2 years; pacemakers were permanently implanted in eight patients. There was only one death, in the unpaced group, caused by a cerebrovascular accident. Clearly, these older studies were limited by the small number of patients with AMI enrolled and monitored and may not be applicable to the current era of post-AMI management. Despite the controversy regarding whether late sudden death in patients with BBB is caused by heart block, permanent ventricular pacing is indicated for transient advanced second- or third-degree infranodal AV block and associated BBB after AMI, according to current practice guidelines (class I indication).21

343

14  Pacing for Atrioventricular Conduction System Disease

ELECTROPHYSIOLOGIC STUDIES IN AV BLOCK AND BUNDLE BRANCH BLOCK Electrophysiologic studies with recording of the His bundle electrogram (HBE) are not performed routinely at present for risk stratification of patients with AV block after AMI. HBE studies after AMI were used primarily in the 1970s and 1980s to identify the sites of AV conduction disturbances, which were shown to be either in the AV node (proximal block) or in the distal conduction system (distal block). The presence of distal block identifies patients at high risk for development of highgrade AV block. In individual cases in which the diagnosis is uncertain (e.g., type I second-degree AV block in patients with BBB) or infranodal or multilevel block is suspected, EPS is helpful in identifying the sites of AV block (Fig. 14-21). In patients with inferior AMI, the site of AV block is usually proximal. Harperet al.214 showed that 30 of 32 patients (94%) with inferior AMI and third-degree AV block had AV nodal block during HBE; the remaining two patients were in normal sinus rhythm during the study and had a normal P-R interval and normal A-H and H-V intervals. Thus, in this group of patients, HBE offered no advantage over conventional ECG criteria in localizing the site of block. In anterior AMI, the block is frequently in the distal conduction system. In the study by Harper et al.,214 50% of patients (9 of 18) with BBB and a normal P-R interval on ECG had a prolonged H-V interval.214 Of the 22 patients who experienced AV block and BBB, five had proximal block, 14 had distal block, and three had both proximal and distal blocks. Thus, in both groups of patients, HBE was the only means of localizing the block in the proximal or distal portion of the conduction system. Distal block indicates disease in either the His bundle or the remaining bundle branches; clinically, this finding is a common antecedent to sudden asystole and a poorer prognosis. Despite that a prolonged H-V interval could identify a group of patients who may be at high risk for high-grade AV block, several studies have shown that it does not help in assessing the short- or long-term prognosis of patients after AMI.214,215 Intracardiac EPS has been evaluated as a means of attempting to predict which patients with MI and BBB are most likely to die. Harper

I aVF V1 H

48 ms

A

S1

HisM

V

S1 137ms

HisP

V1 S1

S1

S1

S1

S1

S1

HisM HisP

168 ms

178 ms

203 ms

233 ms

97 ms

Figure 14-21  Simultaneous surface electrocardiogram (leads I, aVF, and V1) and intracardiac recordings from the His bundle region (HisM and HisP) in a 65-year-old patient with ischemic cardiac disease and a history of syncope. Left upper panel, Sinus rhythm with normal baseline H-V interval (48 msec) and narrow QRS complex with a left anterior fascicle block pattern. Right upper panel, Prolonged H-V interval (137 msec) during atrial overdrive pacing (S1S2 = 650 msec). Lower panel, H-V Wenckebach conduction during atrial overdrive pacing (S1S1 = 600 msec). This case and figure show that serious infranodal conduction disease may be localized to within the His bundle and may be “masked” by a normal QRS as well as a normal P-R interval during sinus rhythm. (Courtesy Drs. Yanfei Yang and Melvin Scheinman, University of California/Cardiac Electrophysiology, San Francisco.)

344

SECTION 2  Clinical Concepts

et al.208 reported on 72 patients with AMI complicated by AV block, BBB, or both who underwent His bundle recording or electrophysiologic (HBE) studies during their CCU stay. Thirty of 32 patients (94%) with AV block and narrow QRS had a proximal block. Hospital mortality was low (13%), and HBE provided no additional information to the surface ECG. Of 18 patients with BBB and a normal P-R interval, nine had distal block, but there were no hospital deaths in this group. Again, of 22 patients with BBB and AV block, five had proximal, 14 distal, and three proximal and distal blocks. Hospital mortality in these patients, who progressed to second- or third-degree AV block, was higher (9 of 12 patients, 75%) than in those who remained in firstdegree AV block (2 of 10 patients, 20%). Lichstein216 and Lie184 also concluded that patients with BBB and AMI who had HBE evidence of a distal block had higher hospital mortality (73% and 81%, respectively) than those with normal H-V intervals (25% and 47%, respectively). On the other hand, Gould et al.217 found that the presence or absence of a prolonged H-V interval did not affect mortality. INDICATIONS FOR PACING Temporary Pacing The use of temporary transvenous pacing in the post-AMI period has diminished in recent years with the greater and more widespread reliance on transcutaneous pacing. Table 14-8 lists situations in which temporary transvenous pacing is recommended or should be considered, according to practice guidelines.175 Current practice guidelines and recommendations for temporary pacing in the setting of AMI, however, are based primarily on clinical experience rather than wellcontrolled clinical trials. Essentially, no trials have evaluated the risks versus the benefits of temporary pacing during the current era of AMI treatment. Furthermore, RV pacing (VVI) may have potential deleterious hemodynamic effects even when compared with spontaneous intrinsic bradycardic rhythms in the absence of BBB (e.g., sinus node dysfunction or heart block with junctional escape rhythms). In addition, there is little scientific evidence of an advantage of temporary RV pacing over intrinsic rhythm in patients with bradycardia after AMI. Thus, temporary ventricular pacing should not be used for hemodynamic support, but rather should be used primarily as “backup pacing” for prophylactic indications to prevent catastrophic bradycardia or to treat sudden CHB without an adequate ventricular escape mechanism.

TABLE

14-8 

Recommended Indications for Temporary Pacing in Patients with Acute Myocardial Infarction (AMI)

Category Symptomatic AVB

Recommended Indications

Marked bradycardia (ventricular rate <40 bpm) Hypotension Heart failure or reduced cardiac output Cardiogenic shock Altered mental status Pause-dependent polymorphic ventricular tachycardia Asymptomatic Third-degree AVB AVB Second-degree AVB, type II: without BBB Patients with anterior AMI Patients with inferior AMI and narrow QRS complex if block recurs or persists despite atropine administration Asymptomatic Third-degree AVB AVB with Second-degree AVB: BBB Type I Type II Prophylactic pacing for those at high risk for high-grade AVB: Bilateral BBB: Alternating left LBBB and RBBB RBBB with alternating LAHB and LPHB New BBB with first-degree AVB Indeterminate-age RBBB with LAHB or LPHB and first-degree AVB AVB, Atrioventricular block; BBB, bundle branch block; LAHB, left anterior hemiblock; LBBB, left bundle branch block; LPHB, left posterior hemiblock; RBBB, right bundle branch block.

After temporary pacing is instituted, the temporary pacing generator should be programmed to minimize RV pacing (i.e., prolonging the AV delay). Atrial or dual-chamber pacing (AV synchronous) leads to better cardiac output than temporary ventricular pacing.218-220 Thus, when hemodynamic support is required in patients with AMI who need temporary pacing, physiologic pacing should be considered. In general, however, because of the risks of infection, limitation in venous access, and difficulties in maintaining stability of atrial pacing during temporary pacing for prolonged periods, and unless there are contraindications, patients who need permanent pacing after AMI should undergo permanent rather than temporary pacemaker implantation as soon as feasible. The requirement for temporary pacing in AMI does not by itself mandate an indication for permanent pacing. Administration of thrombolytic therapy is a priority in AMI patients and should not be delayed by the need to insert a temporary pacing wire. If necessary in the bradycardic patient, temporary transcutaneous pacing can be instituted while thrombolytic therapy is being given. Pharmacologic therapies (with isoproterenol, aminophylline) to treat bradycardia are not recommended in AMI because of their arrhythmogenic effects and adverse effects on myocardial oxygen demand.175 Atropine is generally well tolerated in inferior AMI, but in some cases of inferior AMI, AV block does not respond to atropine. When infranodal conduction disturbances are present, especially in anterior infarction, atropine raises the sinus rate and may worsen AV conduction and decrease the ventricular rate. When temporary pacing is required because of continued, hemodynamically significant bradycardia or profound asystole after thrombolytic therapy or in fully anticoagulated patients, the temporary pacing wire should be inserted by an experienced operator. It also is best to avoid the left subclavian approach for temporary pacemaker insertion because this is the most popular site for permanent pacemaker implantation. Regardless of the site of infarction, a temporary pacemaker should be placed whenever AV block is associated with marked symptomatic bradycardia (<40 bpm), asystole, hypotension, reduced cardiac output, heart failure, altered mental status, shock, or ventricular irritability (e.g., pause-dependent polymorphic VT). In almost all cases, patients with a normal QRS complex or old or new fascicular block (left anterior fascicular block [LAFB] or left anterior hemiblock [LAHB]) and first-degree AV block or type I seconddegree AV block with normal hemodynamics and patients with inferior AMI and block above the His bundle (i.e., normal QRS width) do not require insertion of a temporary pacemaker. These patients are not at risk for sudden asystole. It must be appreciated that a small number of patients with type I second-degree AV block and narrow QRS complexes have block in the His bundle and not in the AV node. Nevertheless, some clinicians believe that the relatively uncommon clinical manifestation of intra-Hisian block in inferior AMI is almost always reversible and rarely requires pacing.221 Insertion of a temporary transvenous pacemaker is recommended in patients with an anterior AMI complicated by the following: (1) type I second-degree AV block with wide QRS in which block is presumed to be below His bundle (class IIa or IIb indication, depending on whether BBB is new or old), (2) type II second-degree AV block with a normal (class IIa indication) or wide QRS (class I or IIa indication, depending on whether BBB is new or old), or (3) complete or advanced AV block (class I indication).175 These patients are at risk for sudden asystole in the setting of anterior AMI. In the setting of a nonanterior wall AMI, temporary transvenous pacing likewise is recommended in patients with (1) type I seconddegree AV block with wide QRS in whom block is presumed to be below His bundle (class IIa or IIb indication, depending on whether BBB is new or old), (2) type II second-degree AV block with a normal (class IIa indication) or wide QRS complex (class I or IIa indication, depending on whether the BBB is new or old), and (3) complete or advanced AV block (class I indication).175 As noted previously, however, in most cases of AV block complicating inferior AMI, AV block is almost always located in the AV node, is reversible, is associated with a junctional (narrow complex) escape rhythm, and does not predict



14  Pacing for Atrioventricular Conduction System Disease

the development of sudden asystole. Thus, temporary pacing can almost always be avoided in these patients. Prophylactic temporary transvenous pacing in the early postinfarction period also is indicated for patients considered at high risk for development of sudden high-grade AV block.175 Such patients are identified by (1) new or indeterminate-age bilateral BBB (alternating LBBB and RBBB or RBBB with alternating left anterior and left posterior hemiblock) with or without first-degree AV block (class I indication), (2) new BBB with first-degree AV block (class IIa indication), or (3) indeterminate-age RBBB with fascicular and first-degree AV blocks (class IIa indication). Because of the risk of sudden asystole, these subgroups of patients probably should receive temporary pacemakers or should be considered for early implantation of permanent pacemakers. Even in these high-risk patients, however, it must be recognized that prophylactic temporary ventricular pacing has not gained widespread acceptance, because it does not improve in-hospital survival and may be associated with serious complications. Thus, the use of standby transcutaneous pacing may be a preferred alternative. Other patient subgroups at moderate risk for development of highgrade AV block who may have to be considered for temporary prophylactic transvenous pacing are those with (1) new BBB without first-degree AV block (class IIb indication), (2) old BBB with firstdegree AV block (class IIb indication), or (3) indeterminate-age RBBB with fascicular block but without first-degree AV block (class IIb indication). However, placement of external pacing pads with the ability to provide prophylactic transcutaneous pacing as standby with close telemetry monitoring may be preferred in these patient subgroups during the acute phase of MI.175 Furthermore, in the absence of highergrade AV block, patients with persistent first-degree AV block in the presence of old or indeterminate-age BBB do not require permanent ventricular pacing after AMI. Permanent Pacing Table 14-9 lists the ACC/AHA/HRS current guidelines for permanent pacemaker implantation after AMI.21 All patients who have an indication for permanent pacing after AMI should also be evaluated for ICD and cardiac resynchronization therapy (CRT) indications. Patients with AV conduction disturbances after AMI in whom documented, symptomatic bradyarrhythmias develop and persist should receive permanent pacemakers. In patients with persistent and symptomatic second- or third-degree AV block, permanent ventricular pacing has a class I indication. Of patients who have second-or thirddegree block in the hospital, regardless of infarction or block location, return to 1 : 1 conduction is seen in 95% of those without BBB and in TABLE

14-9  Class I

Class IIa Class IIb Class III

Indications for Permanent Pacing after Acute Phase of Myocardial Infarction Persistent second-degree AV block in the His-Purkinje system with alternating BBB or third-degree AV block within or below the His-Purkinje system after ST-segment-elevation myocardial infarction (level of evidence: B) Transient advanced second- or third-degree infranodal AV block and associated BBB; if site of block is uncertain, electrophysiologic study may be necessary (level of evidence: B) Persistent and symptomatic second or third-degree AV block (level of evidence: C) None Persistent second- or third-degree AV block at the AV node level, even in the absence of symptoms (level of evidence: B) Transient AV block in the absence of intraventricular conduction defects (level of evidence: B) Transient AV block in the presence of isolated left anterior fascicular block (level of evidence: B) New BBB or fascicular block in the absence of AV block (level of evidence: B) Persistent asymptomatic first-degree AV block in the presence of BBB or fascicular block (level of evidence: B)

Modified from Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities. J Am Coll Cardiol 51:e1-e62, 2008. AV, Atrioventricular; BBB, bundle branch block.

345

89% of those with BBB who survive the infarction and are discharged eventually from the hospital.186 Thus, in patients recovering from AMI who demonstrate AV block, the major determinant of the need for prophylactic permanent pacing beyond symptomatic bradycardia is the presence of intraventricular conduction defects. Patients with persistent second-degree AV block in the His-Purkinje system with bilateral BBB and those with persistent third-degree AV block located within the His-Purkinje system after AMI should receive permanent pacemakers (class I indication). Patients with persistent second- or third-degree AV block at the AV nodal level without BBB may also be considered for permanent pacing (class IIb indication). However, permanent pacing is rarely needed in patients with an inferior wall AMI and narrow QRS. It may take up to 16 days for AV conduction to return. Some conservative clinicians recommend pacemaker implantation only when second- or thirddegree AV block is present for more than 3 weeks after inferior wall MI.222 After reviewing the literature, Barold and Hayes223 asserted that patients who reportedly had “type II AV block” with a narrow QRS in the setting of inferior AMI were misclassified according to incorrect criteria for the diagnosis of type II second-degree AV block.223 Thus, transient or persistent second-degree AV block with inferior AMI is virtually always AV nodal in origin and not an indication for permanent pacing. Development of complete AV block during inferior AMI is associated with a higher in-hospital mortality, which is not altered by temporary or permanent pacing, but a favorable long-term prognosis in those who survive to hospital discharge.172 When transient advanced second- or third-degree infranodal AV block is associated with persistent BBB, permanent ventricular pacing is indicated (class I indication).21,172 EPS may be helpful if the site of block is uncertain. Development of a new intraventricular conduction delay in the setting of an anterior or inferior infarction reflects extensive myocardial damage. Patients with AMI who demonstrate BBB have an unfavorable prognosis and a higher risk of sudden death. Although these patients may be at risk for serious bradyarrhythmias in the posthospitalization period, their adverse prognosis is not necessarily related to the development of high-grade AV block. These patients are at high risk for other post-MI complications, including pump failure and ventricular tachyarrhythmias. In the past, the decision to implant a permanent pacemaker in a survivor of AMI complicated by transient complete or second-degree AV block and persistent BBB during the hospitalization was not always straightforward. In a previous edition of this textbook, it was suggested that there were at least three possible ways of managing these patients: (1) all should receive permanent pacemakers, (2) only those with documented bradyarrhythmias should receive permanent pacemakers, or (3) patients should undergo a diagnostic evaluation, including LVEF measurement, ambulatory 24-hour ECG monitoring, and possibly His bundle studies, and then the need for permanent pacemaker implantation may be considered in some of the patients. In the current era, however, the decision to implant a permanent pacemaker to provide bradycardia support in these patients is less of an issue. Most patients with AMI with AV block and BBB have LV dysfunction and thus are eligible for implantation of an ICD for primary prevention of sudden death and/or a biventricular pacing system to provide CRT. However, the timing of ICD implantation may complicate management of such patients, because Medicare reimbursement guidelines for ICD implantation established in 2005 indicate that patients must not have had an AMI within the past 40 days.224 Furthermore, an important consideration in selection of the mode of pacing and the need for an ICD is the recognition that the extent of myocardial dysfunction in patients with ischemic heart disease may not be a permanent condition. Stunning and hibernation of the myocardium, leading to apparent dysfunction, may resolve as the ischemia resolves and after adequate time has passed for recovery.225,226 Permanent pacing is not recommended for patients with AMI and transient AV block in the absence of intraventricular conduction defects or in the presence of isolated left anterior fascicular block. Patients with persistent first-degree AV block in the presence of BBB

346

SECTION 2  Clinical Concepts

after AMI do not require permanent pacing for bradycardia indications; if advanced LV dysfunction is present, however, such patients should be evaluated for ICD and CRT indications.

Selection of Pacing Mode in Atrioventricular Block Factors to consider in the choice of appropriate pacing mode in patients with AV block are the (1) status and activity level of the patient, (2) importance of AV synchrony, (3) presence of chronotropic incompetence, (4) presence of congestive heart failure, (5) underlying cardiac substrate, and (6) estimated likelihood of the frequency and duration of pacing. The importance of each of these factors varies from patient to patient. The selection of pacing mode for patients with acute AV block usually takes into account many of the same considerations for mode selection in chronic AV block. With acute AV block, however, if the patient was in sinus rhythm, loss of chronotropic competence will have been recent and abrupt, and loss of AV synchrony is usually associated with varying degrees of ventricular dysfunction, which may be severe. For temporary pacing of patients with acute AV block, single-chamber right ventricular VVI pacing usually provides adequate rate correction of the bradyarrhythmia. If there is no or minimal hemodynamic compromise of cardiac function, this mode of pacing may be sufficient to sustain the patient through a usually transient period of high-grade or complete AV block. If the underlying rhythm before acute AV block was AF, single-chamber ventricular pacing should provide a satisfactory rate, with no compromise of hemodynamic status because there was no preexisting AV synchrony. In the presence of sinus rhythm or sinus bradycardia with or without chronotropic competence, restoration of AV synchrony even in the acute situation of temporary pacing may be a desirable therapeutic goal in patients with acute AV block. Dual-chamber pacing with sensing of the native atrial complex and synchronous pacing of the ventricle restores both chronotropic response to activity (provided that sinus node activity is normal) and AV synchrony. Restoration of AV synchrony may result in substantial hemodynamic improvement in a patient in whom correction of bradyarrhythmia by ventricular pacing alone fails to increase cardiac output in the presence of acute RV infarction.218 Similar benefit has been shown for AV sequential pacing in the presence of anterior AMI.219,220 However, optimization of the AV delay apparently is also crucial, because an excessively long A-V interval may result in deterioration with complete loss of the advantages of AV sequential pacing over ventricular pacing alone.227,228 According to world pacing surveys, about 50% of patients with AV block receive permanent dual-chamber pacing devices.152,153,229 In patients with complete persistent AV block and underlying intact sinus node function, dual-chamber pacing maintains or restores AV synchrony at rest and also allows the rate to rise with activity. If sinus node function is impaired and chronotropic incompetence is present, the DDDR mode restores both AV synchrony and rate response to activity, although with substitution of a physiologic parameter other than the P wave. To simulate the physiologic behavior of the P-R interval during exercise, DDD and DDDR units are able to shorten the AV delay during activity-induced increases in heart rate.228 If the indication for permanent pacing is transient advanced AV block, and the patient is expected to be predominantly in sinus rhythm with normal AV conduction, a simple single-chamber VVI system may be adequate as a backup to provide a reasonable minimum heart rate. Restoration of chronotropic adaptation to activity may be achieved through VVIR and DDDR pacing, in which sensor detection of changes in various physiologic stimuli are used to adjust the pacing rate. The selection of a VVIR unit in preference to a VVI unit may be appropriate for patients with more frequent dependence on the pacemaker and a higher projected activity level, in the anticipation that increased cardiac output with activity is a desirable and reasonable therapeutic goal. If, for example, the patient has other comorbid conditions, such as a major stroke, and has minimal chance of regaining even modest levels

of activity, little would be gained through the use of the more expensive rate-adaptive VVIR mode. On the other hand, although rate-adaptive VVIR pacing can achieve increases in work performance and cardiac output, the maintenance of AV synchrony is desirable, particularly at slower heart rates and in patients with impaired ventricular function. Therefore, it has become accepted that in such patients, dual-chamber pacing is advantageous,230 and the VVIR mode would appear to be appropriate only for patients with no preexisting AV synchrony, such as those with permanent AF, those with atrial standstill (i.e., inability to pace the atrium), and those in whom the rate and hemodynamic demands on the pacemaker system are minimal even at rest. Another consideration in choice of pacing mode is the presence of concomitant paroxysmal supraventricular tachyarrhythmias. DDD(R) pacing units have mode-switch algorithms designed to detect and automatically change the pacing mode during atrial tachyarrhythmia episodes. These algorithms automatically switch the device from atrial tracking (DDD) to nontracking modes (DDI or VVI) during atrial tachyarrhythmias to prevent upper-rate tracking. The benefits of AV synchrony are maintained during sinus rhythm because the tachyarrhythmia is monitored and the unit automatically switches back to DDD(R) pacing when the arrhythmia terminates. For permanent pacing, the benefit of restoring the patient’s ability to increase heart rate with activity (chronotropic competence) should be considered. This may be accomplished through the use of VVIR/ DDDR modes in patients with chronotropic incompetence or VDD/ DDD modes in patients with normal sinus node function.231 In the absence of an ability to raise heart rate with activity, the only remaining mechanism for increasing cardiac output is to increase stroke volume. The magnitude of increase in cardiac output (<25%) achieved by this mechanism, however, is relatively small compared with what can be achieved by an increase in heart rate.232 Additionally, in the presence of myocardial dysfunction, the contribution of change in stroke volume to the adaptive response to activity is even more limited. Therefore, if chronotropic competence is impaired in patients with AV block, rate-responsive pacing is considered the preferred mode for improving cardiac output and work capacity during activity in patients with AV block. Furthermore, chronotropic incompetence may develop years after pacemaker implantation, as an acquired condition or induced by medications (e.g., β-blockers, antiarrhythmics).233 More than 95% of all pacemaker generators implanted in the United States have rate modulation as a programmable option. Despite this common clinical practice, the Advanced Elements of Pacing Trial (ADEPT), which compared dual-chamber pacing with and without rate modulation in patients who demonstrated chronotropic incompetence (assessed by specific protocol), failed to demonstrate a benefit of rateresponsive pacing mode on quality of life or exercise duration.234,235 About one third of the patients had AV block as an indication for pacing; whereas two thirds had sinus node dysfunction. In the subgroup of patients with AV block, peak exercise heart rate was higher in the DDDR group; however, there was no difference in exercise duration or quality of life between DDD and DDDR pacing modes. The adverse effects of ventricular dyssynchrony imposed by RV pacing may negate the potential benefits of rate responsiveness. The long-term outcome of patients with AV block who require permanent pacing is most strongly affected by the extent of myocardial dysfunction or the severity of the underlying coronary disease and ischemia. In a 2-year follow-up study of 2021 patients with permanent pacing, the leading causes of the 249 recorded deaths were stroke (30%) and sudden cardiac death (22%).236 The presence of BBB, which was seen predominantly in patients with AV block and MI, was a predictor of sudden cardiac death because 28% of all patients with BBB and 35% of patients with bifascicular or trifascicular block died suddenly. In comparison, the prevalence of sudden death in the remaining 138 patients without such block was 18%. Alpert et al.237 compared the prognoses of 132 patients with highgrade AV block and VVI pacemakers and of 48 patients with DDD pacemakers for high-grade AV block during a 1- to 5-year follow-up. Permanent dual-chamber pacing increased survival more than



permanent VVI pacing in a subgroup of patients with preexisting congestive heart failure (CHF). However, because this was a nonrandomized trial, selection bias may have affected the results. The causes of CHF were variable; about 50% of patients had underlying ischemic heart disease, and the rest had hypertension, valvular heart disease, or idiopathic dilated cardiomyopathy. Most deaths in the patient group with VVI pacemakers were caused by AMI or CHF. Evaluating pacing mode selection in patients with chronic AV block, the United Kingdom Pacing and Cardiovascular Events (UKPACE) trial compared the long-term clinical impact and cost-effectiveness of DDD versus VVI or VVIR pacing in patients 70 years or older with high-grade block undergoing their first pacemaker implantation.238 Between 1995 and 1999, 2021 patients (mean age, 80) were enrolled at 46 centers. One-half the patients were randomly assigned by pacing system hardware to single-chamber pacing (25% VVI and 25% VVIR) and one-half to dual-chamber pacing. Patients were followed for a median of 4.6 years, and clinical events were censored at last follow-up for up to 3 years. There was no significant difference after 5 years of follow-up in the primary endpoint, all-cause mortality, between the single-chamber and dual-chamber groups. Likewise, there were no significant differences in the rates of AF, heart failure, or thromboembolism between the two groups. Thus, in elderly patients with AV block, dual-chamber pacing does not influence all-cause mortality or cardiovascular outcomes in the first 5 years after pacemaker implantation. VDD(R) PACING Despite its availability for more than 20 years, VDD pacing is used in less than 1% of patients receiving pacemakers in the United States and in only 6% in Canada, according to the world survey of cardiac pacing for the calendar year 2005.229 VDD pacing is used more widely in other areas of the world, but its use from country to country is highly variable, ranging from 0% to 20% in South America, Europe, and the Asian-Pacific and Middle East regions. The overall use of single-lead VDD pacing systems fell between the 2001 and 2005 surveys, but substantial use still persisted in Italy, Spain, and Japan. A VDD pacing system uses a single-pass lead with a far-field, floating atrial sensing bipole as well as ventricular electrodes for pacing and sensing. The single VDD lead offers a simpler approach to provide AV synchronous pacing that avoids implantation of two separate pacing leads, thus limiting implanted hardware. VDD or VAT pacing allows preservation of normal AV synchrony and rate responsiveness and is an appropriate pacing mode for patients with high-grade block or CHB and normal sinus node function.231,239 Furthermore, VDD pacemaker implantation can be performed at lower cost and with shorter implantation time than other dual-chamber systems.240-242 Therefore, VDD pacing is a viable alternative to DDD pacing for treatment of patients with high-grade AV block, normal sinus node function, and no need for atrial pacing.21,240-244 The implantation procedure for a VDD system consists of fixing the ventricular tip to allow the atrial electrodes to lie as close as possible to a high-middle location of the lateral RA wall (Fig. 14-22). Care must be taken to ensure an adequate safety margin and amplitude of the atrial signal (>2.0 mV) at implantation to avoid significant atrial undersensing. An atrial signal should be measured at rest, during deep breathing, and during coughing as well as during arm and shoulder movements. The lowest acceptable atrial electrogram (AEGM) signal during any maneuver should be at least 0.5 to 1.0 mV during deep inspiration.231,239 In one study, the mean maximum and minimum values of AEGM characteristics within a complete respiratory cycle were 2.64 ± 1.05 mV and 1.65 ± 0.38 mV amplitude (maximum) and 0.31 ± 0.12 mV and 0.18 ± 0.09 mV (minimum).239,243-245 In general, there is considerable variability between patients and within individuals from moment to moment with respect to AEGM amplitude; for example, it can decrease greatly during exercise. Single-lead VDD pacing is best avoided if the atrial chamber diameter of the right atrium is greater than 3 × 3 cm and if the left atrium is larger than 4

14  Pacing for Atrioventricular Conduction System Disease

347

Figure 14-22  Lateral chest radiograph showing single atrioventricular (AV) lead with narrow-spaced AV ring electrodes connected to a LEM Biomedica/Cardiac Control Systems VDD pacemaker. Arrows indicate atrial electrodes. (From Antonioli EG, Ansani L, Barbieri D, et al: Singlelead VDD pacing. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing, 3. Mt Kisco, NY, 1993, Futura, pp 359-381.)

× 3 cm in the echocardiographic apical four-chamber view. Patients with paroxysmal supraventricular tachyarrhythmias probably should not receive VDD pacemakers. Various electrode configurations for VDD leads have been studied, including bipolar leads with narrow and wide spacing and orthogonal and diagonal atrial electrodes. The optimal spacing of two poles in the floating bipolar lead is 0.5 to 1 cm. Factors influencing AEGM detection include electrode spacing, distance from the atrial wall, orientation of electrodes relative to atrial tissue, and electrode size. Lau et al.246 compared the clinical performance of two systems: a diagonally arranged bipole and closely spaced bipolar ring electrodes. The clinical performance of atrial sensing was similar despite the different electrode configuration. Concerns have been expressed about the long-term reliability of VDD pacing systems with regard to atrial sensing performance of floating VDD leads. Studies with early models of VDD leads reported a high incidence of failure of the floating atrial electrodes with deterioration of atrial pacing and sensing characteristics over time. In one early study, Ramsdale and Charles247 reported difficulty in obtaining an adequate P-wave amplitude at implantation, resulting in prolonged implantation time. Almost 60% of patients showed intermittent failure of P-wave sensing. Marked fluctuations in the paced ventricular rate were noted especially during exercise, when intermittent failure to sense P waves occurred. In other older series, however, atrial pacing and sensing were maintained for 5 years in almost 90% of patients.248 In a 2003 study, Huang et al.249 compared the long-term reliability and complication rates of VDD pacing in 112 consecutive patients with symptomatic AV block and intact sinus node function who received a single-pass bipolar VDD system and in 80 patients who received DDD pacing for the same indication. Implantation times were shorter for VDD systems than for DDD systems (63 ± 20 vs. 97 ± 36 minutes; P < .0001). P-wave amplitude at implantation was lower in the VDD patients but remained stable during long-term follow-up, such that AV synchrony was maintained in 94% to 99% of beats in the VDD group, and only two patients in the VDD group required reprogramming to VVIR mode during follow-up (18 ±10 months). Thus, clinical trials of VDD pacing systems have shown overall good clinical performance.250

348

SECTION 2  Clinical Concepts

Linde-Edelstam et al.251 performed a case-control study comparing consecutive patients who received VDD pacemakers with the firstavailable VVI patients who fulfilled certain “predetermined characteristics.” The two groups were similar with respect to other concomitant diseases and CHF severity. The investigators compared survival in 74 patients treated with VVI pacemakers and in 74 patients with VDD pacemakers over mean follow-up of 5.4 years. The overall survival was better in patients with the VDD pacing mode than in the age-and gender-matched general Swedish population. Survival was no different between patients paced in the VVI and VDD modes if CHF was absent. Pacemaker programming of VDD systems should take into account atrial sensitivity as well as programming of the postventricular atrial refractory period (PVARP), AV delay, and lower rate. Some degree of atrial undersensing (~5% of beats) is often seen during ambulatory ECG monitoring and exercise testing of VDD systems, but rarely is a clinically significant problem when the pacemaker is programmed at high atrial sensitivity (≤0.3 mV). P-wave amplitude should be tested during maneuvers that simulate daily activities, such as coughing, hyperventilation, arm swinging, isometric exercises, and respiration. Some generators allow programming of the bandwidth of the atrial amplifier. This may attenuate interference and oversensing from myopotentials as well as retrograde P waves in patients with ventricular ectopy.245 VDDR generators with programmable atrial amplifier bandwidths allow the implanter to minimize the sensing of myopotentials and retrograde P waves, thus avoiding the need for programming long PVARPs. This period should be programmed to contain retrograde P waves. The AV delay must take into account the delay in detecting atrial depolarization. The lower rate should be programmed to a value below the minimum sinus rate noted during a 24-hour Holter recording. Patients with retrograde VA conduction may experience symptoms if their sinus rate frequently falls below the lower programmed rate, leading to VVI pacing at the lower rate. One can avoid this problem by obtaining a 24-hour Holter monitor recording and then programming the lower rate to a rate below the slowest recorded sinus rate. Atrial oversensing from the floating dipole during upper-body isometric exercises involving the pectoral muscles is an uncommon clinical problem. Use of the VDDR pacing mode allows the option of employing the sensor to differentiate sinus tachycardia from the tracking of myopotentials. The implanted sensor can be used to judge the appropriateness of the atrial rate. In addition, the rate-adaptive sensor allows for rate smoothing of upper-rate behavior. However, ventricular pacing and loss of AV synchrony can arise during exercise if the sensor rate exceeds the sinus rate, or when the atrial rate is slower than the programmed lower rate. Enthusiasm for the VDD pacing mode in North America likely will remain very limited, because implantation of atrial pacing leads is routine and highly reliable with a very low complication rate. In the practices of most implanters, the additional risk and work of positioning an atrial lead do not outweigh the disadvantage of lacking atrial pacing. On the other hand, if a patient experiences sinus node dysfunction and a need for atrial pacing arises, upgrading to a DDDR pacing system can be easily performed.252 OPTIMAL ATRIOVENTRICULAR INTERVAL PROGRAMMING Hemodynamics during dual-chamber pacing is influenced by the A-V interval. During dual-chamber pacing in patients with high-grade AV block, an appropriate electrical A-V interval must be programmed to maintain mechanical synchronization of cardiac chambers (i.e., mechanical AV synchrony). Programming excessively short A-V intervals may result in cannon A waves (i.e., atrial contraction against a closed mitral valve), whereas diastolic mitral regurgitation may occur with excessively long programmed A-V intervals. The A-V interval is considered optimal if it results in maximum cardiac output. A-V interval optimization provides the best timing of LA filling and LA systole. Appropriately timed atrial systole improves LV performance, reduces

mean atrial pressure, and maximizes LV end-diastolic pressure by coordinating AV valve closure, facilitating venous return, and increasing preload. Optimal AV synchrony not only maximizes cardiac output by increasing ventricular preload, thus lowering mean atrial pressure, but also minimizes diastolic mitral regurgitation. Under most circumstances in patients with normal LV function at rest, the optimal A-V interval lies between 100 and 200 msec.253,254 However, shorter A-V intervals have been proposed as a means of achieving higher cardiac output in patients with AV block and dilated cardiomyopathy. Hochleitner et al.255 generated interest when they reported functional improvement in patients with dilated cardiomyopathy who were treated with AV pacing using a short AV delay of 100 msec. Unfortunately, results of this original uncontrolled study could not be reproduced by others. Subsequent studies suggested that the benefit of such an approach with a very short AV delay may be confined to patients with long P-R intervals and significant diastolic mitral regurgitation.256,257 On the other hand, very long A-V intervals may be required to provide effective LA systole in occasional patients with high-grade interatrial conduction delay in the presence of atrial disease and either sick sinus syndrome or heart block. The usual nominally programmed A-V intervals, 125 to 175 msec, may not provide optimal AV synchrony in these patients, and AV delays as long as 250 to 350 msec may be required.253 Such long A-V intervals, however, result in long total atrial refractory periods and limit the upper rate possible during exercise. An alternative approach is to shorten intraatrial conduction time in these patients with RA septal or biatrial pacing.254 Some investigators suggest that when the AV delay is selected empirically, it is incorrectly programmed in approximately two thirds of patients, and the potential contribution of a correctly timed AV delay to cardiac output varies from 13% to 40%.258,259 The optimal A-V interval can vary considerably from patient to patient and is difficult to predict beforehand. Furthermore, AV optimization may be difficult to achieve in any patient, and although generally measured while the patient is supine and at rest, the value may not be applicable while the patient is upright and active. Although many factors are important in the attempt to define the optimal A-V interval—the atrial pacing site, intra-atrial conduction time, atrial size, ventricular function, heart rate, body position, autonomic tone, catecholamine levels, whether the atrial event is paced or sensed—and their interrelationships are variable and complex, a major determinant of the optimal AV delay in an individual patient is the interatrial conduction time. The duration of the optimal A-V interval varies among individuals, substantially as a result of differences in interatrial conduction. The interatrial conduction time determines when the LA depolarization begins and therefore directly determines the LA-LV timing interval. Programming differential A-V intervals for sensing and pacing may give rise to small but significant increases in cardiac output in patients with LV dysfunction, because of differences in paced versus sensed atrial conduction times.253,254 A variety of techniques have been used to determine the optimal A-V interval by comparing the calculated stroke volume at different A-V intervals, as measured by continuous-wave cardiac Doppler echocardiography of the aortic valve, right-sided heart catheterization, radionuclide ventriculography, myocardial thallium scintigraphy, or transthoracic impedance cardiography.260 Ritter’s method of A-V interval optimization, which uses Doppler echocardiography of the mitral valve inflow profile, is the most widely applied technique261 (Fig. 14-23). This technique is based on the assumption that the AV delay that maximizes cardiac output is the one that provides the longest LV filling time without interruption of the A wave (atrial contraction wave) and allows ventricular systole to begin immediately subsequent to maximum diastolic ventricular filling, thus avoiding cannon A waves and diastolic mitral regurgitation. The technique has been validated in patients with both normal and depressed LV function. However, the Ritter method is time-consuming, is subject to significant variability between consecutive measurements, cannot be reliably performed during exercise, and is not readily available in routine



14  Pacing for Atrioventricular Conduction System Disease

349

AV short a

AV long

b

Determination of “a”

Determination of “b”

Figure 14-23  Ritter’s method for determination of the optimal atrioventricular (AV) interval using the following formula: AVopt = AVlong −(a − b). The first step is determination of “a” for a nonphysiologically short A-V interval (e.g., 125 msec), followed by determination of “b” for a nonphysiologically long A-V interval (e.g., 250 msec). The value “a,” the temporal interval between the ventricular contraction spike and the end of the A wave, designates the electromechanical delay between right ventricular stimulation and the beginning of the left ventricular systole (i.e., closure of the mitral valve). The value “b” is the temporal interval between the ventricular contraction spike and the end of the A wave. (From Melzer C, Borges A, Knebel F, et al: Echocardiographic AV-interval optimization in patients with reduced left ventricular function. Cardiovasc Ultrasound 2:30, 2004.)

pacemaker follow-up clinics. An alternative, simplified approach has been proposed that uses the surface ECG alone and defines the optimal AV delay on the basis of a delay of 100 msec from the end of the surface P wave to the peak/nadir of the paced ventricular complex262 (Fig. 14-24). Rate-adaptive A-V interval shortening or automatic rate-adaptive AV delay is a programmable feature on many DDD pacemaker generators, designed to mimic the normal physiologic response of the P-R interval to rising heart rates.263 A-V intervals may be shortened further during atrial tracking; when the patient exercises and the heart rate increases, the sensed P wave to ventricular pacing stimulus can be shortened. This can be accomplished as one-step shortening or multistep shortening in discrete, nonprogrammable, or linear steps as the atrial rate increases. Compared with fixed A-V interval without rate adaptation, rate-adaptive A-V interval shortening improves exercise tolerance by improving stroke volume and prolonging systolic ejection time.264,265 The assumption behind the shortening of the P-V or A-V interval is that it maintains the proper timing of the atrial contraction and thereby optimizes stroke volume (Fig. 14-25). With the shortened P-V (or A-V) intervals, however, there may be a greater proportion of ventricular pacing in patients with intermittent or catecholamine-sensitive AV conduction. If this results in fewer intrinsic beats and more RV pacing, there may be no improvement in hemodynamics and potentially even a worsening of hemodynamics in some patients. The minimum value below which the AV delay is not shortened is calculated on the basis of the programmed pacing rate and the upper ventricular rate limit. In the DDDR mode, the paced AV delay shortens as the pacing rate increases in response to the sensor. The sensed AV delay can also be adapted to the atrial rate on a beatby-beat basis, with linear shortening occurring between maximal and minimal values, the net result being a shortening of the total atrial refractory period, thereby allowing higher 1 : 1 tracking rates. Atrial-based, dual chamber, minimal ventricular pacing algorithms are available in dual chamber pacemakers and ICDs that are designed

to minimize the frequency of undesirable, RV pacing without an increased risk of symptomatic AV block. These algorithms, including managed ventricular pacing (MVP), AAISafeR2 mode, ventricular intrinsic pacing, and AV search hysteresis, have been applied to patients with sinus node dysfunction or intermittent AV block who do not require continuous or frequent ventricular pacing support.266,267 MVP and AAISafeR2 can switch from DDD to AAI mode and pace (or detect) the atria but continue to monitor AV conduction (Figs. 14-26 and 14-27). If a critical number of P waves are not followed by a QRS complex, the pacemaker switches automatically to the DDD/R pacing mode. Gillis et al.268 reported that MVP reduced ventricular pacing by 99.1% in pacemaker patients with sinus node dysfunction and by 60.1% in patients with intermittent heart block compared with the DDD/R mode, without sacrificing AV synchrony. In patients with permanent or intermittent AV block, however, the safety of MVP mode has been questioned. The MVP algorithm permits pauses to occur and delivers backup ventricular pacing only after two atrial events are sensed with no intervening ventricular sensed event. By permitting pauses, MVP may promote the occurrence of shortlong-short coupling intervals that may be proarrhythmic. Sweeney et al.269 assessed the importance of abrupt changes in ventricular cycle lengths in triggering ventricular tachyarrhythmic events in ICD patients. In that study, a total of 351 arrhythmia episodes were recorded in patients with MVP programmed, and 8.2% of these were classified as pacing-facilitated short-long-short-initiated events. Consistent with these observations, case reports have documented pause-mediated polymorphic ventricular tachycardia/ventricular fibrillation developing in patients with permanent or intermittent AV block with MVP programmed “on”270,271 (Fig. 14-28). This potentially life-threatening adverse effect may be especially deleterious in patients with pacemakers and not ICDs. Other pacemaker rhythm anomalies have been associated with MVP mode in patients with AV block. In patients with intact but severely impaired AV conduction, MVP enhanced AV decoupling by promoting very long, AV-PR intervals (>300 msec).272

350

SECTION 2  Clinical Concepts

140

200

250

II

III

aVR

aVL

aVF A-Stim to E-PW

E-PW to QRSnadir

AVintervalprog

Figure 14-24  Determination of optimal paced atrioventricular (AV) delay (AVDopt) by surface electrocardiogram. First, a long AV delay of 250 msec was programmed (AVDprog, programmed interval from atrial to ventricular stimulus). The interval from the end of the P wave to the peak/nadir of the paced ventricular complex (T) was 200 msec. The interval atrial stimulus to the end of P wave (= global atrial conduction time) was 140 msec. According to the algorithm AVDopt = AVDprog + 100 − T the optimized AV delay was 150 msec. A-Stim to E-PW, Interval between the pacing stimulus and the end of P-wave deflection; E-PW to QRSnadir, end of P wave to peak/nadir of paced QRS; AV-intervalprog, long AV delay programmed for testing. (From Strohmer B, Pichler M, Froemmel M, et al: Evaluation of atrial conduction time at various sites of right atrial pacing and influence on atrioventricular delay optimization by surface electrocardiography. ELVIS Study Group. Pacing Clin Electrophysiol 27:468, 2004).

Functional atrial undersensing during the AAI mode of MVP from a long, nonprogrammable atrial refractory period (600 msec if heart rate <75 bpm, or 75% of R-R cycle length if heart rate ≥75 bpm) reportedly caused pacemaker syndrome in a patient with intermittent second-degree AV block; similarly, it resulted in inappropriate atrial pacing in a patient with a slow atrial tachyarrhythmia and complete AV block.273,274 Therefore, careful consideration should be given to the use of MVP algorithms in patients with permanent or transient AV block. SITE-SPECIFIC VENTRICULAR PACING IN AV BLOCK The right ventricular apex (RVA) has been accepted as the traditional ventricular pacing site for decades. The RVA site allows easy placement of endocardial leads while providing stable and reliable long-term pacing parameters. RVA pacing imposes ventricular desynchronization, however, and leads to a myriad of adverse effects on LV systolic and diastolic function, hemodynamics, coronary perfusion, and myocardial structure.275-287

7

Fixed AV delay RAAVD

6 Cardiac index (L/mn/m2)

I

The harmful effects of RVA pacing manifested clinically as an increased risk of heart failure hospitalization, or death associated with an increased frequency of cumulative RV pacing, in the Dual Chamber and VVI Implantable Defibrillator (DAVID) study, Mode Selection Trial (MOST), and Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II).288-290 However, AV block was not the indication for permanent pacing in any of these trials. In the Post AV Nodal Ablation Evaluation (PAVE) trial, patients with chronic AF refractory to pharmacologic therapy underwent radiofrequency catheter ablation of the AV junction, followed in a randomized manner by either RVA or biventricular pacing.291 LV ejection fraction in the RVA pacing group declined from 44.9% before implantation to 40.7% at 6 months. In contrast, LVEF in the biventricular pacing group remained stable over follow-up (45.6% vs. 46.0%, respectively) and was significantly lower in the RVA group than in the biventricular group after 6 months (46.0% vs. 40.7%; P = .03). The deleterious long-term effects of RVA pacing were also demonstrated in a study of 23 young adult patients (24 ± 3 years) with congenital complete AV block who underwent at least 5 years of RVA pacing.50 After 10 ± 3 years of RVA pacing, these patients exhibited abnormal indices of LV intraventricular dyssynchrony, asymmetrical hypertrophy, and dilation as well as lower exercise capacity compared with values in the patients before pacemaker implantation and with values found in matched healthy control subjects. Thus, RVA pacing may lead to deterioration of LV function and CHF caused by LV desynchronization. Although the adverse effects of RVA pacing are well substantiated, the majority of patients who receive pacemakers for standard bradycardia indications do not experience heart failure (HF). In MOST, only about 10% of patients experienced at least one HF hospitalization during a median follow-up of 3 years.289 Sweeney and Hellkamp292 identified clinical variables predictive of HF hospitalization in MOST and suggested that the adverse effects of RV pacing are modulated by the underlying cardiac substrate and frequency of RV pacing. Patients with a very-low-risk substrate (normal LVEF, no history of HF or MI, normal baseline QRS duration) have a correspondingly low risk of HF hospitalization (<2% over 2 years). On the other hand, patients with a very-high-risk substrate (low LVEF, MI, history of symptomatic heart failure, and QRS duration ≥120 msec) have a greatly increased risk of HF hospitalization, almost 40-fold higher compared with patients with a low-risk substrate. Thus, ventricular desynchronization from RVA pacing is less tolerated in patients with preexisting systolic HF. Therefore, efforts to minimize RVA pacing should be greater in patients with poorer cardiac function, larger mechanical asynchrony, and a longer

5 4 3

p = 0.035

2 1 0

2

4

6

8

10

12

14

16

18

20

(mn) Figure 14-25  Comparison of an automatic rate-responsive atrioventricular delay (RAAVD) and a fixed but individually optimized (by Doppler echocardiography) AV delay in a patient with a DDD pacemaker implanted over the long term for complete AV block. At each exercise level, and especially at peak exercise (arrow), rate-responsive AV delay produced a significantly higher cardiac index (CI) than the fixed value. mn, Minutes. (From Daubert C, Ritter P, Mabo P, et al: AV delay optimization in DDD and DDDR pacing. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing 3. Mt Kisco, NY, 1993, Futura, pp 259-287.)



14  Pacing for Atrioventricular Conduction System Disease

351

DDD/R A S

A S

A S

V P

A S

V P

A S

A S

V P

V P

Loss of AV conduction

Programmed SAV delay

A S

V P

Loss of AV conduction

Ventricular backup pace at 80 ms after the scheduled AP

Ventricular backup pace at 80 ms after the scheduled AP

Figure 14-26  Managed ventricular pacing (MVP) mode demonstrating atrioventricular (AV) conduction criteria to switch from AAI/R+ to DDD/R modes. MVP is an enhanced AAI/R mode that continuously monitors ventricular activity for loss of AV conduction and switches to DDD/R mode during AV block. For transient loss of AV conduction (an A-A interval that is missing a ventricular sensed event), a ventricular backup pace is provided and AAI/R pacing continues. For persistent loss of AV conduction (defined as two of four A-A intervals missing a ventricular event), MVP switches to the DDD/R mode for 1 minute. Tests for return of normal AV conduction are performed by inhibiting ventricular pacing for one cycle. If AV conduction is detected, the mode of operation returns to AAI/R with ventricular monitoring. (Figure from Sweeney MO: Algorithms for minimizing right ventricular pacing. In Amin AA, Ellenbogen KA, Natale A, Wang P, editors: Pacemaker and implantable cardioverter defibrillators: an expert’s manual. Minneapolis, 2010, Cardiotext.)

expected duration of pacing, as typically seen with an ICD population. In contrast, most pacemaker patients tolerate chronic RVA pacing reasonably well because usually they have normal ventricular function, no HF history, and normal baseline QRS duration. Growing recognition of the long-term adverse effects of RVA pacing has stimulated interest in strategies to promote physiologic pacing and to minimize or eliminate the deleterious effects. There is controversy, however, regarding the optimal ventricular pacing sites and approach in patients undergoing permanent pacemaker implantation for AV block in whom ventricular pacing cannot be avoided.293 Some investigators advocate LV or biventricular pacing, whereas others suggest a role for selective-site RV pacing. Alternative RV pacing sites (i.e., non-RVA), including the His bundle, RV septum, RV outflow tract (RVOT), and dual-site right ventricle, have been investigated, but the benefits of alternative-site pacing remain unresolved.293-306 The mixed results are difficult to interpret because of small numbers of patients, wide ranges of LV function and underlying heart disease, lack of

standardization of alternative RV pacing sites, differing endpoints, and short duration of follow-up. The His bundle is an ideal RV stimulation site from a hemodynamic standpoint. However, the technical challenge of long-term implementation of permanent His bundle pacing using current lead technology is the major obstacle to its reliable application in routine clinical practice. In a report that demonstrated the feasibility of this approach in a small number of patients after AV junction ablation, excessively high pacing thresholds, unreliable sensing, and failure to achieve consistent pacing were found in a subset of patients.294 Furthermore, the complexity of achieving selective His bundle pacing and the potential for unpredictable distal His-Purkinje conduction make it unlikely to become an accepted alternative RV pacing site in the future. Other studies evaluating long-term stimulation of the interventricular septum from the right ventricle as a potential alternative site demonstrate encouraging preliminary results in a small number of patients.304,305

MODE SWITCH AAI/DDD

179

179

179

546

546

546

Ap

179

Ap

546

Ap

179

Ap

546

Ap

179

Ap 546

Ap 171

Vs

178

265

812

Ap

1000

Vs

Ap 1070

Vs

570

546

531

Vs

Ap

289

Ap

265

Ap

Vp

Vp

Vp

Vp

Vp

Vp

Vp

Type

Start time

AVB III AVB II AVB III exercise AVB II exercise AVB III exercise AVB II exercise AVB III exercise

04/Oct/2004 11:22 08/Oct/2004 17:14 11/Oct/2004 09:53 11/Oct/2004 09:54 11/Oct/2004 09:55 18/Oct/2004 11:07 22/Nov/2004 10:43

Figure 14-27  Pacing mode (AAISafeR2) switch to DDD in response to second-degree atrioventricular block (AVB) during exercise. The device automatically switches to DDD(R), and uses the programmed AV delay(s) in response to >3 blocked atrial events (As/Ap events without Vs) in the last 12 consecutive cycles (second-degree AVB). The device will also switch to DDD(R) if (1) >2 consecutive blocked atrial events (As events without Vs) (high-degree AVB); (2) a ventricular pause of programmable duration (between 2 and 4 sec); or (3) >6 consecutive long AR/PR intervals (AS-VS > 350 msec or AP-VS > 450 msec; programmable) (a situation similar to first-degree AVB) are detected. The atrial and ventricular electrograms are shown on the upper, and the atrial and ventricular markers on the lower tracing. Ap, Atrial pacing; Vp, ventricular pacing; Vs, ventricular sensing. (From Fröhlig G, Gras D, Victor J, et al: Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular pacing. Europace. 8:96101, 2006.)

352

SECTION 2  Clinical Concepts

AEGM

VEGM

9 9 0

A P V S

1000

1000

A P

V P

1810

1530

A P V P

V S

3 5 0

3 3 0

T F

9 1 0

A R V S

3 4 0

2 8 0

T F

T F

3 0 0

F S

2 6 0

8 7 0

A R F S

2 5 0

2 2 0

F S

1 9 0

F S

2 4 0

F S

9 1 0

A R

2 3 0

F S

2 2 0

F S

2 2 0

F S

2 4 0

7 3 0

A R

F S

2 2 0

F S

2 5 0

F S

2 4 0

F S

2 4 0

A R F S

2 6 0

F S

AEGM

VEGM ATP 1330

2 6 0

F D

2 2 0

T P

2 2 0

T P

6 2 0

A S

2 2 0

T P

2 2 0

T P

2 2 0

T P

2 2 0

T P

6 8 0

A S

2 2 0

T P

2 2 0

T P

5 6 0

A S

6 0 0

V S

2 3 0

F S

5 7 0

A R

2 9 0

F S

3 3 0

F S

5 5 0

A R

2 8 0

F S

2 5 0

F S

5 0 0

A R

2 4 0

F S

2 5 0

F S

5 0 0

A R

2 5 0

F S

2 5 0

F S

5 1 0

A R

2 4 0

F S

2 9 0

F S

8 3 0

A R

4 0 0

V S

6 3 0

A S

8 1 0

V S

A S

6 4 0

V S

VF VF Rx 1 burst before charging Figure 14-28  Polymorphic ventricular tachycardia (VT) caused by managed ventricular pacing (MVP). Stored atrial (AEGM) and ventricular (VEGM) electrograms of an episode of polymorphic VT leading to implantable cardioverter-defibrillator (ICD) therapy. The pacemaker initially paces in the atrium when transient AV block occurs. Because of MVP operation, a ventricular pause of 1810 msec occurs. A ventricular premature coupling at a coupling interval of 360 msec initiates a run of polymorphic VT. Antitachycardia pacing (ATP) is delivered by the ICD without successful termination of the arrhythmia. The VT then spontaneously terminates with resumption of sinus rhythm and intact AV conduction. Resumption of AV conduction is associated with a faster sinus rate consistent with a decrease in vagal tone. (From Vavasis C, Slotwiner DJ, Goldner BG, Cheung JW: Frequent recurrent polymorphic ventricular tachycardia during sleep due to managed ventricular pacing. PACE 33:641–644, 2010.)

A review of randomized studies published before 2003 concluded that pacing from the RVOT results in a modest but significant benefit in terms of acute hemodynamic function, particularly in patients with impaired ventricular function.302 However, in the RV Outflow Versus Apical Pacing (ROVA) trial, RVOT and dual-site RV pacing (sequentially from RVOT and RVA) shortened the paced QRS duration but did not consistently result in better quality of life, functional class, exercise capacity, or LVEF than RVA pacing after 3 months.301 ROVA enrolled patients with chronic atrial fibrillation, New York Heart Association (NYHA) Class II or III heart failure, and LV systolic dysfunction (EF ≤ 0.40) who were undergoing permanent VVIR pacing for bradycardia indications; this included AV junction ablation in 64% and chronic AV block in the remaining patients. Likewise, at least two other studies that limited follow-up to 3 to 6 months failed to demonstrate a benefit of RVOT pacing.297,303 In the only published study of long-term RVOT pacing, Tse et al.300 investigated the effects of ventricular pacing site on myocardial perfusion and LV function in 24 patients with high-grade AV block who were randomly assigned to receive RVA or RVOT pacing leads. At 6 months, the incidence of myocardial perfusion defects, regional wall motion abnormalities, and LVEF were similar during RVA and RVOT pacing. At 18 months, however, patients with RVOT

pacing had fewer myocardial perfusion defects, fewer regional wall motion abnormalities, and higher EFs than those with RVA pacing. In view of the lack of sufficient long-term data, it seems premature to abandon completely the traditional RVA pacing site in hopes of preserving ventricular function in patients who require ventricular pacing for AV block. Large, long-term, randomized multicenter studies are needed to determine the impact of nonapical RV pacing sites on major clinical outcomes, including HF hospitalization and death, before a definitive recommendation can be made that selective-site RV pacing prevents the deleterious effects of RVA pacing.306 In patients with significant LV dysfunction (EF ≤ 0.35), biventricular (BiV) pacing seems to be a more attractive approach than RVOT or RV septal pacing in patients with significant AV conduction disturbances who require ventricular pacing support. However, the role of BiV pacing in pacing with AV block and a normal LVEF or only modest depression of LV function remains unsettled. In a study of 177 patients with bradycardia and a normal EF in whom a BiV pacemaker had been successfully implanted, patients randomized to undergo RV pacing had a lower mean LVEF (54.8 ± 9.1% vs. 62.2 ± 7.0%; P < .001) and a larger LV end-systolic volume (35.7 ± 16.3 mL vs. 27.6 ± 10.4 mL; P < .001) than patients in the BiV pacing group at 12 months.307 The



14  Pacing for Atrioventricular Conduction System Disease

Biventricular versus RV Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) study is another ongoing, prospective randomized trial comparing RV with BiV pacing in patients with mild to moderate heart failure (NYHA Class I, II, or III), LV dysfunction (LVEF ≤0.50), and AV block.308 This study is designed to determine whether BiV pacing will slow HF progression. As of 2010, enrollment in BLOCK HF has been completed and follow-up is ongoing. The Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) trial compares the long-term effects (5-year follow-up) of conventional dual-chamber and BiV pacing in patients without any indication for CRT.309 The findings of these studies may further enlarge the population of patients in whom biventricular pacing is indicated.

The first algorithm capable of detecting effective cardiac stimulation after a delivered pulse and adapting RV pacing output according to measured threshold was introduced in 1995 (Autocapture, St. Jude Medical) in a single-chamber pacemaker and later in 1998 in a dualchamber pacemaker. Algorithms for automatic management of stimulation are also available from other manufacturers (Ventricular Capture Management, Medtronic; Automatic Capture, Boston Scientific; Capture Control, Biotronik; Autothreshold, sarin). The algorithms differ, but the basic features of autocapture algorithms comprise four, fully automatic pacemaker functions: capture confirmation, backup high-voltage pulse, threshold search, and output regulation. Virtually every device has one or more unique pacing system behaviors that may occur all the time or in special circumstances. These device eccentricities represent normal, but at times unexpected, device functioning that may raise concern about a system problem, such as confusion created by unanticipated delivery of a backup safety pulse after a ventricular fusion beat on a telemetry tracing during normal autocapture operation. Therefore, it is important at least to be aware of these functions to avoid raising concerns about a pacing system problem. All ventricular autocapture algorithms rely on sensing the evoked response to the test pulse (Figs. 14-29 and 14-30). Capture is confirmed by the ability to detect the presence or absence of an evoked-response potential by the pacemaker circuitry. If the characteristics of the evoked-response signal differ from what is expected, the pacemaker assumes loss of capture. Some algorithms confirm capture on a beatto-beat basis (Autocapture, St. Jude Medical; Automatic Capture, Boston Scientific; Capture Control, Biotronik). Alternatively, the pacemaker automatically monitors threshold by performing a pacing threshold search to determine the threshold at programmable or at fixed periodic intervals (Capture Management, Medtronic). After automatic confirmation of beat-to-beat capture or periodic threshold determination, the pacemaker regulates the output to provide a small margin above the capture threshold that is adequate and safe and will decrease energy consumption. In some devices, the safety margin is programmable. In case of noncapture, the device provides a backup safety pulse at high output. In autocapture pacemakers, there are two sense amplifiers to sense spontaneous R waves and the evoked response. The standard ventricular sense amplifier is absolutely refractory at a time when the evokedresponse signal is present. In the St. Jude Autocapture algorithm, after delivery of a pacing pulse, the evoked-response sense amplifier is blanked for 14 msec (so as to disregard the residual polarization effects

Automatic Capture Verification and Pacing Output Management Algorithms for automatic capture verification monitor cardiac capture on a beat-to-beat basis and deliver an output just above the capture threshold while providing a high-output backup safety pulse in the event of noncapture. The advantages and benefits of automatic capture include increased device longevity, enhanced patient safety, and improved device follow-up. In one study, having the autocapture feature programmed “on” extended the projected device longevity by approximately 16%.310 In a more recent, prospective study, RV stimulation by autocapture was superior in actual pacemaker longevity to fixed-output, RV pacing at nominal device settings (3.5 V at 0.4 msec).311 Pacemaker replacement occurred in 1 of 34 patients (2.9%) whose pacemakers were programmed to autocapture pacing after 105 months, compared to 60 of 92 patients (65%) whose pacemakers were programmed to fixedoutput pacing after a median service life of 82 months (P <.001). Autocapture pacing was the best independent predictor of pacemaker longevity. Adverse clinical events, including syncope caused by ventricular pacing exit block with an increased ventricular threshold, occurred in two patients programmed to fixed-output pacing and no patients with autocapture pacing. Thus, autocapture algorithms may offer increased safety in patients with large, or unanticipated, ventricular threshold variations by providing automatic threshold tracking and output regulation on a beat-to-beat basis or at periodic intervals. Lastly, autocapture management algorithms will inevitably assume increasing importance in the era of remote device follow-up. Figure 14-29  Commanded automatic threshold test from Boston Scientific pacemaker. Electrocardiogram lead II, ventricular electrogram, ventricular evoked response (V-ER), marker channels, and ventricular outputs (1.5 V, 1.3 V) are shown. After two beats of ventricular noncapture, a high-output, backup ventricular pacing (VP) pulse is delivered. After an initial successful threshold test, this manufacturer’s Automatic Capture algorithm enters into a beat-to beat mode, where output is the threshold plus 0.5 V (pulse width, 0.4 msec). The ambulatory threshold test will be automatically performed by the device every 21 hours or if there is a confirmed loss of capture. If the ambulatory threshold test successfully determines a threshold, beat-to-beat mode will resume. Otherwise, Automatic Capture will enter retry mode, and the ventricular output will increase to two times the threshold between 3.5 V and 5.0 V, with a pulse width of 0.4 msec, for up to 21 hours. While in beat-to-beat mode, if a confirmed loss of capture is detected within 1 hour of the last threshold test, Automatic Capture will enter into retry mode directly. AS, Atrial sensing event. (Courtesy Boston Scientific.)

Lead-II Vent V-ER

AS VP

353

(5 mm/mV)

AS VP 1.5V

AS

25 mm/s Filter on

AS VP

VP

AS VP

AS VP

1.3V First loss of capture (LOC) without backup pacing

AS VP VP

AS

AS VP

VP Second LOC which confirms LOC and has backup pacing

354

SECTION 2  Clinical Concepts

THRESHOLD SEARCH Primary pulse V

2.25

2.25 2.0 2.0 1.75 1.75 1.5 1.5 1.25 1.25

1.0

1.0

11

12

0.75 0.75

0.5 0.5

0.63 0.63

Backup pulse V

1

2

3

4

5

6

7

8

9 10

–

– 17

18

Unipolar ventricular IEGM

Event markers AV delay (msec)

AS

AP

AS AS AS AS AS AS AS AS AS

AP

AP

AS AS

AS AS

AS

AS

AP

VPP VPP 150

PV delay (msec)

50

150

24

Figure 14-30  Autocapture threshold search performed in DDD mode from St. Jude Medical pacemaker. Shown are the primary ventricular (V) pulse output, backup pulse output, ventricular evoked response (V-ER), event markers, and atrioventricular (AV) and spontaneous P-wave to ventricular (PV) delays. On commencement at beat 1, the AV delay and PV delay are shortened to 50 msec and 25 msec, respectively. This avoids the potential for fusion resulting in an apparent “loss of capture” while perform capture verification using the V-ER. Capture verification is performed for each test beat. The primary pulse amplitude starts at 2.25 V. After two consecutive capture beats, the pulse amplitude is reduced by 0.25 V (beats 3-16). When capture is lost for two consecutive beats (beats 15 and 16), a high-amplitude (4.5 V) backup pulse (VPP) is output 100 msec following the primary pulse to ensure capture. The amplitude is increased by 0.125 V until two consecutive capture beats have occurred. The threshold search terminates. The capture threshold (0.625 V) is recorded in the device diagnostics. The pulse amplitude is then increased by 0.25 V for safety margin. Auto Capture continues with beat-by-beat capture verification until a loss of capture occurs or a scheduled threshold search begins. AP, Atrial pacing events; AS, atrial sensing; IEGM, intracardiac electrogram. (Courtesy Larry Sloman, Jeff Snell, and Gene Bornzin, St. Jude Medical.)

of the pacing pulse) and then opens from 15 to 62 msec in order to detect the evoked response. The output pulse is labeled as “ineffective” if the evoked-response amplifier does not detect a signal in the 47-msec detection window. In response to noncapture, a high-output backup safety pulse is delivered 100 msec after the primary output pulse. The electrode tissue interface (acute vs. chronic lead characteristics), lead polarization, tip-to-ring spacing, lead tip design, characteristics of the pacing pulse, input circuits of the pacemaker, as well as other factors are known to affect evoked-response sensing.312 The evokedresponse signal also can vary between unipolar and bipolar pacing. Accurate discrimination between the evoked response and the pacepolarization artifact is crucial for capture confirmation. Polarization is the result of the electric charge that remains on the lead tip after the pacing pulse has been delivered. A polarization artifact can occur in the evoked-response detection window. Therefore, a high pacepolarization signal might not allow the pacemaker to distinguish capture from noncapture. Measures to minimize this disturbance by the polarization artifact include the use of high–active surface area electrodes and application of triphasic pacing pulses.313 The relative amplitude of the pace-polarization artifact is more critical with atrial than ventricular autocapture algorithms, because of the small

amplitude of the atrial evoked response. In some pacemakers with early-generation autocapture algorithms, a bipolar lead and a pacing electrode with low lead-polarization characteristics were recommended or mandatory for proper autocapture function. However, with newer-generation autocapture algorithms, these pacing lead requirements are no longer mandatory, and these algorithms generally work with any lead and unipolar or bipolar. However, low-polarization leads are still preferred. More recent autocapture pacemakers also incorporate the ability to switch sensing of the evoked response from bipolar to unipolar. In early studies, about 5% to 7% of patients were found to have unacceptable evoked-response signals, and autocapture could not be activated.314 However, more recent studies indicate that the incidence of inadequate evoked-response signals using current autocapture verification algorithms may be lower, especially when using lowpolarization pacing leads (e.g., titanium nitride–coated or iridium electrodes).311,315 Autocapture algorithms maintain their applicability at long-term follow-up in the vast majority of patients with high reliability. The evoked-response amplitude may decrease over time in some patients compared to that at implantation; however, the evokedresponse sensitivity can be reprogrammed according to the newly



14  Pacing for Atrioventricular Conduction System Disease

355

FUSION AVOIDANCE Unipolar ventricular IEGM

Event markers

1

2

AS VP

AS VP

3

AS VP

AV delay (msec)

150

PV delay (msec)

125

4

AS VP

AS AS AS VP VS VS VPP

AS VS

AS VS

AS VS

AS VS

AS VS

125 + 125 = 250

Figure 14-31  Autocapture fusion avoidance in St. Jude Medical pacemaker. Unipolar ventricular intracardiac electrograms (IEGM), event markers, and atrioventricular (AV) and spontaneous P-wave to ventricular (PV) delays are shown. Capture verification determines that beats 1 to 4 have captured. Beat 5 results in a loss of capture detection resulting from fusion. To avoid further fusion, the AV and PV delays are increased by 125 msec. This allows intrinsic R waves (beats 6-10) to be sensed. Fusion is avoided, and no unnecessary threshold search is performed. The AV and PV delays remain extended until a ventricular pulse is delivered. The AV and PV delays are then shortened (not shown) to the programmed values. AS, Atrial sensing; VP, ventricular pacing events; VS, ventricular sensing. (Courtesy Larry Sloman, Jeff Snell, and Gene Bornzin, St. Jude Medical.)

measured amplitude to prevent evoked response underdetection. In a recent long-term follow-up study of 61 patients, autocapture had to be programmed “off ” in only one patient 1 year after implantation because of a small, inadequate, evoked-response amplitude.311 Autocapture algorithms must also reliably distinguish a fusion beat from actual ventricular capture for the algorithms to function properly. Fusion or pseudofusion phenomena may hinder evoked response detection and cause unnecessary backup stimulation. These backup safety pulses usually have no clinical consequences because they occur approximately 100 msec after the primary pulse in the absolute ventricular refractory period. However, the backup pulse can create a confusing rhythm on the ECG and concern of a system malfunction. The frequent occurrence of fusion beats, particularly during dualchamber pacing, also may limit the energy-saving effect of automatic pacing output regulation. Occasionally, the physician views the highoutput backup pulse as bothersome and anxiety provoking to the patient, choosing to disable the autocapture algorithm. In single-chamber systems, fusion beats can be minimized by changes in the paced rate. For dual-chamber pacemakers, fusion avoidance algorithms have been developed316 (Fig. 14-31). Ventricular fusion can be addressed in autocapture by temporarily shortening the AV delay during a threshold search, to avoid ventricular fusion with a natively conducted complex, which would interfere with the test. Alternatively, fusion versus noncapture in dual-chamber mode can also be managed by automatically extending the paced or sensed AV delay by 100 msec on the next cycle. If the evoked response is not detected on two consecutive beats, the system returns to the programmed AV delay, and the capture threshold is reassessed. If conduction is intact and the extended AV delay allows intrinsic conduction to be recognized, the functionally increased AV delay is allowed to remain in place, and

the ventricular output is not incremented. The fusion avoidance algorithm has substantially reduced the amount of ventricular paced beats, fusion beats, unnecessary backup pulses, and threshold searches.316 If a shorter AV delay is preferred, the fusion avoidance algorithm can be effectively disabled by programming a negative AV/PV hysteresis. This will shorten the paced and sensed AV delays by a programmable interval in response to an R wave, which is detected before completion of the programmed AV delay. More recently, automatic algorithms for pacing output management have been extended successfully to include RA and LV capture management, as well as ICD platforms.317,318 Some of these algorithms continue to use the sensed evoked response, whereas other manufacturers use alternate verification methodologies. Right atrial capture management determines atrial capture by application of a test pace to the atrium and evaluating either the response of the intrinsic rhythm or the timing of the conducted ventricular response.317 Left ventricular capture management determines capture by applying a test pace to the LV lead and comparing the timing of a conducted response in the right ventricle to predetermined A-RV and LV-RV conduction characteristics.318 When programmed to the adaptive mode, pacing output amplitudes are adjusted automatically by applying the programmed safety margin to the measured threshold.

Summary Atrioventricular conduction system disease is relatively common in the general population, and its prevalence rises with advancing age. Most diagnoses of AV conduction disturbances can be made through careful analysis of the surface ECG. The traditional electrocardiographic classification of AV and intraventricular blocks provides insight into the

356

SECTION 2  Clinical Concepts

prognosis and natural history of these disorders and remains clinically useful. Thorough noninvasive and, if necessary, invasive screening for structural heart disease should be performed when AV conduction disturbances are identified on ECG. Electrophysiologic testing has limitations, but in select cases remains a useful diagnostic tool, especially when the anatomic site of AV block is not certain. Many causes of AV block and conduction system disease are recognized, but usually it is difficult to ascribe a specific cause in an individual case. Reversible causes of AV block frequently have a benign prognosis and should be excluded. Structural heart disease is often associated with AV conduction system disorders and has a major effect on prognosis. When AV conduction disorders occur in the setting of structural heart disease, other rhythm disturbances, including atrial and ventricular tachyarrhythmias, are common and increase morbidity and mortality. The development of AV conduction disturbances during acute myocardial infarction is related to the extent of the ischemic/infarcted region. When AV block is associated with intraventricular conduction disturbances in the setting of MI, the risks of mortality and sudden death remain high, even in the reperfusion era. In a patient with an AV conduction disturbance, the decision to institute permanent pacing is based on a correlation of symptoms with an abnormal ECG rhythm and recognition of the likelihood of progression to high-grade AV block. Chronic or intermittent AV block is a major indication for cardiac pacing that is likely to remain so during the next decade. In patients who have experienced AMI, however, there has been greater reliance on transcutaneous rather than transvenous temporary pacing. The decision to institute permanent pacing for AV block in the setting of AMI is largely based on the presence of

intraventricular conduction defects, which appear to be less common in the thrombolytic era. Thus, permanent pacing for AV block is not usually required after MI. Furthermore, expanded indications for ICD and cardiac resynchronization in the current era have largely eliminated the prior debate regarding the need for and benefit of permanent pacing after MI. Clinical trials have not demonstrated clear superiority of dualchamber over single-chamber ventricular pacing. However, dualchamber pacing with separate atrial and ventricular leads likely will remain the major pacing modality for most patients with heart block. Pacing from the right ventricular apex has been used traditionally during both dual-chamber and single-chamber ventricular pacing for AV block. Growing recognition of the potential for deleterious effects of RVA pacing has stimulated interest in ventricular pacing from alternative RV sites, left ventricular, or biventricular pacing sites in patients who need ventricular pacing. Large, long-term, multicenter studies demonstrating that non-RVA or biventricular pacing prevents the deleterious effects of RVA pacing are required before entirely abandoning the traditional RVA pacing site.

Conclusion Insights into the molecular genetic basis of AV conduction disturbances have begun to emerge over the past decade and undoubtedly will have a major effect on the future evaluation and management of these disorders in children and adults. In the decades to come, development of biologic pacemakers using gene therapy or stem cells may supplement or replace electronic implantable pacemakers in the treatment of AV conduction system disease.

REFERENCES 1. James TN: Anatomy of the coronary arteries and veins: Anatomy of the conduction system of the heart. In Hurst JW, editor: The heart, New York, 1978, McGraw-Hill, pp 33-56. 2. Lev M, Bharati S: Anatomic basis for impulse generation and atrioventricular transmission. In Narula OS, editor: His bundle electrocardiography and clinical electrophysiology, Philadelphia, 1975, Davis, p 1. 3. Van der Hauwaert LG, Stroobandt R, Verhaeghe L: Arterial blood supply of the atrioventricular node and main bundle. Br Heart J 34:1045, 1972. 4. Pruitt RD, Essex HE, Burchell BH: Studies on the spread of excitation through the ventricular myocardium. Circulation 3:418, 1951. 5. Massing GK, James TN: Anatomical configuration of the His bundle and bundle branches in the human heart. Circulation 53:609, 1976. 6. Rosenbaum MB: Types of left bundle branch block and their clinical significance. J Electrocardiol 2:197, 1969. 7. Josephson ME: Clinical cardiac electrophysiology: techniques and interpretations, ed 3, Philadelphia, 2002, Lippincott–Williams & Wilkins, pp 92-109. 8. Zipes DP: Second-degree atrioventricular block. Circulation 60: 465, 1979. 9. Barold SS: ACC/AHA guidelines for implantation of cardiac pacemakers: how accurate are the definitions of atrioventricular and intraventricular conduction blocks? Pacing Clin Electrophysiol 16:1221, 1993. 10. Cabeen WR, Roberts NK, Child JS: Recognition of the Wenckebach phenomenon. West J Med 129:521, 1978. 11. Denes P, Levy L, Pick A, Rosen KM: The incidence of typical and atypical AV Wenckebach periodicity. Am Heart J 89:26, 1975. 12. Lange HW, Ameisen O, Mack R, et al: Prevalence and clinical correlates on non-Wenckebach narrow complete second-degree atrioventricular block detected by ambulatory ECG. Am Heart J 115:114, 1988. 13. DeMotss H, Brodeur MTH, Rahimtoola SH: Concealed sinus rhythm: a cause of misdiagnosis of digitalis intoxication. Circulation 50:632, 1974. 14. Denes P, Dhingra RC, Wu D, et al: H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemiblock): clinical, electrocardiographic, and electrophysiologic correlations. Am J Cardiol 35:23, 1975. 15. Dhingra RC, Palileo E, Strasberg B, et al: Significance of the H-V interval in 517 patients with chronic bifascicular block. Circulation 64:1265, 1981. 16. McAnulty JH, Rahimtoola SH, Murphy E, et al: Natural history of “high risk” bundle branch block: final report of a prospective study. N Engl J Med 307:137, 1982. 17. Scheinman MM, Peters RW, Morady F, et al: Electrophysiologic studies in patients with bundle branch block. Pacing Clin Electrophysiol 6:1157, 1983.

18. Zipes DP, Gettes LS, Akhtar M, et al: Guidelines for clinical intracardiac electrophysiologic studies: A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures. J Am Coll Cardiol 14:1827, 1989. 19. Click RL, Gersh BJ, Sugrue DD, et al: Role of invasive electrophysiologic testing in patients with symptomatic bundle branch block. Am J Cardiol 59:817, 1987. 20. Morady F, Higgins J, Peters RW, et al: Electrophysiologic testing in bundle branch block and unexplained syncope. Am J Cardiol 54:587, 1984. 21. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51:e1-62, 2008. 22. Dhingra RC, Wyndham C, Bauernfeind R, et al: Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block. Circulation 60:1455, 1979. 23. Petrac D, Radic B, Birtic K, Gjurovic J: Prospective evaluation of infrahisal second-degree AV block induced by atrial pacing in the presence of chronic bundle branch block and syncope. Pacing Clin Electrophysiol 19:784, 1996. 24. Englund A, Bergfeldt L, Rosenqvist M: Pharmacological stress testing of the His-Purkinje system in patients with bifascicular block. Pacing Clin Electrophysiol 21:1979, 1998. 25. Scheinman MM, Weiss AN, Shaffar A, et al: Electrophysiologic effects of procainamide in patients with interventricular conduction delay. Circulation 49:522, 1974. 26. Bergfeldt L, Rosenqvist M, Vallin H, et al: Disopyramideinduced second- and third-degree atrioventricular block in patients with bifascicular block: an acute stress test to predict atrioventricular block progression. Br Heart J 53:328, 1985. 27. Tonkin AM, Heddle WF, Tornos P: Intermittent atrioventricular block: procainamide administration as a provocative test. Aust NZ J Med 8:594, 1978. 28. Twidale N, Heddle WF, Tonkin AM: Procainamide administration during electrophysiology study: utility as a provocative test for intermittent atrioventricular block. Pacing Clin Electrophysiol 11:1388, 1988. 29. Fujimura O, Yee R, Klein GJ, et al: The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. N Engl J Med 321:1703, 1989. 30. Mymin D, Mathewson FAL, Tate RB, et al: The natural history of first-degree atrioventricular heart block. N Engl J Med 315:1183, 1986.

31. Cheng S, Keyes MJ, Larson MG, et al: Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 301:2571-2577, 2009. 32. Zornosa JP, Crossley GH, Haisty WK, Jr, et al: Pseudopacemaker syndrome: a complication of radiofrequency ablation of the AV junction [abstract]. Pacing Clin Electrophysiol 15:590, 1992. 33. Kim YH, O’Nunain S, Trouton T, et al: Pseudo-pacemaker syndrome following inadvertent fast pathway ablation for atrioventricular nodal reentrant tachycardia. J Cardiovasc Electrophysiol 4:178, 1993. 34. Iliev II, Yamachika S, Muta K, et al: Preserving normal ventricular activation versus atrioventricular delay optimization during pacing: the role of intrinsic atrioventricular conduction and pacing rate. Pacing Clin Electrophysiol 23:74, 2000. 35. Strasberg B, Amat-Y-Leon F, Dhingra RC, et al: Natural history of second-degree atrioventricular nodal block. Circulation 63:1043, 1981. 36. Shaw DB, Kerwick CA, Veale D, et al: Survival in second-degree atrioventricular block. Br Heart J 53:587, 1985. 37. Clarke M, Sutton R, Ward D, et al: Recommendations for pacemaker prescription for symptomatic bradycardia: report of a working party of the British Pacing and Electrophysiology Group. Br Heart J 66:185, 1991. 38. Shaw DB, Gowers JI, Kekwick CA, et al: Is Mobitz type I atrioventricular block benign in adults? Heart 90:169, 2004. 39. Dhingra RC, Denes P, Wu D, et al: The significance of seconddegree atrioventricular block and bundle branch block: observations regarding site and type of block. Circulation 49:638, 1974. 40. Johansson BW: Complete heart block: a clinical hemodynamic and pharmacological study in patients with and without an artificial pacemaker. Acta Med Scand 180(Suppl 451):1, 1966. 41. Edhag O, Swahn A: Prognosis of patients with complete heart block or arrhythmic syncope who were not treated with artificial pacemakers. Acta Med Scand 200:457, 1976. 42. Edhag O: Long-term cardiac pacing: Experience of fixed-rate pacing with an endocardial electrode in 260 patients. Acta Med Scand 502(Suppl):64, 1969. 43. Sherif N, Scherlag BJ, Lazzara R, et al: The pathophysiology of tachycardia-dependent paroxysmal atrioventricular block after myocardial ischemia: experimental and clinical observations. Circulation 50:515, 1974. 44. Rosenbaum MB, Elizari MV, Levi RJ, et al: Paroxysmal atrioventricular block related to hyperpolarization and spontaneous diastolic depolarization. Chest 63:678, 1973. 45. Lee S, Wellens HJJ, Josephson ME: Paroxysmal atrioventricular block. Heart Rhythm 6:1229-1234, 2009. 46. Shohat-Zabarski R, Iakobishvili Z, et al: Paroxysmal atrioventricular block: clinical experience with 20 patients. Int J Cardiol 97:399, 2004. 47. Linzer M, Prystowsky EN, Divine GW, et al: Predicting the outcomes of electrophysiologic studies of patients with unexplained



14  Pacing for Atrioventricular Conduction System Disease syncope: preliminary validation of a derived model. J Gen Intern Med 6:113, 1991. 48. Rosenthal E: Fetal heart block. In Allan L, Hornberger L, Sharland G, editors: Textbook of fetal cardiology, London, 2000, Greenwich Medical Media, pp 438-451. 49. Friedman RA, Fenrich AL, Kertesz NJ: Congenital complete atrioventricular block. Pacing Clin Electrophysiol 24:1681, 2001. 50. Thambo JB, Bordachar P, Garrigue S, et al: Detrimental ventricular remodeling in patients with congenital complete heart block and chronic right ventricular apical pacing. Circulation 110:3766, 2004. 51. Sagar S, Shen WK, Asirvatham SJ, et al: Effect of long-term right ventricular pacing in young adults with structurally normal heart. Circulation 121:1698-1705, 2010. 52. Benson DW: Genetics of atrioventricular conduction disease in humans. Anat Rec A Discov Mol Cell Evol Biol 280:934, 2004. 53. Wolf CM, Berul CI: Inherited conduction system abnormalities: one group of diseases, many genes. J Cardiovasc Electrophysiol 17:446-455, 2006. 54. Brook JD, McCurrach ME, Harley HG, et al: Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 30 end of a transcript encoding a protein kinase family member. Cell 69:385, 1992. 55. Lazarus A, Varin J, Babuty D, et al: Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study. J Am Coll Cardiol 40:1645-1652, 2002. 56. Berul CI, Maguire CT, Aronovitz MJ, et al: DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model. J Clin Invest 103:R1-R7, 1999. 57. Sylvius N, Tesson F. Lamin A/C and cardiac diseases. Curr Opin Cardiol 21:159-165, 2006. 58. Rankin J, Ellard S: The laminopathies: a clinical review. Clin Genet 70:261-274, 2006. 59. Otomo J, Kure S, Shiba T, et al: Electrophysiological and histopathological characteristics of progressive atrioventricular block accompanied by familial dilated cardiomyopathy caused by a novel mutation of lamin A/C gene. J Cardiovasc Electrophysiol 16:137, 2005. 60. Schott JJ, Alshinawi C, Kyndt F, et al: Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 23:20-21, 1999. 61. Grant AO, Carboni MP, Neplioueva V, et al: Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest 110:1201-1209, 2002. 62. Remme CA, Verkerk AO, Nuyens D, et al: Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD. Circulation 114:25842594, 2006. 63. Lupoglazoff JM, Cheav T, Baroudi G, et al: Homozygous SCN5A mutation in long-QT syndrome with functional two-to-one atrioventricular block. Circ Res 89:E16-E21, 2001. 64. Wang DW, Viswanathan PC, Balser JR, et al: Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation 105:341346, 2002. 65. Schott JJ, Alshinawi C, Kyndt F, et al: Cardiac conduction defects associated with mutations in SCN5A. Nat Genet 23:2021, 1999. 66. Kyndt F, Probst V, Potet F, et al: Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation 104:3081-3086, 2001. 67. Tan HL, Bink-Boelkens MT, Bezzina CR, et al: A sodium-channel mutation causes isolated cardiac conduction disease. Nature 409:1043-1047, 2001. 68. Bezzina CR, Rook MB, Groenewegen WA, et al: Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system. Circ Res 92:159168, 2003. 69. Ge J, Sun A, Paajanen V, et al: Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy. Circ Arrhythmia Electrophysiol 1:83-92, 2008. 70. Andelfinger G, Tapper AR, Welch RC, et al: KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet 71:663-668, 2002. 71. Yang Y, Liu Y, Dong X, et al: Human KCNQ1 S140G mutation is associated with atrioventricular blocks. Heart Rhythm. 4:611618, 2007. 72. Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al: Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest 104:15671573, 1999. 73. Jay PY, Harris BS, Buerger A, et al: Function follows form: cardiac conduction system defects in Nkx2-5 mutation. Anat Rec A Discov Mol Cell Evol Biol 280:966-972, 2004. 74. Jay PY, Harris BS, Maguire CT, et al: Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 113:1130-1137, 2004. 75. Li QY, Newbury-Ecob RA, Terrett JA, et al: Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet 15:21-29, 1997. 76. Basson CT, Huang T, Lin RC, et al: Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc Natl Acad Sci USA 96:2919-2924, 1999.

77. Nguyen-Tran VT, Kubalak SW, Minamisawa S, et al: A novel genetic pathway for sudden cardiac death via defects in the transition between ventricular and conduction system cell lineages. Cell 102:671-682, 2000. 78. Gollob MH, Green MS, Tang AS, et al: Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med 344:1823-1831, 2001. 79. MacRae CA, Ghaisas N, Kass S, et al: Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 96:1216–1220, 1995. 80. Arad M, Moskowitz IP, Patel VV, et al: Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-ParkinsonWhite syndrome in glycogen storage cardiomyopathy. Circulation 107:2850-2856, 2003. 81. Guertl B, Noehammer C, Hoefler G: Metabolic cardiomyopathies. Int J Exp Pathol 81:349-372, 2000. 82. Holmgren D, Wahlander H, Eriksson BO, et al: Cardiomyopathy in children with mitochondrial disease: clinical course and cardiological findings. Eur Heart J 24:280-288, 2003. 83. Young TJ, Shah AK, Lee MH, et al: Kearns-Sayre syndrome: a case report and review of cardiovascular complications. Pacing Clin Electrophysiol 28:454-457, 2005. 84. Lev M: The pathology of complete AV block. Prog Cardiovasc Dis 6:317, 1964. 85. Lenegre J: Etiology and pathology of bilateral bundle branch fibrosis in relation to complete heart block. Prog Cardiovasc Dis 6:409, 1964. 86. Narula OS: Atrioventricular conduction defects in patients with sinus bradycardia. Circulation 44:1096, 1971. 87. Rosenqvist M, Obel IWP: Atrial pacing and the risk for AV block: is there a time for change in attitude? Pacing Clin Electrophysiol 12:97, 1989. 88. Sutton R, Kenny RA: The natural history of sick sinus syndrome. Pacing Clin Electrophysiol 9:1110, 1986. 89. Caspi J, Amar R, Elami A, et al: Frequency and significance of complete atrioventricular block after coronary artery bypass grafting. Am J Cardiol 63:526, 1989. 90. Keefe DL, Griffin JC, Harrison DC, et al: Atrioventricular conduction abnormalities in patients undergoing isolated aortic or mitral valve replacement. Pacing Clin Electrophysiol 8:393, 1985. 91. Rosenbaum MB, Corrado G, Oliveri R, et al: Right bundle branch block with left anterior hemiblock in surgically induced tetralogy of Fallot. Am J Cardiol 26:12, 1970. 92. Van Lier TA, Harinck E, Hitchcock JF: Complete right bundle branch block after surgical closure of permembranous ventricular septal defect. Eur Heart J 6:959, 1985. 93. Maron BJ, Merrill WH, Freier PA, et al: Long-term clinical course and symptomatic status of patients after operation for hypertrophic subaortic stenosis. Circulation 57:1205, 1978. 94. Talreja DR, Nishimura RA, Edwards WD, et al: Alcohol septal ablation versus surgical septal myectomy: Comparison of effects on atrioventricular conduction tissue. J Am Coll Cardiol 44:2329, 2004. 95. Baerman JM, Kirsh MM, de Buitleir M, et al: Natural history and determinants of conduction defects following coronary artery bypass surgery. Ann Thorac Surg 44:150, 1987. 96. El-Khally Z, Thibault B, Staniloae C, et al: Prognostic significance of newly acquired bundle branch block after aortic valve replacement. Am J Cardiol 94:1008, 2004. 97. Limongelli G, Ducceschi V, DAndrea A, et al: Risk factors for pacemaker implantation following aortic valve replacement: a single centre experience. Heart 89:901, 2003. 98. Chu A, Califf RM, Pryor DB, et al: Prognostic effect of bundle branch block related to coronary artery bypass grafting. Am J Cardiol 59:798, 1987. 99. Koplan BA, Stevenson WG, Epstein LM, et al: Development and validation of a simple preoperative risk score to predict the need for permanent pacing after cardiac valve surgery. J Am Coll Cardiol 41:795, 2003. 100. Glikson M, Dearani JA, Hyberger LK, et al: Indications, effectiveness, and long-term dependency in permanent pacing after cardiac surgery. Am J Cardiol 80:1309, 1997. 101. Scheinman M, Calkins H, Gillette P, et al: NASPE policy statement on catheter ablation: personnel, policy, procedures, and therapeutic recommendations. Pacing Clin Electrophysiol 26:789, 2003. 102. Delise P, Sitta N, Zoppo F, et al: Radiofrequency ablation of atrioventricular nodal reentrant tachycardia: the risk of intraprocedural, late and long-term atrioventricular block. The Veneto Region multicenter experience. Ital Heart J 3:715, 2002. 103. Pelargonio G, Fogel RI, Knilans TK, Prystowsky EN: Late occurrence of heart block after radiofrequency catheter ablation of the septal region: clinical follow-up and outcome. J Cardiovasc Electrophysiol 12:56, 2001. 104. Ferguson TB, Jr, Cox JL: Surgical treatment for the WolffParkinson-White syndrome: the endocardial approach. In Zipes DP, Jaliffe J, editors: Cardiac electrophysiology: from cell to bedside, Philadelphia, 1990, Saunders, pp 897-906. 105. Kay GN, Ellenbogen KA, Guidici M, et al: The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. J Intervent Cardiac Electrophysiol 2:121, 1998. 106. Brignole M, Giafranchi L, Menozzi C, et al: Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with

357

severely symptomatic paroxysmal atrial fibrillation: a randomized controlled study. Circulation 96:2617, 1977. 107. Williamson BD, Man KC, Daoud E, et al: Radiofrequency catheter modification of atrioventricular conduction to control the ventricular rate during atrial fibrillation. N Engl J Med 331:910, 1994. 108. Rokas S, Gaitanidou S, Chatzidou S, et al: Atrioventricular node modification in patients with chronic atrial fibrillation: role of morphology of RR interval variation. Circulation 103:2942, 2001. 109. Garratt CJ, Skehan JD, Payne GE, Stafford PJ: Effect of sequential radiofrequency ablation lesions at fast and slow atrioventricular nodal pathway positions in patients with paroxysmal atrial fibrillation. Heart 75:502, 1996. 110. Benitez RM, Gold MR: Immediate and persistent complete heart block following a horse kick. Pacing Clin Electrophysiol 22:816, 1999. 111. Lazaros GA, Ralli DG, Moundaki VS, Bonoris PE: Delayed development of complete heart block after a blunt chest trauma. Injury 35:1300, 2004. 112. Anderson DJ, Bulkley BH, Hutchins GM: A clinicopathologic study of prospective valve endocarditis in 22 patients: mor­ phologic basis for diagnosis and therapy. Am Heart J 94:325, 1977. 113. Maguire JH, Hoff R, Sherlock I, et al: Cardiac morbidity and mortality due to Chagas’ disease: prospective electrocardiographic study of a Brazilian community. Circulation 75:1140, 1987. 114. Hagar JM, Rahimtoola SH: Chagas’ heart disease. Curr Probl Cardiol 20:825, 1995. 115. Hagar JM, Rahimtoola SH: Chagas’ heart disease in the United States. N Engl J Med 325:763, 1991. 116. Steere AC: Lyme disease. N Engl J Med 321:586, 1989. 117. Steere AC, Batsford WP, Weinberg M, et al: Lyme carditis: cardiac abnormalities of Lyme disease. Ann Intern Med 93:8, 1980. 118. Van der Linde MR, Crijns HJGM, De Koning J, et al: Range of atrioventricular conduction disturbances in Lyme borreliosis: a report of four cases and review of other published reports. Br Heart J 63:162, 1990. 119. McAlister HF, Klementowicz PT, Andrews C, et al: Lyme carditis: an important cause of reversible heart block. Ann Intern Med 110:339, 1989. 120. Kimball SA, Janson PA, LaRaia PJ: Complete heart block as the sole presentation of Lyme disease. Arch Intern Med 149:1897, 1989. 121. Cohen IS, Bharati S, Glass J, et al: Radiotherapy as a cause of complete atrioventricular block in Hodgkin’s disease. Arch Intern Med 141:676, 1981. 122. Almange C, Lebrestec T, Louvet M, et al: Bloc auriculoventriculaire complet par métastase cardiaque: apropos d’une observation. Sem Hôp Pans 54:1419, 1978. 123. Perloff JK: The heart in neuromuscular disease. In O’Rourke RA, editor: Current problems in cardiology, Chicago, 1986, Yearbook, pp 513-557. 124. Lazarus A, Varin J, Babuty D, et al: Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study. J Am Coll Cardiol 40:1645, 2002. 125. Groh WJ, Groh MR, Saha C, et al: Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med 358:2688-2697, 2008. 126. Wynne J, Braunwald E: The cardiomyopathies and myocarditides. In Braunwald E, editor: Heart disease: a textbook of cardiovascular medicine, 4th ed, Philadelphia, 1992, Saunders, pp 1349-1450. 127. Doughan AR, Williams BR: Cardiac sarcoidosis. Heart 92:282288, 2006. 128. Bargout R, Kelly RF: Sarcoid heart disease: clinical course and treatment. Int J Cardiol 97:173, 2004. 129. Roberts WC, McAllister HA, Jr, Ferrans VJ: Sarcoidosis of the heart: a clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11). Am J Med 63:86-108, 1977. 130. Silverman KJ, Hutchins GM, Bulkley BH: Cardiac sarcoid: A clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 58:1204, 1978. 131. Sharma OP: Diagnosis of cardiac sarcoidosis: an imperfect science, a hesitant art. Chest 123:18-19, 2003. 132. Duke C, Rosenthal E. Sudden death caused by cardiac sarcoidosis in childhood. J Cardiovasc Electrophysiol 13:939-942, 2002. 133. Kato Y, Morimoto S, Uemura A, et al: Efficacy of corticosteroids in sarcoidosis presenting with atrioventricular block. Sarcoidosis Vasc Diffuse Lung Dis 20:133, 2003. 134. Hurd ER: Extraarticular manifestations of rheumatoid arthritis. Semin Arthritis Rheum 8:151, 1979. 135. Owen DS: Connective tissue diseases and the cardiovascular system: a review. Virginia Med 110:426, 1983. 136. Janosik DL, Osborn TG, Moore TL, et al: Heart disease in systemic sclerosis. Semin Arthritis Rheum 19:191, 1989. 137. Rozanski JJ, Castellanos A, Sheps D, et al: Paroxysmal seconddegree AV block induced by exercise. Heart Lung 9:887, 1980. 138. Egred M, Jafary F: Exercise induced atrioventricular (AV) block: important but uncommon phenomenon. Int J Cardiol 97:559, 2004. 139. Finzi A, Bruno A, Perondi R: Exercise-induced paroxysmal atrioventricular block during nuclear perfusion stress testing:

358

SECTION 2  Clinical Concepts

evidence for transient ischemia of the conduction system. G Ital Cardiol 29:1313, 1999. 140. Donzeau JP, Dechandol AM, Bergeal A, et al: Blocs auriculoventriculaires survenant à l’effort: considerations generales à propos de 14 cas. Coeur 15:513, 1985. 141. Woelfel AK, Simpson RJ, Gettes LS, et al: Exercise-induced distal atrioventricular block. J Am Coll Cardiol 2:578, 1983. 142. Petrac J, Gjuroivic J, Vukoskovic D, et al: Clinical significance and natural history of exercise-induced atrioventricular block. In Belhassen B, Feldman S, Copperman Y, editors: Proceedings of the VIII World Symposium on Cardiac Pacing and Electrophysiology, Jerusalem, 1987, R & L Creative Communications, p 265. 143. Huycke EC, Card HG, Sobol SM, et al: Postexertional cardiac systole in a young man without organic heart disease. Ann Intern Med 106:844, 1987. 144. Kasaoka Y, Ajiki K, Hayami N, Murakawa Y: His-bundle parasystole masquerading as exercise-induced 2:1 atrioventricular block. J Cardiovasc Electrophysiol 12:965, 2001. 145. Ovsyshcher IE, Barold SS: Drug induced bradycardia: to pace or not to pace? Pacing Clin Electrophysiol 27:1144, 2004. 146. Zeltser D, Justo D, Halkin A, et al: Drug-induced atrioventricular block: prognosis after discontinuation of the culprit drug. J Am Coll Cardiol 44:105, 2004. 147. Jonas EA, Kosowsky BD, Ramaswamy K: Complete His-Purkinje block produced by carotid massage. Circulation 50:192, 1974. 148. Hart G, Oldershaw PJ, Cull RE, et al: Syncope caused by coughinduced complete atrioventricular block. Pacing Clin Electrophysiol 5:564, 1982. 149. Wik B, Hillestad L: Deglutition syncope. Br Med J 3:747, 1975. 150. Strasberg B, Lam W, Swiryn S, et al: Symptomatic spontaneous paroxysmal AV nodal block due to localized hyperresponsiveness of the AV node to vagotonic reflexes. Am Heart J 103:795, 1982. 151. Zaman L, Moleiro F, Rozanski JJ, et al: Multiple electrophysiologic manifestations and clinical implications of vagally mediated AV block. Am Heart J 106:92, 1983. 152. Ector H, Rickards AF, Kappenberger L, et al: The world survey of cardiac pacing and implantable cardioverter defibrillators: calendar year 1997—Europe. Pacing Clin Electrophysiol 24:863, 2001. 153. Bernstein AD, Parsonnet V: Survey of cardiac pacing and implanted defibrillator practice patterns in the United States in 1997. Pacing Clin Electrophysiol 24:842, 2001. 154. Hreybe H, Saba S: Effects of race and health insurance on the rates of pacemaker implantation for complete heart block in the United States. Am J Cardiol 94:227, 2004. 155. Frye RL, Collins JJ, DeSanctis RW, et al: Guidelines for permanent cardiac pacemaker implantation, May 1984: a report of the Joint American College of Cardiology/American Heart Association Task Force on Assessment of Cardiovascular Procedures (Subcommittee on Pacemaker Implantation). Circulation 70: 331A, 1984. 156. Dreifus LS, Fisch C, Griffin JC, et al: Guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Pacemaker Implantation). J Am Coll Cardiol 18:1, 1991. 157. Gregoratos G, Abrams J, Epstein AE, et al: ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices. Summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines/North American Society for Pacing and Electrophysiology Committee (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation 106:2145, 2002. 158. Bassan R, Maia IG, Bozza A, et al: Atrioventricular block in acute inferior wall myocardial infarction: harbinger of associated obstruction of the left anterior descending coronary artery. J Am Coll Cardiol 8:773, 1986. 159. Forsberg SA, Juul-Moller S: Myocardial infarction complicated by heart block: treatment and long-term prognosis. Acta Med Scand 206:483, 1979. 160. Tans AC, Lie KI, Durrer D: Clinical setting and prognostic significance of high degree atrioventricular block in acute inferior myocardial infarction: a study of 144 patients. Am Heart J 99:4, 1980. 161. Archbold RA, Sayer JW, Ray S, et al: Frequency and prognostic implications of conduction defects in acute myocardial infarction since the introduction of thrombolytic therapy. Eur Heart J 19:893, 1998. 162. Escosteguy CC, Carvalho Mde A, Medronho Rde A, et al: Bundle branch and atrioventricular block as complications of acute myocardial infarction in the thrombolytic era. Arq Bras Cardiol 76:291, 2001. 163. Aplin M, Engstrom T, Vejlstrup NG, et al: Prognostic importance of complete atrioventricular block complicating acute myocardial infarction. TRACE Study Group. Am J Cardiol 92:853, 2003. 164. Meine TJ, Al-Khatib SM, Alexander JH, et al: Incidence, predictors, and outcomes of high-degree atrioventricular block complicating acute myocardial infarction treated with thrombolytic therapy. Am Heart J 149:670, 2005. 165. Sutton R, Davies M: The conduction system in acute myocardial infarction complicated by heart block. Circulation 38:987, 1968. 166. Wei JY, Markis JE, Malagold M, et al: Cardiovascular reflexes stimulated by reperfusion of ischemic myocardium in acute myocardial infarction. Circulation 67:796, 1983.

167. Koren G, Weiss AT, Ben-David Y, et al: Bradycardia and hypotension following reperfusion with streptokinase (Bezold-Jarisch reflex): a sign of coronary thrombolysis and myocardial salvage. Am Heart J 112:468, 1986. 168. Berger PB, Ruocco NA, Ryan TJ, et al: Incidence and prognostic implications of heart block complicating inferior myocardial infarction treated with thrombolytic therapy: results from TIMI II. J Am Coll Cardiol 20:533, 1992. 169. Blondeau M, Maurice P, Reverdy, et al: Troubles du rythme et de la conduction auriculo-ventriculaire dans l’infarctus du myocarde récent: considérations anatomiques. Arch Mal Coeur 60:1733, 1967. 170. Bilbao FJ, Zabalza IE, Vilanova JR, et al: Atrioventricular block in posterior acute myocardial infarction: a clinicopathologic correlation. Circulation 75:733, 1987. 171. Rosen KM, Ehrsani A, Rahimtoola SH: Myocardial infarction complicated by conduction defect. Med Clin North Am 57:155, 1973. 172. Clemmensen P, Bates ER, Califf RM, et al: Complete atrioventricular block complicating inferior wall acute myocardial infarction treated with reperfusion therapy. TAMI Study Group. Am J Cardiol 67:225, 1991. 173. Wesley RC, Jr, Lerman BB, DiMarco JP, et al: Mechanism of atropine-resistant atrioventricular block during inferior myocardial infarction: possible role of adenosine. J Am Coll Cardiol 8:1232, 1986. 174. Bertolet BD, McMurtrie EB, Hill JA, Belardinelli L: Theophylline for the treatment of atrioventricular block after myocardial infarction. Ann Intern Med 123:509, 1995. 175. Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: executive summary—a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol 44:671, 2004. 176. Cohen HC, Gozo EG, Jr, Pick A: The nature and type of arrhythmias in acute experimental hyperkalemia in the intact dog. Am Heart J 82:777, 1971. 177. Sugiura T, Iwasaka T, Takayama Y, et al: The factors associated with fascicular block in acute anteroseptal infarction. Arch Intern Med 148:529, 1988. 178. Rotman M, Wagner GS, Wallace AG: Bradyarrhythmias in acute myocardial infarction. Circulation 45:703, 1972. 179. Hunt D, Lie JY, Vohra J, et al: Histopathology of heart block complicating acute myocardial infarction. Circulation 48:1252, 1973. 180. Wilber D, Walton J, O’Neill W, et al: Effects of reperfusion on complete heart block complicating anterior myocardial infarction. J Am Coll Cardiol 4:1315, 1984. 181. Norris RM: Heart block in posterior and anterior myocardial infarction. Br Heart J 31:352, 1969. 182. Brown RW, Hunt D, Sloman JG: The natural history of atrioventricular conduction defects in acute myocardial infarction. Am Heart J 78:460, 1969. 183. Ginks WR, Sutton R, Winston DH, et al: Long-term prognosis after acute myocardial infarction with atrioventricular block. Br Heart J 39:186, 1977. 184. Lie KI, Wellens HJ, Schuilenburg RM, et al: Factors influencing prognosis of bundle branch block complicating acute anteroseptal infarction. Circulation 50:935, 1974. 185. Hindman MC, Wagner GS, JaRo H, et al: The clinical significance of bundle branch block complicating acute myocardial infarction. 2. Indications for temporary and permanent pacemakers. Circulation 58:689, 1978. 186. De Guzman M, Rahimtoola SH: What is the role of pacemakers in patients with coronary artery disease and conduction abnormalities? In Rahimtoola SH, editor: Controversies in coronary artery disease, Philadelphia, 1983, Davis, pp 191-207. 187. Rosen KM, Loeb HS, Chiquimia R, et al: Site of heart block in acute inferior myocardial infarction. Circulation 42:925, 1970. 188. Goldberg RJ, Zevallos JC, Yarzebski J, et al: Prognosis of acute myocardial infarction complicated by complete heart block (the Worcester Heart Attack Study). Am J Cardiol 69:1135, 1992. 189. Behar S, Zissman E, Zion M, et al: Prognostic significance of second-degree atrioventricular block in inferior wall acute myocardial infarction. SPRINT Study Group. Am J Cardiol 72:831, 1993. 190. Kostuk WJ, Beanlands DS: Complete heart block with acute myocardial infarction. Am J Cardiol 26:380, 1970. 191. Bigger JT, Dresdale RJ, Heissenbuttal RH, et al: Ventricular arrhythmias in ischemic heart disease: Mechanism, prevalence, significance, and management. Prog Cardiovasc Dis 19:255, 1977. 192. Mullins CB, Atkins JM: Prognoses and management of ventricular conduction blocks in acute myocardial infarction. Mod Concepts Cardiovasc Dis 45:129, 1976. 193. Hindman MC, Wagner GS, JaRo H, et al: The clinical significance of bundle branch block complicating acute myocardial infarction. 1. Clinical characteristics, hospital mortality, and one-year follow-up. Circulation 58:679, 1978. 194. Norris RM, Croxson MS: Bundle branch block in acute myocardial infarction. Am Heart J 79:728, 1970. 195. Scheinman M, Brenman B: Clinical and anatomic implication of intraventricular conduction blocks in acute myocardial infarction. Circulation 46:753, 1972. 196. Lie KI, Wellens HJ, Schuilenburg RM: Bundle branch block and acute myocardial infarction. In Wellens HJ, Lie KI, Janse MI,

editors: The conduction system of the heart: structure, function, and clinical implications, Philadelphia, 1976, Lea & Febiger, pp 662-672. 197. Newby KH, Pisano E, Krucoff MW, et al: Incidence and clinical relevance of the occurrence of bundle-branch block in patients treated with thrombolytic therapy. Circulation 94:2424, 1996. 198. Godman MJ, Lassers BW, Julian DG: Complete bundle branch block complicating acute myocardial infarction. N Engl J Med 282:237, 1970. 199. Scanlon PJ, Pryor R, Blount G: Right bundle branch block associated with left superior or inferior intraventricular block. Circulation 42:1135, 1970. 200. Godman MJ, Alpert BA, Julian DG: Bilateral bundle branch block complicating acute myocardial infarction. Lancet 2:345, 1971. 201. Nimetz AA, Shubrooks SJ, Hutter AM, et al: The significance of bundle branch block during acute myocardial infarction. Am Heart J 90:439, 1975. 202. Lamas GA, Muller JE, Turi AG, et al: A simplified method to predict occurrence of complete heart block during acute myocardial infarction. Am J Cardiol 57:1213, 1986. 203. Roos C, Dunning AJ: Right bundle branch block and left axis deviation in acute myocardial infarction. Br Heart J 32:847, 1970. 204. Sgarbossa EB, Pinski SL, Topol EJ, et al: Acute myocardial infarction and complete bundle branch block at hospital admission: clinical characteristics and outcome in the thrombolytic era. GUSTO-I Investigators. Global utilization of streptokinase and t-PA [tissue-type plasminogen activator] for occluded coronary arteries. J Am Coll Cardiol 31:105, 1998. 205. Melgarejo-Moreno A, Galcera-Tomas J, Garcia-Alberola A, et al: Incidence, clinical characteristics, and prognostic significance of right bundle-branch block in acute myocardial infarction: a study in the thrombolytic area. Circulation 196:1139, 1997. 206. Atkins J, Leshin S, Blomqvist CG, et al: Ventricular conduction blocks and sudden death in acute myocardial infarction. N Engl J Med 288:281, 1973. 207. Ritter WS, Atkins J, Blomqvist G, et al: Permanent pacing in patients with transient trifascicular block during acute myocardial infarction. Am J Cardiol 38:205, 1976. 208. Harper R, Hunt D, Vohra J, et al: His bundle electrogram in patients with acute myocardial infarction complicated by atrioventricular or intraventricular conduction disturbances. Br Heart J 37:705, 1975. 209. Murphy E, DeMots H, McAnulty J, et al: Prophylactic permanent pacemakers for transient heart block during myocardial infarction? Results of a prospective study. Am J Cardiol 49:952, 1982. 210. Lie K, Liem KL, Schuilenberg RM, et al: Early identification of patients developing late inhospital ventricular fibrillation after discharge from the coronary care unit: a 5 1 2 -year retrospective and prospective study of 1,897 patients. Am J Cardiol 41:674, 1978. 211. Waugh RA, Wagner GS, Haney TL, et al: Immediate and remote prognostic significance of fascicular block during acute myocardial infarction. Circulation 47:765, 1973. 212. Watson RDS, Glover DR, Page AJF, et al: The Birmingham Trial of permanent pacing in patients with intraventricular conduction disorders after acute myocardial infarction. Am Heart J 108:496, 1984. 213. Talwar KK, Kalra GS, Dogra B, et al: Prophylactic permanent pacemaker implantation in patients with anterior wall myocardial infarction complicated by bundle branch block and transient complete atrioventricular block: a prospective long-term study. Indian Heart J 39:22, 1987. 214. Harper R, Hunt D, Vohra J, et al: His bundle electrogram in patients with acute myocardial infarction complicated by atrioventricular or intraventricular conduction disturbances. Br Heart J 37:705, 1975. 215. Gould L, Reddy CVR, Kim SG, et al: His bundle electrogram in patients with acute myocardial infarction. Pacing Clin Electrophysiol 2:428, 1979. 216. Lichstein E, Gupta P, Liu MM, et al: Findings of prognostic value in patients with incomplete bilateral bundle branch block complicating acute myocardial infarction. Am J Cardiol 32:913, 1973. 217. Gould L, Reddy CV, Kim SG, et al: His bundle electrogram in patients with acute myocardial infarction. Pacing Clin Electrophysiol 2:428, 1979. 218. Topol EJ, Goldschlager N, Ports TA, et al: Hemodynamic benefit of atrial pacing in right ventricular myocardial infarction. Ann Intern Med 96:594, 1982. 219. Chamberlain DA, Leinbach RC, Vassaux CE, et al: Sequential atrioventricular pacing in heart block complicating acute myocardial infarction. N Engl J Med 282:577, 1970. 220. Murphy P, Morton P, Murtagh JG, et al: Hemodynamic effects of different temporary pacing modes for the management of bradycardias complicating acute myocardial infarction. Pacing Clin Electrophysiol 15:391, 1992. 221. Barold SS, Herweg B, Gallardo I: Acquired atrioventricular block: the 2002 ACC/AHA/NASPE guidelines for pacemaker implantation should be revised. Pacing Clin Electrophysiol 26:531, 2003. 222. Barold SS: American College of Cardiology/American Heart Association guideline for pacemaker implantation after acute myocardial infarction: what is persistent advanced block at the atrioventricular node? Am J Cardiol 80:770, 1997. 223. Barold SS, Hayes DL: Second-degree atrioventricular block: a reappraisal. Mayo Clin Proc 76:44, 2001.



224. McClellan MB, Tunis SR: Medicare coverage of ICDs. N Engl J Med 352:222, 2005. 225. Rahimtoola SH: The hibernating myocardium. Am Heart J 117:211, 1989. 226. Braunwald E, Rutherford JD: Reversible ischemic left ventricular dysfunction: evidence for the “hibernating myocardium.” J Am Coll Cardiol 8:1467, 1986. 227. Nordlander R, Hedman A, Pehrsson SK: Rate-responsive pacing and exercise capacity: a comment. Pacing Clin Electrophysiol 12:749, 1989. 228. Luceri RM, Brownstein SL, Vardeman L, et al: PR interval behavior during exercise: Implications for physiological pacemakers. Pacing Clin Electrophysiol 13:1719, 1990. 229. Mond HG, Irwin M, Ector H, Proclemer A: The world survey of cardiac pacing and cardioverter-defibrillators: calendar year 2005. An International Cardiac Pacing and Electrophysiology Society (ICPES) project. PACE 31:1202-1212, 2008. 230. Dreifus LS, Fisch C, Griffin JC, et al: Guidelines for implantation of cardiac pacemaker and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Pacemaker Implantation). Circulation 84:455, 1991. 231. Lau CP: Rate-adaptive cardiac pacing: simple and dual chamber, Mt Kisco, NY, 1993, Futura, pp 249-264. 232. Benditt DG, Milstein S, Buetikofer J, et al: Sensor-triggered ratevariable cardiac pacing. Ann Intern Med 107:714, 1987. 233. Gwinn N, Lemen R, Kratz J, et al: Chronotopic incompetence: a common and progressive finding in pacemaker patients. Am Heart J 123:1216, 1992. 234. Lamas GA, Ellenbogen KA: Evidence base for pacemaker mode selection: from physiology to randomized trials. Circulation 109:443, 2004. 235. Lamas GA, Knight JD, Sweeney MO, et al: Impact of ratemodulated pacing on quality of life and exercise capacity: evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT). Heart Rhythm 4:1125-1132, 2007. 236. Zehender M, Buchner C, Meinertz T, et al: Prevalence, circumstances, mechanisms, and risk stratification of sudden cardiac death in unipolar single-chamber ventricular pacing. Circulation 85:596, 1992. 237. Alpert MA, Curtis JJ, Sanfelippo JF, et al: Comparative survival after permanent ventricular and dual-chamber pacing for patients with chronic high-degree atrioventricular block with and without preexistent congestive heart failure. J Am Coll Cardiol 7:925, 1986. 238. Toff WD, Camm AJ, Skehan JD, et al: Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med 353:145, 2005. 239. Antonioli GE, Anscani L, Barbieri D, et al: Single-lead VDD pacing. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing 3, Mt Kisco, NY, 1993, Futura, pp 359-381. 240. Wiegand UK, Potratz J, Bode F, et al: Cost-effectiveness of dual chamber pacemaker therapy: does single lead VDD pacing reduce treatment costs of atrioventricular block? Eur Heart J 22:174, 2001. 241. Ovsyshcher IE, Crystal E: Permanent and temporary single-lead VDD and DDD pacemakers: state of the art. In Barold SS, Mugica J, editors: The fifth decade of cardiac pacing, New York, 2003, Blackwell Scientific. 242. Ovsyshcher IE, Crystal E: VDD pacing: underevaluated, undervalued, and underused. Pacing Clin Electrophysiol 27:1335, 2004. 243. Lau CP, Tai YT, Li JPS, et al: Initial clinical experience with a single pass VDDR pacing system. Pacing Clin Electrophysiol 15:1894, 1992. 244. Antonioli GE, Ansani L, Barbieri D, et al: Italian multicenter study on a single-lead VDD pacing system using a narrow atrial dipole spacing. Pacing Clin Electrophysiol 15:1890, 1992. 245. Sermasi S, Marconi M: VDD single pass lead pacing: Sustained pacemaker-mediated tachycardias unrelated to retrograde atrial activation. Pacing Clin Electrophysiol 15:1902, 1992. 246. Lau CP, Leung S-K, Lee IS-F: Comparative evaluation of acute and long-term clinical performance of two single lead atrial synchronous ventricular (VDD) pacemakers. Pacing Clin Electrophysiol 19:1574, 1996. 247. Ramsdale DR, Charles RG: Rate-responsive ventricular pacing: clinical experience with the RS4-SRT pacing system. Pacing Clin Electrophysiol 8:378, 1985. 248. Gross JN, Moser S, Benedek ZM, et al: DDD pacing mode survival in patients with a dual-chamber pacemaker. J Am Coll Cardiol 19:1536, 1992. 249. Huang M, Krahn AD, Yee R, et al: Optimal pacing for symptomatic AV block: a comparison of VDD and DDD pacing. Pacing Clin Electrophysiol 26:2230, 2003. 250. Wiegand UK, Bode F, Schneider R, et al: Atrial sensing and AV synchrony in single lead VDD pacemakers: a prospective comparison to DDD devices with bipolar atrial leads. J Cardiovasc Electrophysiol 10:513, 1999. 251. Linde-Edelstam C, Gulberg B, Norlander R, et al: Longevity in patients with high-degree atrioventricular block paced in the atrial synchronous mode or the fixed-rate ventricular inhibited mode. Pacing Clin Electrophysiol 15:304, 1992. 252. Nakata Y, Ogura S, Tokano T, et al: VDD pacing with a previously implanted single-lead system. Pacing Clin Electrophysiol 15:1425, 1992.

14  Pacing for Atrioventricular Conduction System Disease 253. Wish M, Fletcher RD, Gottdiener JS, et al: Importance of left atrial timing in the programming of dual-chamber pacemakers. Am J Cardiol 60:566, 1987. 254. Daubert C, Ritter P, Mabo P, et al: AV delay optimization in DDD and DDDR pacing. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing 3, Mt Kisco, NY, 1993, Futura, pp 259-287. 255. Hochleitner M, Hortnagl H, Ng CK, et al: Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy. Am J Cardiol 66:198, 1990. 256. Nishimura RA, Hayes DL, Holmes DR, Jr, Tajik AJ: Mechanism of hemodynamic improvement by dual-chamber pacing for severe left ventricular dysfunction: an acute Doppler and catheterization hemodynamic study. J Am Coll Cardiol 25:281, 1995. 257. Brecker SJ, Xiao HB, Sparrow J, Gibson DG: Effects of dualchamber pacing with short atrioventricular delay in dilated cardiomyopathy. Lancet 340:1308, 1992. 258. Crystal E, Ovsyshcher IE: Cardiac output-based versus empirically programmed AV interval: how different are they? Europace 1:121, 1999. 259. Ovsyshcher IE: Toward physiological pacing: optimization of cardiac hemodynamics by AV delay adjustment. Pacing Clin Electrophysiol 20:861, 1997. 260. Ovsyshcher I, Zimlicheman R, Katz A, et al: Measurement of cardiac output by impedance cardiography in pacemaker patients at rest: effects of various atrioventricular delays. J Am Coll Cardiol 21:761, 1993. 261. Ritter P, Dib JC, Lelievre T: Quick determination of the optimal AV delay at rest in patients paced in DDD mode for complete AV block [abstract]. Eur J CPE 4:A163, 1994. 262. Strohmer B, Pichler M, Froemmel M, et al: Evaluation of atrial conduction time at various sites of right atrial pacing and influence on atrioventricular delay optimization by surface electrocardiography. ELVIS Study Group. Pacing Clin Electrophysiol 27:468, 2004. 263. Haskell RJ, French WJ: Physiological importance of different atrioventricular intervals to improved exercise performance in patients with dual-chamber pacemakers. Br Heart J 61:46, 1989. 264. Khairy P, Talajic M, Dominguez M, et al: Atrioventricular interval optimization and exercise tolerance. Pacing Clin Electrophysiol 24:1534, 2001. 265. Sheppard RC, Ren JF, Ross J, et al: Doppler echocardiographic assessment of the hemodynamic benefits of rate adaptive AV delay during exercise in paced patients with complete heart block. Pacing Clin Electrophysiol 16:2157, 1993. 266. Sweeney MO, Ellenbogen KA, Casavant D, et al. Multicenter, prospective, randomized safety and efficacy study of a new atrial-based managed ventricular pacing mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol 16:811-817, 2005. 267. Fröhlig G, Gras D, Victor J, et al: Use of a new cardiac pacing mode designed to eliminate unnecessary ventricular pacing. Europace 8:96-101, 2006. 268. Gillis AM, Purerfellner H, Israel CW, et al: Reducing unnecessary right ventricular pacing with the managed ventricular pacing mode in patients with sinus node disease and AV block. Medtronic Enrhythm Clinical Study Investigators. Pacing Clin Electrophysiol 29:697-705, 2006. 269. Sweeney MO, Ruetz LL, Belk P, et al: Bradycardia pacing– induced short-long-short sequences at the onset of ventricular tachyarrhythmias. J Am Coll Cardiol 50:614–622, 2007. 270. Van Mechelen R, Schoonderwoerd R: Risk of managed ventricular pacing in a patient with heart block. Heart Rhythm 3:13841385, 2006. 271. Vavasis C, Slotwiner DJ, Goldner BG, Cheung JW: Frequent recurrent polymorphic ventricular tachycardia during sleep due to managed ventricular pacing. PACE 33:641-644, 2010. 272. Sweeney MO, Ellenbogen KA, Tang AS, et al: Severe atrioventricular decoupling, uncoupling, and ventriculoatrial coupling during enhanced atrial pacing: incidence, mechanisms, and implications for minimizing right ventricular pacing in ICD patients. J Cardiovasc Electrophysiol 19:1175-1180, 2008. 273. Pascale P, Pruvot E, Graf D: Pacemaker syndrome during managed ventricular pacing mode: what is the mechanism? J Cardiovasc Electrophysiol 20:574-576, 2009. 274. Perez MV, Al-Ahmad AA, Wang PJ, Turakhia MP: Inappropriate pacing in a patient with managed ventricular pacing (MVP): what is the cause? Heart Rhythm 7:1336, 2010. 275. Wiggers CJ: The muscle reactions of the mammalian ventricles to artificial surface stimuli. Am J Physiol 73:346, 1925. 276. Barold SS: Adverse effects of ventricular desynchronization induced by long-term right ventricular pacing. J Am Coll Cardiol 42:624, 2003. 277. Burkhoff D, Oikawa RY, Sagawa K: Influence of pacing site on canine left ventricular contraction. Am J Physiol 251:J428, 1986. 278. Rosenqvist M, Bergfeldt L, Haga Y, et al: The effect of ventricular activation sequence on cardiac performance during pacing. Pacing Clin Electrophysiol 19:1279, 1996. 279. Tantengco MV, Thomas RL, Karpawich PP: Left ventricular dysfunction after long-term right ventricular apical pacing in the young. J Am Coll Cardiol 37:2093, 2001. 280. Betocchi S, Piscione F, Villari B, et al: Effects of induced asynchrony on left ventricular diastolic function in patients with coronary artery disease. J Am Coll Cardiol 22:1124, 1993. 281. Lee MA, Dae MW, Langberg JJ, et al: Effects of long-term ventricular apical pacing on left ventricular perfusion, innervation, function and histology. J Am Coll Cardiol 24:225, 1994.

359

282. Tse HF, Lau CP: Long-term effect of right ventricular pacing on myocardial perfusion and function. J Am Coll Cardiol 29:744, 1997. 283. Prinzen FW, Augustijn CH, Arts T, et al: Redistribution of myocardial fiber strain and blood flow by asynchronous activation. Am J Physiol 259:330, 1990. 284. Van Oosterhout MFM, Prinzen FW, Arts T, et al: Asynchronous electrical activation induces inhomogeneous hypertrophy of the left ventricular wall. Circulation 98:588, 1998. 285. Prinzen FW, Cheriex EM, Delhaas T, et al: Asymmetric thickness of the left ventricular wall resulting from asynchronous electrical activation: a study in patients with left bundle branch block and in dogs with ventricular pacing. Am Heart J 130:1045, 1986. 286. Adomian GE, Beazell J: Myofibrillar disarray produced in normal hearts by chronic electrical pacing. Am Heart J 112:79, 1986. 287. Karpawich PP, Rabah R, Haas JE: Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block. Pacing Clin Electrophysiol 22:1372, 1999. 288. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115, 2002. 289. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. MOST Investigators. Circulation 107:2932, 2003. 290. Steinberg JS, Maniar P, Zareba W, et al: The relationship between right ventricular pacing and outcomes in MADIT-II patients. Presented at the North American Society of Pacing and Electrophysiology Annual Scientific Sessions, Washington, DC, 2003. 291. Doshi R, Daoud E, Fellows C, et al: Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 16:1160, 2005. 292. Sweeney MO, Hellkamp AS: Heart failure during cardiac pacing. Circulation 113:2082, 2006. 293. Gammage MD, Marsh AM: Randomized trials for selective site pacing: do we know where we are going? Pacing Clin Electrophysiol 27:878, 2004. 294. Deshmukh P, Casavant DA, Romanyshyn M, Anderson K: Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation 101:869, 2000. 295. Giudici MC, Thornburg GA, et al: Comparison of right ventricular outflow tract and apical permanent pacing on cardiac output. Am J Cardiol 79:209, 1997. 296. Buckingham TA, Candinas R, Attenhofer C, et al: Systolic and diastolic function with alternate and combined site pacing in the right ventricle. Pacing Clin Electrophysiol 21:1077, 1998. 297. Victor F, Leclercq C, Mabo P, et al: Optimal right ventricular pacing site in chronically implanted patients: a prospective randomized crossover comparison of apical and outflow tract pacing. J Am Coll Cardiol 33:311, 1999. 298. Schwaab B, Frohlig G, Alexander C, et al: Influence of right ventricular stimulation site on left ventricular function in atrial synchronous ventricular pacing. J Am Coll Cardiol 33:317, 1999. 299. Mera F, DeLurgio DB, Patterson RE, et al: A comparison of ventricular function during high right ventricular septal and apical pacing after His-bundle ablation for refractory atrial fibrillation. Pacing Clin Electrophysiol 22:1234, 1999. 300. Tse HF, Yu C, Wong KK, et al: Functional abnormalities in patients with permanent right ventricular pacing: the effect of sites of electrical stimulation. J Am Coll Cardiol 40:1451, 2002. 301. Stambler BS, Ellenbogen K, Zhang X, et al: Right ventricular outflow versus apical pacing in pacemaker patients with congestive heart failure and atrial fibrillation. ROVA Investigators. J Cardiovasc Electrophysiol 14:1180, 2003. 302. De Cock CC, Giudici MC, Twisk JW: Comparison of the haemodynamic effects of right ventricular outflow-tract pacing with right ventricular apex pacing: a quantitative review. Europace 5:275, 2003. 303. Bourke JP, Hawkins T, Keavey P, et al: Evolution of ventricular function during permanent pacing from either right ventricular apex or outflow tract following AV junctional ablation for atrial fibrillation. Europace 4:219, 2002. 304. Victor F, Mansour H, Pavin D, et al: Optimal right ventricular pacing site in classical pacemaker indications: A randomized crossover comparison of apical and septal pacing [abstract]. Heart Rhythm 1:S70, 2004. 305. Peschar M, Marsh AM, Verbeek XAAM, et al: Site of right ventricular pacing in patients with atrioventricular block. Heart Rhythm 1:S245, 2004. 306. Kaye G, Stambler BS, Yee R: Search for the optimal right ventricular pacing site: Design and implementation of three randomized multicenter clinical trials. PACE 32:426-433, 2009. 307. Yu CM, Chan JY, Zhang Q, et al: Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 361:2123-2134, 2009. 308. Curtis AB, Adamson PB, Chung E, et al: Biventricular versus Right Ventricular Pacing in Patients with AV Block (BLOCK HF): clinical study design and rationale. J Cardiovasc Electrophysiol 18:965-971, 2007. 309. Funck RC, Blanc JJ, Mueller HH, et al: Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the Biventricular Pacing for Atrioventricular Block

360

SECTION 2  Clinical Concepts

to Prevent Cardiac Desynchronization (BioPace) study. Europace 8:629-635, 2006. 310. Koplan BA, Gilligan DM, Nguyen LS, et al: A randomized trial of the effect of automated ventricular capture on device longevity and threshold measurement in pacemaker patients. ULTRA Study Investigators. PACE 31:1467-1474, 2008. 311. Biffi M, Bertini M, Saporito D, et al: Actual pacemaker longevity: the benefit of stimulation by automatic capture verification. PACE 33:873-881, 2010. 312. De Voogt WG, Vonk BF, Albers BA, Hintringer F: Understanding capture detection. Europace 6:561-569, 2004.

313. Sutton R, Frohlig G, de Voogt WG, et al: Reduction of the pace polarization artifact for capture detection applications by a tri-phasic stimulation pulse. Europace 6:570e9, 2004. 314. Schubert A, Ventura R, Meinertz T: Automatic threshold tracking activation without the intraoperative evaluation of the evoked response amplitude. AUTOCAP Investigators. Pacing Clin Electrophysiol 23:321-324, 2000. 315. Pecora D, Morandi F, Liccardo M, et al: Performance of a ventricular automatic-capture algorithm in a wide clinical setting. PACE 31:1546-1553, 2008.

316. Candinas R, Liu B, Leal J, et al: Impact of fusion avoidance on performance of the automatic threshold tracking feature in dual chamber pacemakers: a multicenter prospective randomized study. Pacing Clin Electrophysiol 25:1540-1545, 2002. 317. Murgatroyd FD, Helmling E, Lemke B, et al: Manual vs. automatic capture management in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators. Europace 12:811-816, 2010. 318. Crossley GH, Mead H, Kleckner K, et al: Automated left ventricular capture management. LVCM Study Investigators. PACE 30:1190-1200, 2007.

15  15

Pacing in Neurally Mediated Syncope Syndromes JANNEKE BERECKI-GISOLF  |  ROBERT S. SHELDON

Syncope is the transient loss of consciousness with subsequent com-

plete resolution and without focal neurologic deficits, resulting from cerebral hypoperfusion, and not requiring specific resuscitative measures. The neurally mediated syncope syndromes are a collection of clinical disorders of heart rate and blood pressure regulation, caused by autonomic reflexes.1,2 These often include bradycardia, which has led to attempts to use cardiac pacing as a therapy for carotid sinus syncope and vasovagal syncope, the most common of the neurally mediated syncopes. Vasovagal syncope generally begins at a much younger age than carotid sinus syncope, usually occurs in the absence of any underlying structural heart disease, and can have a long and sporadic course lasting decades. Terminology is still variable, and diagnostic synonyms for vasovagal syncope include ventricular syncope, “empty heart syndrome,” neuromediated syncope, cardioneurogenic or neurocardiogenic syncope, and “neurally mediated hypotension bradycardia.” We prefer the term vasovagal syncope, partly for historical deference, partly because of its descriptive accuracy, and partly in the absence of a compelling reason to adopt another term. In contrast to vasovagal syncope, carotid sinus syncope occurs in elderly patients and is often associated with hypertension, peripheral vascular disease, or coronary artery disease. There are now several expert consensus conferences and position papers on these syndromes.3,4 This chapter reviews recent progress in determining the usefulness of pacemakers in the neurally mediated syncope syndromes.*

Carotid Sinus Syncope CLINICAL PERSPECTIVE Carotid sinus syncope (CSS) is a syndrome of syncope associated with a consistent clinical history, carotid sinus hypersensitivity, and the absence of other potential causes of syncope. Historical features that suggest the diagnosis are syncope or presyncope occurring with carotid sinus stimulation that reproduces clinical symptoms, or fortuitous Holter monitoring or other documentation of asystole during syncope following maneuvers that could presumably stimulate the carotid sinus.5-9 The incidence of carotid sinus syncope is low, about 35 per 1 million population per year.10 CSS occurs in older patients, mainly in men. It tends to occur abruptly, with minimal prodrome, and only half of patients may recognize a precipitating event. These events typically include wearing tight collars, shaving, head turning (as in looking to the back in a car), coughing, heavy lifting, and looking up. Symptoms of CSS range from mild presyncope to profound loss of consciousness, occasionally with significant injuries. Some patients may not recall losing consciousness, instead presenting with unexplained falls. In Great Britain, fits, faints, and falls are often investigated in an integrated setting with a comprehensive clinical pathway. Elderly patients with unexplained falls may have positive carotid sinus massage (CSM) responses, suggesting that carotid sinus syncope is responsible *This study was supported in part by grants 73-1976 and 130312 from the Canadian Institute for Health Research (CIHR).

for many unexplained or recurrent falls.11,12 However, physiologic carotid sinus hypersensitivity is much more common than carotid sinus syncope, and care should be taken in the interpretation of these results. NATURAL HISTORY Little is known about the natural history of CSS. Even though it may have a substantial effect on quality of life, CSS has not been shown to affect mortality significantly, and patients who receive therapy do not appear to have worse prognoses than the general population. Even in the absence of pacing, only 25% of patients may have a syncope recurrence.13,14 RATIONALE FOR PACING Table 15-1 lists recommendations and other considerations in pacing for CSS. Physiology The carotid sinus reflex is an integral component of the homeostatic mechanisms of blood pressure regulation.15 Increases in intrasinus pressure stimulate mechanoreceptors, which participate in an afferent arc terminating in the brainstem. The efferent arc travels to peripheral end organs through vagal efferents, which augment cardiac vagal input and slow heart rate, and through the spinal cord to inhibit peripheral sympathetic activity in skeletal vasculature, resulting in peripheral vasodilatation. This reflex maintains blood pressure within a narrow range. An abnormal carotid sinus reflex can cause exaggerated responses of heart rate and blood pressure. Some evidence suggests that the major defect in carotid sinus hypersensitivity does not reside in the carotid sinus or in its neural efferents,16,17 or in the brainstem. Rather, the neuromuscular structures surrounding the carotid sinus may be involved in CSS. Blanc et al.18 found similar results in 30 patients without known carotid sinus hypersensitivity or syncope. Abnormal sternocleidomastoid electromyograms were associated with abnormal responses to CSM. Because the denervated sternocleidomastoid muscle cannot provide or contribute information to the central nervous system baroreflex centers, any output from the carotid sinus is inappropriately interpreted as increased blood pressure. Other Therapies When CSS is the likely cause of syncopal episodes, the initial treatment recommendation should be simple elimination of any recognized maneuvers that may precipitate an event. Discontinuation of wearing tight collars and ties and shaving more carefully may help. Hypovolemia should be corrected. The addition of high salt intake, volume expanders such as fludrocortisone acetate (Florinef),19 or oral vasopressors such as midodrine (ProAmatine) may be helpful, but these interventions are frequently limited in older patients by comorbidities (e.g., hypertension, heart failure). In the pre–pacemaker era, recalcitrant cases of carotid sinus syncope were treated with carotid sinus denervation by surgical technique.20 Surgical sinus denervation currently is reserved for cases secondary to

361

362

TABLE

15-1 

SECTION 2  Clinical Concepts

Summary of Pacing for Carotid Sinus Syncope (CSS)

Factor Goal

Level of evidence for success Consensus recommendations Patient selection Programming considerations

Description Prevent reflex bradycardia and compensate for reflex hypotension Prevent syncope Observational studies and open-label, randomized controlled trials (RCTs) No double-blind studies Class I: Recurrent syncope, with syncope induced by carotid sinus massage Class IIa: Recurrent syncope, with profound bradycardia induced by carotid sinus massage Syncope and positive carotid sinus massage Atrioventricular sequential pacing

head or neck tumors or lymphadenopathy, or it is performed in conjunction with carotid endarterectomy or in patients with severe refractory carotid sinus syncope of the purely vasodepressor type. EVIDENCE OF CLINICAL BENEFIT Observational Studies Table 15-2 summarizes studies of pacing for CSS.13,21-25 Earlier studies tended to be retrospective reports of pacing practices for CSS and therefore were inherently biased toward patients with a clear diagnosis of CSS who would truly benefit from pacing. Randomized Trials More recently, prospective, randomized trials have examined outcomes on the basis of presence of pacing and mode. A prospective, randomized Italian trial reaffirmed the important role of permanent pacing; 60 patients with CSS were randomized to pacing (32) or no pacing (28) therapy.14 During a follow-up of about 3 years, syncope recurred in 16 patients of the no-pacing group (51%) and in three (9%) of the pacing group (P = .002). This finding somewhat confirms the

TABLE

15-2 

Clinical Studies of Pacing for Carotid Sinus Syncope*

Treatment Follow-up (mo) Sugrue et al.22 (OBS) No pacing 39 Pacing 23 Huang et al.13 (OBS) No pacing 42 VVI 42 DDD 42 23 Morley et al. (OBS) VVI 18 DVI 18 DDD 18 25 Brignole et al. (RCT) No pacing 8.4 Pacing 7.2 VVI 7.2 DDD 7.2 Brignole et al.24 (crossover) VVI 2 DDD 2 Parry et al.31† ODO 6 DDD/RDR 6

Patients (N)

Syncope Free (%)

11 23

73 91

8 9 4

88 100 100

54 13 3

89 92 66

19 16 11 5

53 100 100 100

26 26

92 100

25 25

44‡ 36

*No differences were statistically significant. The most striking feature is how well patients appear to do regardless of attempted therapy. †Double-blind, crossover RCT among patients with carotid sinus hypersensitivity and recurrent, unexplained falls. ‡Percentage of patients free of falls. OBS, Observational study; RCT, randomized controlled trial.

usefulness of pacing for the prevention of carotid sinus syncope, although potent placebo effects cannot be ruled out (see later). Falls.  Pacing of patients with CSS has been associated with a reduction in falls.26 Furthermore, among patients with unexplained and recurrent falls, carotid sinus hypersensitivity may be an important risk factor.27,28 In 2001, Kenny et al.29 reported the open-label SAFE PACE trial, designed to determine whether cardiac pacing reduces falls in older patients with unexplained falls and a cardioinhibitory response to CSM. The 187 patients were randomized to receive a dual-chamber pacemaker, with rate-drop responsiveness, or no intervention. Patients who received a pacemaker had a highly significant 58% reduction in falls and a 40% reduction in syncope. Although these results suggest that many unexplained falls in the elderly are caused by carotid sinus syncope, and that these can be prevented with pacing, one must remember that this was an open-label trial. In 2010, Ryan et al.30 reported the SAFEPACE-2 study, in which 141 older patients with unexplained falls and cardioinhibitory carotid sinus hypersensitivity were randomized to receive a rate-drop responsive dual-chamber pacemaker or an implantable loop recorder (ILR). Although the relative risk (RR) of reporting a fall after implantation of a device decreased (0.23; 95% confidence interval [CI] = 0.15 to 0.37), there were no significant differences in falls reported between the paced group (67%) and the ILR group (53%) (difference RR = 1.25; 95% CI = 0.93 to 1.67). These results are at odds with the findings in SAFE PACE; possibly because of differences in patient population (patients were older and frailer). Furthermore, due to recruitment difficulties, SAFEPACE-2 may have been underpowered; according to sample size calculations, 226 patients were needed to detect a 20% difference with 80% power. Only one double-blind, placebo-controlled crossover trial has reported pacing in patients with recurrent, unexplained falls and carotid sinus hypersensitivity.31 All study participants received a dualchamber pacemaker with rate-drop response programmer and were randomized to DDD/RDR mode (on) versus ODO mode (off); after 6 months, patients switched to the opposite mode. Only 25 of the 34 recruited patients completed the study. The total number of falls decreased after pacemaker implantation, but risk of falling with the pacemaker on versus off was not statistically significant (RR = 0.82; 95% CI = 0.62 to 1.10). Although this suggests a placebo effect, similar to that seen in pacing of vasovagal syncope patients, the results must be interpreted with caution; the study was underpowered because of an unexpectedly high attrition rate of 26%. PATIENT SELECTION Careful patient selection may help provide effective and efficient therapy for CSS. Permanent pacemaker therapy is indicated for patients with recurrent, frequent, or severe CSS, particularly for predominant cardioinhibitory syncope.32,33 Predictors of success with permanent pacing include multiple episodes before implantation; episodes that occur while upright or sitting; and episodes preceded by a recognized stimulus.34 Syncope recurrence after implantation of a permanent pacemaker may be caused by a prominent vasodepressor component. PHYSICAL DIAGNOSIS WITH CAROTID SINUS MASSAGE The carotid sinus is located high in the neck below the angle of the mandible. Carotid massage is contraindicated in the presence of bruits or a history of cerebrovascular disease, transient ischemic attacks (TIAs), or endarterectomy. Sequential application of CSM to the left and right carotid arteries should be performed with at least 10 to 20 seconds between applications. The duration of carotid massage should be 5 to 10 seconds, and it should be terminated with the onset of characteristic asystole or severe presyncope. In most series, the predominant responses to CSM were obtained on the right side.5 CSM



15  Pacing in Neurally Mediated Syncope Syndromes

should be performed while the patient is both supine and upright, either sitting or while secured safely on a tilt table. It may be difficult to document transient hypotension with standard sphygmomanometric methods, and noninvasive continuous digital plethysmography is often used. Physiologic Responses Carotid sinus massage elicits both cardioinhibitory and vasodepressor responses (Fig. 15-1). A cardioinhibitory response to CSM is defined as 3 seconds or longer of ventricular standstill or asystole. Ventricular asystole usually results from a sinus pause caused by sinus node exit block,35 but it can result from atrioventricular (AV) block as well. A vasodepressor response to CSM is defined as a drop in systolic blood pressure of 50  mm Hg or more during massage; this may be difficult to demonstrate in patients who have a significant cardioinhibitory component. In contrast to the induced cardioinhibitory component of carotid sinus hypersensitivity, the vasodepressor response may have a slower, more insidious onset and a more prolonged resolution.

363

Carotid Sinus Hypersensitivity and Carotid Sinus Syncope Carotid sinus hypersensitivity denotes abnormal physiologic responses to CSM, either cardioinhibitory or vasodepressor (or both). The presence of asymptomatic carotid sinus hypersensitivity is quite common in older adults. For example, a positive cardioinhibitory response to CSM was noted in 32% of patients undergoing coronary angiography.36 CSS is the syndrome of syncope in association with carotid sinus hypersensitivity, and in the absence of other apparent causes of syncope. Complications Carotid sinus massage is safe if done carefully. CSM is contraindicated in patients with a history of cerebrovascular disease or carotid bruits, because it can cause cerebrovascular accident (CVA, stroke). In a review of 3100 episodes of CSM performed on 1600 patients, the seven complications (0.14%) were neurologic and transient.37 In another review of CSM on 4000 patients, complications were observed in 11 patients (0.28%);38 all were neurologic. After 1 month, nine patients

V1 I II III AVR

5s 140/76 Arterial 100 pressure (mm Hg) 0

CSM On

76/42 CSM Off

Arterial 100 pressure (mm Hg) 0

Arterial 100 pressure (mm Hg) 0 1s Figure 15-1  Combined cardioinhibitory and vasodepressor response to carotid sinus massage (CSM). Note slow return of blood pressure despite resolution of asystole. (From Almquist A, Gornick C, Benson W, et al: Carotid sinus hypersensitivity: evaluation of the vasodepressor component. Circulation 71:927, 1985. Copyright 1985 American Heart Association.)

SECTION 2  Clinical Concepts

PROGRAMMING Pacing in AAI mode is contraindicated because many patients may eventually demonstrate associated reflex AV block.40 In general, patients appear to benefit most from AV sequential pacing, even when a significant component of vasodepressor CSS is present. VVI pacing should not be used in patients with intact ventriculoatrial (VA) conduction,41 because of possible pacemaker syndrome. Lack of VA conduction at a given time, however, does not ensure against its future development. Therefore, we recommend dual-chamber pacemakers for patients with CSS and normal sinus rhythm. Few studies have examined the role of rate-responsive pacing in CSS. Patients are generally older and therefore may have bradycardic comorbidities such as sick sinus syndrome or chronotropic incompetence, either intrinsic or pharmacologic. Therefore, rate-responsive pacing might be beneficial. Similarly, few studies have prospectively examined pacing with rate-drop or hysteresis capabilities, which has the theoretical advantage of providing rapid, higher-rate AV sequential pacing to counteract the vasodepressor component during CSS attacks.42 RECOMMENDATIONS Evidence is weak to support use of pacing in patients with carotid sinus syncope. No persuasive evidence supports pacing in patients with falls and carotid sinus hypersensitivity.

Vasovagal Syncope CLINICAL PERSPECTIVE Vasovagal syncope is the most common of the neurally mediated syncopal syndromes. Most people who faint probably do not seek medical attention for isolated events.2 Prolonged standing, sight of blood, pain, and fear are common precipitating stimuli for this, the common faint. Patients develop nausea, diaphoresis, pallor, and loss of consciousness from hypotension with or without significant bradycardia. Return to consciousness typically occurs after seconds or 1 to 2 minutes. Those with adequate warning may be able to use physical counterpressure maneuvers, or simply sit or lie down, to prevent a full faint. However, some patients have little or no prodrome, no recognized precipitating stimulus, or marked bradycardia accompanying the faint.43-47 These patients have sparked interest in permanent pacing as a therapy. Epidemiology About 40% of people faint at least once in their life, and at least 20% of adults faint more than once.48,49 Fainters usually present first in their teenage years and 20s and may faint sporadically for decades. This long, usually benign, and sporadic history can make for difficult decisions about therapy. Syncope is responsible for 1% to 6% of emergency room visits and 1% to 3% of hospital admissions.50-52 Tilt tests are often used as a diagnostic tool, although they are limited by difficulties with sensitivity, specificity, and reproducibility, and with little evidence-based agreement on methodologic details and outcome criteria. Positive tilt tests are characterized by presyncope, syncope, bradycardia, and hypotension, as well as a reproduction of the patient’s perisyncopal symptoms53,54 (Fig. 15-2). Although many patients of all ages simply have vasovagal syncope, clinicians need to remain vigilant and look for other causes, including valvular and structural heart disease, sick sinus syndrome, CSS, and orthostatic hypotension. Symptom Burden and Quality of Life The vasovagal syncope syndrome has an extremely wide range of symptoms. The symptom burden varies from a single syncopal spell

120 MAP (mm Hg)

had made a full recovery; neurologic symptoms persisted in two patients. Rare, arrhythmic complications include asystole and ventricular fibrillation.39

100 80 60 40 20 120

HR (beats/min)

364

100 80 Head-up tilt

60 40 20 300

Supine

SYNCOPE 400

500

600 700 800 Time (seconds)

900 1000 1100

Figure 15-2  Hypotension and bradycardia induced during a positive drug-free passive tilt-table test. HR, Heart rate; MAP, mean arterial pressure.

in a lifetime to daily faints. Some patients have very sporadic presentations, with periods of intense symptoms interspersed with long periods of quiescence. Other patients faint at more regular intervals, although they may be months or years apart. Several observational studies and randomized clinical trials reported that patients have a median of 5 to 15 syncopal spells, with fainting episodes occurring over 2 to 60 years.55-58 Patients with recurrent syncope are impaired similar to those with severe rheumatoid arthritis or chronic low back pain and psychiatric inpatients.55 The quality of life decreases as the frequency of syncopal spells increases.56 After clinical assessment, many patients continue to do poorly. After 1, 2, and 3 years, 28%, 38%, and 49% of patients faint again, respectively.59 Interestingly, several groups reported a 90% reduction in the total number of faints in this patient population after the tilt test. The reason for this apparently great reduction in syncope frequency after assessment is unknown, but it does lead to a large number of patients who request further treatment. Therefore, when assessing syncope patients, clinicians need to be alert to the surprising impairment of quality of life that many patients endure, to provide a perspective that lasts decades, and to remember that the patient’s clinical state will probably fluctuate. RATIONALE FOR PACING Table 15-3 lists recommendations and other considerations in pacing for vasovagal syncope. PHYSIOLOGY Syncope is a transient loss of neurologic function caused by a global reduction of cerebral blood flow (CBF). Sudden cessation of CBF results in loss of consciousness within 4 to 10 seconds.60 Lesser CBF reductions may result in presyncope. Almost all vasovagal syncope occurs while the patient is in an upright position. Syncope is usually associated with heightened physiologic or psychological stress, such as prolonged orthostatic stress; arising quickly and walking; pain, fear, emotion, or seeing blood or medical procedures; and strenuous exercise. Transient hypotension is the most common hemodynamic manifestation of vasovagal syncope. Many patients have inappropriate peripheral sympathetic responses to physiologic and psychological stressors. Under conditions in which the normal response may be vasoconstriction, syncope patients usually fail to do so. Abnormalities have been documented in arteriolar vasoconstriction, splenic venoconstriction, and venous capacitance. The ultimate cause of hypotension is an



15  Pacing in Neurally Mediated Syncope Syndromes

TABLE

15-3 

Summary of Pacing for Vasovagal Syncope

Factor Goal Level of evidence for success Consensus recommendations Patient selection

Programming considerations

Description Prevent reflex bradycardia and compensate for reflex hypotension Prevent syncope Limited evidence for benefit based on double-blind RCTs May be a subset of patients with proved bradycardia who benefit Class IIa: Recurrent vasovagal syncope with clinically documented bradycardia, or bradycardia induced on tilt test Medically refractory, frequent, disabling vasovagal syncope Documented pauses during syncope Tilt test results not helpful Dual-chamber pacemaker Benefit from specific sensor to drive rate-response or pacing algorithm (rate-drop response, ventricular impedance) not proved

abrupt cessation of vascular sympathetic traffic, causing withdrawal of α-adrenergic tone. Evidence for Bradycardia Permanent pacemaker therapy could be effective if bradycardia is a common and symptomatically important feature of vasovagal syncope. The evidence for clinically important bradycardia comes from studies that have used tilt tests, pacemaker memory, and implantable loop recorders to record heart rate during syncopal spells. Tilt-Table Tests.  Bradycardia frequently occurs during vasovagal syncope induced by tilt-table testing.61,62 The mean heart rate during syncope induced by passive head-up tilt tests is 30 beats/min (bpm), and asystole longer than 3 seconds is often documented. However, uncertainty surrounds the relationship between the hemodynamics of tilt testing and clinical vasovagal syncope. For example, the ISSUE investigators found no relationship between the heart rate during syncope on tilt testing and during syncope in the community population. Patients with tilt test–induced bradycardia frequently do not have bradycardia during clinical syncope.63,64 Therefore, although bradycardia is the rule rather than the exception during a positive tilt test, the bradycardia evoked on a tilt test may not resemble the hemodynamics during syncope in that patient in the community. Pacemaker Memory.  Is asystole in patients in the community frequently associated with syncope? Evaluation of frequent fainters with pacemakers programmed to act as event recorders demonstrated that while transient asystole is common during documented syncope, many other asymptomatic asystolic episodes also occurred. Only 0.7% of asystolic events lasting 3 to 6 seconds and 43% of events lasting longer than 6 seconds resulted in symptoms of presyncope or syncope.65 Therefore, even asystole of several seconds’ duration does not necessarily cause syncope. Implantable Recorders.  The ILR permits prolonged electrocardiographic monitoring and is a reasonable approach to diagnosing patients with infrequent syncope. Current ILRs weigh only 17 grams and have battery life of 14 months. The ECG signal is stored in a buffer that can be frozen with a manual activator. The ILR has programmable, automatic detection parameters for high and low rates and pause. In a Canadian study of 206 patients, symptoms recurred in 69% of patients. Bradycardia was detected more frequently than tachycardia (17% vs. 6%).66,67 The European International Study on Syncope of Uncertain Aetiology (ISSUE) enrolled 111 patients with syncope and previous tilt-table testing; not all tilt tests were positive.68 Patients with positive or with negative tilt tests both had events in 34% of each group over a follow-up of 3 to 15 months. Marked sinus bradycardia (46%) or asystole (62%)

365

were detected during syncope. Therefore, bradycardia reported during syncope varies widely; 17% to 62% of patients with vasovagal syncope had significant bradycardia during syncope in the ILR studies. The heart rate response during tilt testing did not predict spontaneous heart rate response, with more frequent asystole than expected based on tilt response. Thus, many patients with positive tilt tests may develop some degree of bradycardia at presyncope or syncope, and pacing may be a plausible treatment. CONSERVATIVE THERAPY Pacing should be tried only in patients with vasovagal syncope who have not responded to, or who are not candidates for, other treatments. Currently, most clinicians first teach patients about the causes of syncope, encourage fluid and salt intake, and coach physical counterpressure maneuvers. If this initial approach is unsuccessful, pharmacologic therapy is used (fludrocortisone, midodrine, β-blockers, SSRIs). Only after these options have been explored should permanent pacing be considered (Table 15-4). Reassurance and Education Most patients with vasovagal syncope simply require reassurance and education. Many of the patients with more frequent syncope also benefit from these conservative measures. In particular, patients should be taught to recognize their prodromal symptoms and to sit or lie down as quickly as possible to minimize injury during recurrences and lessen the severity of attacks. Salt and Fluids Blood volume is an important factor in the pathophysiology of vasovagal syncope. Syncope almost only occurs in the upright position, and many patients faint only from orthostatic stress in situations such as attending religious services, parades, or outdoor events and taking showers. Prolonged drug-free head-up tilt provokes syncope in a large number of syncope patients; this depends on the duration and angle of head-up tilt.69 Finally, many patients report avoiding dietary salt and have low daily urinary sodium excretion.70 Physical Counterpressure Maneuvers Physical counterpressure maneuvers may be quite helpful, although no blinded, controlled studies have been reported. Patients must have a prodrome long enough that they can react by isometrically tightening muscles using maneuvers such as squatting, leg crossing, and fist clenching. Van Dijk et al.71 reported the Physical Counterpressure Maneuvers Trial, a multicenter, randomized clinical trial to evaluate the effectiveness of physical counterpressure in preventing syncope recurrence. A total of 223 patients were randomized to receive optimal conventional therapy (lifestyle changes; e.g., avoiding triggers,

TABLE

15-4 

Principles of Management of Vasovagal Syncope

Area Diagnosis and prognosis

Assessment of patient needs Conservative advice

Medical options

Permanent pacing

Intervention Confirm diagnosis with history, tilt-table tests, and loop recorder. Assess likelihood of syncope recurrence (>2 spells or recent worsening). Insight into diagnosis Cause of syncope Probability of syncope recurrences Treatment options Maximizing salt and fluid intake Physical counterpressure maneuvers Driving and reporting to authorities Avoidance and management of triggers Fludrocortisone (weak evidence) Midodrine (good evidence) Serotonin reuptake inhibitors (weak evidence) β-Blockers in patients age >42 (modest evidence) Weak evidence

366

TABLE

15-5 

SECTION 2  Clinical Concepts

Summary of Major RCTs of Treatment for Vasovagal Syncope

Treatment Metoprolol Fluoxetine, propranolol Midodrine Fludrocortisone

Study Sheldon et al.132 Theodorakis et al.133

Sites (N) 14 1

Subjects (N) 208 96

Mean Age 42 42

Qingyou et al.134 Salim and Di Sessa90

1 1

26 33

12 14

Clinical Outcome Syncope recurrence Syncope or presyncope recurrence Syncope recurrence Syncope or presyncope recurrence

Effect 36% controls, 36% metoprolol 41% controls, 51% propranolol, 22% fluoxetine 80% controls, 22% midodrine 36% controls, 55% fludrocortisone

P 0.99 <0.05 0.023 <0.04

Data from Kuriachan V, Sheldon RS, Platonov M: Evidence-based treatment for vasovagal syncope. Heart Rhythm 5:1609-1614, 2008.

increasing salt intake) with or without additional training in physical counterpressure. During the follow-up of up to 18 months, 50.9% of conventional therapy patients and 31.6% of conventional therapy with counterpressure patients experienced syncope recurrence, a relative risk reduction of 0.36 (95% CI = 0.11 to 0.53). These results provide sufficient evidence to support including the low-risk, low-cost therapy of physical counterpressure in the recommended first-line treatment of vasovagal syncope. MEDICAL THERAPY Table 15-5 summarizes major randomized clinical trials of treatment for vasovagal syncope. No therapies have proved effective in large, randomized clinical trials in preventing vasovagal syncope. Few have been subjected to rigorous clinical trials, and when interpreting openlabel studies, one should remember that most patients appear to improve after assessment. There is an estimated 90% reduction in syncope in the population after tilt testing.72 The four major drug classes used are α1-adrenergic agonists, β-blockers, selective serotonin reuptake inhibitors (SSRIs), and salt-retaining mineralocorticoids. Vasopressors (Midodrone) Reasonably good evidence exists for the effectiveness of the α1adrenergic agonist midodrine (ProAmatine). Midodrine, a prodrug, reduced symptoms of syncope and presyncope in three small, randomized clinical trials;73-75 overall, midodrine is probably helpful.76 The major limitations of midodrine are the need for frequent dosing and its tendency to increase supine blood pressure. The latter side effect is usually seen at higher doses (>30 mg/day). Midodrine should not be used in patients with hypertension. Side effects include piloerection and “crawling” paresthesias in the scalp. Selective Serotonin Reuptake Inhibitors Numerous small, open-label studies in the early 1990s reported that SSRIs prevented the induction of syncope on tilt tests and reduced symptoms in patients in the community. Paroxetine was effective in TABLE

15-6 

preventing syncope77 in one randomized placebo-controlled study and numerous case-report series. In contrast, Takata et al.78 reported that the same drug did not block the vasovagal reaction elicited by lowerbody negative pressure. SSRIs do not appear to be used widely for the prevention of syncope, and the treatment effect is debatable.76 Beta-Adrenergic Blockers The evidence for the effectiveness of β-blocker therapy is mixed. It has a strong physiologic rationale, and two positive and one negative openlabel studies involving 42 to 153 patients.79-81 Five randomized clinical trials studied the efficacy or effectiveness of β-blockers for the prevention of syncope.82-86 Although not completely consistent, these studies indicate that metoprolol and atenolol, and possibly β-adrenergic receptor blockade in general, are ineffective in preventing vasovagal syncope in the broad patient population. A substudy showed a possible benefit in middle-aged and elderly patients. Fludrocortisone Acetate Fludrocortisone has mineralocorticoid activity without appreciable glucocorticoid effect at doses up to 0.2 mg, the usual clinical doses for various disorders.87 The acute actions of fludrocortisone acetate are sodium and water retention, at the expense of urinary potassium excretion. Two open-label trials examined fludrocortisone in patients with “neurocardiogenic syncope.” Both revealed clinical improvement but neither were placebo-controlled.88,89 Recently, Salim and Di Sessa90 reported a small, placebo-controlled, randomized clinical trial (RCT) of fludrocortisone (Florinef) in children with vasovagal syncope. Patients taking fludrocortisone did significantly worse (P < .04) than those taking placebo. An RCT powered to detect a 40% relative risk reduction is nearing conclusion.91 Other drugs have been studied, but not in adequately powered, placebo RCTs. EVIDENCE OF CLINICAL BENEFIT Four groups assessed the effect of pacing in preventing syncope induced by tilt-table testing (Table 15-6). Forty-one patients with a

Clinical Studies of Rate Drop–Responsive Pacing in Vasovagal Syncope

Study Petersen et al.97 Benditt et al.98 Sheldon et al.99 First North American Vasovagal Pacemaker Study (VPS-I)100 Vasovagal Syncope International Study (VASIS)101 Syncope Diagnosis and Treatment (SYDAT) Study102 Ammirati et al.103 VPS-II118 McLeod et al.107

Type 2-period 2-period 2-period Unblinded RCT

Patients (N) 31 28 12 54

Unblinded RCT

42

Rate hysteresis

Unblinded RCT

93

Rate drop vs. atenolol

Unblinded RCT Blinded RCT Blinded RCT

20 100 12

Vasovagal Syncope and Pacing Trial (SYNPACE)109

Blinded RCT

HR, hazard ratio; RCT, randomized controlled trial.

29

Treatment Tested Rate hysteresis Rate drop Rate smoothing Rate drop

Rate drop vs. rate hysteresis DDD-rate drop vs. ODO No pacing vs. VVI-rate hysteresis vs. DDD-rate drop DDD-rate drop vs. ODD

Results 62% stopped fainting 78% stopped fainting 50% stopped fainting HR ↓85% 78% stopped fainting HR ↓80% 95% stopped fainting HR ↓87% 95% stopped fainting Rate drop better than rate hysteresis No significant difference Pacing better than not; pacing modes equivalent No difference

positive initial tilt test and a marked bradycardia underwent a second tilt test with temporary pacing at rates of 85 to 100 bpm. Taken together,61,62,65,90,92-96 the studies showed that temporary dual-chamber pacing prevented the development of syncope in 24 of the 41 patients (57%).92-94 However, almost all the conscious patients developed the vasovagal reaction and had significant presyncope. Temporary pacing may be partly effective in preventing vasovagal syncope, but it does not prevent presyncope. Rate Drop–Responsive Pacemakers The strategy that emerged in the early 1990s was to attempt to use cardiac pacing not only to overcome transient bradycardia during syncope, but also to provide enough heart rate support to compensate for the transient hypotension that is part of the vasovagal reflex. The major issues in developing pacing strategies are (1) detection of the onset of syncope and (2) whether pacing is effective during the episode. Given the modest efficacy of simple bradycardia support in preventing syncope induced by tilt tests, investigators soon turned to more flexible and sophisticated modes of sensing and pacing. Sensors of Transient Heart Rate Decrease Three combined sensing-pacing options have been assessed clinically: rate hysteresis, rate smoothing, and rate-drop sensing. In rate hysteresis, pacing at a relatively high rate is triggered by a drop in heart rate below a low detection rate. An example of settings is a sensing rate of 40 bpm and response rate of 90 bpm. Typically, the high-rate pacing might be interrupted periodically to permit the pacemaker to detect an underlying rate, as well as cease pacing if the rate is high enough. Rate smoothing is used to avoid abrupt and sustained changes in heart rate. Here, an abrupt drop in heart rate over only one to three beats elicits a pacing response at a slightly lower rate, and this pacing rate gradually slows until it is below the accelerating intrinsic heart rate. Rate drop–responsive pacing is a more sensitive and sophisticated variant of rate hysteresis. An abrupt drop in heart rate of a programmable magnitude over a programmable duration elicits a burst of high-rate pacing for 1 to 2 minutes. The drop in heart rate needs to be only about 10 bpm, over a few seconds, with the high rate about 90 to 110 bpm. Observational Studies Three groups reported studies of the usefulness of chronic pacing in the prevention of vasovagal syncope (see Table 15-6). Petersen et al.97 reported the first clinical study of dual-chamber pacing with rate hysteresis in 37 syncope patients. The patients had had a median of six syncopal spells, and a positive tilt test with bradycardia. Of the 37 patients, 31 received pacemakers with rate hysteresis. Over a mean follow-up of 50 months 62% of the patients remained free of syncope, and the number of syncopal spells in the total population fell from an expected number of 136 to only 11. Benditt et al.98 reported equally encouraging results in a study of 36 patients with predominantly vasovagal syncope. The patients were very symptomatic, with a median of 10 syncopal spells over about 2 years, or about five spells annually. All patients received a pacemaker with rate-drop responsiveness. The patients were followed for a mean of 6 months. During this time, syncope recurred in only six patients, compared to expected recurrences in about 30 patients. Therefore, in this relatively short-term study, pacing may have benefited about 80% of patients. We studied 12 extremely symptomatic patients who had had a median syncope frequency of three spells monthly.99 All had a positive tilt test and recurrent syncope while receiving medical therapy. All received a pacemaker with a rate-smoothing feature but without a high rate response. Following implantation of the pacemaker, the actuarial syncope-free survival increased 20-fold, the syncope frequency dropped by 93%, and quality of life improved highly significantly. All the previous trials were sequential design studies, with no control for time-dependent effects or for the placebo effect.

15  Pacing in Neurally Mediated Syncope Syndromes

367

100 90 Cumulative risk (%)



80

No pacemaker

70 60 2P0.000022

50 40 30

Pacemaker

20 10 0 0

3

6

9

12

15

1 11

0 8

Time in months Number C 27 at Risk P 27

9 21

4 17

2 12

Figure 15-3  Cumulative likelihood of a recurrence of syncope in patients randomized to receive or not to receive a pacemaker in VPS-I. (From Connolly SJ, Sheldon RS, Roberts RS, Gent M: The North American Vasovagal Pacemaker Study. A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol 33:16-20, 1999.)

Open-Label Randomized Studies of Rate-Drop Responsiveness North American Vasovagal Pacemaker Study.  The VPS-I Study tested whether permanent pacing with rate-drop responsiveness would reduce the likelihood of syncope in patients with frequent vasovagal syncope.100 Patients were eligible if they had fainted six or more times before tilt testing, or fainted within the first year after a positive tilt test, and had a predefined degree of bradycardia. Fifty-four patients were randomized evenly to receive a pacemaker with automatic ratedrop responsiveness or the best medical therapy (no pacemaker), according to their treating physicians. Syncope recurrence was lower in the pacemaker patients (6 of 27) than in the medical patients (19 of 27). The hazard ratio for a recurrence of syncope in the paced versus medically treated patients was 0.087 (P = .000016). Figure 15-3 shows the likelihood of a first syncope recurrence among patients randomized to receive a pacemaker (or not) in VPS-I. Although the first randomized controlled trial (RCT) to show benefit from pacing, VPS-I appeared to have several limitations. First, with insufficient evidence for pacemaker effectiveness to implant a device in all subjects, the investigators selected an open-label design. Second, the patients were highly select; all had fainted frequently, had positive tilt tests with development of bradycardia, and agreed to participate in a study with only a 50% chance of receiving new therapy (i.e., pacemaker). The pacemaker could have benefited these patients by either conventional bradycardia support or sophisticated rate drop–responsiveness algorithm. Also, medical therapy was not standardized. Ammirati et al.100 performed a small, randomized clinical trial in 20 patients with moderately frequent syncope who received a pacemaker with either rate hysteresis or rate-drop responsiveness. Three patients with rate hysteresis fainted while no patients with rate-drop responsiveness fainted (P < .05). This study suggested that rate-drop responsiveness is superior to rate hysteresis in preventing syncope, and therefore not all the pacemaker effect was caused by placebo. Vasovagal Syncope International Study.  The VASIS Investigators randomly assigned 19 patients to receive a dual-chamber pacemaker with rate hysteresis and 23 patients to no pacemaker implant.101 The patients all had three or more (median six) syncopal spells over the previous 2 years and a cardioinhibitory response to tilt testing. Patients had a lower syncope burden than those of VPS-I. During a mean

SECTION 2  Clinical Concepts

Intention-to-treat analysis No. of pts40

31

23

16

14

% Syncope-free

12

7

Pacemaker

100 80

P0.0004

60 40

No pacemaker

20

1

2

3

4

5

6

Years Figure 15-4  Cumulative likelihood of a recurrence of syncope in patients randomized to receive or not receive a pacemaker in VASIS. (From Sutton R, Brignole M, Menozzi C, et al: Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope: pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators. Circulation 102:294-299, 2000.)

follow-up of 3.7 ± 2.2 years, the pacemaker group had a lower likelihood of a syncope recurrence than the no-pacemaker group (5% vs. 61%; P = .0006). Figure 15-4 shows the intent-to-treat results. Similar to VPS-I, VASIS was an open-label study that included highly select patients and could not eliminate the impact of placebo effect. Syncope Diagnosis and Treatment Study.  The SYDAT trial tested whether pacemakers or atenolol best prevented vasovagal syncope.102 Randomized to receive a DDD pacemaker with rate-drop response (46) or atenolol (47), the 93 patients were older than 35, had three or more syncopal spells in the preceding 2 years, and had a positive tilt test, with a trough heart rate of 60 bpm or less. At least one syncope recurred in 4.3% of the pacing group versus 26% in the atenolol group (odds ratio [OR] = 0.13; P = .004). This was another open-label study of pacing in vasovagal syncope using a highly select population. One confounding issue is a possible deleterious effect from the atenolol, rather than a beneficial effect from the pacemaker implantation. This seems unlikely given the overall neutral effect of β-blockers in the randomized trials previously summarized. Summary Observational reports42,97,99 and open-label RCTs100,101,103 strongly suggested that patients have less syncope after they receive a permanent pacemaker. The question is whether this effect is real. All these studies were unblinded to both patients and physicians. Syncope is an outcome that can be difficult to verify objectively. Also, surgical procedures can have a placebo-effect.104-106 Patients receiving a pacemaker may have benefited from the psychological effects of receiving a surgical procedure from enthusiastic health professionals. Given these uncertainties, the invasiveness and cost of pacing mandated that placebo-controlled or blinded RCTs be used to determine the true benefit of pacing. Blinded Randomized Studies of Rate-Drop Responsiveness Three blinded studies have compared the benefit of rate drop– responsive pacemakers with therapy anticipated to be of lesser benefit. McLeod Crossover Study.  McLeod et al.107 reported the efficacy of rate drop–responsive dual-chamber pacing in the prevention of vasovagal syncope in 12 highly symptomatic young children who had frequent syncope associated with asystolic pauses longer than 4 seconds. In this three-way, double-blind, randomized crossover study, the

pacemakers were programmed to no active pacing, ventricular pacing with rate hysteresis, or dual-chamber pacing with rate-drop responsiveness. Both pacing modes were equivalently more effective than no pacing in preventing syncope, and dual-chamber pacing was superior to ventricular pacing in preventing presyncope. This small study concluded that rate drop–responsive pacing was more efficacious than no pacing in preventing vasovagal syncope in children. Second Vasovagal Pacemaker Study.  To ascertain the therapeutic effect of permanent pacing in vasovagal syncope, we performed the Second Vasovagal Pacemaker Study (VPS-II).108 We expected that the risk of syncope in the control group would be reduced to some extent by the placebo effect of receiving a device, and we increased the study sample size accordingly. VPS-II was a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients were eligible if they had recurrent vasovagal syncope with at least six lifetime syncope spells, or at least three spells in the 2 years before enrollment, and a positive tilt-table test performed according to the protocol in each center. A requirement for a specific degree of bradycardia during tilt testing was not included because trough heart rate during tilt testing did not correlate in patients with heart rate during clinical syncope,69 and because trough heart rate during tilt testing did not appear to predict response to pacing. All 100 patients received a dual-chamber pacemaker and were randomized to either rate-drop responsiveness or sensing without pacing. The care providers remained blinded to treatment allocation, except for an unblinded nurse or physician who did all the programming but did not disclose any details. The study was designed to have 80% power to detect a 50% relative reduction in the risk of recurrent syncope from a rate of 60% in the control group to 30% in the treatment group. A total of 38 patients had recurrent syncope during the 6-month follow-up: 22 of 52 patients in the sensing-only group and 16 of 48 in the active pacing group. The cumulative risk of syncope at 6 months was 40% (95% Cl = 25% to 52%) for the sensing-only group and 31% (95% CI = 17% to 43%) for the rate drop–responsive group (Fig. 15-5). The relative risk reduction in time to syncope with active pacing was 30% (95% CI = −33% to 63%; P = 0.14 one-sided). A retrospective analysis found no variable that predicted benefit from pacing, other than patients who received isoproterenol during the tilt test. Most importantly, VPS-II found no statistically significant benefit in favor of pacemaker therapy for prevention of syncope. The most 1.0 Cumulative risk

368

Only sensing without pacing (ODO) Dual-chamber pacing (DDD)

0.8 0.6 0.4 0.2 0 0

1

2

3

4

5

6

Months since randomization No. at Risk Only sensing without pacing 52 Dual-chamber pacing 48

37 37

35 35

32 34

31 34

21 18

Figure 15-5  Kaplan-Meier plots of time to first recurrence of syncope in 48 patients randomized to receive active dual-chamber pacing and 52 patients randomized to receive a pacemaker in sense-only mode by intention-to-treat analysis in VPS-II. (From Connolly SJ, Sheldon R, Thorpe KE, et al: The Second Vasovagal Pacemaker Study (VPS-II). A double-blind randomized controlled trial of pacemaker therapy for the prevention of syncope in patients with recurrent severe vasovagal syncope. JAMA 289:2224-2249, 2003.)



important difference between VPS-I and VPS-II results is the observed risk of syncope in the nonpaced group. In VPS-I, almost 80% of control patients fainted within 6 months, versus only 41% in VPS-II. In contrast, the 6-month likelihood of syncope in the patients receiving active pacing therapy was similar: 20% in VPS-I and 31% in VPS-II. Vasovagal Syncope and Pacing Trial.  SYNPACE involved 29 patients who had had a median of 12 lifetime syncopal spells, a positive tilt test, and bradycardia during the syncope induced by the tilt test.109 They received a dual-chamber rate drop–responsive pacemaker and were randomized to either active pacing or no pacing. The trial was stopped early after the VPS-II results were released. Thirteen patients had at least one syncope recurrence, and there was no benefit from active pacing with rate-drop responsiveness. Although extremely underpowered, the study did not provide any support for the usefulness of pacing in preventing vasovagal syncope. Why Were VPS-II and SYNPACE Not Positive? Both VPS-II and SYNPACE failed to demonstrate a statistically significant benefit of pacemaker therapy for prevention of vasovagal syncope. Although SYNPACE was underpowered because of early termination, VPS-II was the largest RCT of pacemaker therapy for vasovagal syncope, whether open label or double blind. There was considerable effort to maintain blindedness and no known protocol violation. This strict adherence sets the standard for RCTs of treatment for vasovagal syncope. Reasons for the negative outcomes include early termination of previous studies, inability to overcome vasodepression with highrate pacing, and a placebo effect in open-label studies. Early Termination of Open-Label Studies.  An important difference between VPS-II and the four open-label trials was that three of the four previous trials were stopped prematurely. Early termination of a trial for unexpected efficacy tends to overestimate the treatment effect. Vasodepression Cannot Be Paced.  Prevention of bradycardia is the main physiologic mechanism by which a pacemaker can prevent attacks of syncope. During positive tilt tests, however, reductions in blood pressure begin earlier than the development of bradycardia.93,94 Pacing therapy might not help patients with hypotension caused by vasodepression even if bradycardia or asystole also occurs at syncope. The results of VPS-II and SYNPACE suggest that most episodes of vasovagal syncope may be associated with profound vasodepression as the cause of syncope, rather than simply bradycardia. In this light, pacing may simply be ineffective in the setting of profound vasodepression, and future progress in devices might best target implantable drug delivery systems. Placebo Effect.  The history of attempts to treat patients with implanted devices has other examples of initial promises of therapeutic success being followed by subsequent well-controlled, negative studies. For example, open-label studies suggested that dual-chamber pacing causes a marked improvement in the hemodynamics and functional status of patients with hypertrophic cardiomyopathy. Later blinded RCTs revealed evidence of a much smaller effect size. Similarly, preliminary open-label studies suggested that atrial-based pacing might prevent atrial fibrillation, but a well-controlled randomized crossover trial showed much less benefit of conventional atrial pacing in prevention of atrial fibrillation.110,111 Large open-label studies also provided strong evidence for the ability of atrial pacing to reduce stroke and death in patients with pacemakers. A large, blinded RCT showed that patients with atrial-based pacemakers versus those with single-lead ventricular pacemakers had no benefit with respect to death, stroke, quality of life, or exercise tolerance for several years after implantation.112 Therefore, care should be taken in the assessment of open-label or nonrandomized pacemaker studies. The placebo effect can be substantial. Pacemaker therapy may be associated with an initial spurious benefit for two major reasons. First, patients receiving expensive or invasive

15  Pacing in Neurally Mediated Syncope Syndromes

369

therapy may not want to admit that such therapy may be ineffective. The placebo effect can be pronounced, particularly with surgical procedures.104-106 Second, many patients with vasovagal syncope appear to improve spontaneously after tilt testing.52,57,58 This effect may account for up to 90% of the apparent benefit. The mechanism is unknown but may involve the counseling received at the clinic visit, a regression to the mean, and the sporadic timing of vasovagal syncope. This effect is of a similar magnitude to the beneficial effect of pacing in sequential design trials. In the unblinded studies, patients who hoped to receive a pacemaker and were disappointed not to receive one may have been more prone to report syncope. Conversely, patients receiving a pacemaker may have benefited from the psychological effects of receiving a surgical procedure from enthusiastic health professionals. The double-blind trial design to a considerable extent removes this type of potential bias. CLINICAL TRIALS OF PACING IN VASOVAGAL SYNCOPE: A META-ANALYSIS To assess the efficacy of pacing in vasovagal syndromes based on clinical trials, Sud et al.113 conducted a meta-analysis of nine randomized trials: four active pacemaker versus medical or no therapy,101,102,114,115 three active pacemaker comparisons (open label or single blind),103,116,117 and two double-blind active pacemaker versus sensing only or pacemaker off.109,118 When pooled, the nine trials showed significant heterogeneity; when based on trial methodology, however, the trials no longer showed evidence of heterogeneity. In open-label single-blind studies, risk of syncope recurrence was reduced with pacing; doubleblind studies showed no effect (Figure 15-6). These results suggest that the main benefit of pacemaker insertion is an expectation effect; the expectation response appeared to explain most of the observed pacemaker response (OR = 0.16; 95% CI = 0.06 to 0.40; P = .0001).113 However, the two double-blind placebo-controlled RCTs conducted to date were small (129 total patients). A larger study is needed for definite conclusions on pacing in vasovagal syncope patients. International Study on Syncope of Uncertain Aetiology A multicenter double-blind RCT is in progress to study the effectiveness of pacing for the prevention of asystolic neurally mediated syncope.119 Patients 40 or older with at least three syncopal spells (suspected or confirmed as neurally mediated) over the preceding 2 years and with a severe clinical presentation requiring treatment initiation are eligible for the International Study on Syncope of Uncertain Aetiology (ISSUE-3). The exclusion criteria include carotid sinus hypersensitivity. In Phase I, participants undergo ILR until (a) first syncope with asystole of 3 seconds or longer in the loop recording; (b) asystole of 6 seconds or longer without reported syncope; or (c) 24 months of recording without (a) or (b). In Phase II, patients with (a) or (b) are randomized to receive a dual-chamber pacemaker switched on (active therapy) or off (placebo therapy). Patients, follow-up physicians, and study personnel are blinded to treatment allocation. The primary outcome is the time to first syncope recurrence in both study arms. The study will enroll up to 710 patients to randomize 60 patients to each study arm. The total study duration is estimated at 4 years. PATIENT SELECTION Patients should have a definite history of vasovagal syncope based on a positive tilt test, suggestive ILR findings, or scrupulous history. Given the weakness of the evidence supporting the efficacy of pacing, it is reasonable to pace only patients with documented profound bradycardia or asystole during syncope. Only patients at high risk of syncope recurrence should be paced. Any patient with at least one syncopal spell in the preceding year has almost a 50% risk of at least one syncopal spell in the next year. Otherwise, similar syncope patients with either negative or positive tilt-table tests have similar likelihood of syncope after assessment.120,121 The outcome of the tilt test (negative vs. positive) does not predict subsequent clinical outcome. Similarly, the lowest

370

SECTION 2  Clinical Concepts

Study or sub-category

Treatment n/N

Control n/N

OR (random) 95% Cl

OR (random) 95% Cl

01 Active pacemaker versus medical/no therapy Flammang 0/10 6/10 SYDAT 2/46 12/47 VASIS 1/19 14/23 VPS I 6/27 19/27 Subtotal (95% Cl) 102 107 Total events: 9 (Treatment), 51 (Control) Test for heterogeneity: Chi2 = 1.56, df = 3 (P = 0.67), I2 = 0% Test for overall effect: Z = 5.48 (P = 0.00001)

0.03 (0.00, 0.72) 0.13 (0.03, 0.63) 0.04 (0.00 0.32) 0.12 (0.04, 0.41) 0.09 (0.04, 0.22)

02 Active pacemaker comparison Ammairati 0/12 3/8 Deharo 0/23 4/23 INVASY I 0/17 7/9 Subtotal (95% Cl) 52 40 Total events: 0 (Treatment), 14 (Control) Test for heterogeneity: Chi2 = 1.18, df = 2 (P = 0.55), I2 = 0% Test for overall effect: Z = 3.56 (P = 0.0004)

0.06 (0.00, 1.44) 0.09 (0.00, 1.82) 0.01 (0.00, 0.22) 0.04 (0.01, 0.23)

03 Double-blind active pacemaker versus sensing only/pacemaker off SYNPASE 8/16 5/13 VPS I 16/48 22/52 Subtotal (95% Cl) 64 65 Total events: 24 (Treatment), 27 (Control) Test for heterogeneity: Chi2 = 0.97, df = 1 (P = 0.32), I2 = 0% Test for overall effect: Z = 0.51 (P = 0.61)

1.60 (0.36, 7.07) 0.68 (0.30, 1.54) 0.83 (0.41, 1.70)

Total (95% Cl) 218 212 Total events: 33 (Treatment), 92 (Control) Test for heterogeneity: Chi2 = 24.06, df = 8 (P = 0.002), I2 = 86.7% Test for overall effect: Z = 3.55 (P = 0.0004) 0.01

0.15 (0.05, 0.42)

0.1

Favors treatment

1

10

100

Favors control

Figure 15-6  Forest plot of primary study and summary odds ratios (OR) for recurrent syncope in meta-analysis of nine studies. For each study, the red squares and horizontal lines represent the random effects OR and 95% confidence intervals (CI). Area of red square is proportional to amount of statistical information contributed by the trial. Diamond at the bottom of each category and overall represents OR with 95% CI. (From Sud S, Massel D, Klein GJ, et al: The expectation effect and cardiac pacing for refractory vasovagal syncope. Am J Med 120:54-62, 2007.)

heart rate (including asystole) during tilt testing does not predict the eventual likelihood of syncope in clinical follow-up.69,97 Utility of Loop Recordings Sud et al.122 and Brignole et al.124 assessed spontaneous bradycardia patterns from internal and external loop recordings of patients with unexplained syncope who later underwent pacemaker implantation for bradycardia. The ISSUE classification of detected rhythm from ILRs was used. Although severity of bradycardia or asystole during the loop recording did not predict response to pacemaker therapy, mechanism of bradycardia did; syncope associated with abrupt bradycardia was associated with better response to pacing therapy than syncope with gradual-onset bradycardia. These results suggest that the ISSUE classification is useful in distinguishing between bradycardia as part of vasovagal syncope and primary bradycardia, the latter of which is more responsive to pacing therapy.

pacemakers greatly overdetect, with therapies delivered many times daily. This is usually well tolerated, particularly if the patient perceives a benefit in syncope prevention, but in some patients the palpitations are intolerable. This can be particularly true at night, when respiratory sinus arrhythmia is greater and the patient is quieter. Although the understandable tendency is to program the rate-drop feature off at night, this affords patients no potential protection should they arise. This can be a problem because patients usually have had no fluids for hours and can have syncope provoked by either orthostatic changes or micturition. Pacing therapy is usually a relatively high-rate burst. The pacemaker should be programmed to deliver dual-chamber pacing at rates of 90 to 110 bpm for 1 to 2 minutes. There is no evidence of increased benefit from any particular rate or duration. EVOLVING PARADIGMS AND TECHNOLOGY

PROGRAMMING

Contractility Sensors

Rate-drop response is only present with dual-chamber programming. There is an inexorable trade-off between sensitivity and specificity in programming rate-responsive pacemakers to detect the early stages of syncope. The main detection features include the range over which heart rate must fall, the time interval during which the fall must take place, and the number of confirmation beats below the minimumdetection heart rate. Decreasing the specified heart rate range or number of confirmation beats increases the sensitivity, as does increasing the time in which the heart rate fall must occur. Generally, the

The search continues for alternate sensing strategies such as QT intervals, respiratory volumes or frequency, right ventricular pressure transduction (dP/dt), and indices of contractility. These are intended to sense either early hypovolemia or early rises in sympathetic activity that may precede frank syncope. Some evidence indicates that contractility can be estimated with measures of endocardial acceleration, using a microaccelerometer in the pacemaker lead to estimate right ventricular myocardial contractility,124,125 or with intracardiac impedance measurements.126,127 The theory behind contractility sensors is that



15  Pacing in Neurally Mediated Syncope Syndromes CLS

100

on right ventricular impedance changes is effective sensing for syncope; and (3) this may be the placebo effect, again. A larger and properly blinded study is being planned.

% Syncope-free

80 P0.0001

60 40

Placebo 20 Time since randomization

3 m6 m9 m 1 y N. of pts 50 50 in CLS arm N. of pts 9 5 in placebo arm

4

3

2

371

2y

3y

29

4

0

0

Figure 15-7  Probability of remaining free of syncope recurrence by Kaplan-Meier estimation in 41 patients in closed-loop stimulation (CLS) arm and nine patients in control group in INVASY study. (From Occhetta E, Bortnik M, Audoglio R, Vassanelli C: Closed-loop stimulation in prevention of vasovagal syncope. Inotropy Controlled Pacing in Vasovagal Syncope (INVASY): a multicentre randomized single-blind controlled study. Europace 6:538-547, 2004.)

vasovagal syncope might be preceded by small but significant increases in contractility caused by a sympathetic surge. These devices increase pacing rates in response to increases in apparent contractility, then slowly decrease rates after contractility subsides toward baseline. Discouragingly, Brignole et al.124 found that endocardial acceleration did not predict the occurrence of tilt table–induced syncope. Griesbach et al.127 evaluated the use of closed-loop stimulation (CLS) in a preliminary study in 2002. CLS pacemaker technology reacts to a change in the right ventricular intracardiac impedance, felt to be a surrogate measure of contractility and therefore sympathetic tone. This study of 22 patients demonstrated that syncope sensed with this modality could be prevented on tilt testing of patients with cardioinhibitory syncope. A subsequent study used CLS prospectively in 34 patients with recurrent vasovagal syncope. Over 12 to 50 months of follow-up, 30 of 34 patients had not experienced a recurrent event. Based on this pilot study, a larger, multicenter RCT, the Inotropy Controlled Pacing in Vasovagal Syncope (INVASY), was partly carried out in 2004.128,129 In this open-label trial, 26 patients with recurrent vasovagal syncope and a positive tilt test with induced bradycardia received a dual-chamber CLS pacemaker, then were asymmetrically randomized to simple DDI pacing (9) or dual-chamber CLS pacing (17). INVASY was stopped early after a preliminary analysis showed that, after a mean of 19 months, seven of the nine DDI patients and none of the 17 CLS patients had syncope recurrences (P < .0001) (Fig. 15-7). These positive results suggest three possible conclusions: (1) pacing can be useful in patients with vasovagal syncope; (3) CLS based

Automatic Drug Delivery Systems Current pacemaker therapies focus only on heart rate support. This might not be as useful in patients with a predominantly vasodepressor response. Giada et al.130 described an acute study assessing a novel implantable system that delivers phenylephrine when activated at the onset of syncope (prodrome with blood pressure drop). When treated with the phenylephrine, 15 of 16 patients had an immediate blood pressure rise and their tilt-induced syncope terminated, despite ongoing tilt testing. In contrast, none of the patients was able to abort the episodes when a placebo infusion was delivered. The one patient who fainted despite the phenylephrine experienced a severe cardioinhibitory response to the tilt test. This small study suggests the promise of combined approach using pacing for the cardioinhibitory component, as well as acute pharmacologic support for the vasodepressor component of syncope. IMPLICATIONS FOR FUTURE TRIALS Four main lessons can be learned from the studies previously discussed. First, clinical trials of vasovagal syncope must be placebo controlled and double blinded to mitigate the sizable potential for the placebo effect. Second, the potential for the placebo effect must be considered when population sample is calculated. Third, initial efforts might be directed toward understanding whether physiologic differences exist between patients who faint while paced and those who do not faint. Fourth, accurate patient selection may be even more important in vasovagal syncope trials. GUIDELINES FOR PACING IN VASOVAGAL SYNCOPE Pacing at least should not be used early in patients with vasovagal syncope. First, pacing should be reserved for patients with frequent, highly symptomatic vasovagal syncope whose quality of life is greatly diminished and who have not responded to lifestyle and dietary changes, education, reassurance, counterpressure maneuvers,3,131 and at least three medication attempts. Second, pacing might be more effectively used in patients with documented asystole at syncope. Third, all patients considering pacing should have frank and detailed education about the limited (at best) evidence for its efficacy. According to the 2009 recommendations of the Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology, (1) cardiac pacing should be considered in patients with frequent, recurrent reflex syncope, age over 40, and documented spontaneous cardioinhibitory response during monitoring; (2) cardiac pacing may be indicated in patients with tilt-induced cardioinhibitory response with recurrent frequent unpredictable syncope and age over 40, after alternative therapy has failed; and (3) cardiac pacing is not indicated in the absence of a documented cardioinhibitory reflex.4

REFERENCES 1. Benditt DG, Remole S, Milstein S, et al: Causes, clinical evaluation and current therapy. Annu Rev Med 43:283, 1992. 2. Brignole M, Alboni P, Benditt DG, et al: Guidelines on mangement (diagnosis and treatment) of syncope: update 2004— exective summary. Eur Heart J 25:2054-2072, 2004. 3. Gregoratos G, Cheitlin MD, Conill A, et al: ACC/AHA Guidelines for implantation of cardiac pacemakers and antiarrhythmic devices: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Committe on Pacemaker Implantation. Circulation 97:1325-1335, 1998. 4. Moya A, Sutton R, Ammirati F, et al: Guidelines for the diagnosis and management of syncope (version 2009). The Task Force for the Diagnosis and Management of Syncope of the European Society of Cardiology (ESC). Eur Heart J 30:26312671, 2009. 5. Thomas JE: Hyperactive carotid sinus reflex and carotid sinus syncope. Mayo Clin Proc 13:2065, 1969.

6. Volkmann H, Schnerch B, Kuhnert B: Diagnosis value of carotid sinus hypersensitivity. Pacing Clin Electrophysiol 13:2065, 1990. 7. Hartzler GO, Maloney JD: Cardioinhibitory carotid sinus hypersensitivity. Arch Intern Med 137:727, 1977. 8. Weiss S, Baker JP: The carotid sinus reflex in health and disease: Its role in the causation of fainting and convulsions. Medicine 12:297, 1933. 9. Zee-Cheng CS, Gibbs HR: Pure vasodepressor carotid sinus hypersensitivity. Am J Med 81:1095, 1986. 10. Morley CA, Sutton R: Carotid sinus syncope. Int J Cardiol 6:287, 1984. 11. Kenny RA, Traynor, G: Carotid sinus syndrome: clinical characteristics in elderly patients. Age Ageing 20:499, 1991. 12. Richardson DA, Bexton RS, Shaw FE, Kenny RA: Prevalence of cardioinhibitory carotid sinus hypersensitivity in patients 50 years or over presenting to the accident and emergency department with “unexplained” or “recurrent” falls. Pacing Clin Electrophysiol 15:820, 1997.

13. Huang SKS, Ezi MD, Hauser RG: Carotid sinus hypersensitivity in patients with unexplained syncope: clinical, electrophysiological, and long-term follow-up observations. Am Heart J 116:989, 1988. 14. Brignole M, Menossi C, Lolli G: Long-term outcome of paced and non-paced patients with severe carotid sinus syndrome. Am J Cardiol 69:1039, 1992. 15. Lown B, Levine SA: The carotid sinus: clinical value of its stimulation. Circulation 23:766, 1961. 16. Baig MW, Kaye GC, Perrins EJ: Can central neuropeptides be implicated in carotid sinus reflex hypersensitivity? Med Hypotheses 28:255, 1989. 17. Strasburg B, Sagie A, Erdman S: Carotid sinus hypersensitivity and carotid sinus syndrome. Prog Cardiovasc Dis 31:376, 1989. 18. Blanc JJ, L`Heveder G, Mansourati J: Assessment of a newly recognized association, carotid sinus hypersensitivity and denervation of sternocleidomastoid muscles. Circulation 95:2548, 1997.

372

SECTION 2  Clinical Concepts

19. DaCosta D, Mclntoch S, Kenny RA: Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome. Br Heart J 69:308, 1993. 20. Trout HH, Brown LL, Thompson JE: Carotid sinus syndrome: treatment by carotid sinus denervation. Ann Surg 189:575, 1979. 21. Katritsis D, Ward DE, Camm AJ: Can we treat carotid sinus syndrome? Pacing Clin Electrophysiol 14:1367, 1991. 22. Sugrue DD, Gersh BJ, Holmes DR: Symptomatic “isolated” carotid sinus hypersensitivity: natural history and results of treatment with anticholinergic drugs or pacemaker. J Am Coll Cardiol 158:1986, 1986. 23. Morley CA, Perrins EJ, Grant P: Carotid sinus syncope treated by pacing. Br Heart J 47:411, 1982. 24. Brignole M, Menozzi C, Lolli G: Validation of a method for choice of pacing mode in carotid sinus syndrome with or without sinus bradycardia. Pacing Clin Electrophysiol 14:196, 1991. 25. Brignole M, Menossi C, Lolli G: Natural and unnatural history of patients with severe carotid sinus hypersensitivity: a preliminary study. Pacing Clin Electrophysiol 11:1678, 1988. 26. Bexton RS, Davies A, Kenny RA: The rate-drop response in carotid sinus syndrome: the Newcastle experience. Pacing Clin Electrophysiol 20(3 Pt 2):840, 1997. 27. Davies AJ, Kenny RA: Falls presenting to the accident and emergency department: types of presentation and risk factor profile. Age Ageing 25:362-366, 1996. 28. Kenny RA, Traynor G: Carotid sinus syndrome: clinical characteristics in elderly patients. Age Ageing 20:449-454, 1991. 29. Kenny RA, Richardson DA, Steen N, et al: Carotid sinus syndrom: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE). J Am Coll Cardiol 38:1491-1496, 2001. 30. Ryan DJ, Nick S, Colette SM, Roseanne K: Carotid sinus syndrome, should we pace? A multicentre, randomised control trial (SAFEPACE-2). Heart 96:347-351, 2010. 31. Parry SW, Steen N, Bexton RS, et al: Pacing in elderly recurrent fallers with carotid sinus hypersensitivity: a randomised, doubleblind, placebo controlled crossover trial. Heart 95:405-409, 2009. 32. Madigan NP, Flaker GC, Curtis JJ: Carotid sinus hypersensitivity: beneficial effects of dual-chamber pacing. Am J Cardiol 53:1034, 1984. 33. Stryjer D, Friedensohn A, Schlesinger Z: Ventricular pacing as the preferable mode for long-term pacing in patients with carotid sinus syncope of the cardioinhibitory type. Pacing Clin Electrophysiol 9:705, 1986. 34. Walter F, Crawley IS, Dorney ER: Carotid sinus hypersensitivity and syncope. Am J Cardiol 42:396, 1978. 35. Gang ES, Oseran DS, Mandel WJ: Sinus node electrogram in patients with the hypersensitivity carotid syndrome. J Am Coll Cardiol 5:1484, 1985. 36. Brown KA, Maloney JD, Smith HC: Carotid sinus reflex in patients undergoing coronary angiography: relationship of degree and location of coronary artery disease to response to carotid sinus massage. Circulation 62:697, 1980. 37. Munro NC, McLntoch S, Lawson J: Incidence of complications after carotid sinus massage in older patients with syncope. J Am Geriatr Soc 42:1248, 1994. 38. Davies AJ, Kenny RA: Frequency of neurologic complications following carotid sinus massage. Am J Cardiol 81:1256-1257, 1998. 39. Alexander S, Ding WC: Fatal ventricular fibrillation during carotid sinus stimulation. Am J Cardiol 18:289, 1966. 40. Probst P, Muhlberger V, Lederbauer M: Electrophysiologic findings in carotid sinus massage. Pacing Clin Electrophysiol 6:689, 1983. 41. Alicandri C, Fouad FM, Tarazi RC: Three cases of hypotension and syncope with ventricular pacing. Am J Cardiol 42:137, 1978. 42. Benditt DG, Sutton R, Gammage MD, et al: Clinical experience with Thera DR rate-drop response pacing algorithm in carotid sinus syndrome and vasovagal syncope. Pacing Clin Electrophysiol 20:832-839, 1997. 43. Maloney JD, Jaeger FJ, Fouad-Tarazi FM: Malignant vasovagal syncope: prolonged asystole provoked by head-up tilt—case report and review of diagnosis, pathophysiology and therapy. Cleve Clin J Med 55:543, 1988. 44. Sutton R: Vasovagal syncope: could it be malignant? Eur Heart J 2:89, 1992. 45. Fitzpatrick AP, Ahmed R, Williams S: A randomized trial of medical therapy in “malignant vasovagal syndrome” or “neurally mediated bradycardia/hypotension syndrome”. Eur J Card Pacing Electrophysiol 2:99, 1991. 46. Fitzpatrick AP, Sutton R: Tilting toward a diagnosis in recurrent unexplained syncope. Lancet 1:658, 1989. 47. Grubb BP, Temesy-Armos P, Moore J: Head-upright tilt-table testing in the evaluation and management of the malignant vasovagal syndrome. Am J Cardiol 69:904, 1990. 48. Ganzeboom KS, Colman N, Reitsma JB, et al: Prevalence and triggers of syncope in medical students. Am J Cardiol 91:10061008, 2003. 49. Sheldon R, Sheldon A, Connolly SJ, et al: Investigators of the Syncope Symptom Study and the Prevention of Syncope Trial. Age of first faint in patients with vasovagal syncope. J Cardiovasc Electrophysiol 17:49, 2006. 50. Day SC, Cook EF, Funkenstein H, Goldman L: Evaluation and outcome of emergency room patients with transient loss of consciousness. Am J Med 73:15-23, 1982.

51. Savage DD, Corwin L, McGee DL, et al: Epidemiologic feature of isolated syncope: the Framingham Study. Stroke 16:626-629, 1985. 52. Dermkasian G, Lamb LE: Syncope in a population of healthy young adults. J Am Med 168:1200, 1958. 53. Benditt DG, Ferguson DW, Grubb BP, et al: Tilt-table testing for assessing syncope. J Am Coll Cardiol 28:263-275, 1996. 54. Mosqueda-Garcia R, Furlan R, Tank J, Femandez-Violante R: The elusive pathophysiology of neurally mediated syncope. Circulation 102:2898-2906, 2000. 55. Linzer M, Pontinen M, Gold DT, et al: Impairment of physical and psychosocial function in recurrent syncope. J Clin Epidemiol 44:1037-1043, 1991. 56. Rose MS, Koshman ML, Spreng S, Sheldon RS: The relationship between health-related quality of life and frequency of spells in patients with syncope. J Clin Epidemiol 53:1209-1216, 2000. 57. Lamb L, Green HC, Combs JJ, et al: Incidence of loss of consciousness in 1980 Air Force personnel. Aerospace Med 12:973988, 1960. 58. Murdoch BD: Loss of consciousness in healthy South African men: incidence, causes and relationship to EEG abnormality. S Afr Med J 57:771-774, 1980. 59. Sheldon R, Flanagan P, Koshman ML, Killam S: Risk factors for syncope recurrence after a positive tilt-table test in patients with syncope. Circulation 93:973-981, 1996. 60. Rossen R, Kabat H, Anderson JP: Acute arrest of cerebral circulation in man. Arch Neurol Psych 50:510-528, 1943. 61. Morillo CA, Eckberg DL, Ellenbogen KA, et al: Vagal and sympathetic mechanisms in patients with orthostatic vasovagal syncope. Circulation 96:2509-2513, 1997. 62. Mosqueda-Garcia R, Furlan R, Tank J, et al: Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. J Clin Invest 11:2736-2744, 1997. 63. Thomson HL, Atherton JJ, Khafagi FA, Frenneaux MP: Failure of reflex venoconstriction during exercise in patients with vasovagal syncope. Circulation 93:953-959, 1996. 64. Thomson HL, Wright K, Frenneaux MP: Baroreflex sensitivity in patients with vasovagal syncope. Circulation 95:395-400, 1997. 65. Menozzi C, Brignole M, Lolli G, et al: Follow-up of asystolic episodes in patients with cardioinhibitory, neurally mediated syncope and VVI pacemaker. Am J Cardiol 72:1152-1155, 1993. 66. Krahn AD, Klein GJ, Fitzpatrick A, et al: Predicting the outcome of patients with unexplained syncope undergoing prolonged monitoring. Pacing Clin Electrophysiol 25:37-41, 2002. 67. Krahn AD, Klein GJ, Yee R: Randomized Assessment of Syncope Trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation 104:46-51, 2001. 68. Krahn AD, Klein GJ, Yee R, et al: Cost implication of testing in patients with syncope: Randomized Assessment of Syncope Trial. J Am Coll Cardiol 42:495-501, 2003. 69. Sheldon R: Tilt testing for syncope: a reappraisal. Curr Opin Cardiol 1:38-41, 2005. 70. El-Syed H, Hainsworth R: Salt supplement increases plasma volume and orthostatic tolerance in patients with unexplained syncope. Heart 75:134-140, 1996. 71. Van Dijk N, Quartieri F, Blanc JJ, et al: Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: the Physical Counterpressure Manoeuvres Trial (PC-Trial). J Am Coll Cardiol 48:1652-1657, 2006. 72. Sheldon RS, Rose S, Flanagan P, et al: Risk factors for syncope recurrence after a positive tilt-table test in patients with syncope. Circulation 93:973-981, 1996. 73. Ward CR, Gray JC, Gilroy JJ, Kenny RA: Midodrine: a role in the management of neurocardiogenic syncope. Heart 79:45-49, 1998. 74. Perez-Lugones A, Schweikert R, Pavia S, et al: Usefulness of midodrine in patients with severly symptomatic neurocardiogenic syncope: a randomized controlled study. J Cardiovasc Electrophysiol 12:935-938, 2001. 75. Kaufmann H, Saadia D, Voustianiouk A: Midodrine in neurally mediated syncope: double-blind, randomized, crossover study. Ann Neurol 52:342-345, 2002. 76. Kuriachan V, Sheldon RS, Platonov M: Evidence-based treatment for vasovagal syncope. Heart Rhythm 5:1609-1614, 2008. 77. Di Girolamo E, Di Lorio C, Sabatini P, et al: Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 33:1227-1230, 1999. 78. Takata TS, Wasmund SL: Serotonin reuptake inhibitor (Paxil) does not prevent vasovagal reaction: association with carotid sinus massage and/or lower body negative pressure in healthy volunteers. Circulation 106:1500, 2002. 79. Sheldon R, Rose S, Flanagan P, et al: Effect of beta blockers on the time to first syncope recurrence in patients after a positive isoproterenol tilt table test. Am J Cardiol 78:536-539, 1996. 80. Cox MM, Perlman BA, Mayor MR, et al: Acute and long-term beta-adrenergic blockade for patients with neurocardiogenic syncope. J Am Coll Cardiol 26:1293-1298, 1995. 81. Alegria JR, Gersh BJ, Scott CG, et al: Comparison of frequency of recurrent syncope after beta-blocker therapy versus conservative management for patients with vasovagal syncope. Am J Cardiol 92:82-84, 2003. 82. Mahanonda N, Bhuripanyo K, Kangkagate C: Randomized, double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results. Am Heart J 130:1250-1253, 1995.

83. Madrid AH, Ortega J, Rebollo JG, et al: Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study. J Am Coll Cardiol 37:55545559, 2001. 84. Flevari P, Livanis EG, Theodorakis GN, et al: Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and paients’ well-being. J Am Coll Cardiol 40:499-504, 2002. 85. Ventura R, Maas R, Zeidler D: A randomized and controlled pilot trial of beta-blockers for the treatment of recurrent syncope in patients with a positive or negative response to head-up tilt test. Pacing Clin Electrophysiol 25:816-821, 2002. 86. Sheldon R, Rose S, Connlly S: Prevention of Syncope Trial (POST): a randomized clinical trial of beta-blocker in the prevention of vasovagal syncope—rationale and study design. Europace 5:71-75, 2003. 87. Schimmer BP, Parker KL: Adrenocorticotropic hormone. In Hardman JG, Limbird LE, Gilman AG, editors: Goodman & Gilman’s the pharmacological basis of therapeutics, New York, 2001, McGraw-Hill, pp 1649-1677. 88. Balaji S, Oslizlok PC, Allen MC, et al: Neurocardiogenic syncope in children with a normal heart. J Am Coll Cardiol 23:779-785, 1994. 89. Scott WA, Pongiglione G, Bromberg BI, et al: Randomized comparison of atenolol and fludrocortisone acetate in the treatment of pediatric neurally mediated syncope. Am J Cardiol 76:400402, 1995. 90. Salim MA, Di Sessa TG: Effectiveness of fludrocortisone and salt in preventing syncope recurrence in children. J Am Coll Cardiol 45:484-488, 2005. 91. Raj SR, Rose S, Ritchie D, Sheldon RS: The Second Prevention of Syncope Trial (POST II): a randomized clinical trial of fludrocortisone for the prevention of neurally mediated syncope— rationale and study design. Am Heart J 151:1186, e11-e17, 2006. 92. El-Bedawi KM, Wahba MA, Hainsworth R: Cardiac pacing does not improve orthostatic tolerance in patients with vasovagal syncope. Clin Auton Res 4:233-237, 1994. 93. Fitzpatrick AP, Theodorakis G, Ahmed R, et al: Dual-chamber pacing aborts vasovagal syncope induced by head-up 60 degrees tilt. Pacing Clin Electrophysiol 14:13-19, 1991. 94. Samoil D, Grubb BP, Brewster P, et al: Comparison of single- and dual-chamber pacing techniques in prevention of upright tiltinduced vasovagal syncope. Eur J Card Pacing Electrophysiol 1:36-41, 1991. 95. Sra JS, Jazayeri MR, Avitall B: Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole. N Engl J Med 328:10851109, 1993. 96. Moya A, Brignole M, Menozzi C, et al: International Study on Syncope of Uncertain Etiology (ISSUE) Investigators. Circulation 104:1261-1267, 2001. 97. Petersen ME, Chamberlain-Webber R, Fitzpatrick AP, et al: Permanent pacing for cardioinhibitory malignant vasovagal syndrome. Br Heart J 71:274-281, 1994. 98. Benditt DG, Sutton R, Gammage MD: Clinical experience with Thera DR rate drop response pacing algorithm in carotid sinus syndrome and vasovagal syncope. Pacing Clin Electrophysiol 20:832, 1997. 99. Sheldon R, Wilson W, Kiesser T, Rose S: Effect of dual-chamber pacing automatic rate-drop sensing on recurrent neurally mediated syncope. Am J Cardiol 81:158-162, 1998. 100. Connolly SJ, Sheldon RS, Roberts RS, Gent M: The North American Vasovagal Pacemaker Study. J Am Coll Cardiol 33:16-20, 1999. 101. Sutton R, Brignole M, Menozzi C, et al: Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope: pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS). Circulation 102:294-299, 2000. 102. Ammirati F, Colivicchi F, Santini M: Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: a multicenter randomized, controlled trial. Circulation 104:52-57, 2001. 103. Ammirati F, Colivicchi F, Toscano S: DDD pacing with rate drop response function versus DDI with rate hysteresis pacing for cardioinhibitory vasovagal syncope. Pacing Clin Electrophysiol 21:2178-2181, 1998. 104. Beecher HK: Surgery as placebo. JAMA 176:1102-1107, 1961. 105. Moerman DE, Jonas WB: Deconstructing the placebo effect and finding the meaning response. Ann Intern Med 136:471-476, 2002. 106. Redelmeier DA, Tu JV, Schull MJ, et al: Problems for clinical judgement. 2. Obtaining a reliable past medical history. Can Med Assoc J 164:809-813, 2001. 107. McLeod KA, Wilson N, Hewitt J: Cardiac pacing for severe childhood neurally mediated syncope with reflex anoxic seizures. Heart 82:721-725, 1999. 108. Connolly SJ, Sheldon R, Thorpe KE, et al: Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope. JAMA 289:2224-2228, 2003. 109. Raviele A, Giada F, Menpzzi C, et al: A randomized, doubleblind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The Vasovagal Syncope and Pacing Trial (SYNPACE). Eur Heart J 25:1741-1748, 2004.



110. Gillis AM, Connolly SJ, Lacombe P, et al: Randomized crossover comparison of DDDR versus VDD pacing after atrioventricular junction ablation for prevention of atrial fibrillation. The Atrial Pacing Peri-Ablation for Paroxysmal Atrial Fibrillation Study Investigators. Circulation 102:736-741, 2000. 111. Gillis AM, Connolly SJ, Lacombe P, et al: Atrial pacing periablation for prevention of paroxysmal atrial fibrillation. Circulation 99:2553-2558, 1999. 112. Connolly SJ, Kerr CR, Gent M, et al: Effects of physiological pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physioloic Pacing Investigators. N Engl J Med 342:1385-1391, 2000. 113. Sud S, Massel D, Klein GJ, et al: The expectation effect and cardiac pacing for refractory vasovagal syncope. Am J Med 120:54-62, 2007. 114. Flammang D, Antiel M, Church T, et al: Is a pacemaker indicated for vasovagal patients with severe cardioinhibitory reflex as identified by the ATP test? A preliminary randomized trial. Europace 1:140-145, 1999. 115. Connolly SJ, Sheldon R, Roberts RS, Gent M: The North American Vasovagal Pacemaker Study (VPS): a randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol 33:16-20, 1999. 116. Deharo JC, Brunetto AB, Bellocci F, et al: DDDR pacing driven by contractility versus DDI pacing in vasovagal syncope: a multicenter, randomized study. Pacing Clin Electrophysiol 26:447450, 2003. 117. Occhetta E, Bortnik M, Audoglio R, Vassanelli C: Closed loop stimulation in prevention of vasovagal syncope. Inotropy Controlled Pacing in Vasovagal Syncope (INVASY): a multicentre randomized, single-blind, controlled study. Europace 6:538-547, 2004.

15  Pacing in Neurally Mediated Syncope Syndromes 118. Connolly SJ, Sheldon R, Thorpe KE, et al: Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial. JAMA 289:2224-2229, 2003. 119. Brignole M: International Study on Syncope of Uncertain Aetiology 3 (ISSUE 3): pacemaker therapy for patients with asystolic neurally mediated syncope—rationale and study design. Europace 9:25-30, 2007. 120. Sheldon R, Rose S, Koshman ML: Comparison of patients with syncope of unknow cause having negative or positive tilt-table tests. Am J Cardiol 80:581-585, 1997. 121. Grimm W, Degenhardt M, Hoffman J, et al: Syncope recurrence can better be predicted by history than by head-up tilt testing in untreated patients with suspected neurally mediated syncope. Pacing Clin Electrophysiol 18:1465-1469, 1997. 122. Sud S, Klein GJ, Skanes AC, et al: Implications of mechanism of bradycardia on response to pacing in patients with unexplained syncope. Europace 9:312-318, 2007. 123. Brignole M, Moya A, Menozzi C, et al: Proposed electrocardiographic classification of spontaneous syncope documented by an implantable loop recorder. Europace 7:14-18, 2005. 124. Brignole M, Menozzi C, Corbucci G: Detecting incipient vasovagal syncope: intraventricular acceleration. Pacing Clin Electrophysiol 20:801-808, 1997. 125. Osswald S, Cron T, Gradel C: Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dtmax and intracardiac impedance during dobutamine stress test. Pacing Clin Electrophysiol 23:1502-1508, 2000. 126. Binggeli C, Duru F, Corti R: Autonomic nervous system– controlled cardiac pacing: a comparison between intracardiac impedance signal and muscle sympathetic nerve activity. Pacing Clin Electrophysiol 23:1632-1637, 2000.

373

127. Griesbach L Huber T, Knote B, et al: Closed-loop stimulation: therapy for malignant neurocardiogenic syncope. Prog Biomed Res 7:242-247, 2002. 128. Occhetta E BM, Vassanelli C: The DDDR closed-loop stimulation for the prevention of vasovagal syncope: results from the INVASY Prospective Feasibility Registry. Europace 5:153-162, 2003. 129. Ochetta E, Bortnik M, Audoglio R, Vassanelli C: Closed-loop stimulation in prevention of vasovagal syncope. Inotropy Controlled Pacing in Vasovagal Syncope (INVASY): a multicentre randomized single-blind controlled study. Europace 6:538-547, 2004. 130. Giada F, Raviele A, Gasparini G: Efficacy of a patient-activated drug delivery system using phenylephrine as active drug in aborting tilt-induced syncope [abstract]. Pacing Clin Electrophysiol 24:573, 2001. 131. Brignole M, Alboni P, Benditt DG, et al: Task Force on Syncope, European Society of Cardiology. Guidelines on managemnet (diagnosis and treatment) of syncope. Eur Heart J 22:1256-1306, 2001. 132. Sheldon R, Connolly S, Rose S, et al: Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. Circulation 113:11641170, 2006. 133. Theodorakis GN, Leftheriotis D, Livanis EG, et al: Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study. Europace 8:193-198, 2006. 134. Qingyou Z, Junbao D, Chaoshu T: The efficacy of midodrine hydrochloride in the treatment of children with vasovagal syncope. J Pediatr 149:777-780, 2006.

374

SECTION 2  Clinical Concepts

16  16

Defibrillation Testing, Implant Testing, and Relation to Empiric ICD Programming PATRICK J. TCHOU  |  MARK J. NIEBAUER

Testing of the implantable cardioverter defibrillator (ICD) for its

ability to terminate ventricular fibrillation (VF) and ventricular tachycardia (VT) has been an important part of device implantation procedures since the inception of human implants in the early 1980s. For the first decade of human implantation, testing of adequate safety margins for defibrillation was crucial to the implantation procedure. With the advent of the biphasic waveform, better understanding of optimal shock waveform/duration, and higher–shock energy devices, inadequate safety margins for defibrillation have become uncommon. Nevertheless, at times such testing reveals a high defibrillation threshold (DFT) at which the reliability of defibrillation might be questioned.

Defibrillation testing also provides important information that could be used to program a device. Such testing would also verify that the sensing thresholds are adequate to detect VF reliably. A low DFT can allow the programming of a low-output initial shock that would reduce postshock ventricular dysfunction.1 Treatment with antiarrhythmic medication such as amiodarone may raise DFTs such that defibrillation testing may be indicated.2 When a patient is known to have a sustained monomorphic VT, testing of antitachycardia pacing efficacy may allow optimal programming of such parameters to terminate clinical events more expeditiously and to lessen acceleration of VT or conversion to VF. Thus, the many possible benefits of postimplant testing of ICDs should be considered against the risks of testing in a particular patient. In addition, ICD function may need to be tested at times other than implantation. Changes in ventricular sensing after implant may necessitate adjustments of programmed sensing parameters. Defibrillation testing to verify appropriate device function may require testing of the device’s ability to sense VF adequately.

Strength-Duration Nature of Defibrillating Shocks Similar to pacing impulses, defibrillation waveforms also have a strength-duration relationship3-11 (Fig. 16-1). However, important differences exist. In pacing, the strength-duration curve, marking the necessary current strength for a particular pulse duration that would elicit myocardial capture, separates the two-dimensional graph plane into two zones, one where capture consistently occurs and the other where there is no capture. These two zones are sharply demarcated by the strength-duration curve. That is, the probability of capture rises extremely steeply as one crosses the strength-duration curve from one zone to the other, so steeply that it appears to be almost an all-or-none phenomenon (Fig. 16-2). In contrast, the strength-duration relationship for defibrillation, described for monophasic waveforms or for the first phase of biphasic waveforms, is more probabilistic.12-14 For a particular pulse width, the probability of defibrillation changes over a much wider range of current strengths. Rather than a narrow line forming the strengthinterval curve for pacing, this is a wide, fuzzy band where, at a particular pulse width, the probability of defibrillation at the lower end of the

374

band is near zero and at the upper end of the band, near 100%. Alternatively, the strength-duration relation of defibrillation can be seen as a family of strength-duration curves having varying probabilities of defibrillation. For example, one curve can define the strength-duration of a waveform that would achieve a 50% successful defibrillation rate (DFT50). Another curve, located higher on the graph, would represent 90% successful defibrillation rate (DFT90). The differences between the pacing and defibrillation strengthduration curves can be attributed to several factors. Pacing occurs during diastole, where the resting membrane state is quite stable. Defibrillation, in contrast, occurs when the myocardium is in a highly inhomogeneous state of depolarization and repolarization. Multiple wavefronts may exist, the paths of which vary over time. Thus, the distribution of such depolarizing and repolarizing wavefronts is continuously changing. During pacing, the impulse needs to elicit an action potential in only a small volume of myocardium directly under the electrode, whereas the defibrillation shock needs to extinguish all or a critical number of wavefronts throughout the myocardium. It has been demonstrated that a minimum gradient of around 5 V/cm needs to be achieved throughout the myocardium to defibrillate at 80% effectiveness with a monophasic waveform, to obtain a high probability of terminating VF.15 The postulated mechanisms by which defibrillation shocks terminate VF have changed over the years. Multiple factors influence DFT, including size of the heart, location of the right ventricular (RV) electrode, polarity of the first phase, waveform durations, system impedance, heterogeneity of conduction and repolarization, number of propagating wavelets,16 virtual electrode effect, and non-RV electrode locations. Several reports have detailed these factors, primarily antiarrhythmic drugs17-21 (Table 16-1); a thorough discussion is beyond the scope of this chapter.

Shock Waveform Shock waveforms have several components. The monophasic truncated exponential waveform, for example, was common before 1990. The waveform has a polarity defined as that of the RV shock electrode. This electrode can have a positive charge (anodal) or a negative charge (cathodal), during the shock. A similar definition is used to describe biphasic waveforms using the polarity of the first phase. The waveform has a pulse width that can or cannot be programmed, depending on the particular device. The size of the capacitor in the device also determines the rate of exponential voltage/current decay during the shock. Although early implantable defibrillators tended to have larger capacitors, experimental studies demonstrate that lower capacitance values of 60 to 90 microfarad (µF) offer more efficient defibrillation energies, thus minimizing use of battery power.22-27 Technology limits the maximum voltage that capacitors can be charged, and concerns regarding the adequacy of small capacitor pulse width in the presence of low impedance have resulted in most defibrillators now having capacitance in the 90-µF range. This capacitance allows an adequate pulse width of the first phase at typical impedances seen in human implants and still preserves enough charge for delivery during the second phase.



375

16  Defibrillation Testing, Implant Testing, and Relation to Empiric ICD Programming 20

Required current (A)

Chronaxie

Figure 16-1  Generalized strength-duration curve for defibrillation. The rheobase current in the human heart is generally in the range of 2 to 6 A, whereas the chronaxie is typically 2 to 4 msec. Optical mapping measurements of the transmembrane response to a shock show that the membrane time constant is in the same approximate range as the chronaxie.

15

10

5 Rheobase 0 0

16-1 

Drugs and Clinical Conditions Affecting Defibrillation Threshold (DFT)

Drugs

Clinical/Other

Drugs/Condition Atropine, azimilide, diltiazem, fentanyl, halothane, isoflurane, lidocaine, mexiletine, moricizine, phenylephrine, sildenafil (IV), verapamil Sotalol, dofetilide, ibutilide, β-blockers Amiodarone,* epinephrine, flecainide, isoproterenol High shock impedance, intracellular hypercalcemia, pneumopericardium, pneumothorax Hyperkalemia, atrial natriuretic peptide (ANP) Electrode polarity,* electrode position

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20

Pulse duration (ms)

Pulse width is important because the effect of a shock delivered to the myocardium is to depolarize the cell membrane. When the myocardial cell is exposed to a sudden voltage gradient generated by the shock, the cell membrane responds by changing the transmembrane voltage. The rate of such change in transmembrane voltage is not instantaneous but exponential. Experimental studies have defined the

TABLE

1

Effect on DFT Increase

Decrease Variable Increase Decrease Variable

ranges of time constants of such depolarization.28,29 These time constants indicate that charging of the cell membranes would essentially be near maximum with pulse widths of 4 to 5 msec. Thus, pulse widths beyond 5 to 7 msec probably do not add much to the defibrillation effect30,31 (Fig. 16-3). In fact, very long pulse widths (>10 msec) may have detrimental effects in defibrillation.32,33 Capacitors larger than 90 µF can easily deliver waveforms with optimal duration, but would leave a large residual charge in the capacitor at the end of a shock, wasting battery power. In addition, because the capacitors occupy the largest volume in an ICD generator, these larger capacitors would result in larger ICD generators. Much of the reduction in current generator size has resulted from the ability to reduce the capacitor size used in earlier ICDs. Since the early 1990s, biphasic waveforms have become standard in all implantable defibrillators. Early work on the biphasic waveform33 led to experimental34-38 and then human39,40 studies that demonstrated the superiority of the biphasic waveforms over the monophasic in achieving lower DFTs.34-40 However, the mechanism of this superiority was postulated theoretically and demonstrated experimentally much later. The “charge burping” theory was postulated in 1994 to explain this superiority.41 Essentially, this theory proposed that the residual charge on the myocardial cell membrane at the end of a monophasic

*Significant individual variability.

400 100%

350 300

80%

Shock voltage

Probability of success

90% 70% 60% 50% 40%

250 Membrane response

200 150 100

30% 20%

50

10%

0

0% 0

5

10

15

20

25

Shock energy (J) Figure 16-2  Typical defibrillation success curve. Probability of successful defibrillation according to amount of energy used. This type of success curve can just as easily be described for the average current or voltage of the shock. More effective waveforms would shift this curve to the left and generate a steeper slope.

Wasted energy

0

1

2

3

4

5

6

7

8

Time (msec) Figure 16-3  Shock waveform and pulse width. Purple line shows a 400-V capacitive discharge shock waveform. Arrow and blue line identify a typical passive cardiac membrane response. Note that the energy delivered does not help charge the cardiac membrane and is actually counterproductive. This applies to a monophasic shock as well as the first phase of a biphasic shock.

376

SECTION 2  Clinical Concepts

1 0.9 0.8 0.7 0.6

Relative voltage

0.5 0.4

Membrane response

0.3 0.2 0.1 0

1

2

3

4

6

5

7

8

9

0.1 0.2 0.3 0.4 0.5 Time (msec)

Figure 16-4  “Charge burping.” Biphasic shock voltage (blue) and typical membrane response (red) are shown. Charge-burping theory of the biphasic shock holds that the function of the first phase is to charge the membrane maximally, and the function of the second phase is to discharge the membranes of the uncaptured cells back to zero. In this example the second phase is too long because the membrane is pulled past zero.

shock is proarrhythmic, because it could initiate new waves to continue VF. Thus, the second phase of the biphasic waveform served to discharge the residual transmembrane polarization so as to eliminate this proarrhythmic effect (Fig. 16-4). Clinical testing supported the predictions of the charge-burping theory.42 Experimentally, the phenomenon of the second-phase effects corroborated this theory and provided additional insight into how polarity matters. Recordings of actual transmembrane voltage changes during the shock waveform became possible once technology to record transmembrane voltages using optical techniques became available. Before this, transmembrane voltages could be measured only by direct electrical recordings. Such recordings, in the millivolt range, are completely overwhelmed by the electrical artifacts of the shock, in the hundreds of volts, three to five orders of magnitude larger. The optical techniques essentially utilize voltage-sensitive dyes impregnated into the cell membrane, whose florescence changes depending on the transmembrane voltage. This fluorescence can be measured optically; thus the electrical artifacts of the shock would not affect such measurements. Until the development of these optical techniques, the

TABLE

16-2 

transmembrane effects of the shock waveform could not be directly observed.43 A series of experimental studies using optical techniques then provided direct observational data on the potential mechanisms of the superiority of biphasic waveforms.44 Furthermore, these studies also demonstrated how anodal shocks, especially with monophasic waveforms, could be more effective. During delivery of the shock, the cardiac cell membrane surrounding the region of the shock electrode does not depolarize or hyperpolarize in a uniform manner. This nonuniform depolarization pattern has been labeled the virtual electrode effect and was predicted to occur based on computer modeling of cardiac tissue response to an externally applied, single-source (or point-source) voltage gradient.45 Interestingly, the nonhomogeneous pattern consists of a depolarization area near the electrode, surrounded by areas of hyperpolarization in the case of a cathodal shock, and vice versa with an anodal shock. At the end of a cathodal shock, the depolarized area in the center of the virtual electrode effect enhances propagation of a new wavefront toward surrounding tissue of hyperpolarized membranes. This increases the propensity to generate new wavefronts that would perpetuate VF. With an anodal shock, the favored propagation is from the surrounding areas toward the center of the virtual electrode effect. This direction of propagation favors the extinguishing of wavefronts as they collide toward the center, thus reducing the propensity to generate new wavefronts that would perpetuate VF. These same effects explain why cathodal pacing has a somewhat lower threshold than anodal pacing. These observations also provide a mechanistic explanation of why monophasic shocks with an anodal polarity have a lower DFT. Observations of biphasic shocks using optical recordings of transmembrane voltages show that reentrant wavefronts generated at the end of a monophasic shock cannot propagate when the second phase reduces (cancels out) the virtual electrode effect. Thus, the basic mechanism of the “burping” hypothesis was experimentally confirmed.46 Theoretically, a biphasic waveform in which the second phase appropriately cancels out the remaining transmembrane voltages at the end of the first phase should demonstrate no difference in DFT between anodal and cathodal shocks. Clinical studies with the monophasic waveforms consistently demonstrate that anodal shocks are more effective than cathodal shocks.47,48 With the biphasic waveform, anodal shocks have been more effective in a majority of clinical studies,49-52 although one study reported slightly improved cathodal (9.9 J) versus anodal (9.5 J) DFT53 (Table 16-2). Experimental animal studies using more optimized first-phase and second-phase waveforms, in which more thorough testing of DFT is feasible, have shown no difference in anodal versus cathodal firstphase shocks.54 The occasional patient who demonstrates a better cathodal then anodal DFT may be explained in two ways. First, clinical testing necessarily limits the number of defibrillation trials during an implantation. Thus, based on the probabilistic nature of defibrillation, an occasional patient may show a defibrillation at slightly lower shock strength with a cathodal shock than with an anodal shock, especially if the biphasic waveform is near ideal, such that the two waveforms would be comparable. Second, but less likely, when the second phase delivers an excessive amount of charge, a cathodal-type virtual electrode effect would occur at the end of the second phase if the first phase was anodal, thus making the shock less effective than the reverse

Influence of Right Ventricular (RV) Electrode Polarity on Defibrillation Threshold (DFT)

Study Schauerte et al.49 Shorofsky and Gold50 Natale et al.51 Strickberger et al.53 Keelan et al.52 Total or merged % of patients

N 27 26 20 15 10 12 110

RV+ (J) 11.1 11.1 16.3 9.9 6.6 12

RV− (J) 13.3 12.2 21.5 9.5 10.8 16.3

Reduction in Mean (%) 17 9 24 −4 39 26 16

Lower RV+ 10

Equal DFT 14

Lower RV+ 3

12 3 7 7 39 46

6 9 3 3 35 42

2 3 0 2 10 12

16  Defibrillation Testing, Implant Testing, and Relation to Empiric ICD Programming

polarity. Kroll et al.55 explored first-phase shock polarity and advocated for routine programming of an anodal first phase. In practice, it is difficult to determine exactly how to optimize the first and second phases so as to achieve the best cancellation of the virtual electrode effect across the entire myocardium. Thus, programming the first phase as an anodal shock is generally the best practice. Calculations have been reported of the “optimal” first and second phases to provide the proper charging and then “burping.”56,57 In devices where the pulse width of the two phases can be programmed, optimizing these parameters can sometimes yield an acceptable DFT when the “standard” pulse widths do not provide an adequate DFT safety margin.

Postimplant Testing ARRHYTHMIA DETECTION Implantable defibrillators are generally tested at implantation or generator replacement for appropriate detection, pacing, and therapy effectiveness. Once the generator has been attached to the new or existing lead(s), sensing parameters of intrinsic cardiac rhythm (if present) are usually tested first. In some devices, lead testing is performed using a pacing analyzer before attachment to the ICD generator. R waves of 5 mV or greater are usually considered the minimum necessary amplitude, but in some clinical situations, lower amplitudes may be acceptable. During tachyarrhythmias, in particular VF, ventricular detection amplitudes may be substantially reduced, which is why ICD generators contain “autogain” amplifiers.58 This function automatically increases the sensitivity of the device to detect R waves of lower amplitude. In most cases, it is desirable to position the ICD lead where the greatest R-wave amplitude is observed, to minimize underdetection. ICD manufacturers provide additional programmable detection functions to improve or reduce these sensitivity settings for specific clinical situations. For example, patients with long QT syndrome may exhibit oversensing caused by T-wave detection outside the usual detection “window” where various T-wave rejection algorithms are active. This can result in inappropriate shocks caused by “double counting.” Reprogramming the parameters affecting the autogain/autothreshold functions of the ICD after a sensed R wave may help prevent this problem. Ventricular undersensing is an occasional problem during lead implantation. In rare situations, it may be necessary to implant a separate bipolar pacing lead in the right ventricle for detection (or pacing) to maintain a more optimal RV shock coil location for successful defibrillation. Ventricular oversensing in most patients is caused by baseline low-amplitude signals, requiring the sensing algorithms to overcompensate, resulting in sensing T waves or far-field P waves. However, R-wave amplitude in sinus rhythm may not always correlate with sensing of VF. Because of the bipolar nature of ICD sensing of the QRS complex, especially with “dedicated bipolar” leads having closely spaced bipolar electrodes, the orientation of the wavefront as it propagates through the myocardium near the electrodes may have a significant effect on the amplitude of the detected R wave. A wavefront in sinus rhythm parallel to the two-electrode axis will generate a large R wave, whereas one perpendicular to the axis may have a greatly diminished R wave. During VF, however, the multidirectional wavefronts crossing the electrodes may show no decrease in the sensed R waves. Clinically, a sudden reduction in R waves can occur when the chronic lead has not changed position and no damage has occurred to myocardial tissue near the electrode. Typically, this occurs with development of a new bundle branch block. The resultant change in the wavefront orientation to the sensing electrodes during sinus rhythm can explain this change without affecting detection of VF. PACING Other important functions that are assessed at ICD implantation (and generator replacement) are pacing threshold and impedance, particularly in pacing-dependent patients. Repositioning of the lead may be

377

necessary to achieve acceptable sensing, pacing, and defibrillation thresholds. As previously noted, the addition of a separate bipolar pacing electrode is sometimes necessary to attain adequate defibrillation success and acceptable pacing thresholds. Measurement of the pacing impedance is routinely done at this time to assess conductor integrity, as well as connection from the leads to the ICD generator. High impedance values generally indicate conductor fracture or poor lead connection to the ICD generator. Low impedance values may indicate inner lead insulation damage, resulting in a short circuit between the tip and ring electrode conductors. The same concerns are true for any atrial or left ventricular leads that may be present in the implanted system. DEFIBRILLATION TESTING There is some controversy as to whether defibrillation testing should be part of a new implant or generator change. We favor such testing for the reasons listed here, provided the patient’s clinical condition makes this a low-risk test. Defibrillation testing usually consists of induction of VF by various means: T-wave shocks, delivery of a lowamplitude direct current (DC) through the lead, or more rarely, rapid burst pacing. The T-wave shock method is based on the presence of a vulnerable window surrounding the peak of the T wave within which a low-amplitude shock will induce VF59 (Fig. 16-5). The DC method captures the heart at rapidly accelerating rates generating polymorphic VT that quickly degenerates into VF. In most cases, a lowered ventricular sensitivity (higher sensing threshold of 1.0-1.2 mV) is used to assess adequate detection. If VF is promptly sensed with minimal “dropout” of fibrillation waves, an optimal sensitivity may be assumed. In some patients, testing at 0.45 to 0.9 mV may be necessary to achieve an acceptable sensitivity. Most patients are sent from the implant procedure at a sensitivity of 0.3 mV or less to ensure prompt clinical arrhythmia detection. VF detection criteria are usually set at this time, as discussed later. Once VF is detected, the ICD charges its capacitors to deliver the high-energy shock. Most current devices have a maximal energy output of 35 to 40 J, with additional programmable lowerenergy settings. Energy testing can be done by different methods. In some cases, a single shock may be adequate to ensure defibrillation adequacy. For example, if a single shock at 15 J is successful in terminating VF, a device having a maximum output of 35 J using the same waveform would likely have a high probability (>90%) of defibrillating on the first shock. If tested at 25 J, it is advisable to have two consecutive successful defibrillation shocks to ensure a high probability of successful defibrillation on the first shock. Ideally, the first shock would be programmed with a safety margin of 7 to 10 J from the DFT90 (90% successful defibrillation). However, such testing in a particular patient should be weighed against the potential risks in a patient with tenuous cardiac function, in a marginal state of decompensated heart failure, or with minimally adequate cardiac output. Induction of VF ULV

Shock strength



Vulnerable zone VF threshold

Figure 16-5  Vulnerable zone. A region of shock amplitude and time in which shocks will usually produce ventricular fibrillation (VF). The period is within the T wave, and the shock strength lies between the VF threshold and upper limit of vulnerability (ULV).

378

SECTION 2  Clinical Concepts

accompanied by a defibrillation shock is frequently followed by a short period of depressed mechanical function that usually recovers over 5 to 10 seconds. In a patient with severe heart failure, this may be longer, lasting several minutes.1,60 With multiple consecutive shocks to convert VF, this may take much longer. In a patient with marginally compensated heart failure, this period may turn into prolonged electricalmechanical dissociation requiring cardiopulmonary resuscitation (CPR). Such myocardial mechanical depression may be related to electroporation61-63 or disruption of calcium fluxes.64 This degree of risk may be too high to warrant defibrillation testing. Interestingly, the presence of ST-segment elevation on the postshock RV electrogram, an indication of myocardial injury, may be a prognostic factor predicting the progression of heart failure in these patients.65 Programming their devices to maximal output on the first shock may well be the best approach without testing. Testing can be reconsidered once the patient’s heart failure has improved with optimal medical therapy or biventricular pacing. In stable, well-compensated patients, more extensive DFT testing may be performed. In this situation, initial shock energy of about 15 J may be tested, and if successful, additional tests at progressively lower energies are attempted. Usually, a rest period of 2 to 5 minutes is observed between shocks to ensure that the patient’s hemodynamic status has returned to an acceptable level. Once a test shock fails, testing is complete. A “backup” shock of higher amplitude from the ICD or from an external defibrillator would then be promptly delivered to convert or “rescue” the patient. The lowest-amplitude successful test shock is then considered the defibrillation “threshold.” A first shock of 7 to 10 J above the threshold is usually programmed, as previously noted, to provide a safety factor. The DFT has proved fairly reliable as a guide for programming of the postimplant ICD energy output. However, as noted earlier, defibrillation effectiveness is better estimated as a sigmoidal probability curve, with higher energies providing a higher probability of success. Because of this relationship, single-shock testing may be unreliable in some patients, because a single success can be seen at low as well as higher probabilities. The greater the number of successful test shocks, the higher is the confidence that the successful test shock is near the DFT90, assuming that the procedure itself does not alter the result of subsequent test shocks. This may occur in patients who have lower left ventricular ejection fraction (LVEF) and impaired capacity to recover from even short episodes of ventricular fibrillation and defibrillation. An alternative defibrillation testing protocol is termed the upper limit of vulnerability (ULV) method. Multiple studies have demonstrated a close correlation between ULV and DFT, at about 90% success rates.66-74 The ULV approach, well summarized by Swerdlow et al.,75 can reduce the number of actual VF episodes during testing and any adverse hemodynamic responses to such testing. During ULV testing, a test shock of appropriate amplitude is delivered during intrinsic or paced rhythm at the T-wave peak. This point in ventricular repolarization is considered the vulnerable period, and low-energy shocks delivered during this interval often result in VF induction (i.e., T-wave shock induction). Theoretically, there is an upper energy limit above which T-wave shocks cannot induce VF. In this manner, testing of progressively lower shocks delivered during the vulnerable period is performed until VF occurs. Thus, the final test shock intensity that results in VF is considered the “upper limit” of vulnerability and the next highest energy, where VF does not occur, might be considered to be comparable to the defibrillation “threshold.” Therefore, only the final test shock results in VF (and requires a “rescue” shock). The recent multicenter ASSURE study compared limited ULV with limited DFT testing.76 The Arrhythmia Single Shock Defibrillation Threshold Testing versus Upper Limit of Vulnerability: Risk Reduction Evaluation with ICD Implantations study randomized 426 patients to an initial 14-J defibrillation test versus a test of “vulnerability” to 14-J T-wave synchronized shock in sinus rhythm, with crossover testing after the initial randomized method. The first shock and overall success rates were comparable between both methods (P > 0.10). ASSURE did not directly compare the two methods but suggests that either may be

acceptable. Posttesting hemodynamic events were assessed at only one test center, and 2 of 87 patients demonstrated a systolic blood pressure drop greater than 20 mm Hg after a defibrillation test, with spontaneous resolution, whereas no events were seen after T-wave shocks at that center. Another approach is not to perform defibrillation testing.77-79 Gula et al.80 compared the 5-year survival of patients who underwent DFT testing to patients using a decision analysis model and found a “small and non-significant survival advantage with routine DFT testing.” An Italian survey of DFT testing performed at implantation showed that of 7857 first ICD implant procedures, no defibrillation testing was done in 30% (n = 2356) of patients .81 Of the remaining 70% of implant procedures where testing was performed, only 0.4% (n = 22) had lifethreatening procedural complications, with two patients dying as a result. The ICD shock failure rate in the tested group was 2.7% (n = 148), in which a backup external defibrillator was required for conversion. The main reasons for not testing the ICD at implant were use of a cardiac resynchronization therapy (CRT) device and primary prevention. Other, less common reasons include age over 70, LVEF 30% or less, dilated cardiomyopathy, and New York Heart Association (NYHA) functional class above II. Therefore, some evidence suggests that defibrillation testing provides no survival benefit. However, no large prospective trials have been performed to answer this question. Risks of Defibrillation Testing Most studies of defibrillation testing safety have been comparatively small and retrospective. Russo et al.82 retrospectively looked at 1139 patients undergoing ICD implant at the University of Pennsylvania Heath system between October 1997 and November 2003 to determine the need for system modification based on the testing performed. Ninety-five percent (n = 1085) of patients underwent defibrillation testing. The remaining 54 patients did not undergo testing at implant for various clinical reasons, including presence of left atrial (LA) or left ventricular (LV) thrombus, hemodynamic instability, recent cerebrovascular accident (CVA, stroke)/transient ischemic attack (TIA) or atrial fibrillation (AF) without adequate anticoagulation, as well as severe coronary artery disease (CAD) or aortic stenosis. Of patients undergoing defibrillation testing, 71 (6.2%) required modification because of inadequate defibrillation safety margin. The majority received a higher-output device, subcutaneous leads, reversal of shock polarity, or a combination. Controversy on whether to perform defibrillation testing focuses on the possible adverse clinical events. A recent analysis of more than 19,000 ICD procedures in Canada between January 2000 and September 2006 showed a low incidence of death (0.016%) and CVA/TIA (0.026%).83 However, the percentage of implantations with defibrillation testing was estimated to be significantly lower (80% in 2005 alone), and the results may underestimate the incidence of complications. In addition, the lack of defibrillation testing was likely not random, and the clinicians performing the procedures may have elected not to perform testing on the sickest patients, in whom risk of complications is considered high. The controversy over defibrillation testing generally refers to this group of patients, with impaired cardiovascular reserve, although no good studies have been performed to establish the actual risk associated with testing in this group. As mentioned, defibrillation testing may be delayed until the patient’s status improves, or completely avoided because of concern about the patient’s ongoing clinical status. This practice appears to have arisen from unfortunate clinical experiences in which patients with particularly severe LV dysfunction or those who are not optimally treated have demonstrated hypotension, occasionally requiring aggressive resuscitation efforts after defibrillation testing. This can sometimes occur despite prompt, successful defibrillation by the implanted device. Another concern about defibrillation testing is neurologic damage from repeated episodes of cerebral hypoperfusion caused by VF. Reports of electroencephalographic and neurocognitive changes after ICD implant and testing prompted Silva et al.84 to perform mental status examinations on ICD patients preoperatively and 24 hours



16  Defibrillation Testing, Implant Testing, and Relation to Empiric ICD Programming

postoperatively. As a control group, patients undergoing pacemaker implant surgery underwent identical preoperative and postoperative testing. No significant decrease in mental status was seen in either group after implant surgery. Thus, this concern appears to be unfounded. Patients with High Defibrillation Threshold Occasionally, patients undergoing defibrillation testing will exhibit failure to defibrillate at acceptable energy settings (i.e., 7-10 J below maximum programmable energy). The approach to management of these patients can be challenging. It is initially important to ensure that all the lead connections are correct, specifically, that the RV coil is properly connected to the ICD generator plug. If it is misplaced in the superior vena cava (SVC) coil plug, the RV coil may not receive the maximal current output of the device. Most current ICD generators employ a “hot can” configuration in which the ICD casing and SVC coil connector are joined electrically. Therefore, when the RV and SVC coil connections to the device header are reversed in dual-coil lead systems, only part of the shock current will be delivered to the right ventricle. The remaining current will travel directly from the SVC coil to the ICD generator casing. In some generators, the coil or the ICD casing can be deselected as an electrode. When the RV and SVC electrodes are inserted into the header in reverse manner, deselecting the ICD casing as an electrode can improve the DFT because the full current is now delivered through the RV electrode. However, programming the SVC electrode “off ” can greatly depress the DFT because the RV electrode now receives no current. If a single-coil lead is used and the RV coil is incorrectly placed, the opposite connector is usually “plugged,” and no significant current will be delivered. This shock will exhibit extremely high impedance and may damage the ICD generator. Thus, it is important to verify proper insertion of the SVC and RV electrodes into the ICD generator. The newer DF4 standard for connecting ICD leads to the ICD header will avoid the potential of making this error. If the connections are correct, polarity reversal is a useful next step in the high-DFT patient. In some devices (out of the box) the nominal biphasic waveform polarity is programmed for the RV lead having an initial negative polarity (cathodal) in the first phase. However, a metaanalysis of biphasic shock polarity studies showed that although 41% of patients failed to show a difference in DFT between the two polarities, another 41% exhibited lower DFT when the RV was programmed to the positive polarity (anodal). Only 18% of patients exhibited a lower DFT if the RV cathodal polarity was used. Thus, Kroll et al.55 suggest that the initially tested polarity should always be the RV anodal polarity. Another simple change that can be made, in the case of a dual-coil lead, is to remove the SVC coil from the shock configuration altogether. This can be done through the device programmer in some models, but in others the SVC coil connector needs to be completely removed and capped, with the SVC connector port on the ICD plugged. This may be helpful in some patients, whereas the addition of an SVC coil to a single-coil system may be helpful in other cases. If the previous changes do not result in defibrillation success at acceptable energies, repositioning of the RV coil is a useful next step. One study reported that repositioning RV leads initially placed more laterally, nearer the RV free wall, to a position nearer the RV septum significantly reduced the DFT.85 The addition of auxiliary leads in less common positions has also been reported. Cooper et al.86 reported a series of seven patients implanted from either the left subclavian or the right subclavian approach.86 When unacceptably high DFTs were encountered, the addition of another intravenous coil lead in the right azygos vein was successful in reducing DFT energy to acceptable levels. Another, more common approach is to implant a nontransvenous subcutaneous coil. This is usually best performed on the left side, often laterally and posteriorly, and has been shown to reduce the DFT.87 If none of these approaches is successful, it may be necessary to add an epicardial patch to the system. However, this is a much more invasive approach and increases the implant complexity and morbidity. In rare patients, a left azygos vein or a left-sided SVC may be present. These locations, because of their posterior lateral location from the heart,

379

could be used for locating another electrode to improve the direction of current propagation through the myocardium. Another noninvasive option available in some ICD generators is manually changing the biphasic waveform parameters. This is particularly useful in patients with high DFT values and elevated lead impedance, in whom standard, fixed “tilt” biphasic waveforms will be prolonged and may not be optimal for defibrillation. By using a “tuned” waveform of shorter duration, the DFT can be reduced to acceptable levels.88 It is also important to consider metabolic or pathologic causes for the elevated energy requirements. Metabolic abnormalities such as hyperkalemia, acidosis, and hypoxia should be reversed and pathologic causes such as pneumothorax89-92 and possibly pneumomediastinum corrected before further testing. Mainigi and Callans93 have extensively reviewed these considerations and provide a useful flow diagram for management of high-DFT patients (Fig. 16-6).

Postimplant Programming of Tachyarrhythmia Therapy Once an acceptable endpoint to the implantation is achieved, the ICD detection zones and therapies need to be programmed before sending the patient home. In some cases, this programming is done before testing, especially when the patient has previously exhibited a sustained clinical VT. Reported data to the American College of Cardiology ICD Registry, established in 2006, indicates that approximately 83.4% of all ICD implants reported between January 2006 and June 2007 were placed for primary prevention.94 In most patients, therefore, ICD programming is not designed to treat a previously encountered arrhythmia. Poole et al.95 analyzed response to therapy of 811 ICD patients from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Patients received single-chamber Medtronic ICDs programmed to a single zone of therapy (shocks only) for rates above 188 beats per minute (bpm), equivalent to a cycle length of 320 msec, and were followed for a median of 45.5 months. Of 269 patients who received a shock, 182 received an “appropriate” shock and 87 received “inappropriate” shocks, as judged by two independent cardiologists. Appropriate shocks were defined as those received for ventricular tachycardia or fibrillation, and inappropriate shocks as those resulting from supraventricular arrhythmias, oversensing of P or T waves, double counting of R waves, or artifact from lead fractures or electromagnetic interference. Patients receiving the appropriate shocks had a worse survival rate, with a higher hazard ratio for death (5.68) than the 542 patients who received no shocks (P < .001). This group was also found to have a lower LVEF and higher NYHA class for heart failure than those who received no shocks. The patients who received inappropriate shocks also exhibited a higher hazard ratio for death (1.98) than those receiving no shocks (P < .002). No ATP therapies were programmed for these patients. Antitachycardia pacing (ATP) has been used to treat VT episodes by the delivery of pacing impulses that are slightly faster than the detected arrhythmia. The aim is to “break” the tachycardia by forcing the myocardial circuit to conduct the faster impulses beyond its physiologic limits. Two types of ATP therapy are generally available: burst and ramp. Burst ATP consists of a sequence of paced beats delivered at a programmable rate that is faster (i.e., shorter cycle length) than the detected VT. This sequence has a stable cycle length of variable but programmable duration (generally 8 cycles). Ramp pacing also consists of a sequence of paced beats, faster than the detected VT, but with a detrimental cycle length; that is, each paced impulse in the sequence is faster (i.e., shorter cycle length) than the preceding cycle. The number of beats in each ramp is programmable, as is the rate by which each cycle shortens from the prior cycle. The most recent comparison study of ATP effectiveness showed that burst pacing of eight beats at 88% of the VT confidence limit (CL) results in a higher percentage of conversions (75.2%) than ramp pacing (52.1%) of VTs detected in the fast-VT

380

SECTION 2  Clinical Concepts

High-output device

No

Successful defibrillation at maximum output

Consider empiric treatment with sotalol

If unsuccessful

If unsuccessful

Confirm apical position of RV coil (reposition if necessary)

Yes

If unsuccessful

If unsuccessful

Treat

Reverse polarity Retest If unsuccessful

Waveform modification

Consider alternative RV coil location, i.e., RVOT

Pneumothorax?

If unsuccessful

Remove SVC coil, especially if impedance <40

Add additional coil 1. Left brachiocephalic vein 2. Left subclavian vein 3. Coronary sinus 4. Azygos vein If unsuccessful If unsuccessful

Add SQ array

Figure 16-6  High-DFT patient management. Suggested flow chart to manage patients with high defibrillation thresholds during initial implant or follow-up. RVOT, Right ventricular outflow tract; SVC, superior vena cava; SQ, subcutaneous. (From Mainigi SK, Callans DJ: How to manage the patient with a high defibrillation threshold. Heart Rhythm 3:492-495, 2006.)

zone of 320 to 240 msec (P < .015). The ramp consisted of eight beats with 91% decrement between successive beats.96 The advantage of ATP is painless and more rapid disruption of the arrhythmia, as well as reducing the energy drain of the ICD. Unfortunately, crafting an ATP strategy for each patient individually can be time-consuming, with concerns that this may result in acceleration of the tachycardia to a more rapid and hemodynamically unstable form. However, the PainFREE Rx II trial tested an empirically programmed ATP strategy for rapid VT up to 250 bpm, which would have triggered shock therapy with standard programmed parameters. Successful conversion of these rapid VTs occurred in 72% of patients using the empiric ATP strategy.97 The subsequent reduction in shock therapies resulted in improved quality of life indicators. The EMPIRIC and PREPARE studies were designed to test a more standardized and safe approach to overall ICD programming. The EMPIRIC study randomized 900 unselected primary and secondary prevention patients to receive a standardized programming strategy versus physician-selected programming at Medtronic ICD implantation.98 The standardized (termed empiric) programming included three zones of therapy. A VT zone of 150 to 200 bpm was programmed to receive two trials of burst ATP therapy, one trial of ramp ATP therapy, then a 20-J shock, and then three 30-J shocks. A fast-VT zone at 200 bpm was programmed to receive one burst of ATP and then five 30-J shocks. Finally, the VF zone at 250 bpm was programmed to deliver six 30-J shocks. The empiric programming was comparable to physician-tailored therapy for time to first all-cause shock and percentage of VT/VF and non-VT/VF episodes. However, the number of patients experiencing five or more all-cause shocks was less in the empirically programmed group (P < .018). The PREPARE study was specifically aimed at comparing somewhat less intensive empiric therapy selections to physician-tailored programming in a cohort of 700 primary prevention patients receiving a Medtronic ICD.99 The standard programming prescribed for half the group was for two zones of fast-VT and VF therapy plus a monitor zone for VT. The slower VT zone was programmed between 167 and 182 bpm, with all therapies “off ” (e.g., Monitor zone). The fast-VT zone was programmed from 182 to 250 bpm with one burst of ATP and then five shocks of 30 to 35 J (maximum output). The VF zone was programmed to detect at more than 250 bpm and deliver up to six shocks at maximum energy output. The detection scheme was also prolonged to minimize device therapies triggered by self-terminating ventricular

tachyarrhythmias of short durations. Fast-VT and VF therapies were triggered only for tachyarrhythmias that met rate cutoff criteria for 30 of 40 consecutive beats. This particular detection and therapy strategy significantly reduced the morbidity index (P < .003) and the number of patients who received a shock during the first year of therapy (P < .01) compared to the physician-directed programming group. These studies underline the importance of randomized controlled trials (RCTs) to help select optimal ICD programming parameters. Patient survival outcomes of ATP versus shocks from ICDs were recently studied in a retrospective meta-analysis of four trials of ICD programming, including the EMPIRIC and PREPARE studies.100 A total of 2135 patients were included, and the investigators found that those with VT/VF episodes successfully treated with ATP, without the need for shocks, had a significantly lower 1-year mortality rate than those who received shocks in the same period. Interestingly, mortality was not significantly different between patients receiving ATP therapies and those who experienced no VT/VF episodes. The baseline clinical characteristics of the ATP and shock groups were indistinguishable. It is unclear from this study whether the shocks contributed to the increased mortality or were simply a marker of increased risk. However, ICD shocks have produced microscopic cardiac damage and biomarker evidence of myocardial cell disruption.101 Future studies of therapeutic shock and ATP therapies may help explain this phenomenon. RECOMMENDATIONS Given the results of the previous trials, we recommend initially programming different strategies in the primary prevention and secondary prevention groups (Table 16-3). For patients implanted for primary prevention indications, the PREPARE results provide the most useful guidelines, with two zones of therapies, specifically recommending longer detection periods to prevent unneeded ATP or shocks.99 For patients implanted for secondary prevention indications, the EMPIRIC trial provides the most useful guidelines, using two zones of VT therapy in addition to the VF zone.98 The VT and VF zones use longer detection periods than generally programmed in the past, although not as prolonged as in the PREPARE trial. In addition, supraventricular tachycardia (SVT) discriminators, as with morphology discrimination and rate stability, should be routinely used in the VT zones for both primary and secondary prevention patients, to prevent unnecessary therapies for nonventricular arrhythmias.



16  Defibrillation Testing, Implant Testing, and Relation to Empiric ICD Programming

TABLE

16-3 

381

Initial ICD Programming Recommendations for Primary and Secondary Prevention Devices* Primary Prevention

Zone VT

Lower Rate (bpm) 167

Fast VT

182

VF

220 to 250

Duration 30/40 intervalsa 16-20 intervalsb 7 secondsc SVT on‡ 30/40 intervalsa 16-20 intervalsb 7 secondsc SVT ON‡ 32 intervalsa 16 intervalsb 5 secondsc

Secondary Prevention Therapy Off (Monitor)

Lower Rate (bpm) 150

1 burst† ≥30 J × 5

200

≥30 J × 6

220 to 250

Duration 16 intervalsa 16 intervalsb 7 secondsc SVT on‡ 18/24 intervalsa 9-12 intervalsb 5 secondsc SVT ON‡ 18/24 intervalsa 16 intervalsb 5 secondsc

Therapy 3 bursts†d 20 J × 1 ≥30 J × 3 1 burst†d ≥30 J × 5 ≥30 J × 6

*For three major U.S. device manufacturers: aMedtronic; bSt. Jude Medical; cBoston Scientific; dAll three major U.S. manufacturers. †Bursts are 88% of detected cycle length with 20-msec decrement between bursts (for >1 burst). ‡SVT discriminators include morphology and stability. VF, Ventricular fibrillation; VT, ventricular tachycardia; SVT, supraventricular tachycardia.

REFERENCES 1. Tokano T, Bach D, Chang J, et al: Effect of ventricular shock strength on cardiac hemodynamics. J Cardiovasc Electrophysiol 9:791-797, 1998. 2. Leong-Sit P, Gula LJ, Diamantouros P, et al: Effect of defibrillation testing on management during implantable cardioverter-defibrillator implantation. Am Heart J 152:11041108, 2006. 3. Koning G, Schneider H, Hoelen AJ, et al: Amplitude-duration relation for direct ventricular defibrillation with rectangular current pulses. Med Biol Eng 13:388-395, 1975. 4. Gold JH, Schuder JC, Stoeckle H, et al: Transthoracic ventricular defibrillation in the 100 kg calf with unidirectional rectangular pulses. Circulation 56:745-750, 1977. 5. Bourland JD, Tacker WA, Geddes LA: Strength-duration curves for trapezoidal waveforms of various tilts for transchest defibrillation in animals. Med Instr 12:38-41, 1978. 6. Geddes LA, Bourland JD, Tacker WA: Energy and current requirements for ventricular defibrillation using trapezoidal waves. Am J Physiol 238:H231-H236, 1980. 7. Niebauer MJ, Babbs CF, Geddes LA, et al: Efficacy and safety of defibrillation with rectangular waves of 2 to 20-milliseconds duration. Crit Care Med 11:95-98, 1983. 8. Geddes LA, Niebauer MJ, Babbs CF, et al: Fundamental criteria underlying the efficacy and safety of defibrillating current waveforms. Med Biol Eng Comp 23:122-130, 1985. 9. Wessale JL, Bourland JD, Tacker WA, Geddes LA: Bipolar catheter defibrillation in dogs using trapezoidal waveforms of various tilts. J Electrocardiol 13:359-365, 1980. 10. Gold MR, Shorofsky SR: Strength-duration relationship for human transvenous defibrillation. Circulation 18(96):35173520, 1997. 11. Yamanouchi Y, Mowrey K, Mazgalev TN, et al: The strengthduration relationship of monophasic waveforms with varying capacitance sizes in external defibrillation. Pacing Clin Electrophysiol 26:2213-2218, 2003. 12. Davy JM, Fain ES, Dorian P, Winkle RA: The relationship between successful defibrillation and delivered energy in openchest dogs: reappraisal of the “defibrillation threshold” concept. Am Heart J 113:77-84, 1987. 13. Malkin RA, Souza JJ, Ideker RE: The ventricular defibrillation and upper limit of vulnerability dose-response curves. J Cardiovasc Electrophysiol 8:895-903, 1997. 14. Degroot PJ, Church TR, Mehra R, et al: Derivation of a defibrillator implant criterion based on probability of successful defibrillation. Pacing Clin Electrophysiol 20:1924-1935, 1997. 15. Zhou X, Daubert JP, Wolf PD, et al: Epicardial mapping of ventricular defibrillation with monophasic and biphasic shocks in dogs. Circ Res 72:145-160, 1993. 16. Hsu W, Lin Y, Lang DJ, Jones JL: Improved internal defibrillation success with shocks timed to the morphology electrogram. Circulation 98:808-812, 1998. 17. Dillon SM, Kwaku KF: Progressive depolarization: a unified hypothesis for defibrillation and fibrillation induction by shocks. J Cardiovasc Electrophysiol 9:529-552, 1998. 18. Chen PS, Swerdlow CD, Hwang C, Karacueuzian HS: Current concepts of ventricular defibrillation. J Cardiovasc Electrophysiol 9:552-562, 1998. 19. Cheng Y, Mowrey KA, Van Wagoner DR, et al: Virtual electrode induced reexcitation: a mechanism of defibrillation. Circ Res 85:1056-1066, 1999. 20. Efimov IR, Cheng Y, Yamanouchi Y, Tchou PJ: Direct evidence of the role of virtual electrode induced phase singularity in success and failure of defibrillation. J Cardiovasc Electrophysiol 11:861-868, 2000. 21. Dopp AL, Miller JM, Tisdale JE: Effect of drugs on defibrillation capacity. Drugs 68:607-630, 2008.

22. Leonelli FM, Kroll MW, Brewer JE: Defibrillation thresholds are lower with smaller storage capacitors. Pacing Clin Electrophysiol 18:1661-1665, 1995. 23. Rist K, Tchou PJ, Mowrey K, et al: Smaller capacitors improve the biphasic waveform. J Cardiovasc Electrophysiol 5:771-776, 1994. 24. Bahu M, Knight BP, Weiss R, et al: Randomized comparison of a 90-µF capacitor three-electrode defibrillation system with a 125-µF two-electrode defibrillation system. J Interv Card Electrophysiol 2:41-45, 1998. 25. Swerdlow CD, Brewer JE, Kass RM, Kroll MW: Application of models of defibrillation to human defibrillation data: implications for optimizing implantable defibrillator capacitance. Circulation 96:2813-2822, 1997. 26. Yamanouchi Y, Brewer JE, Mowrey KA, et al: Optimal smallcapacitor biphasic waveform for external defibrillation: influence of phase-1 tilt and phase-2 voltage. Circulation 98:2487-2493, 1998. 27. Yamanouchi Y, Brewer JE, Olson KF, et al: Fully discharging phases: a new approach to biphasic waveforms for external defibrillation. Circulation 100:826-831, 1999. 28. Mowrey KA, Cheng Y, Tchou PJ, Efimov R: Kinetics of defibrillation shock-induced response: design implications for the optimal defibrillation waveform. Europace 4:27-39, 2002. 29. Mowrey KA, Efimov IR, Cheng Y: Membrane time constant during internal defibrillation strength shocks in intact heart: effects of Na+ and Ca2+ channel blockers. J Cardiovasc Electrophysiol 20:85-92, 2009. 30. Kroll MW: A minimal model of the monophasic defibrillation pulse. Pacing Clin Electrophysiol 16:769-777, 1993. 31. Irnich W: Optimal truncation of defibrillation pulses. Pacing Clin Electrophysiol 18:673-688, 1995. 32. Lampert R, Soufer R, McPherson CA, et al: Implantable cardioverter-defibrillator shocks increase T-wave alternans. J Cardiovasc Electrophysiol 18:512-517, 2007. 33. Al-Khadra A, Nikolski V, Efimov IR: The role of electroporation in defibrillation. Circ Res 87:797-804, 2000. 34. Gurvich NL, Makarychev VA: Defibrillation of the heart with biphasic electric impulsation. Kardiologiia 7:109-112, 1967. 35. Dixon EG, Tang AS, Wolf PD, et al: Improved defibrillation thresholds with large contoured epicardial electrodes and biphasic waveforms. Circulation 76:1176-1184, 1987. 36. Chapman PD, Vetter JW, Souza JJ, et al: Comparative efficacy of monophasic and biphasic truncated exponential shocks for nonthoracotomy internal defibrillation in dogs. J Am Coll Cardiol 12:739-745, 1988. 37. Fain ES, Sweeney MB, Franz MR: Improved internal defibrillation efficacy with a biphasic waveform. Am Heart J 117:358-364, 1989. 38. Kavanagh KM, Tang AS, Rollins DL, et al: Comparison of the internal defibrillation thresholds for monophasic and double and single capacitor biphasic waveforms. J Am Coll Cardiol 114:1343-1349, 1989. 39. Winkle RA, Mead RH, Ruder MA, et al: Improved low-energy defibrillation efficacy in man with the use of a biphasic truncated exponential waveform. Am Heart J 117:122-127, 1989. 40. Bardy GH, Ivey TD, Allen MD, et al: A prospective randomized evaluation of biphasic versus monophasic waveform pulses on defibrillation efficacy in humans. J Am Coll Cardiol 14:728-733, 1989. 41. Kroll MW: A minimal model of the single capacitor biphasic defibrillation waveform. Pacing Clin Electrophysiol 17:17821792, 1994. 42. Swerdlow CD, Fan W, Brewer JE: Charge-burping theory correctly predicts optimal ratios of phase duration for biphasic defibrillation waveforms. Circulation 94:2278-2284, 1996.

43. Efimov IR, Cheng YN, Biermann M, et al: Transmembrane voltage changes produced by real and virtual electrodes during monophasic defibrillation shock delivered by an implantable electrode. J Cardiovasc Electrophysiol 8:1031-1045, 1997. 44. Efimov IR, Cheng Y, Van Wagoner DR, et al: Shock induced phase singularities: mechanism for the failure to defibrillate. Circ Res 82:918-925, 1998. 45. Roth BJ, Wikswo JP, Jr: Electrical stimulation of cardiac tissue: a bidomain model with active membrane properties. IEEE Trans Biomed Eng 41:232-240, 1994. 46. Efimov IR, Cheng Y, Yamanouchi Y, Tchou PJ: Direct evidence of the role of virtual electrode induced phase singularity in success and failure of defibrillation. J Cardiovasc Electrophysiol 11:861, 868, 2000. 47. Strickberger SA, Hummel JD, Horwood LE, et al: Effect of shock polarity on ventricular defibrillation threshold using a transvenous lead system. J Am Coll Cardiol 24:1069-1072, 1994. 48. Thakur RK, Souza JJ, Chapman PD, et al: Electrode polarity is an important determinant of defibrillation efficacy using a nonthoracotomy system. Pacing Clin Electrophysiol 17:919-923, 1994. 49. Schauerte P, Stellbrink C, Schondube FA, et al: Polarity reversal improves defibrillation efficacy in patients undergoing transvenous cardioverter defibrillator implantation with biphasic shocks. Pacing Clin Electrophysiol 20:301-306, 1997. 50. Shorofsky SR, Gold MR: Effects of waveform and polarity on defibrillation thresholds in humans using a transvenous lead system. Am J Cardiol 78:313-316, 1996. 51. Natale A, Sra J, Dhala A, Jazayeri M, et al: Effects of initial polarity on defibrillation threshold with biphasic pulses. Pacing Clin Electrophysiol 18:1889-1893, 1995. 52. Keelan ET, Sra JS, Axtell K, et al: The effect of polarity of the initial phase of a biphasic shock waveform on the defibrillation threshold of pectorally implanted defibrillators. Pacing Clin Electrophysiol 20:337-342, 1997. 53. Strickberger SA, Man KC, Daoud E, et al: Effect of first-phase polarity of biphasic shocks on defibrillation threshold with a single transvenous lead system. J Am Coll Cardiol 25:1605-1608, 1995. 54. Yamanouchi Y, Mowrey KA, Nadzam GR, et al: Effects of polarity on defibrillation thresholds using a biphasic waveform in a hot can electrode system. Pacing Clin Electrophysiol 20:2911-2916, 1997. 55. Kroll MW, Efimov IR, Tchou PJ: Present understanding of shock polarity for internal defibrillation: the obvious and non-obvious clinical implications. PACE 29:885-891, 2006. 56. Natarajan S, Henthorn R, Burroughs J, et al: “Tuned” defibrillation waveforms outperform 50/50% tilt defibrillation waveforms: a randomized multi-center study. PACE 30:14-24, 2007. 57. Denman RA, Umesan C, Martin PT, et al: Benefit of millisecond waveform durations for patients with high defibrillation thresholds. Heart Rhythm 3:536-541, 2006. 58. Gillberg J: Detection of cardiac tachyarrhythmias in implantable devices. J Electrocardiol 40(Suppl 6):123-128, 2007. 59. Sharma AD, Fain E, O’Neill PG, et al: Shock on T versus direct current voltage for induction of ventricular fibrillation: a randomized prospective comparison. Pacing Clin Electrophysiol 27:89-94, 2004. 60. Mollerus M, Naslund L: Myocardial stunning following defibrillation threshold testing. J Interv Card Electrophysiol 19:213-216, 2007. 61. Tokano T, Bach D, Chang J, et al: Effect of ventricular shock strength on cardiac hemodynamics. J Cardiovasc Electrophysiol 9:791-797, 1998. 62. Tovar O, Tung L: Electroporation of cardiac cell membranes with monophasic or biphasic rectangular pulses. Pacing Clin Electrophysiol 14:1887-1892, 1991.

382

SECTION 2  Clinical Concepts

63. Nikolski VP, Efimov IR: Electroporation of the heart. Europace 7:S146-S154, 2005. 64. Jones DL, Narayanan N: Defibrillation depresses heart sarcoplasmic reticulum calcium pump: a mechanism of postshock dysfunction. Am J Physiol Heart Circ Physiol 274:98-105, 1998. 65. Tereshchenko LG, Faddis MN, Fetics BJ, et al: Transient local injury current in right ventricular electrogram after implantable cardioverter-defibrillator shock predicts heart failure progression. J Am Coll Cardiol 54:822-828, 2009. 66. Chen PS, Feld GK, Kriett JM, et al: Relation between upper limit of vulnerability and defibrillation threshold in humans. Circulation 88:186-192, 1993. 67. Behrens S, Li C, Franz MR: Timing of the upper limit of vulnerability is different for monophasic and biphasic shocks: implications for the determination of the defibrillation threshold. Pacing Clin Electrophysiol 20:2179-2187, 1997. 68. Hwang C, Swerdlow CD, Kass RM, et al: Upper limit of vulnerability reliably predicts the defibrillation threshold in humans. Circulation 90:2308-2314, 1994. 69. Swerdlow CD, Ahern T, Kass RM, et al: Upper limit of vulnerability is a good estimator of shock strength associated with 90% probability of successful defibrillation in humans with transvenous implantable cardioverter defibrillators. J Am Coll Cardiol 27:1112-1118, 1996. 70. Swerdlow CD, Davie S, Ahern T, Chen PS: Comparative reproducibility of defibrillation threshold and upper limit of vulnerability. Pacing Clin Electrophysiol 19:2103-2111, 1996. 71. Souza JJ, Malkin RA, Ideker RE: Comparison of upper limit of vulnerability and defibrillation probability of success curves using a nonthoracotomy lead system. Circulation 91:1247-1252, 1995. 72. Behrens S, Li C, Franz MR: Effects of myocardial ischemia on ventricular fibrillation inducibility and defibrillation efficacy. J Am Coll Cardiol 29:817-824, 1997. 73. Martin DJ, Chen PS, Hwang C, et al: Upper limit of vulnerability predicts chronic defibrillation threshold for transvenous implantable defibrillators. J Cardiovasc Electrophysiol 8:241-248, 1997. 74. Huang J, KenKnight BH, Walcott GP, et al: Effects of transvenous electrode polarity and waveform duration on the relationship between defibrillation threshold and upper limit of vulnerability. Circulation 96:1351-1359, 1997. 75. Swerdlow CD, Shehata M, Chen PS: Using the upper limit of vulnerability to assess defibrillation efficacy at implantation of ICDs. Pacing Clin Electrophysiol 30:258-270, 2007. 76. Day JD, Doshi RN, Belott P, et al: Inductionless or limited shock testing is possible in most patients with implantable

cardioverter-defibrillators/cardiac resynchronization therapy defibrillators: results of the multicenter ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing versus Upper Limit of Vulnerability: Risk Reduction Evaluation with Implantable Cardioverter-Defibrillator Implantations). Circulation 115:2382-2389, 2007. 77. Blatt JA, Poole JE, Johnson GW, et al: SCD-HeFT Investigators. No benefit from defibrillation threshold testing in the SCDHeFT (Sudden Cardiac Death in Heart Failure Trial). J Am Coll Cardiol 52:551-556, 2008. 78. Kolb C, Tzeis S, Zrenner B: Defibrillation threshold testing: tradition or necessity? PACE 32:570-572, 2009. 79. Pires LA, Johnson KM: Intraoperative testing of the implantable defibrillator: how much is enough? J Cardiovasc Electrophysiol 17:140-145, 2006. 80. Gula LJ, Massel D, Krahn AD, et al: Is defibrillation testing still necessary? A decision analysis and Markov model. J Cardiovasc Electrophysiol 19:400-405, 2008. 81. Brignole M, Raciti G, Borgiorni MG, et al: Defibrillation testing at the time of implantation of cardioverter defibrillator in clinical practice: a nation-wide survey. Europace 9:540-543, 2007. 82. Russo AM, Sauer W, Gerstenfeld EP, et al: Defibrillation threshold testing: is it really necessary at the time on implantable cardioverter-defibrillator insertion? Heart Rhythm 2:456-461, 2005. 83. Birnie D, Tung S, Simpson C, et al: Complications associated with defibrillation threshold testing: the Canadian experience. Heart Rhythm 5:387-390, 2008. 84. Karaoguz R, Altln T, Atbasoglu EC, et al: Defibrillation testing and early neurologic outcome. Int Heart J 49:553-563, 2008. 85. Winter J, Zimmermann N, Lidolt H, et al: Optimal method to achieve consistently low defibrillation energy requirements. Am J Cardiol 86:71K-75K, 2000. 86. Cooper JA, Latacha MP, Soto GE, et al: The azygos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series. PACE 31:1405-1410, 2008. 87. Osswald BR, DeSimone R, Most S, et al: High defibrillation threshold in patients with implantable defibrillator: how effective is the subcutaneous finger lead? Eur J Cardiothorac Surg 35:489-492, 2009. 88. Mouchawar G, Kroll M, Val-Mejias JE, et al: ICD waveforms optimization: a randomized, prospective, pair sampled multicenter study. Pacing Clin Electrophysiol 23:1992-1995, 2000. 89. Luria D, Stanton MS, Eldar M, Glikson M: Pneumothorax: an unusual cause of ICD defibrillation failure. Pacing Clin Electrophysiol 21:474-475, 1998.

90. Schuchert A, Hoffmann M, Steffgen F, Meinertz T: Several unsuccessful internal and external defibrillations during active can ICD implantation in a patient with pneumothorax. Pacing Clin Electrophysiol 21:471-473, 1998. 91. Cohen TJ, Lowenkron DD: The effects of pneumothorax on defibrillation thresholds during pectoral implantation of an active can implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 21:468-470, 1998. 92. Furman S: Defibrillation threshold and pneumothorax. Pacing Clin Electrophysiol 21:337-338, 1998. 93. Mainigi SK, Callans DJ: How to manage the patient with a high defibrillation threshold. Heart Rhythm 3:492-495, 2006. 94. Curtis JP, Luebbert JJ, Wang Y, et al: Association of physician certification and outcomes among patients receiving an implantable cardioverter-defibrillator. JAMA 301:1661-1670, 2009. 95. Poole JE, Johnson GW, Hellkamp AS, et al: Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 359:1009-1017, 2008. 96. Gulizia MM, Piraino L, Scherillo M, et al: A randomized study to compare ramp versus burst antitachycardia pacing therapies to treat fast ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. Circ Arrhythm Electrophysiol 2:146-153, 2009. 97. Wathen MS, DeGroot PJ, Sweeney MO, et al: PainFREE Rx II Investigators. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 110:2591-2596, 2004. 98. Wilkoff BL, Ousdigian KT, Sterns LD, et al: A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators. J Am Coll Cardial 48:330-339, 2006. 99. Wilkoff BL, Williamson BD, Stern RS, et al: Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients. J Am Coll Cardiol 52:541-550, 2008. 100. Sweeney MO, Sherfesee L, DeGroot PJ, et al: Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients. Heart Rhythm 7:353-360, 2010. 101. Epstein AE, Kay GN, Plumb VJ, et al: Gross and microscopic pathological changes associated with nonthoracotomy implantable defibrillator leads. Circulation 98:1517-1524, 1998.

17  17

ICD Therapy in Channelopathies PAOLA BERNE  |  JOSEP BRUGADA

C

ardiac channelopathies, also called ion channel disorders, include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. This group of genetically determined diseases has low prevalence in the general population, usually less than 5 per 10,000.1 Affected individuals have a structurally normal heart but an increased risk of syncope and sudden cardiac death (SCD) caused by ventricular tachycardia (VT) or ventricular fibrillation (VF). The genes affected by causative mutations encode proteins that form cardiac ion channels, regulate their function, or participate in ionic-cellular imbalance, regulating the electrical function of the heart and resulting in primary electrical diseases. The penetrance of channelopathies is variable, and individuals who show the most severe phenotype are at higher risk of presenting with life-threatening episodes of ventricular arrhythmias. Symptoms usually begin early in life, and risk stratification is paramount because patients might present with SCD, in some cases as the first symptom. Although genetic information is entering clinical practice and being integrated in the risk stratification schemes,2,3 family history of SCD has not been identified as a reliable marker of high risk in patients with channelopathies. There are no large, randomized trials of treatment for these diseases, and probably never will be. Current indications for risk stratification and treatment are based on information from large registries and retrospective analysis. Thus, the level of evidence for all indications is low. Patients diagnosed with channelopathies are advised to restrict exercise, even if exercise is not a recognized trigger for their arrhythmic events.4 This chapter reviews risk stratification and implantable cardioverter-defibrillator (ICD) indications for the channelopathies, as well as benefits and drawbacks of ICD implantation in these patients.

Long QT Syndrome Described for the first time by Jervell and Lange-Nielsen5 in 1957 (autosomal recessive pattern of inheritance; associated genes: KCNQ1 and KCNE1)6 and by Romano et al. in 1963 and Ward et al.7 in 1964 (autosomal dominant inheritance; associated genes: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, and SNTA1),6 long QT syndrome (LQTS) is the most studied cardiac channelopathy. Established in 1979, the International LQTS Registry includes more than 3000 patients and provides information about causative mutations, clinical course, risk factors, and response to treatment.8 The typical features of LQTS are prolonged corrected QT (QTc) interval in the 12-lead electrocardiogram (ECG), T-wave abnormalities, and symptoms that vary from syncope to SCD. Symptoms are secondary to torsades de pointes (TdP), a rapid polymorphic VT that may be self-limited or may degenerate into VF (mean age of onset, 12 years).9 The arrhythmic episodes are often triggered by adrenergic stimuli (e.g., exercise, emotion) but may also occur at rest.10 TdP may be pause dependent or adrenergic dependent.11,12 Pause-dependent TdP mainly follows post-extrasystolic pauses but may also appear after pauses during sinus arrhythmia or sinus arrest. These pauses enhance early afterdepolarizations (EADs), manifesting on ECG as more prolonged QT interval and U-wave augmentation in the beat immediately after the pause, and may trigger TdP. Adrenergic-dependent TdP follows sinus tachycardia during physical or emotional stress. In this case, tachycardia and high sympathetic tone increase the dispersion of

repolarization by shortening it in different degrees across the myocardial layers. Also during sinus tachycardia, however, ventricular extrasystoles and the following post-extrasystolic pause are able to trigger TdP.13 RISK STRATIFICATION Factors in risk stratification of LQTS patients include ECG, age, gender, genotype, and symptoms. Electrocardiogram Many studies have confirmed a direct relationship between prolonged QTc interval and risk of arrhythmia-related symptoms in patients with LQTS.3,14-19 A QTc interval of 500 msec or higher implies high risk for arrhythmic events.3 The strength of QTc interval to predict arrhythmic risk varies when dividing patients into subgroups according to age or gender, but it always maintains a strong value as an independent risk factor. Serial QTc measurements may have a role in risk stratification, because maximum QTc interval during adolescence was the strongest predictor of cardiac events.20 Age and Gender Observation of the natural history of LQTS reveals how gender and age interact as risk factors.8,21,22 Several analyses of the probability of arrhythmic events during different decades of life showed that risk is significantly higher in boys than girls (5% vs. 1%).17 Also, the genderrelated risk reverses in the final stage of adolescence, about age 17, with respect to any cardiac events, and about age 23 with SCD and sudden cardiac arrest (SCA).15-18 Genotype Genotype testing identifies a causative mutation in up to 68% of probands of LQTS; 90% of patients are LQT1, LQT2, or LQT3.23,24 Genotype is useful for risk stratification. Patients with LQT1 and LQT2 have more cardiac events (mainly syncope) than patients with LQT3, who present a higher rate of lethal or potentially lethal events.2 Triggers for the arrhythmic events in LQTS are also associated with the genotype: exercise (especially swimming) in patients with LQT1, sudden loud noise in LQT2, and rest/sleep in LQT3 patients.10 Furthermore, the response to β-blocker therapy for prevention of cardiac events is significantly better in LQT1 than in LQT2 or LQT3 patients.9 A given type of mutation or its location in the affected gene can influence risk.25-27 Symptoms Syncope is the strongest predictor of cardiac events and SCD in the patient with LQTS. In all age groups, recent or remote syncope is associated with a 2.7- to 18-fold increased risk of SCD.15-18 Unrelated Factors Electrophysiologic study (EPS)1,28 and family history of SCD29 have proved not to influence risk stratification in LQTS. Aborted Cardiac Arrest A simplified scheme for risk stratification of aborted cardiac arrest (ACA) or SCD in LQTS patients divides patients in three groups: (1) high risk (history of ACA or documented TdP), with an estimated rate of ACA or SCD of 14% at 5-year follow-up; (2) intermediate risk (QTc >500 msec and/or time-dependent syncopal history), with an

383

384

SECTION 2  Clinical Concepts

estimated rate of ACA or SCD at 5-year follow up of 3%; and (3) low risk (QTc ≤500 msec and/or no history of prior syncope), with 0.5% estimated rate of ACA or SCD at 5-year follow-up.30 CURRENT THERAPEUTIC RECOMMENDATIONS Current guidelines suggest that all patients diagnosed with LQTS should avoid triggers of arrhythmias (exercise, emotional stress, loud noises) as well as drugs that prolong the QTc interval. Patients should receive β-blockers (class I indication in clinical diagnosis, i.e., prolonged QTc interval; class IIa indication in molecular diagnosis and normal QTc interval). Beta-adrenergic blockers should be given at the highest dose tolerated by the patient, and the dose may be titrated by exercise testing.1 Torsades de pointes in patients with congenital LQTS is often pause dependent (up to 74%),31 and cardiac pacing at lower rate limit (LRL) >70 bpm has proved helpful for preventing TdP development in acquired LQTS,32 in which TdP is almost always pause dependent. Therefore, strategies to avoid “short-long-short” sequences were proposed in these patients as a complement to pharmacologic treatment. However, patients undergoing pacemaker implantation and β-blocker therapy still presented unacceptably high rates of aborted SCD (aSCD) and SCD, leading to further indication for ICDs in high-risk patients with LQTS.33 Even though this is currently the preferred approach, LQTS patients can still obtain additional benefits from their ICD if antibradycardia therapy is correctly programmed, in combination with pharmacologic treatment and antitachycardia settings (see later Antibradycardia Therapy in Long QT Syndrome). The LQTS patients with aSCD are at high risk of repeating a fatal or near-fatal arrhythmic event and thus are candidates for ICD implantation. Patients who continue to experience syncope or TdP while taking maximally tolerated β-blockers also are candidates. These two groups of LQTS patients are also candidates for left sympathetic cardiac denervation.34 Genotype information may help guide the decision about ICD implantation. However, it is also important to consider other clinical markers of high risk, which have proved very useful and simple to evaluate, such as QTc duration, symptoms, presence of sinus pauses, T-wave alternans, and 2 : 1 atrioventricular (AV) block.35 Several studies support a role for ICDs in preventing or reducing SCD in high-risk patients with LQTS. However, most patients do not belong to this subgroup and remain at a relatively low risk of cardiac events; these patients may be appropriately protected from arrhythmic events by a combination of noninvasive and simple measures. Moss et al.14 reported a 5%/yr incidence of syncope and 0.9%/yr incidence of SCD in probands. In affected family members, incidence of cardiac events was even lower: 0.5%/yr for syncope and 0.2%/yr for SCD. Some studies may have overestimated the benefits of ICD implantation, comparing ICD patients with non-ICD patients who were not adequately treated with drugs,22 or by making “appropriate ICD therapy” synonymous with SCD. Considering that TdP is often nonsustained, and that the rates of “lifesaving therapies” in several studies were higher than the expected mortality in LQTS, some “appropriate ICD shocks” likely were inappropriate, delivered for ventricular arrhythmia that otherwise would have terminated spontaneously.36-39

Short QT Syndrome Initially described in 2000, short QT syndrome (SQTS) is characterized by an abnormally short QT interval, often followed by morphologic T-wave abnormalities (tall, narrow), and increased susceptibility to atrial fibrillation (AF) and VF.40,41 To date, mutations in five genes have been found in almost 25% of SQTS patients. Mutations in KCNH2, KCNQ1, and KCNJ242-44 result in gain of function in the encoded potassium ion (K+) channels and lead to shortening of the ventricular repolarization phase. Mutations in CACNA1C and CACNB2 cause loss of function in the cardiac L-type calcium ion (Ca2+) channel and produce an overlap between Brugada syndrome and SQTS.45 At

present, it is still unclear whether diagnosis of SQTS should be based on QT or QTc interval; sensitivity and specificity of different QT/QTc cutoff values also remain undefined.1 Age of onset of symptoms varies from 4 months to 62 years, and incidence of SQTS is higher among males. Atrial and ventricular effective refractory periods are shortened and AF/VF easily induced in patients undergoing EPS (up to 60%).46 The risk for arrhythmic events is high in SQTS patients. Cardiac arrest is frequently the first manifestation of disease and may occur during the first year of life. Patients also present with syncope and AF (up to 30%) at any age (even intrauterine), making SQTS a differential diagnosis to rule out in young patients with lone AF. The use of quinidine in a group of patients with SQT1 proved useful in making VT noninducible by prolonging ventricular refractory periods.47 RISK STRATIFICATION Up to 2008, only 51 patients with SQTS had been diagnosed worldwide.48 Thus, risk stratification is based on limited data; currently, symptoms are the only tool available to evaluate risk of arrhythmic events. Patients with SQTS and SCA and those with syncope of unknown origin should have an ICD for secondary and primary prevention, respectively, even if no data exist on the usefulness of syncope to predict cardiac events.49 Although ECG helps diagnose the disease, its role in risk stratification is still undefined (e.g., it is unknown if degree of QT shortening identifies patients at higher risk of arrhythmic events). Age, gender, genotype, and inducibility of ventricular tachyarrhythmias during EPS have not yet proved to have a predictive value for cardiac events in this group of patients. CURRENT THERAPEUTIC RECOMMENDATIONS Management of patients with SQTS is poorly established. Although limited data show that quinidine may suppress inducibility of ventricular arrhythmias during EPS,50,51 whether it confers long-term protection for malignant arrhythmias remains unknown. Most SQTS patients receive an ICD, with a high rate of complications reported, mostly inappropriate shocks caused by T-wave oversensing.52

Brugada Syndrome The Brugada syndrome (BS) is one of the leading causes of SCD in patients with structurally normal hearts.53 A characteristic electrocardiographic pattern (“type 1 ECG”) in at least two right precordial leads, spontaneously or after pharmacologic challenge with a class I antiarrhythmic agent confirms the diagnosis, in conjunction with at least one clinical diagnostic criterion reflecting documented ventricular arrhythmias, a positive family history of SCD or BS, or arrhythmiarelated symptoms.54 The disease has autosomal dominant inheritance; to date, mutations in eight genes have been linked to BS,55-60 identified in up to 30% of patients, most affecting SCN5A.53 Patients are predominantly male, up to 83% in most series.61-67 Diagnosis is made and cardiac events occur mainly in the fourth decade of life,3,53,63-65 although cardiac arrest has been reported in neonates and children.62,63,68 Fever is a predisposing factor for cardiac arrest in the BS patient.68-72 RISK STRATIFICATION There is an ongoing controversy about risk stratification in BS. All groups agree that patients who recover from an episode of SCD are at high risk of repeating a fatal or near-fatal arrhythmic event (17%-62% at follow-up of 24-40 months)62,63,65 and should receive an ICD.1 However, the best management of patients without a history of SCD remains unclear, specifically asymptomatic patients. Brugada et al.63,64 described a high rate of events in patients with previous syncope (19%) and even in asymptomatic patients (8%) after mean follow-up of 24 months, and inducibility during EPS and previous syncope were independent predictors of cardiac events. Giustteto et al.66 emphasized the



role of symptoms as predictors of future cardiac events in 136 consecutive BS patients, supporting the role of EPS as a valuable tool for risk stratification. However, Priori et al.,62 Eckardt et al.,65 and more recently Probst et al.67 found that the incidence of cardiac events was much lower, and inducibility in EPS did not prove useful as a predictor of future arrhythmic events. Current guidelines state that the use of EPS for risk stratification in asymptomatic BS patients with spontaneous type 1 ECG is a class IIb indication. Importantly, with low event rates and relative short follow-up in patients with diseases that carry lifelong risk of arrhythmias, it is difficult to draw definitive conclusions about the predictive value of any test. The role of EPS for risk stratification in BS will likely remain undefined until prospective data are obtained with a uniform protocol in a large population with adequate follow-up. CURRENT THERAPEUTIC RECOMMENDATIONS In 2002 and 2005, first and second consensus meetings on Brugada syndrome defined diagnostic criteria, risk assessment, and therapeutic approach. However, current guidelines have evolved from the first to the second consensus. The implantation of an ICD is considered a class I indication only in BS patients for secondary prevention, and a class IIa indication only in those with spontaneous type 1 ECG and syncope, or documented VT that did not result in cardiac arrest. Quinidine has proved useful in BS patients with ICD and frequent shocks.73 It is also effective in episodes of electrical storm,74 a class IIb indication.1 Some studies show that quinidine in BS patients with inducible VF may render the EPS noninducible for sustained ventricular arrhythmias.75-77 Isoproterenol is also indicated in patients with BS and electrical storm74,78 (class IIa indication).1 Other pharmacologic options are currently being investigated.79-82

Catecholaminergic Polymorphic Ventricular Tachycardia Catecholaminergic polymorphic ventricular tachycardia (CPVT) is considered one of the most malignant channelopathies. Clinical manifestations include syncope and SCD triggered by adrenergic stimuli (exercise, emotion) from ventricular arrhythmias: bidirectional VT (35% of cases) and polymorphic VT (PVT), which sometimes degenerate into VF. Symptoms often begin early in life (age 7-9 years), and by age 40, up to 80% of patients have developed symptoms.83 Overall mortality without treatment is 30% to 50%.84 The diagnosis of CPVT is often missed or delayed up to 2 years after the first symptom, a result of the usually normal resting ECG and the absence of structural heart disease among these patients. A high degree of suspicion is required to achieve diagnosis. The main diagnostic tool is an exercise test, which allows reproducible progressive worsening of ventricular arrhythmias as the workload increases, from isolated ventricular extrasystoles to bidirectional VT, PVT, or VF, typically starting at 110 to 130 bpm, which gradually disappear when exercise stops. Holter recordings are useful in patients of syncope triggered by emotions and in children. Main differential diagnoses are LQT1 (patients also present with syncope triggered by physical exertion, but rarely with arrhythmias during exercise testing) and arrythmogenic right ventricular cardiomyopathy. To date, mutations in two genes have been linked to CPVT. RyR2 (encoding cardiac receptor of ryanodine)85 and CASQ2 (calsequestrin 2)86 are involved in intracellular management of Ca2+ in the myocardium.87,88 Mutations in both genes result in a cytosolic Ca2+ overload from the sarcoplasmic reticulum in the myocytes, giving rise to delayed afterdepolarizations (DADs). During β-adrenergic stimulation, DADs increase in number and magnitude and may trigger multiple action potentials, resulting in symptomatic ventricular arrhythmias. Mutations in RyR2 account for 50% to 55% of genotyped CPVT patients,89 with autosomal dominant inheritance and mean penetrance of 83%.90 Mutations in CASQ2 represent only 5% to 10% of patients, with autosomal recessive inheritance.

17  ICD Therapy in Channelopathies

385

RISK STRATIFICATION Current risk stratification is based on limited data because the number of patients identified with CPVT is low. The largest published series includes 101 patients,83 estimated prevalence of CPVT is 1 : 10,000, and available follow-up periods are short. As in other channelopathies, family history of SCD has not proved a predictive factor for cardiac events in CPVT. The baseline ECG is not useful as a diagnostic or prognostic tool. The natural history does not differ among CPVT patients with or without identified mutations or among patients with RyR2- and CASQ2-related mutations. Silent mutation carriers (asymptomatic, with no arrhythmias at exercise testing or on Holter monitoring) present a similar event rate to symptomatic patients.83 Neither gender seems to have a higher risk of cardiac events or SCD. EPS is not useful to diagnose or evaluate risk of cardiac events, because arrhythmias in CPVT patients are usually not inducible. Young age at diagnosis, history of ACA, and absence of β-blocker therapy have been identified as independent predictors of fatal or near-fatal cardiac events. Syncope before diagnosis did not identify patients at higher risk for cardiac events; however, these results may be biased because most patients with a diagnosis of CPVT and syncope were receiving β-blockers, resulting in a significant reduction of cardiac events and SCD.83 CURRENT THERAPEUTIC RECOMMENDATIONS Exercise testing is the most useful tool for diagnosis of CPVT because the ventricular arrhythmias are highly reproducible with exercise. It is also of value to titrate the dose of β-blockers. All patients diagnosed with CPVT must be treated with β-blockers; asymptomatic gene carriers show a similar rate of arrhythmic events to symptomatic patients.83 Patients who recovered from an episode of SCD are considered at high risk of cardiac events, and ICD implantation plus β-blockers for secondary prevention are mandatory. Patients with complex ventricular arrhythmias or symptoms despite full doses of β-blockers are also candidates for ICD (class IIa indication). Some reports suggest that the use of Ca2+ antagonists (in combination with β-blockers)91 and left cardiac sympathetic denervation may be useful in patients with recurrent ventricular arrhythmias despite full-dose β-blockers and in those with ICD and electrical storm.92

  General Considerations Correct risk stratification and treatment in patients with cardiac channelopathies is challenging. Some patients are at risk of fatal or nearfatal arrhythmias at a very young age, and all efforts should be directed to avoid these events. Table 17-1 summarizes current indications for ICD implantation, according to the American College of Cardiology/ American Heart Association (ACC/AHA) Task Force and the European Society of Cardiology (ESC) guidelines.1 ICD therapy has proved the most effective tool to prevent arrhythmic SCD,22 and its indication in high-risk patients is clearly justified (Fig. 17-1), especially considering the cumulative increased risk of very young patients who present for primary or secondary prevention. However, it is important to highlight that ICD therapy does have associated complications. Some series of BS patients with an ICD reported low rates of appropriate shocks (8%-15%; median follow-up, 45 months; annual appropriate discharge rate, 2.6%) and high rates of complications (28%), including inappropriate shocks (20%-36%), which often greatly exceeded (2-2.5 times) the rate of appropriate shocks.93-95 However, some studies of LQTS patients may have promoted ICD use based on incidence of ICD shock delivery, considering “appropriate ICD therapy” equivalent to SCD, with resulting rates of “livesaving therapies” higher than the expected mortality for the disease. In randomized trials for primary and secondary prevention of SCD in LQTS patients, the number of appropriate shocks consistently exceeded the sudden death rate in the control group by 2 : 1. Because most TdP episodes terminate spontaneously, some of those “appropriate ICD shocks” may

386

TABLE

17-1 

SECTION 2  Clinical Concepts

Indications for ICD Therapy in Patients with Cardiac Channelopathies*

Channelopathy Long QT syndrome (LQTS) Short QT syndrome (SQTS) Brugada syndrome (BS) CPVT

Class I Class IIa Class IIb Previous aSCD (in Syncope and/or documented VT while LQT2, LQT3 (possibly associated with higher risk combination with BB) taking BB (in combination with BB) of SCD; in combination with BB) Management of these patients is still poorly defined, (no recommendations in current guidelines about ICD implantation). Previous aSCD Syncope and spontaneous type 1 BS Documented VT that has not resulted in SCD Previous aSCD (in Syncope and/or documented sustained VT combination with BB) while taking BB (in combination with BB)

Data from Zipes DP, Camm AJ, Borggrefe M, et al: ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation 114:e385-e484, 2006. *Class I indicates clear evidence that the procedure/treatment is beneficial, useful, and effective; Class II, conflicting evidence about usefulness/efficacy; Class IIa, weight of evidence in favor of usefulness/efficacy; Class IIb, usefulness/efficacy less well established. aSCD, Aborted SCD; BB, beta-adrenergic blockers; CPVT, catecholaminergic polymorphic ventricular tachycardia; ICD, implantable cardioverter-defibrillator; SCD, sudden cardiac death; VT, ventricular tachycardia.

have been inappropriate, treating a ventricular arrhythmia that would have terminated spontaneously.36-39 Other studies also showed excellent response to β-blocker therapy (especially in LQT1) when patients were fully compliant and avoided QT-prolonging medications.96

Antibradycardia Therapy in Long QT Syndrome Most episodes of TdP in congenital LQTS are preceded by “short-longshort” sequences. Therefore, antibradycardia therapy was proposed in these patients to avoid sudden increases in R-R intervals, which may be arrhythmogenic. The simplest way to avoid pauses when the patient

carries a pacemaker or ICD is to increase the lower rate limit. Different groups suggest programming LRL above 70 bpm,32 between 70 and 80 bpm,13 or at 80 bpm or higher97 in adults diagnosed with LQTS, increasing this value for short periods when the patient is known to be at increased risk for developing TdP (e.g., postpartum period, surgical procedures). Maintenance of higher LRL for long periods, however, may lead to tachycardia-induced cardiomyopathy. Programming LRL of 70 to 80 bpm will result in permanent pacing in these patients, who often present with basal sinus bradycardia and are receiving β-blockers. Most LQTS patients have normal AV conduction, and ventricular pacing may increase dispersion of repolarization (vs. atrial pacing) by increasing the dispersion of activation time (dispersion of repolarization = dispersion of activation time + difference in

Figure 17-1  Ventricular fibrillation (VF) in patient with Brugada syndrome, effectively detected and treated with 31-J shock delivered by singlechamber ICD. VP, Ventricular-paced event; VR, ventricular rate; VS, ventricular-sensed event (outside the tachycardia zone).



17  ICD Therapy in Channelopathies

action potential duration at different areas of the myocardium). Thus the preferred pacing mode is DDD, with a long AV interval, resulting in permanent pacing of the atria, and conducted to the ventricles by the normal conduction system. This is why double-chamber ICDs are preferred in high-risk LQTS patients. Avoidance of ventricular pacing also saves battery power, increasing the working life of the ICD. To prevent pauses in LQTS patients through pacing, other antibradycardia parameters of the ICD should be correctly programmed, as follows98: 1. Careful programming to avoid failure of capture and oversensing (e.g., T wave). 2. All features that allow heart rate inferior to programmed LRL (e.g., hysteresis, sleep function, rate hysteresis) search should be programmed off. 3. The “+ post-ventricular atrial refractory period [PVARP] on premature ventricular complex [PVC]” algorithm, designed to avoid endless-loop tachycardia if a PVC is conducted retrograde to the atrium by increasing the PVARP, should be programmed off. 4. Sudden termination of pacemaker-mediated tachycardia (PMT) by any PMT algorithm may trigger torsades de pointes (TdP), unless combined with rate smoothing. 5. Rate-smoothing algorithms have two programmable features: ratesmoothing down (RSD) and rate-smoothing up (RSU). • When RSD is programmed on, the R-R interval cannot increase by more than a programmed percentage of the previous cycle. If a PVC occurs, provoking a “short cycle” (R-R1 interval), the next paced R-R interval (R-R2) will be faster than the LRL: R-R1 interval plus a stipulated percentage of R-R1 interval (x, usually 9%-15%). The subsequent R-R intervals will increase in the same way (R-R3 interval = R-R2 interval + x% of R-R2 interval, and so on), progressively decreasing pacing rate until LRL is reached, and avoiding post-extrasystolic pauses. Also, pacing needs to be avoided on the QT interval of the PVC (which may also trigger TdP), by programming a relatively long upper-rate interval (500 msec), or its equivalent, a long upper-rate limit (120-130 bpm). • RSU determines the maximal shortening of consecutive cycles and therefore should be programmed off. 6. Rate-drop response, an algorithm design to prevent vasovagal syncope, may cause TdP because it does not prevent, but rather is activated by, pauses. This results in high-frequency pacing after a short-long cycle, capable of provoking T-wave alternans and tachycardia-dependent TdP. Thus, rate-drop response should be programmed off.

Complications Implantable cardioverter-defibrillators have several disadvantages, especially in patients with channelopathies who have a similar profile: young, long-term ICD therapy, and multiple device replacements, as well as longer life expectancy after implantation. IMPLANTATION Complications derived from implantation include bleeding, hematoma, pneumothorax (1%-2% of patients), cardiac tamponade (<0.5%), and pericarditis of acute or late presentation. Lead displacement may lead to inappropriate ICD therapy and inability to convert a true VT or VF; this complication occurs more often in dual-chamber devices. Death (≤0.1%) is caused by cardiac perforation or defibrillation testing and refractory VF or development of pulseless electrical activity. Patients with channelopathies usually do not have comorbidities, and their risk with single implantation is low. However, their cumulative implantation risk is high with multiple device (and possibly lead) replacements. The reported overall risk of any early complication after device implant was 6.7%, with 4.9% of patients requiring an invasive treatment; rate of late procedure-related complications was 3.1%.99 Diagnosis of implant complications requires a high index of suspicion.

387

Routine examination after implantation should include physical examination, chest radiograph, and device interrogation. INFECTION Pocket infection and device infection are some of the most severe complications related to ICD implantation, requiring aggressive and expensive treatment: prolonged in-hospital antibiotic administration and usually surgical explantation of the device. Identified risk factors for device infections in patients with channelopathies include multiple implant procedures (up to fivefold increased risk)100,101 and young age at implantation,102 especially during childhood. Lead and infection complications were more prevalent in children, doubling the incidence of device infection in patients under 40 versus over age 40.103 Evidence also indicates that ICDs become infected more frequently than pacemakers.104,105 INAPPROPRIATE SHOCKS Inappropriate shocks are defined as shocks delivered by the ICD for a non-VT/VF rhythm. Identified causes of inappropriate shocks are common in patients with channelopathies, including sinus tachycardia (Fig. 17-2); atrial tachyarrhythmias (Fig. 17-3), found in up to 30% of BS patients,53 in 70% of SQTS patients, and in CPVT patients; and T-wave oversensing, especially in SQTS. Young patients may lead more active physical lives and inadvertently damage their leads, causing inappropriate shocks by sensing artifacts (“noise”) or myopotentials. Lead failures, which cause one third to one half of inappropriate shocks in younger patients, are more frequent in children than adults.102,106-108 In adults, the lead failure rate reaches 2% to 3% in short-term follow-up, versus a 10-fold rate among the pediatric population. There have been reports of a high rate of lead failure beyond 10 years after implantation (up to 20% cumulative risk), which is relevant in this population, who have a long survival expectation (especially after ICD implantation).109 The incidence of inappropriate shocks in young patients is high: 25% after 16-month follow-up.106 Reported rate of inappropriate shocks in BS patients is 20% at 38 months and 36% at 54 months.94 Inappropriate shocks leading to cardiac arrest or SCD by triggering VT or VF are extremely rare. Even if these do not trigger fatal or near-fatal arrhythmias, inappropriate shocks have negative consequences on the quality of life of these patients.95,110 In CPVT patients, an important concern is electrical storms, which may lead to death secondary to exhaustion of therapies by the ICD after shocks (appropriate and inappropriate).111 Inappropriate shocks after sinus tachycardia or supraventricular arrhythmias cause increased release of endogenous catecholamines, leading to polymorphic VT and more shocks.112 The patient also may receive an inadequate shock for nonsustained ventricular tachycardia (NSVT), which is common in patients with channelopathies (Fig. 17-4). Special care must be taken during programming the ICD to avoid treating NSVT (see Strategies to Avoid Complications). DEVICE DEFECTS Defects in ICDs mainly result from lead failure, as well as generator failure, and may lead to inappropriate shocks or catastrophic failure to deliver needed shocks. Both lead and generator failure may be detected by abnormal electrical parameters at routine device check or through symptoms. Remote monitoring may increase detection of these complications. System failure is inherent in all biomedical products, and patients should be informed appropriately. RISK OF NEVER USING DEVICE In patients with no myocardial disease, the percentage of surviving patients in the “never used device” category may remain high, because death from heart failure is low or completely unexpected.53,94 In patients with BS and LQTS, mortality was near or at 0%, and survival without

388

SECTION 2  Clinical Concepts

Figure 17-2  Sinus tachycardia during strenuous exercise in young patient with Brugada syndrome and dual-chamber ICD. Ventricular rate (VR) exceeds ventricular fibrillation (VF) rate cutoff of 192 bpm (green arrow), resulting in inappropriate detection (blue arrow) and shock delivery (red arrow). SVT, Supraventricular tachycardia; AR, atrial rate; AS, atrial-sensed event.



17  ICD Therapy in Channelopathies

389

Figure 17-3  Inappropriate shock for atrial fibrillation in patient with Brugada syndrome and single-chamber ICD. Ventricular rate (VR) reaches ventricular fibrillation (VF) cutoff rate zone (blue arrow), a diagnostic reading of VF occurs (green arrow), and the patient receives an inappropriate high-voltage shock (HV; red arrow) that does not convert to sinus rhythm. Misdiagnosis of VF continues seconds after the shock (black arrow), leading to more inappropriate shocks (not shown). F-FV, Ventricular fibrillation; FS, fibrillation-sensed event; T, fast ventricular tachycardia zone; T2, slow ventricular tachycardia zone.

appropriate discharge was 85% to 93%.39,94 In young patients, this poses a special problem; besides being exposed for decades to the risk of sudden death, they will also be exposed to the risks of ICD implantation, but accrue none of the benefit, which may fade over time.113 STRATEGIES TO AVOID COMPLICATIONS Table 17-2 summarizes suggested strategies to avoid complications with ICD therapy. Other recommendations include the following: 1. Absolute contraindication of competitive sports, and limitations on recreational sports,4 especially rowing, swimming, and weightlifting (higher risk of lead damage).

2. In patients with LQTS and CPVT, use of maximum tolerated doses of β-blockers is mandatory, as well as the addition of Ca2+ antagonists if polymorphic VT is not suppressible with β-blockers. 3. Aggressive treatment of supraventricular arrhythmias is also recommended, to avoid inappropriate shocks (including radiofrequency catheter ablation). 4. In patients with LQTS and CPVT with recurrent arrhythmic events despite full-dose β-blockers and Ca2+ antagonists, as well as in those with ICD and electrical storms, left cardiac sympathetic denervation should be considered a valuable option. 5. More durable leads, improved detection of lead fracture, and better algorithms to differentiate SVT are currently being developed.

390

SECTION 2  Clinical Concepts

A

Diverted Therapy

B

Diverted Change

Figure 17-4  A, Nonsustained polymorphic ventricular tachycardia (NSVT) in patient diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT), lasting 3.87 seconds. B, Self-limited CPVT in patient diagnosed with Brugada syndrome, lasting 3 seconds. CD, Charge delivered; CE, charging cycle end; Detct, ventricular fibrillation detected; Chrg, capacitor charging; FD, fibrillation detected; FV Rx 1 Defib, capacitor charging; V-Epsd, ventricular episode detected.

TABLE

17-2 

Tips to Avoid Complications with ICD Therapy in Patients with Channelopathies

Tips at Implantation 1.  IV antibiotic prophylaxis ≥30 min before surgery. 2. Lead implantation via cephalic vein. • Less risk of pneumothorax • Less risk of lead complications 3.  Favor implantation of one-lead ICDs (except in LQTS). 4. Optimize implantation site. • Maximum R-wave amplitude and • Minimum T-wave amplitude

Programming Tips 1.  Only one therapy zone (VF). 2. Program a high cutoff rate. • COR = 250 bpm – Age (yr) or • COR >210-220 bpm 3.  Program ATP during charge “on” (if available). 4. Increase detection window to avoid shocking NSVT, by increasing NID. • 18 of 24 or • 30 of 40

ATP, Antitachycardia pacing; IV, intravenous; LQTS; long QT syndrome; NID, number of intervals to detect; NSVT, nonsustained ventricular tachycardia; VF, ventricular fibrillation.

6. Because β-blockers are contraindicated in patients with Brugada syndrome, higher rate limits may be even more important in this group.

Conclusion Although “rare,” cardiac channelopathies constitute an increasingly important cause of sudden cardiac death in younger patients. Some of these patients are candidates for ICD therapy, to prevent fatal or nearfatal outcomes. A careful risk stratification scheme, pharmacologic therapy and lifestyle modifications tailored to the patient, and careful device programming help to decrease mortality in this patient population as well as the complications associated with these devices. Acknowledgment The authors want to thank Dr. Fadi Mansour, Dr. José María Tolosana, and Dr. Antonio Berruezo for helpful discussions of this chapter.

REFERENCES 1. Zipes DP, Camm AJ, Borggrefe M, et al: ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death), developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114:e385-e484, 2006.

2. Zareba W, Moss AJ, Schwartz PJ, et al: Influence of genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group. N Engl J Med 339:960-965, 1998. 3. Priori SG, Schwartz PJ, Napolitano C, et al: Risk stratification in the long QT syndrome. N Engl J Med 348:1866-1874, 2003. 4. Heidbuchel H, Corrado D, Biffi A, et al: Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II. Ventricular arrhythmias,

channelopathies and implantable defibrillators. Eur J Cardiovasc Prev Rehabil 13:676-686, 2006. 5. Jervell A, Lange-Nielsen F: Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 54:59-68, 1957. 6. Hedley PL, Jorgensen P, Schlamowitz S, et al: The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat 30:1486-1511, 2009. 7. Ward OC: A new familial cardiac syndrome in children. J Ir Med Assoc 54:103-106, 1964.



17  ICD Therapy in Channelopathies 8. Moss AJ, Schwartz PJ, Crampton RS, et al: The long QT syndrome: a prospective international study. Circulation 71:17-21, 1985. 9. Priori SG, Napolitano C, Schwartz PJ, et al: Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA 292:1341-1344, 2004. 10. Schwartz PJ, Priori SG, Spazzolini C, et al: Genotype-phenotype correlation in the long QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 103:89-95, 2001. 11. Jackman WM, Friday KJ, Anderson JL, et al: The long QT syndromes: a critical review, new clinical observations and a unifying hypothesis. Prog Cardiovasc Dis 31:115-172, 1988. 12. Roden DM, Lazzara R, Rosen M, et al: Multiple mechanisms in the long-QT syndrome: current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS. Circulation 94:1996-2012, 1996. 13. Moss AJ, Liu JE, Gottlieb S, et al: Efficacy of permanent pacing in the management of high-risk patients with long QT syndrome. Circulation 84:1524-1529, 1991. 14. Moss AJ, Schwartz PJ, Crampton RS, et al: The long QT syndrome: prospective longitudinal study of 328 families. Circulation 84:1136-1144, 1991. 15. Hobbs JB, Peterson DR, Moss AJ, et al: Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome. JAMA 296:1249-1254, 2006. 16. Sauer AJ, Moss AJ, McNitt S, et al: Long QT syndrome in adults. J Am Coll Cardiol 49:329-337, 2007. 17. Goldenberg I, Moss AJ, Peterson DR, et al: Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long QT syndrome. Circulation 117:2184-2191, 2008. 18. Goldenberg I, Moss AJ, Bradley J, et al: Long-QT syndrome after age 40. Circulation 117:2192-2201, 2008. 19. Spazzolini C, Mullally J, Moss AJ, et al: Clinical implications for patients with long QT syndrome who experience a cardiac event during infancy. J Am Coll Cardiol 54:832-837, 2009. 20. Goldenberg I, Mathew J, Moss AJ, et al: Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification. J Am Coll Cardiol 48:1047-1052, 2006. 21. Locati EH, Zareba W, Moss AJ, et al: Age- and sex-related differences in clinical manifestations in patients with congenital long QT syndrome: findings from the International LQTS Registry. Circulation 97:2237-2244, 1998. 22. Zareba W, Moss AJ, Locati EH, et al: Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol 42:103-109, 2003. 23. Tester DJ, Will ML, Haglund CM, Ackerman MJ: Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm 2:507-517, 2005. 24. Splawski I, Shen J, Timothy KW, et al: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 102:1178-1185, 2000. 25. Moss AJ, Shimizu W, Wilde AA, et al: Clinical aspects of type-1 long QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene. Circulation 115:2481-2489, 2007. 26. Jons C, Moss AJ, Lopes CM, et al: Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long QT syndrome. J Cardiovasc Electrophysiol 20:859-865, 2009. 27. Moss AJ, Zareba W, Kaufman ES et al: Increased risk of arrhythmic events in long QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel. Circulation 105:794-799, 2002. 28. Bhandari AK, Shapiro WA, Morady F, et al: Electrophysiologic testing in patients with the long QT syndrome. Circulation 71:63-71, 1985. 29. Kaufman ES, McNitt S, Moss AJ, et al: Risk of death in the long QT syndrome when a sibling has died. Heart Rhythm 5:831-836, 2008. 30. Goldenberg I, Moss AJ: Long QT syndrome. J Am Coll Cardiol 51:2291-2300, 2008. 31. Viskin S, Fish R, Zeltser D, et al: Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent? Heart 83:661-666, 2000. 32. Pinski SL, Eguia LE, Trohman RG: What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers. Pacing Clin Electrophysiol 25:16121615, 2002. 33. Dorostkar PC, Eldar M, Belhassen B, Scheinman MM: Longterm follow-up of patients with long-QT syndrome treated with beta-blockers and continuous pacing. Circulation 100:24312436, 1999. 34. Schwartz PJ, Priori SG, Cerrone M, et al: Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation 109:1826-1833, 2004. 35. Schwartz PJ, Spazzolini C, Crotti L: All LQT3 patients need an ICD: true or false? Heart Rhythm 6:113-120, 2009. 36. Groh WJ, Silka MJ, Oliver RP, et al: Use of implantable cardioverter-defibrillators in the congenital long QT syndrome. Am J Cardiol 78:703-706, 1996. 37. Etheridge SP, Sanatani S, Cohen MI, et al: Long QT syndrome in children in the era of implantable defibrillators. J Am Coll Cardiol 50:1335-1340, 2007.

38. Goel AK, Berger S, Pelech A, Dhala A: Implantable cardioverterdefibrillator therapy in children with long QT syndrome. Pediatr Cardiol 25:370-378, 2004. 39. Monnig G, Kobe J, Loher A, et al: Implantable cardioverterdefibrillator therapy in patients with congenital long QT syndrome: a long-term follow-up. Heart Rhythm 2:497-504, 2005. 40. Gussak I, Brugada P, Brugada J, et al: Idiopathic short QT interval: a new clinical syndrome? Cardiology 94:99-102, 2000. 41. Gaita F, Giustetto C, Bianchi F, et al: Short QT syndrome: a familial cause of sudden death. Circulation 108:965-970, 2003. 42. Brugada R, Hong K, Dumaine R, et al: Sudden death associated with short QT syndrome linked to mutations in HERG. Circulation 109:30-35, 2004. 43. Bellocq C, van Ginneken AC, Bezzina CR, et al: Mutation in the KCNQ1 gene leading to the short QT interval syndrome. Circulation 109:2394-2397, 2004. 44. Priori SG, Pandit SV, Rivolta I, et al: A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 96:800-807, 2005. 45. Antzelevitch C, Pollevick GD, Cordeiro JM, et al: Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 115:442-449, 2007. 46. Giustetto C, Di MF, Wolpert C, et al: Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur Heart J 27:2440-2447, 2006. 47. Gaita F, Giustetto C, Bianchi F, et al: Short QT syndrome: pharmacological treatment. J Am Coll Cardiol 43:1494-1499, 2004. 48. Maury P, Extramiana F, Sbragia P, et al: Short QT syndrome: update on a recent entity. Arch Cardiovasc Dis 101:779-786, 2008. 49. Gaita F, Giustetto C, Bianchi F, et al: Short QT syndrome: a familial cause of sudden death. Circulation 108:965-970, 2003. 50. Gaita F, Giustetto C, Bianchi F, et al: Short QT syndrome: pharmacological treatment. J Am Coll Cardiol 43:1494-1499, 2004. 51. Wolpert C, Schimpf R, Giustetto C, et al: Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol 16:54-58, 2005. 52. Schimpf R, Wolpert C, Bianchi F, et al: Congenital short QT syndrome and implantable cardioverter-defibrillator treatment: inherent risk for inappropriate shock delivery. J Cardiovasc Electrophysiol 14:1273-1277, 2003. 53. Antzelevitch C, Brugada P, Borggrefe M, et al: Brugada syndrome: report of the Second Consensus Conference, endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 111:659-670, 2005. 54. Wilde A, Antzelevitch C, Borggrefe M, et al: Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation 106:2514-2519, 2002. 55. Chen Q, Kirsch GE, Zhang D, et al: Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 392:293-296, 1998. 56. London B, Michalec M, Mehdi H, et al: Mutation in glycerol-3phosphate dehydrogenase 1-Like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation 116:2260-2268, 2007. 57. Watanabe H, Koopmann TT, Le SS, et al: Sodium channel beta-1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest 118:22602268, 2008. 58. Delpon E, Cordeiro JM, Nunez L, et al: Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol 1:209-218, 2008. 59. Hu D, Barajas-Martinez H, Burashnikov E, et al: A mutation in the beta-3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ Cardiovasc Genet 2:270-278, 2009. 60. Medeiros-Domingo A, Tan BH, Crotti L, et al: Gain-of-function mutation, S422L, in the KCNJ8-encoded cardiac K ATP channel Kir6.1 as a pathogenic substrate for J wave syndromes. Heart Rhythm ••:••2010. 61. Benito B, Sarkozy A, Mont L, et al: Gender differences in clinical manifestations of Brugada syndrome. J Am Coll Cardiol 52:15671573, 2008. 62. Priori SG, Napolitano C, Gasparini M, et al: Natural history of Brugada syndrome: insights for risk stratification and management. Circulation 105:1342-1347, 2002. 63. Brugada J, Brugada R, Antzelevitch C, et al: Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 105:73-78, 2002. 64. Brugada J, Brugada R, Brugada P: Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation 108:3092-3096, 2003. 65. Eckardt L, Probst V, Smits JPP, et al: Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 111:257-263, 2005. 66. Giustetto C, Drago S, Demarchi PG, et al: Risk stratification of the patients with Brugada type electrocardiogram: a communitybased prospective study. Europace 11:507-513, 2009. 67. Probst V, Veltmann C, Eckardt L, et al: Long-term prognosis of patients diagnosed with Brugada syndrome: results from the FINGER Brugada Syndrome Registry. Circulation 121:635-643, 2010. 68. Brugada P, Brugada J: Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical

391

and electrocardiographic syndrome—a multicenter report. J Am Coll Cardiol 20:1391-1396, 1992. 69. Dumaine R, Towbin JA, Brugada P, et al: Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res 85:803809, 1999. 70. Mok NS, Priori SG, Napolitano C, et al: A newly characterized SCN5A mutation underlying Brugada syndrome unmasked by hyperthermia. J Cardiovasc Electrophysiol 14:407-411, 2003. 71. Saura D, Garcia-Alberola A, Carrillo P, et al: Brugada-like electrocardiographic pattern induced by fever. Pacing Clin Electrophysiol 25:856-859, 2002. 72. Ortega-Carnicer J, Benezet J, Ceres F: Fever-induced ST-segment elevation and T-wave alternans in a patient with Brugada syndrome. Resuscitation 57:315-317, 2003. 73. Hermida JS, Denjoy I, Clerc J, et al: Hydroquinidine therapy in Brugada syndrome. J Am Coll Cardiol 43:1853-1860, 2004. 74. Maury P, Hocini M, Haissaguerre M: Electrical storms in Brugada syndrome: review of pharmacologic and ablative therapeutic options. Indian Pacing Electrophysiol J 5:25-34, 2005. 75. Belhassen B, Glick A, Viskin S: Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation 110:1731-1737, 2004. 76. Belhassen B, Glick A, Viskin S: Excellent long-term reproducibility of the electrophysiologic efficacy of quinidine in patients with idiopathic ventricular fibrillation and Brugada syndrome. PACE 32:294-301, 2009. 77. Belhassen B, Viskin S, Fish R, et al: Effects of electrophysiologicguided therapy with class IA antiarrhythmic drugs on the longterm outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome. J Cardiovasc Electrophysiol 10:1301-1312, 1999. 78. Maury P, Couderc P, Delay M, et al: Electrical storm in Brugada syndrome successfully treated using isoprenaline. Europace 6(2):130-133, 2004. 79. Antzelevitch C: Brugada syndrome. PACE 29:1130-1159, 2006. 80. Yan GX, Antzelevitch C: Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 100:1660-1666, 1999. 81. Tsuchiya T, Ashikaga K, Honda T, Arita M: Prevention of ventricular fibrillation by cilostazol, an oral phosphodiesterase inhibitor, in a patient with Brugada syndrome. J Cardiovasc Electrophysiol 13:698-701, 2002. 82. Abud A, Bagattin D, Goyeneche R, Becker C: Failure of cilostazol in the prevention of ventricular fibrillation in a patient with Brugada syndrome. J Cardiovasc Electrophysiol 17:210-212, 2006. 83. Hayashi M, Denjoy I, Extramiana F, et al: Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 119:2426-2434, 2009. 84. Cerrone M, Napolitano C, Priori SG: Catecholaminergic polymorphic ventricular tachycardia: a paradigm to understand mechanisms of arrhythmias associated to impaired Ca2+ regulation. Heart Rhythm 6:1652-1659, 2009. 85. Priori SG, Napolitano C, Tiso N, et al: Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103:196-200, 2001. 86. Lahat H, Eldar M, Levy-Nissenbaum E, et al: Autosomal recessive catecholamine- or exercise-induced polymorphic ventricular tachycardia: clinical features and assignment of the disease gene to chromosome 1p13-21. Circulation 103:2822-2827, 2001. 87. Di Barletta MR, Viatchenko-Karpinski S, Nori A, et al: Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia. Circulation 114:1012-1019, 2006. 88. Marks AR, Priori S, Memmi M, et al: Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia. J Cell Physiol 190:1-6, 2002. 89. Priori SG, Napolitano C, Memmi M, et al: Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 106:69-74, 2002. 90. Napolitano C, Priori SG, Bloise R: Catecholaminergic polymorphic ventricular tachycardia. In Pagon RA, Bird TD, Dolan CR, Stephens K, eds: GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2004. 91. Rosso R, Kalman JM, Rogowski O, et al: Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 4:1149-1154, 2007. 92. Wilde AA, Bhuiyan ZA, Crotti L, et al: Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia. N Engl J Med 358:2024-2029, 2008. 93. Sacher F, Probst V, Iesaka Y, et al: Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study. Circulation 114:2317-2324, 2006. 94. Sarkozy A, Boussy T, Kourgiannides G, et al: Long-term follow-up of primary prophylactic implantable cardioverterdefibrillator therapy in Brugada syndrome. Eur Heart J 28:334344, 2007. 95. Rosso R, Glick A, Glikson M, et al: Outcome after implantation of cardioverter-defibrillator in patients with Brugada syndrome: a multicenter Israeli study (ISRABRU). Isr Med Assoc J 10:435439, 2008. 96. Vincent GM, Schwartz PJ, Denjoy I, et al: High efficacy of betablockers in long QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to the occurrence of

392

SECTION 2  Clinical Concepts

beta-blocker treatment “failures.” Circulation 119:215-221, 2009. 97. Viskin S, Alla SR, Barron HV, et al: Mode of onset of torsade de pointes in congenital long QT syndrome. J Am Coll Cardiol 28:1262-1268, 1996. 98. Viskin S: Cardiac pacing in the long QT syndrome: review of available data and practical recommendations. J Cardiovasc Electrophysiol 11:593-600, 2000. 99. Kiviniemi MS, Pirnes MA, Eranen HJ, et al: Complications related to permanent pacemaker therapy. Pacing Clin Electrophysiol 22:711-720, 1999. 100. Harcombe AA, Newell SA, Ludman PF, et al: Late complications following permanent pacemaker implantation or elective unit replacement. Heart 80:240-244, 1998. 101. Catanchin A, Murdock CJ, Athan E: Pacemaker infections: a 10-year experience. Heart Lung Circ 16:434-439, 2007. 102. Link MS, Hill SL, Cliff DL, et al: Comparison of frequency of complications of implantable cardioverter-defibrillators in children versus adults. Am J Cardiol 83:263-266, 1999.

103. Klug D, Vaksmann G, Jarwe M, et al: Pacemaker lead infection in young patients. Pacing Clin Electrophysiol 26:1489-1493, 2003. 104. Voigt A, Shalaby A, Saba S: Rising rates of cardiac rhythm management device infections in the United States: 1996 through 2003. J Am Coll Cardiol 48:590-591, 2006. 105. Uslan DZ, Sohail MR, St Sauver JL, et al: Permanent pacemaker and implantable cardioverter-defibrillator infection: a population-based study. Arch Intern Med 167:669-675, 2007. 106. Alexander ME, Cecchin F, Walsh EP, et al: Implications of implantable cardioverter-defibrillator therapy in congenital heart disease and pediatrics. J Cardiovasc Electrophysiol 15:72-76, 2004. 107. Korte T, Koditz H, Niehaus M, et al: High incidence of appropriate and inappropriate ICD therapies in children and adolescents with implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 7:924-932, 2004. 108. Eicken A, Kolb C, Lange S, et al: Implantable cardioverterdefibrillator (ICD) in children. Int J Cardiol 107:30-35, 2006.

109. Kleemann T, Becker T, Doenges K, et al: Annual rate of transvenous defibrillation lead defects in implantable cardioverterdefibrillators over a period of >10 years. Circulation 115:24742480, 2007. 110. DeMaso DR, Lauretti A, Spieth L, et al: Psychosocial factors and quality of life in children and adolescents with implantable cardioverter-defibrillators. Am J Cardiol 93:582-587, 2004. 111. Mohamed U, Gollob MH, Gow RM, Krahn AD: Sudden cardiac death despite an implantable cardioverter-defibrillator in a young female with catecholaminergic ventricular tachycardia. Heart Rhythm 3:1486-1489, 2006. 112. Pizzale S, Gollob MH, Gow R, Birnie DH: Sudden death in a young man with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol 19:1319-1321, 2008. 113. Sherrid MV, Daubert JP: Risks and challenges of implantable cardioverter-defibrillators in young adults. Prog Cardiovasc Dis 51:237-263, 2008.

18  18

Pediatric Pacing and Defibrillator Use GERALD A. SERWER  |  IRA SHETTY

Permanent cardiac pacemakers have been used in children for 60

years.1 Technologic advances have increased pediatric use through customized pacemaker design and a smaller, longer-lasting generator. Although many aspects of pediatric pacing are similar to adult pacing, children are not only physically smaller than adults, but also have different underlying cardiac diseases. Life circumstances differ, and pediatric patients face longer lifetime therapy. Therefore, differences exist not only in selection of the optimal pacing system, but also in implantation techniques, programming considerations, and follow-up methods. With advances in medical and surgical therapy for structural heart disease, longevity is increasing, and patients with congenital heart disease are reaching adulthood. This chapter, although focused on pediatric pacing, pertains to any patient with structural heart disease. Adolescent and adult patients often have undergone surgical repair and present unique problems closer to those of a younger child than an adult with acquired cardiac disease. Our center provides care and devices for patients ranging from newborns through middle-age adults. Much of the experience cited here includes these adult patients, and many of the therapy decisions presented apply to structural congenital disease in all age groups. Few pacemakers and a limited number of electrodes are designed specifically for patients with congenital heart disease and tend to be “scaled down” versions of existing units. Therefore, the manner in which devices are used often requires modifications from the standard practice employed in patients with acquired disease. This chapter discusses the unique aspects of this patient group, specifically focusing on pacing indications, electrode and generator selection, implantation techniques, follow-up considerations and methods, and lifestyle adjustments, particularly in children, necessitated by implantation. Most discussion in other chapters applies equally well to this patient group, and this chapter offers a supplement rather than a replacement for similar material. The expanding use of implantable cardioverter-defibrillators (ICDs), antitachycardia pacing, and cardiac resynchronization therapy in patients with congenital heart disease is also discussed. Although limited, such devices are finding increasing utility, especially as their size decreases and newer features are developed. Because of differing causes of tachyarrhythmias and ventricular dysfunction, as well as different cardiac anatomy, adjustments in their use must be considered in the patient with congenital heart disease.

Midwest Pediatric Pacemaker Registry Because the number of patients with congenital heart disease requiring pacemakers is small, a large study at one center is lacking. Therefore, conclusions are based on limited experience susceptible to statistical inaccuracies. To address this problem, the Midwest Pediatric Cardiology Society formed the Midwest Pediatric Pacemaker Registry (MPPR) in 1980. Member institutions submit data on patient demographics, pacing indication, associated structural cardiac disease, type of generator/electrode and threshold data at implantation, and device explantation data (Table 18-1). No long-term follow-up data are provided. Annual reports are presented to promote data submission and validity, address concerns about the types of data collected and the

methods used, and ensure uniformity among participating institutions. The Registry contains information on more than 1100 patients who have had implantations of more than 1500 pulse generators and more than 1600 electrodes. These data present a representative sample of current pacing practices among pediatric cardiologists and avoid the bias inherent in data obtained from a single institution. The data are obtained at implantation and at subsequent invasive electrode evaluation. Chronic follow-up data are confined to the date and reason that a generator or electrode was removed from service. Noninvasive electrode threshold data and reprogramming information after implantation are not collected. The Registry collects no ICD data. The MPPR provides much of the information in this chapter on pacing indications, device selection, and acute thresholds. However, registry data are less detailed and less well controlled than data from a single center. In larger centers, patient volume may not be sufficient to answer specific questions. Thus, some data are from our center.

Indications for Permanent Pacemaker Implantation SINUS NODE DYSFUNCTION Historically, the most common indication for pacemaker placement was surgically induced heart block. However, this has changed with improved surgical techniques and longer patient survival after cardiac surgery. Often occurring many years after surgical repair, the most common indication for cardiac pacing in patients with congenital heart disease is now sinus node dysfunction, or sick sinus syndrome. Since 2000, this indication has accounted for 40% to 60% of new implantations, compared with 20% to 25% during the previous decade. Most of these patients have undergone cardiac surgery many years earlier, usually involving extensive atrial procedures. The most common procedure is the atrial switch operation for transposition of the great arteries.2 The likelihood of these patients needing permanent pacing increases with time since surgery.3 Even though the use of this procedure for simple dextrotransposition of the great arteries is now rare, its use is increasing in more complex disease, such as levotransposition of the great arteries combined with the arterial switch procedure (“double switch”) to place the morphologic right ventricle in the pulmonary circuit and the morphologic left ventricle in the systemic circuit. With increased use of the Fontan procedure, or right-sided heart bypass, the incidence of sinus node dysfunction is increasing. The indications are similar to those for congenital complete heart block. In addition, the presence of tachyarrhythmias, with the subsequent risk for prolonged asystole after acute termination of the tachycardia, is also an indication for pacemaker implantation (Fig. 18-1). In patients with sinus node dysfunction after cardiac surgery, our practice is to recommend pacemaker implantation in all patients with a sleeping heart rate of less than 30 beats per minute (bpm) even in the absence of symptoms, a decreasing exercise tolerance with inadequate heart rate increase with exercise (see later discussion), or sinus pauses for longer than 3 to 4 seconds. The need for medications known to affect atrioventricular (AV) conduction for the control of tachyarrhythmias in these patients would also necessitate pacemaker placement.3

393

394

TABLE

18-1 

SECTION 2  Clinical Concepts

Midwest Pediatric Pacemaker Registry: Data Collection*

Information Patient

Generator

Electrode

Data Collected Identification (ID) number and institution Date of birth Date of initial implantation Pacing indication Associated structural cardiac disease Manufacturer and model Implantation date Programming at implantation Explantation date Programming at explantation Manufacturer and model Implantation site and route Pacing thresholds (multiple pulse widths) Sensing values (RMS amplitude, slew rate)

*Data are collected on all new patients entered in the Registry, all generators implanted and explanted, and all electrodes implanted, explanted, or invasively tested. RMS, Mean spontaneous waveform amplitude.

SURGICALLY INDUCED HEART BLOCK The second major indication for pacemaker implantation in children is surgically induced heart block, which classically has accounted for 30% to 40% of children undergoing pacemaker implantation.4-9 MPPR data show that the indication for initial pacemaker placement was surgically induced heart block in an average of 35% of patients before 2000 (Fig. 18-2). The percentage varies from year to year and reached a low of 20% in 2001-2005. There has been no definite downward trend since 2000, with the percentage remaining near 20%, although the underlying structural cardiac diseases in patients with surgically induced heart block have changed dramatically. Since 2000, surgical heart block has accounted for 15% to 25% of initial implantations. Most recent data from our center show that the incidence is 22% over the last 5 years. Most children acquiring surgical heart block in the last 5 years have had complex disease and have undergone complex surgical repairs. The surgical procedure resulting in the greatest incidence of heart block is the repair of atrioventricular septal defect, which has accounted for 17% of patients with surgical heart block since 1988. Table 18-2 lists the other common diagnoses associated with surgical heart block in the recent era. Currently, it is unusual for a child with an isolated ventricular septal defect (VSD) to acquire heart block; previously, this was not the case. Since 1988, VSD closure has accounted for only 14% of children with surgical complete heart block; atrial switch procedures (Mustard or Senning) for the correction of dextrotransposition of the great arteries have accounted for 12%. Other common lesions associated with surgical heart block are levotransposition of the great arteries, repair of tetralogy of Fallot, and aortic valvular replacement, which usually is associated with the resection of a subaortic obstruction. Surgical heart block can develop at the initial cardiac repair or later. In addition, the heart block acquired at repair may be temporary, with return of reliable AV conduction. For this reason, our current practice is to implant only temporary pacing electrodes at the initial surgery and to defer permanent pacemaker implantation for 10 to 14 days in the hope of a return of AV conduction. However, ventricular escape

TABLE

18-2 

Most Prevalent Structural Cardiac Defects Associated with Surgically Induced Complete Heart Block*

Defect Atrioventricular septal defects Isolated ventricular septal defect Dextrotransposition of the great arteries Levotransposition of the great arteries Tetralogy of Fallot Aortic valve replacement

Percentage of Cases 17 14 12 12 7 3

Data from Midwest Pediatric Pacemaker Registry. *The most common structural cardiac lesions associated with surgically induced heart block at the time of complete repair for children undergoing initial implantation since 1988.

rhythms are unstable, and no child with a permanent, surgically acquired complete heart block is discharged without a permanent pacemaker. Even in the hospital, all children are supported with an external pacemaker through temporary pacing wires placed at surgery until consistent AV conduction returns or a permanent pacemaker is inserted. Monitoring should consist of both electrocardiographic (ECG) monitoring and non-ECG monitoring, such as arterial pressure measurements or pulse oximetry. Many ECG monitors detect the pacing artifact and do not recognize the lack of capture with subsequent bradycardia or asystole. This is avoided by the use of a non-ECG method of detecting cardiac ejection, such as pulse oximetry.10 Late recovery of AV conduction can be seen even years after surgery. However, rarely does such recovery result in 100% conduction. Most patients who do recover some conduction will still rely on the pacemaker 30% to 50% of the time, with intact conduction the rest of the time. CONGENITAL COMPLETE HEART BLOCK The next most common indication for pacemaker implantation is congenital complete heart block. The cause of congenital heart block varies; an autoimmune mechanism is often implicated, with clinical or laboratory evidence of connective tissue disease in the mother.11 All mothers of infants with congenital heart block should have antibody determinations performed. Even children born to such mothers but with intact conduction at birth must be monitored for the development of heart block over time. Treatment of antibody-positive mothers with steroids during pregnancy has not been shown to alter outcomes

INCIDENCE OF SURGICAL HEART BLOCK BY YEAR 50 40 30 20 10 0 <1980

80–85

86–90

91–95

96–00

01–05

06–09

Year Figure 18-1  Electrocardiogram from a patient with sick sinus syndrome shows 1.5 seconds of asystole after acute termination of tachyarrhythmia. Long pauses can result in syncope and are indications for pacemaker implantation. Paper speed is 25 mm/sec.

Figure 18-2  Percentage of all children undergoing initial pacemaker implantation in a given period whose indication was surgically induced complete heart block. There has been no significant change in this percentage during the last 10 years. (Data from Midwest Pediatric Pacemaker Registry.)



18  Pediatric Pacing and Defibrillator Use ACTUARIAL ANALYSIS OF YEARS PACEMAKER FREE 100

Percent of patients remaining pacemaker free

90 80 70 60 50 40 30 20 10 0 0

5

10

15

20

Age (yrs) Figure 18-3  Actuarial analysis of months free from pacemaker need for children with congenital complete heart block and structurally normal hearts. By age 20 years, fewer than 30% of patients are pacemaker free. Brackets represent 1 standard error around the mean. (Data from Dorostkar P, Serwer CA, LeRoy S, Dick M II: Long-term course of children and young adults with congenital complete heart block. J Am Coll Cardial 21:295A, 1993.)

or reverse the development of heart block. Congenital heart block is also associated with specific forms of structural disease, particularly those involving abnormalities of the AV junction, such as levotransposition of the great arteries with AV discordance and atrial situs ambiguus.12 It is common for fetal heart block to “develop” in utero with intact conduction present in the young fetus and heart block developing at 20 to 30 weeks of gestation. Data from the MPPR indicate that 10% to 25% of patients have congenital heart block as the primary indication for permanent pacing. Most recent data from our center show that 17% of patients receiving pacemakers have congenital heart block. The age at which the pacing system is implanted varies, ranging from a few hours to more than 20 years. Most children with associated structural cardiac disease who need pacing before 1 year of age have congestive heart failure (CHF) requiring an increased heart rate for adequate therapy. The mortality rate in such children is also high, with 43% dying by 2 years of age.13 For children with structurally normal hearts and congenital heart block, the incidence of pacemaker implantation is lower in younger children but increases with age, associated with a gradually decreasing ventricular rate.14 The gradual and steady increase in the need for permanent pacing continues with advancing age, reaching 75% by age 20 years (Fig. 18-3). The need for permanent pacing results from the development of syncope, CHF, or increasing ventricular ectopy, often associated with prolongation of the corrected QT interval (QTc). Death is rare in children with no structural cardiac disease (only 5% by age 20) but can occur suddenly.

395

Current recommendations call for the implantation of a permanent pacemaker system whenever CHF is present. In addition, implantation is recommended if the average heart rate is less than 50 bpm in the awake child and 55 bpm in the infant, if there is a history of a syncopal or presyncopal event, if significant ventricular ectopy is present, or if there is exercise intolerance.15,16 However, symptoms of exercise intolerance can be difficult to elicit. Many children deny such symptoms, as do their parents, when in fact their exercise tolerance would be improved with permanent pacing. Many parents return after pacemaker implantation to relate that the activity level of their child has greatly increased. They are amazed at this change, because they did not believe that the child was significantly hindered before pacemaker implantation. Exercise testing is often useful as an indicator of the child’s exercise capabilities compared with those of a normal child. The physician should also periodically assess the child for increasing cardiac size by chest radiography and for decreasing cardiac function by echocardiography. The presence of either of these conditions should be considered an indication for permanent pacemaker placement. Some children with congenital complete heart block develop a tachydysrhythmia, specifically ventricular tachycardia (VT), which can be controlled only with permanent pacing.17 The maintenance of a minimal heart rate often suppresses the tendency toward ventricular ectopy, particularly during exercise. The development of tachyarrhythmias with the stress of exercise, even in children with otherwise asymptomatic disease, necessitates pacemaker implantation. Controversy surrounds the need for pacing in symptom-free older children with bradycardia of less than 50 bpm while asleep. This is not an absolute indication for pacemaker implantation. However, if bradycardias lower than 50 bpm are present, a detailed history and close follow-up are required to determine the need for pacemaker implantation. Although maternal antibody is associated with congenital heart block in the absence of structural disease, there is no known correlation with the need for or the timing of pacemaker placement. In addition, congenital heart block can be associated with the development of a dilated cardiomyopathy with or without pacing. The use of biventricular pacing in this group is discussed later with the indications for cardiac resynchronization therapy in children. OTHER INDICATIONS Patients with long QT syndrome and uncontrollable VT may also benefit from pacemaker placement, as well as those with intermittent complete heart block18 (Fig. 18-4). A chronic increase in heart rate shortens the QT interval and decreases the occurrence of VT. The combined use of pacing and an ICD may be even more efficacious, particularly with the advent of the dual-chamber ICD. Other indications for pacemaker placement reported in the MPPR include the need for control of atrial tachyarrhythmias unresponsive to pharmacologic therapy, second-degree heart block associated with symptoms, and concern about a sudden loss of AV conduction in patients receiving certain antiarrhythmic therapies known to interfere with AV conduction. Although such indications are rare, the clinician should not restrict pacemaker use to those children with complete

CHB

HR = 60

1:50.1P1

Figure 18-4  Recording from 24-hour ambulatory electrocardiogram showing a period of complete heart block (CHB) with acute bradycardia (between arrowheads) in a patient with tuberous sclerosis and cardiac rhabdomyomas. Paper speed is 25 mm/sec. HR, Heart rate (bpm).

396

SECTION 2  Clinical Concepts

Selection of the Appropriate Pacemaker System Many factors must be considered in the selection of the most appropriate pacemaker generator and electrode system. Unlike that in the adult patient, the 5-year patient survival rate after pacemaker implantation in children exceeds 70% (Fig. 18-5), and death is usually related to the underlying structural heart defect.8,21 Therefore, pacing may be needed for more than 50 years in the average child. This affects pacing choices, because the number of replacement generators and electrodes may be high. The average longevity of currently available pulse generators is only 5 years when all children are grouped together (Fig. 18-6). However, when children are divided into those younger and those older than 4 years at generator implantation, longevity is much different (Fig. 18-7). The generator half-life is 5 years for children younger than 4 at implantation and increases to 7 years for the older children. This is presumably a result of the higher heart rates present in younger patients, when the device is used in dual-chamber mode to track the

Survival (%)

100

100

Survival (%)

heart block. First-degree heart block and trifascicular block with no documented loss of AV conduction are not considered indications for pacemaker implantation.19 A relatively controversial indication for pacemaker placement is symptomatic hypertrophic obstructive cardiomyopathy with significant outflow tract obstruction. Although pacemaker placement is not effective in all children with this disorder, both hemodynamic and symptomatic improvements have been observed,20 with decreases in gradient and measures of diastolic performance. Generators used for this indication must allow programming of relatively short AV intervals and rate-adaptive AV intervals to maximize the QRS width and degree of preexcitation. Younger patients with more rapid heart rates may present insurmountable difficulties, and other therapies are probably indicated initially. When pacing is employed in this setting a dualchamber ICD should be used (see later). Categorization of pacing indications is helpful only as a general guide. Each patient must be carefully evaluated to determine the potential benefits from permanent pacing in light of the risks of implantation and the burden placed on the family and child for subsequent care. When all patients in need of pacing are considered together, again, the indication most often present is sinus node dysfunction. The largest group requiring pacing is those with dextrotransposition of the great arteries, most of whom have undergone an atrial switch procedure (Mustard or Senning) for sinus node dysfunction.

0 60

0

120

Months postimplantation Figure 18-6  Actuarial survival curve for generators using various battery types. Even for lithium-powered generators, only one half last 5 years. Blue squares, Current models using lithium batteries; purple triangles, models using mercury-zinc batteries; red triangles, models using mercury-silver batteries; yellow circles, models using rechargeable batteries. (From Serwer GA, Mericle JM: Evaluation of pacemaker pulse generator and patient longevity in patients aged 1 day to 20 years. Am J Cardiol 59:824, 1987.)

atrial rate, and the higher programmed lower rates used in younger children. Initially, epicardial electrodes used in the younger children contributed to higher current drain. With newer epicardial electrodes, this difference has largely disappeared. The average epicardial electrode lasts 7 years.22 With improvements in epicardial electrode design, it is hoped that this will increase. Although the average endocardial electrode’s longevity in children is significantly increased, it is still only slightly more than 10 years23 (Fig. 18-8). For the child undergoing an initial implantation at age 1 year, a minimum of nine electrode changes and 17 generator changes can be expected. The multiple procedures that will be needed and the effects of one on subsequent procedures must be considered. GENERATOR SELECTION The major factors to consider are the generator features that are of significant benefit to the individual child, such as antitachycardia pacing, special pacing modes, and diagnostic capabilities, together with battery capacity and projected generator longevity and size. Because newer generators are smaller than earlier ones, size is becoming less of a factor, although not all generators are the same size. Large generators not only create unsightly protuberances that can have negative psychological consequences, but also increase the risk for skin breakdown over the generator from its erosion or trauma to the skin over the generator, especially in the active child, with a subsequent infection leading to pacing system removal. GENERATOR MODE SELECTION

0 0

96

192

Months postimplantation Figure 18-5  Actuarial survival for pediatric patients after pacemaker implantation. Excellent patient longevity is demonstrated. Brackets represent 1 standard error around the estimate. (From Serwer GA, Mericle JM: Evaluation of pacemaker pulse generator and patient longevity in patients aged 1 day to 20 years. Am J Cardiol 59:824, 1987.)

The choices concerning pacing mode are related to single-chamber versus dual-chamber pacing and fixed-rate versus variable-rate pacing. In general, it has been our policy to avoid the use of fixed-rate pacing, except in situations in which sinus node and AV node function are intact most of the time, with the pacemaker serving only as a backup for those rare periods when such function is not adequate. This is often the situation when sinoatrial (SA) and AV node function is marginal and antiarrhythmic drugs are required. In addition, should a sudden rate drop occur during exercise, the lower rate of a fixed-rate generator may be inadequate to provide adequate cardiac output, and even in this patient, rate-variable programming is desired. Although cardiac output increases with exercise, even during fixedrate pacing (Fig. 18-9), this results from a large increase in stroke



18  Pediatric Pacing and Defibrillator Use

397

IMPLANT AGE <4 YEARS 100

Survival (%)

80 60 40 20 0 0

1

2

A

3

4

5

6

7

8

7

8

Years postimplantation IMPLANT AGE >4 YEARS 100

Survival (%)

80 60 40 20 0 0

1

2

B

3

4

5

6

Years postimplantation

Figure 18-7  Dual-chamber (DDD) generator longevity with the use of epicardial electrodes as a function of patient age at time of implantation. A, Life-table analysis of longevity when devices are implanted in children younger than 4 years. More than one half require replacement within 5 years. B, Longevity analysis when patient is older than 4 years at implant. Half-life has risen to 6.5 years, presumably because of the lower average heart rate in older children. ELECTRODE LONGEVITY CARDIAC INDEX

100 6 5

80

Normal Pts Pacemaker Pts

4

70

L/min/m2

Survival (%)

90

60 Endocardial Epicardial

50

p = 0.05

3 2 1

40 0

1

2

3

4

5

6

7

8

9

10

Years postimplantation Figure 18-8  Actuarial analysis of endocardial and epicardial electrode survival. One half of epicardial electrodes last about 8 years; for endocardial electrodes, 50% survival time is longer than 10 years. Curves are significantly different (P = .05). (Epicardial electrode data from Serwer GA, Mericle JM, Armstrong BE: Epicardial ventricular pacemaker electrode longevity in children. Am J Cardiol 61:104, 1988; endocardial electrode data from Serwer G, Uzark K, Dick M II: Endocardial pacing and electrode longevity in children. J Am Coll Cardiol 15:212A, 1990.)

0 Pre-exercise

Post-exercise

Figure 18-9  Changes in cardiac index as measured by acetylene rebreathing from rest to maximal exercise in normal children and in children with fixed-rate ventricular pacing. The cardiac indices were identical at rest and at maximal exercise. Brackets represent 1 standard error around the mean. Pts, Patients. (Data from Serwer G, Dick M II, Eakin B: Cardiac output response to treadmill exercise in children with fixed-rate pacemakers. Circulation 84:511-514, 1991.)

398

SECTION 2  Clinical Concepts

STROKE INDEX

high septal pacing near the bundle of His, which has a narrower QRS morphology, is striking; the clinical implication of these changes is unknown.27 A newer pacing mode, managed ventricular pacing (MVP; Medtronic) has great utility in a patient with predominantly sinus node dysfunction but also with intermittent lack of AV conduction.28 In this mode, pacing is AAIR, but the device monitors for ventricular activity between two consecutive P waves without regard to timing. If two consecutive P waves occur without an intervening R wave, a ventricular pace is generated. If this occurs twice within four P waves, the device shifts mode to DDD(R). After a predetermined time, the ventricular output is inhibited, and the device searches for an R wave between two P waves. If one occurs, the mode reverts to AAIR; if not, DDDR mode remains in force (Fig. 18-11). Atrial electrodes are somewhat less reliable than ventricular electrodes, even when they are placed endocardially. Therefore, conditions associated with potential early atrial electrode failure should serve as a contraindication to AAI pacing. Such conditions include prior extensive atrial surgery in which extensive atrial fibrosis is likely, small atrial size, and prior placement of a large intra-atrial baffle, limiting venous access to viable atrial tissue. After a Fontan procedure (right atrial–to– pulmonary artery connection), patients may have a low flow velocity within the atrium, increasing the risk for venous thrombosis when endocardial electrodes are placed; long-term anticoagulation may be indicated in these patients. In addition, the amount of excitable tissue that can be accessed from a transvenous approach may be limited. Most current Fontan procedures use either a lateral tunnel created along the lateral right atrial wall, limiting this area for pacemaker placement, or an extracardiac conduit, in which case no atrial tissue is accessible. Single-chamber ventricular pacing, or VVI(R), allows the use of more stable electrode systems and, in the rate-responsive mode, still allows rate variability to be maintained in the ambulatory child. The importance of atrial systole in the maintenance of cardiac output is debatable and varies from child to child. Because most children have good myocardial function, the atrial contribution is probably minimal. The cardiac output increase with exercise is improved in children with DDD versus VVI pacing. It is unclear, however, whether this increase is the result of atrial synchrony or rate variability. Pacemaker syndrome from VVIR pacing is uncommon but can occur, especially over time. In one series, 19 of 33 patients developed symptoms suggestive of pacemaker syndrome over time (median, 11 years) that resolved with upgrading to dual-chamber pacing.29 The major factor to be considered in such a choice is the difficulty in placing an adequate atrial electrode. If prior surgery or underlying structural disease precludes atrial electrode placement, single-chamber pacing is an acceptable alternative. However, dual-chamber pacing should be considered for all patients, with single-chamber pacing used only if contraindications

90 80 70

Normal Pts Pacemaker Pts

mL/m2

60 50 40 30 20 10 0 Pre-exercise

Post-exercise

Figure 18-10  Stroke index changes from rest to maximal exercise in normal children and in children with fixed-rate ventricular pacemakers. Pre-exercise values were similar. With exercise, stroke index increased significantly in patients with pacemakers, to provide an increased output in the presence of a fixed heart rate. Brackets represent 1 standard error around the mean. Pts, Patients. (Data from Serwer G, Dick M II, Eakin B: Cardiac output response to treadmill exercise in children with fixed-rate pacemakers. Circulation 84:511-514, 1991.)

volume (Fig. 18-10), with presumed increased wall stress and potentially increased myocardial work compared with the same change in cardiac output, when a heart rate increase is possible.24 However, enhanced exercise tolerance is achieved when rate-variable pacing is used.25 This suggests an advantage to rate-variable pacing in the child who is expected to lead an active life. The rate-responsive mode should always be used unless the patient can demonstrate an adequate intrinsic rate response to exercise by exercise testing or ambulatory electrocardiogram. Single-chamber pacing in either the atrium or the ventricle has been advocated for the treatment of sick sinus syndrome.15 When atrial pacing is chosen, the presence of normal AV node function must be established by provocative electrophysiologic testing before implantation, especially in the postsurgical patient, because AV nodal disease can accompany SA nodal disease and may not be apparent in the resting, nonprovoked state. AAI(R) pacing has the advantage of preserving the normal ventricular activation sequence with potentially better cardiovascular function. In addition, some evidence in animals points toward the long-term development of myocardial changes when an abnormal pattern of myocardial activation is present.26 A comparison of cardiac myocyte changes in ventricular free wall pacing versus

A P

A P

V S

A P

V S

A P

V P

A P

A P

V P

A P

A P

V P

V P

Figure 18-11  Example of managed ventricular pacing function (MVP; Medtronic). Note the intact AV conduction (AP) for the first 2 beats, then the loss of AV conduction for the third beat, with the ventricular-paced beat after the fourth paced P wave (VP). After this occurs again, the pacemaker converts to DDD pacing.



18  Pediatric Pacing and Defibrillator Use

TABLE

18-3 

Major Contraindications to Dual-Chamber Pacing in Children

Contraindication Inability to place both an atrial and a ventricular electrode Persistent atrial tachyarrhythmia

Causes Small patient size Limited venous access Extensive epicardial fibrosis Uncontrolled atrial flutter Arrhythmia easily triggered by atrial pacing Pacemaker inability to detect atrial arrhythmia and limit ventricular rate

to dual-chamber pacing exist, as discussed later. Even in patients with sinus node dysfunction, dual-chamber pacing should be considered, particularly if AV nodal function is suspect. We now consider dual-chamber pacing to be the mode of choice in children. We use single-chamber pacing only if a contraindication to dual-chamber pacing exists, as well as in some small infants who will need cardiac surgery in the immediate future, with an upgrade to dualchamber pacing performed at that time. The major contraindications to dual-chamber pacing are (1) persistent atrial tachyarrhythmias; (2) changing AV nodal status, making numerous programming changes necessary; and (3) inability to place reliable atrial and ventricular electrodes. An example of the third contraindication is the small child in whom endocardial pacing is preferred, but the presence of two electrodes in the superior vena cava might present a high risk for thrombosis. Another example is the child requiring epicardial electrode placement in whom atrial electrode placement would necessitate a greatly enhanced surgical procedure. One must remember that rate sensors do not function in nonambulatory infants. Therefore, in young infants, single-chamber pacing becomes fixed-rate pacing. The generator’s size and functionality are no longer considerations, because dualand single-chamber pacemakers are comparable in both regards. Table 18-3 lists the most common contraindications to dual-chamber pacing. Dual-chamber pacing in children has previously been underused. MPPR data show a significant increase in dual-chamber pacing, with 43% of generators implanted in 1991 to 1992 using the DDD or DDDR mode, increasing to a majority (68%) of implantations by 1995 to 1996, and with a further increase, to more than 80%, since 2000. This is in marked contrast to the years before 1985, when fewer than 10% of generators were in the DDD mode (Fig. 18-12). This increase in dual-chamber pacing has been the result of improvements in atrial USE OF SINGLE- VS. DUAL-CHAMBER PACING BY YEAR OF IMPLANTATION 100 80

%

60 40 20 0 <1980

81−85

86−90

91−95

96−00

01−05

06−09

Year range Single chamber

Dual chamber

Figure 18-12  Percentage of single-chamber versus dual-chamber generators implanted by year. Note the gradual shift from singlechamber to dual-chamber use. (Data from Midwest Pediatric Pacemaker Registry.)

399

epicardial electrodes, increased experience with endocardial pacing in children, the smaller size of dual-chamber generators, and a better understanding of the benefits of dual-chamber pacing. GENERATOR FEATURES Current pacemakers permit innumerable programming combinations, allowing more programming possibilities than will ever be used in any given patient. Because of the diversity of patients with congenital heart disease, however, such programmability is necessary. Again, certain features are more important for children than adults. This section discusses programming features considered essential, which should influence the choice of the most appropriate pacing generator for a given patient. The discussion begins with those features that are applicable to all generators, both single and dual chamber, and then covers features that are unique to rate-responsive pacemakers and dualchamber pacing. General Characteristics The most important consideration is related to the range of energy output available, which includes both the pulse width and the pulse amplitude programmability. Although most pacemakers are programmed to have 2.5 or 5 V of amplitude, the presence of other amplitudes is of key importance. Specifically, when a generator is used with an epicardial electrode, high-output features are mandatory. Although few children require long-term pacing at output greater than 5 V, many have an initial threshold rise and temporarily require such high output. Even with endocardial implants, acute increases in threshold can occur, and the ability to increase the pacemaker amplitude to values greater than 5 V may avert the necessity for emergency electrode replacement. In addition, threshold testing at multiple low-pulse amplitudes allows a more accurate determination of the characteristics of the strengthduration curve. This testing is mandatory to determine the lowest, but still safe, pulse amplitude and width settings. The strength-duration curve characteristics are not constant, varying not only with time but also in relation to activity and time of day.30 Such changes are discussed more fully in the consideration of appropriate follow-up. Knowing where the steep part of the strength-duration curve begins is crucial for appropriate programming; the clinician wants to ensure an adequate safety margin while minimizing the energy output, to maximize generator longevity. The ability to determine thresholds at a multitude of pulse amplitudes is a necessity. The same argument also applies to the ability to vary the duration of the pulse width. Again, although the pacemakers in most children are programmed to a relatively small number of pulse durations, the ability to choose from a much larger number of such settings increases the accuracy with which the clinician can characterize the strengthduration curve. Newer pacemakers now can automatically determine the voltage threshold, either on a beat-to-beat basis or at predetermined intervals throughout the day, and then adjust the pulse amplitude within a predetermined range to minimize energy drain and potentially increase generator longevity. This is accomplished by looking for an evoked potential after the test pulse, within a predetermined window of time indicating myocardial depolarization. Initially, these pacemakers required special low-polarization electrodes to distinguish true evoked potentials from electrode polarization. Newer designs have improved this discrimination, and now this feature has been expanded to function with most types of electrodes. Some devices still require bipolar electrode systems; some do not. Both endocardial electrodes31 and epicardial electrodes32,33 have been employed with newer devices. Once the voltage threshold has been determined, the amplitude is adjusted to a predetermined value above the threshold. Threshold data are saved in the pacemaker, and later interrogation can provide the clinician with the threshold trend over time. Such a feature has been extended to the atrium as well as the ventricle in some devices. Even if the clinician is reticent to allow automatic changes to the output parameters, use of the feature in a “monitor only” mode can provide information as to

400

SECTION 2  Clinical Concepts

VP

VS

Figure 18-13  Intracardiac electrogram from a patient with VVI pacing shows duration of ventricular refractory period (“dashed” line) after either ventricular pacing (VP) or ventricular sensing (VS). In this example, the ventricular refractory period extends well beyond the termination of electric activity seen by the electrode, to prevent inappropriate T-wave sensing. AS

AS

Figure 18-14  Intracardiac atrial electrogram recorded from a patient with AAI pacing. The refractory period (“dashed” line) must be long enough to prevent sensing of ventricular events by the atrial sensing (AS) electrode. Note the marked increase in refractory period required compared with VVI pacing (see Fig. 18-13).

Rate-Responsive Pacing For the single-chamber rate-responsive pacemaker, appropriate settings to mimic the pediatric response to exercise are mandatory. During exercise, the healthy child’s heart rate increases linearly with the increasing intensity of the exercise34 (Fig. 18-15). When healthy children are exercised using the Bruce treadmill protocol, the heart rate increases an average of 20 bpm with each increase in exercise stage. This continues throughout the course of the exercise. After an abrupt increase in exercise intensity (from stage I to II), the heart rate shows a sudden rapid increase, reaching a plateau value. The child’s pacemaker should increase its rate in an appropriate manner with increasing exercise intensity—and this must occur quickly, reaching a plateau value rapidly for that level of intensity. Therefore, not only must the heart rate increase to an appropriate degree, but also must increase in an appropriate time frame to mimic the normal physiologic response to exercise in the pediatric patient.

NORMAL HEART RATE RESPONSE TO EXERCISE 140 120

Change from resting rate

the long-term changes in threshold and the potential need for programming changes. This feature has the potential to increase generator longevity and decrease the number of pacemaker replacements needed. The third parameter of key importance to children is the rate. Although the use of fixed-rate pacemakers is becoming less common, the availability of a wide range of both lower and upper pacing rate limits is important in meeting the varying metabolic demands of the patient with congenital heart disease. Programming the upper rate limit (URL) of dual-chamber or rate-responsive pacemakers to less than 150 bpm is inadequate, particularly in a small child. Even older patients can raise their heart rates well above this value when exercising maximally in the absence of heart block; therefore, pulse generators must provide URL of at least 180 bpm, and preferably higher. Newer devices now provide a maximal URL of 210 bpm. The lower rate limit (LRL) needs are also variable. Immediately after surgery, greater LRLs are often necessary to maintain an adequate cardiac output. This is especially important after atrial surgery for patients in whom sinus node function may be impaired. In our opinion, lower rates must be programmable from at least 50 to 120 bpm. Higher LRLs may also be needed to decrease the incidence of tachyarrhythmias. Another parameter often overlooked is the refractory period. In single-chamber pacing, this is often fixed to an arbitrary value of 325 msec, without much thought about whether this value is appropriate. For the ventricular channel, the refractory period must be of sufficient duration to prevent inappropriate T-wave sensing but not prevent sensing of spontaneous ventricular depolarizations. Measurement of the pace or sensing point to well beyond the T wave using the intracardiac electrogram (EGM) is straightforward (Fig. 18-13). In healthy children, the QT interval decreases with an increasing heart rate. When rate-variable pacing is used, the ventricular refractory period may be appropriate at rest but too long during exercise. Ideally, the period should vary with the pacing rate. Therefore, this value must be long enough to prevent T-wave sensing at the resting heart rate and short enough not to limit appropriate sensing at the upper pacing rate. Children with complete heart block may have spontaneous ventricular beats during the stress of exercise, which must be appropriately sensed. Appropriate programming is discussed later. Again, the wider the range of available refractory periods, the more universally applicable the pacemaker generator is to the entire pediatric population. For AAIR pacing, the refractory period must be long enough to prevent sensing of ventricular events, but again, must not be too limiting in terms of the upper rate. Recording of the intracardiac EGM shows the extent to which ventricular events are sensed by the pacemaker and the minimum value to which the atrial refractory period may be safely programmed (Fig. 18-14).

100 80 60 40 20 0 0

3

6

9

12

15

Time (min) Figure 18-15  Normal heart rate increases from the resting value in normal children exercised using the Bruce treadmill protocol. Brackets represent 1 standard error around the estimate. (Data from Serwer GA, Uzark K, Beckman R, Dick M II: Optimal programming of rate altering parameters in children with rate-responsive pacemakers using graded treadmill exercise testing. Pacing Clin Electrophysiol 13:542, 1990.)



18  Pediatric Pacing and Defibrillator Use NORMAL HEART RATE DECREASE FOLLOWING EXERCISE

Change from resting rate

120 100 80 60 40 20 0 0

2

4

6

8

10

12

Time (min) Figure 18-16  Normal heart rate decreases after exercise compared with pre-exercise value in normal children. Even at 10 minutes after exercise, the heart rate has not yet reached the resting value. Brackets represent 1 standard error around the estimate. (Data from Serwer GA, Uzark K, Beckman R, Dick M II: Optimal programming of rate altering parameters in children with rate-responsive pacemakers using graded treadmill exercise testing. Pacing Clin Electrophysiol 13:542, 1990.)

After termination of exercise, the heart rate decreases exponentially (Fig. 18-16). Although an initial rapid drop occurs, the heart rate does not reach resting levels for at least 10 minutes. Inappropriate rapid declines in heart rate after exercise termination may not meet the body’s metabolic demands and may result in inadequate cardiac output and a syncopal episode. With normal heart rate responses to exercise in children taken into account, the ideal rate-responsive pediatric pacemaker must have the ability to offer a variety of linear increases in heart rate with increasing exercise intensity (rate-response curves). In addition, it should offer a range of acceleration times (rate of heart rate increase with increased exercise intensity), with more rapid times preferred. Such increases in heart rate should be independent of resting and maximal rates. After the termination of exercise, the heart rate decline should be exponential but slow enough that the LRL is not reached for at least 10 minutes. Also, the pacemaker must be able to tailor its detection of increasing exercise levels to the individual patient. Different approaches address this problem; manufacturers realize that not all patients produce the same characteristics detectable by the pacemaker in response to the same degrees of exercise. Although simplicity in programming is desirable, the clinician must weigh against it the ability to tailor the pacemaker’s settings and optimize its performance for a given patient. Numerous types of sensors have been used, the most common being activity (as a function of body vibration), blood temperature, and minute ventilation. Body vibration sensing is the most useful in children because it does not require special electrodes and is much the same in the child as in the adult. Blood temperature and minuteventilation sensing35 have been used in children, but to a lesser degree. Dual-Chamber Pacing The previous considerations also apply to dual-chamber pacing. Additional programmable settings must also be considered, however, primarily the ability to program an appropriate AV interval and decrease it with increasing atrial rate. Such shortening of the AV interval is clearly desirable in children and should occur with changes in the sensed atrial rate as well as with increases in the paced atrial rate during DDDR pacing. Because this decrease mimics the physiologic response more closely and provides a shorter total atrial refractory period (TARP) at higher rates, the multiblock rate is higher. This is probably the most important feature of dual-chamber generator selection, because children often reach much higher atrial rates than adults. If TARP is

401

inappropriately long, multiblock occurs during the course of normal exercise, with a subsequent sudden decline in ventricular rate and the potential for syncope. Children typically reach atrial rates in excess of 180 bpm during routine exercise. If TARP, of which the AV delay is a major part, is abnormally long, problems will occur. In addition, multiple settings for the postventricular atrial refractory period (PVARP) also are considered desirable, because of its contribution to TARP and ultimately to the multiblock rate. This parameter must have enough programmability to prevent inappropriate ventricular sensing by the atrial electrode while allowing a multiblock rate of at least 200 bpm (preferably 220 bpm), particularly in younger children. Many newer devices automatically decrease the PVARP with increasing rate to raise the multiblock rate. One should always check the minimal value to be sure it is short enough to provide an adequate multiblock rate. Also, one must be aware of the PVARP value at rest, to ensure it is not inappropriately long. One closely allied feature that is mandatory is the ability to control the degree of PVARP extension after a spontaneous ventricular depolarization. An automatic extension of the PVARP after spontaneous ventricular depolarization is often used to prevent sensing of retrograde atrial activation, thus avoiding pacemaker-mediated tachycardia. This is not necessarily desirable in children, because the presence of retrograde-only ventriculoatrial conduction is rare, and therefore the risk for pacemaker-mediated tachycardia is rare. With exercise, spontaneous ventricular depolarizations do occur, and if an inappropriate PVARP extension occurs, normal atrial depolarizations may not be sensed, resulting in a sudden overall decline in the heart rate. The ability to disable this feature must be present for the generator to be appropriate for use in children. This concern is discussed later in regard to the use of exercise testing in follow-up. Other dual-pacing features that must be considered include the ability to lower the URL in the presence of atrial tachycardia. Such rhythms, especially atrial flutter, may occur, particularly in the postoperative patient. Another potentially useful feature is the ability to decrease the LRL based on time of day. Children, who tend to have a much more predictable schedule than adults, can benefit from having their pacemakers programmed to a lower pacing rate during sleep than during the daytime hours, when a higher heart rate may be needed. This is particularly useful for the child with sinus node disease, because the intrinsic atrial rate cannot be relied on to govern the paced ventricular rate. With an intact sinus node, the pacing rate can simply be set at an appropriately low level for sleep and rest, knowing that it will be at an appropriate rate during waking hours. If sinus node disease is present, however, this may not be the case, and the ability to vary the lower pacing rate with the time of day may be helpful, because this feature can lower the average daily rate and prolong generator life. This feature may also be helpful in the single-chamber rate-responsive pacemaker. Another feature recently introduced is the ability to extend temporarily the AV interval searching for AV conduction. If conduction is found, the AV delay can be lengthened. This is an attempt to promote AV conduction and limit unnecessary ventricular pacing. Summary Traditional factors in pediatric pacing, such as generator longevity and size, are now less important in the selection of a generator. All generators are much smaller than previous models, and yet longevity has not been sacrificed, a result of improved circuit efficiency. The difference in size among single-chamber, dual-chamber, and rate-responsive pacemakers is often undetectable. Pediatric patients generally have long life expectancy, and the ability to have a highly programmable pacemaker implanted to meet changing metabolic demands of growth, age, or patient choices is indispensable. The difference in cost between a highly programmable unit and one with fewer features is minimal, particularly when the cost is spread over the life of the pacemaker. Box 18-1 summarizes the features that must be considered for the appropriate selection of a generator. The choice of a pacemaker should be based solely on the features it possesses and its ability to meet the demands of the patient.

402

SECTION 2  Clinical Concepts

CHANGE IN EPICARDIAL VERSUS ENDOCARDIAL ELECTRODE USE

Box 18-1 

DESIRABLE GENERATOR FEATURES IN PEDIATRIC PACING Highly programmable for mode, output, and AV intervals, with capability to change pacing mode automatically Rate-responsive mode available Diagnostic rate counters available Performance indicators provided (battery voltage, battery current drain, electrode impedance) Intracardiac electrograms provided Automatic adjustments to changing status (e.g., change in URL with onset of atrial tachyarrhythmias) Variable AV interval with increasing heart rate, either atrial or sensor driven AV, Atrioventricular; URL, upper rate limit.

PACING ELECTRODE SELECTION There are many aspects to the choice of an appropriate electrode system in children. The first obvious choice is between the placement of an endocardial or an epicardial system. Other choices are equally important and often overlooked, however, including unipolar versus bipolar system, type of electrode fixation, and steroid-eluting versus non-steroid-eluting capabilities.

100% 80% 60% 40% 20% 0% <1980

81–85

86–90

91–95

96–00

01–05

06–09

Year range Endocardial

Epicardial

Figure 18-17  Change in endocardial versus epicardial electrode use in children. Note the gradually increasing use of endocardial electrodes, although almost half of all electrodes placed are epicardial. (Data from Midwest Pediatric Pacemaker Registry.)

Endocardial versus Epicardial Pacing Initially, almost all electrode systems implanted in children were epicardial, because of the large size of the endocardial electrodes and pacing generators. The development of smaller electrodes and generators has changed this, although children still undergo epicardial lead placement as a result of small patient size or other factors that do not allow placement of an endocardial electrode system. MPPR data show a gradual increase in endocardial electrode use, but almost one half of all patients still receive epicardial electrodes (Fig. 18-17). Our basic approach is to assume that all children should undergo the placement of an endocardial system; we then evaluate the child for factors that do not allow endocardial electrode use. The major factors to be considered, in addition to patient size, are (1) venous access to the ventricle, (2) presence of intracardiac right-to-left shunting, (3) increased pulmonary vascular resistance, (4) right-sided prosthetic valves, and (5) severe right ventricular (RV) dysfunction or fibrosis causing either increased risk of thrombus formation or an inability to stimulate the endocardium. Initially, it was believed that children weighing less than 15 kg (33 lb) and those younger than 4 years should not undergo placement of endocardial electrodes.36 This was based on the belief that the subclavian vein and superior vena cava (SVC) were too small, leading to a high risk for thrombosis with vessel occlusion, and that the large size of the generators made implantation in the subclavicular area impractical. With increased experience and smaller generator and electrode sizes, however, many centers now routinely implant endocardial lead systems in children weighing less than 15 kg.9,37-39 The lower range for weight is not yet known. From a technical standpoint, children as small as 3 kg (6.6 lb) can undergo endocardial electrode placement, but the follow-up of such children is too limited to know whether this is in their best interest. A study of 39 patients weighing 2.3 to 10 kg showed that 23% had some pacing system problem related to endocardial electrode placement.39 Such problems included skin necrosis over the generator, subclavian vein thrombosis, and endocarditis on the electrode. Another 23% required electrode extraction. All except one patient had received a single-chamber device. The risk for vessel thrombosis appears to be less than once believed, at least in the short term.40 Although SVC thrombosis has been reported,41,42 the true incidence is unknown, because noninvasive methods of detecting thrombosis are not sensitive and angiography is not routinely done unless thrombosis is suspected clinically (Fig. 18-18). Lead displacement secondary to growth remains a concern,

although techniques have been proposed to deal with this problem.9,38 The placement of large electrode loops within the atrium was proposed to allow for growth, but these loops may not be as effective as originally believed because they can fibrose to the cardiac wall, precluding uncoiling with growth. The major objection to endocardial electrode use in the small child is related to long-term problems. Because young children can be expected to require numerous electrodes over their lifetime, many more than in adult patients, the clinician must consider how many electrodes can be left in place before problems with vessel obstruction or tricuspid valve dysfunction occur, as well as the difficulty of extraction of old electrodes. Although now more widely used,43,44 lead extraction still represents a significant problem in children, with the potential for damage to the cardiac structures, mainly the tricuspid valve. To commit a child to potentially numerous lead extractions is still a

Figure 18-18  Venous angiogram in a patient after endocardial pacemaker implantation through the left subclavian vein. Note the complete obstruction of the subclavian vein at the site of electrode entry (arrow), with collateral flow around the obstruction.



18  Pediatric Pacing and Defibrillator Use

concern. In our institution, current guidelines call for the placement of dual-chamber endocardial systems in children weighing 15 kg or more and the placement of single-chamber endocardial systems, if single-chamber pacing is appropriate, in children heavier than 8 kg (17.5 lb). These guidelines may change as electrode development continues and as data on the long-term follow-up of children with endocardially placed electrodes become available. The next factor that must be considered is the presence of intracardiac shunting. Electrodes are potential sources of small particulate matter, with the risk for subsequent embolization until endothelialization occurs.45 This does not tend to be a problem when particulate matter goes only to the lungs, where it is filtered out of the circulation and eventually absorbed, except in the presence of preexisting elevated pulmonary vascular resistance (PVR) or after a Fontan procedure. In the presence of right-to-left shunting, however, the potential for systemic embolization is great. The general recommendation is to avoid such electrodes in patients with documented right-to-left shunting.36 This also must be considered in patients with the potential for rightto-left shunting, even if their net intracardiac shunt is left to right. Children with atrial and ventricular septal defects can show right-toleft shunting in the setting of elevated RV pressure, even with a net left-to-right shunt.46,47 The specific hemodynamic situation of the individual child must be considered before endocardial electrode implantation is performed. The same concerns apply to the child with elevated PVR or Fontan physiology, in whom pulmonary embolization of even small matter may further elevate PVR. Whether short-term anticoagulation of such Figure 18-19  Echocardiogram from a patient after placement of pacing electrode across bioprosthetic tricuspid valve. A, Electrode is coursing between the valve struts. B, Color Doppler tracing shows only trivial regurgitation (arrow).

A

B

403

patients until lead endothelialization can occur would preclude such concerns and permit transvenous pacemaker placement has yet to be investigated. If epicardial pacing is not possible, this may be an acceptable alternative, but given the current lack of knowledge on the benefit of anticoagulation in this setting, it should not be general practice. The presence of a mechanical tricuspid valve prosthesis negates the ability to use an endocardial pacing system. There have been isolated reports of endocardial electrode placements at open-heart surgery through the perivalvular area.48 This requires cardiopulmonary bypass and can be done only at valve placement. This technique cannot be used in the usual transvenous implantation; and it prevents lead extraction should that become necessary, except during repeat openheart surgery. In cases of a heterograft valve rather than a mechanical one, the new, smaller transvenous leads have been placed without interfering with valve function (Fig. 18-19). Placement of a ventricular lead through the coronary sinus in the patient with an artifical tricuspid valve has been reported.49 The physician also must consider the state of the right ventricle. Severe RV dysfunction and endocardial fibrosis can occur in children with congenital cardiac disease and may prevent adequate pacing of the right ventricle. This tends to be more prevalent in the older child with long-standing disease. In such children, left ventricular (LV) pacing and therefore epicardial pacing may become necessary. In the patient with severe RV dysfunction and dilatation, an appropriate endocardial site that permits both adequate sensing and pacing may not be achievable. In addition, severe RV dysfunction can lead to an increased risk of thrombus formation.

404

SECTION 2  Clinical Concepts

ENDOCARDIAL ELECTRODE USE

CHRONIC THRESHOLDS OF EPICARDIAL AND ENDOCARDIAL ELECTRODES

Threshold at 2.5 volts (ms)

1 Unknown 4%

0.8

Bipolar 68%

Epicardial Endocardial

0.6 0.4

Unipolar 28%

0.2 0 0

2

4

6

8

Years after implantation Figure 18-20  Comparison of long-term pulse-width thresholds for endocardial versus epicardial electrodes measured at a pulse amplitude of 2.5 V. Thresholds for both groups show no significant rise, and do not differ significantly from each other. Brackets represent 1 standard deviation around the mean.

The patient who has undergone a Fontan procedure presents a somewhat unique situation. As mentioned previously, controversy surrounds the best approach for electrode placement in these children. If ventricular pacing is required, the epicardial approach is the only one available. However, many of these patients have intact AV conduction, require pacing only for sinus node dysfunction, and are best served by atrial-only pacing. The original Fontan procedure connected the right atrial appendage to the pulmonary artery, leaving the entire right atrial chamber available for electrode placement. The more common techniques at present either create a tunnel along the lateral right atrial wall from the inferior vena cava to the pulmonary artery or use an extracardiac prosthetic conduit. Often, a communication exists from the system to the pulmonary atrial chamber, resulting in a right-to-left shunt. Transvenous pacing has been performed in such patients despite anticoagulation,50 but electrode placement can be difficult because of the small-system venous chamber, and right-to-left embolization with neurologic sequelae has been reported.50 For these reasons, our approach has been to avoid the transvenous approach unless the epicardial approach is not possible because of extensive fibrosis. Pacing in this group of patients can be extremely challenging regardless of the approach chosen. In summary, endocardial pacing is generally preferable because of the ease of implantation and the improved longevity of the electrode. Long-term thresholds are as stable as epicardial electrodes and tend to be lower (Fig. 18-20). This permits lower-output programming of the pacing generator, enhancing its longevity. However, endocardial electrode use is contraindicated in many situations (Box 18-2). As such, epicardial electrodes still play a significant role in pediatric pacing.

Box 18-2 

CONTRAINDICATIONS TO ENDOCARDIAL PACING Small patient size (relative) Presence of intracardiac right-to-left shunting No venous access Elevated pulmonary vascular resistance Prosthetic tricuspid valve Severe right ventricular dilatation or endocardial fibrosis Presence of hypercoagulable state

Figure 18-21  More than two thirds of endocardial electrode systems use bipolar electrodes. (Data from Midwest Pediatric Pacemaker Registry.)

Unipolar versus Bipolar Pacing The choice between a unipolar and a bipolar electrode configuration was formerly an issue only for endocardial implantation. Since the development of bipolar epicardial electrodes, bipolar epicardial pacing is an available option. MPPR data show an increasing trend toward bipolar epicardial pacing. In our institution, more than 95% of all epicardial implants now use bipolar electrodes. The epicardial electrode used is the Model 4968 (Medtronic, Minneapolis), which has two electrode heads that are sutured to the epicardial surface. This electrode has thresholds comparable to unipolar models but much higher impedance, often 600 to 1200 Ω, comparable to endocardial electrodes. For endocardial pacing systems, the choice between unipolar and bipolar pacing becomes more controversial. Again, MPPR data show that most endocardial systems are bipolar (Fig. 18-21). It was initially believed that unipolar pacing was preferable because of the smaller size of the unipolar pacing electrode.51 With improved electrode design, however, this size difference has become negligible. Electrode body diameter is important in determining the risk for venous thrombosis, currently with minimal difference in size. For example, the Model 4057M unipolar screw-in electrode (Medtronic) has a body diameter of 2.2 mm and the 4058M bipolar version, 2.4 mm. Such minimal difference is also seen in passive-fixation electrodes, such as the Model 4023 unipolar steroid-eluting electrode, which has a body diameter of 1.2 mm, compared with 1.9 mm for the bipolar version (Model 4024). Newer electrodes have continued this trend toward small bipolar electrodes; the Medtronic SelectSecure has a lead body diameter of 1.4 mm (4.1 French). In all cases, diameter of the electrode head is smaller for a unipolar electrode, which may make insertion easier, although once implanted, size of the head is of little consequence. An MPPR comparison of acute implantation characteristics between unipolar and bipolar electrodes of similar design showed no significant difference for threshold values of voltage, current, or resistance (Fig. 18-22). However, some believe that long-term thresholds are improved in unipolar pacing.51 This may result from the smaller size of the head and its lower weight, which creates less tension on the endocardial surface, particularly with active-fixation electrodes, and therefore results in less tip fibrosis. However, this issue appears to affect only active-fixation leads and has not been reported with passive-fixation tined electrodes. Although sensing using a bipolar electrode was initially thought to be inferior to unipolar sensing because of the proximity of the two electrodes, MPPR data show this is not the case. Acute-implantation R-wave amplitudes and slew rates show no significant difference between unipolar and bipolar electrodes (Fig. 18-23). However, unipolar sensing is more affected by myopotentials and is more prone to oversensing and inappropriate pacemaker inhibition, affecting an



18  Pediatric Pacing and Defibrillator Use EPICARDIAL ELECTRODE USAGE SINCE 2000

3

600

2

400 Ohms

Volts MA

BIPOLAR VS. UNIPOLAR ENDOCARDIAL ELECTRODE THRESHOLDS

1

0 Volts

Current Bipolar

Impedance

Unipolar

Figure 18-22  Acute implantation thresholds for bipolar versus unipolar endocardial electrodes are not significantly different for voltage, current, or electrode impedance. All were measured at a 0.5-msec pulse width. Brackets represent 1 standard deviation around the mean. MA, milliamperes (current). (Data from Midwest Pediatric Pacemaker Registry.)

estimated 31% to 93% of patients, as discussed later. Bipolar sensing is rarely affected by such myopotential inhibition because of the closer proximity of the electrodes. The degree to which such inappropriate inhibition is seen depends on the location of the generator, the provocative tests used, and the generator model implanted. All series, however, report a significant incidence of this problem, which can be a particular concern in active children. In most active children, bipolar pacing is preferable, particularly with the smaller electrode sizes now available. Sensing does not appear to be a problem, and myopotential inhibition is seen less often than in the past. In addition, with bipolar pacing, the risk for extracardiac pacing of the surrounding muscle is minimized, particularly if it is difficult to position the generator in a location where all such stimulation of surrounding muscles can be avoided. This is particularly relevant to implantations with the pocket placed in the subclavicular

20

4

15

3

10

2

5

1

0

Volts/sec

BIPOLAR VS. UNIPOLAR ENDOCARDIAL SENSING

Millivolts

4965 5017 4968 4951

200

0

405

0 R-wave amplitude Bipolar

Slew rate Unipolar

Figure 18-23  Acute implantation electrode sensing for bipolar versus unipolar endocardial electrodes demonstrates no significant difference in either R-wave amplitude (millivolts) or slew rate (volts per second). Brackets indicate 1 standard deviation around the mean. (Data from Midwest Pediatric Pacemaker Registry.)

Figure 18-24  Distribution of epicardial electrode types used since 2000 (Medtronic models). The most common epicardial electrode is the true epicardial bipolar (4968), followed by true epicardial unipolar (4965), screw-in (5017/6917/5069/5071), and fishhook (4951M) electrode. The Medtronic 4968 has become the most widely used epicardial electrode in both the atrium and the ventricle (>90%).

region. In many children, the lack of significant subcutaneous tissue requires placement of the generator in the subpectoral position, where the risk for extracardiac pacing with a unipolar system increases. Epicardial Electrode Types Compared with endocardial electrodes, relatively few epicardial electrode types are available. Previously, all electrodes were intramyocardial, with this portion either a corkscrew coil or a single wire with barbed end (fishhook).52-54 A true epicardial electrode with steroideluting capabilities is sutured to the epicardial surface and requires direct contact of the electrode with excitable myocardium55-58 (see later discussion). Based on MPPR data, since 2000 the most widely used electrode types are the bipolar true epicardial (>90% of implants), unipolar true epicardial, screw-in corkscrew, and barbed fishhook, used exclusively in the atrium (Fig. 18-24). The choice of electrode depends on the chamber to be paced and the preference of the implanting physician. Atrial epicardial implantation requires an electrode that sits on the epicardial surface or has only shallow penetration into the atrial myocardium. Should the electrode extend through the chamber wall into the atrial cavity, a low-resistance circuit is established through the blood pool, with an inability to pace reliably. Few data can be found on the longevity or thresholds of atrial epicardial electrodes, partly because of the constant change in electrode design, making long-term comparisons difficult. The most widely used atrial electrode is the fishhook or stab-in electrode, because it does not penetrate deeply into the myocardium, compared with the screw-in or corkscrew type. The Medtronic Model 4951M(P), which has a platinized coating, has resulted in slightly improved thresholds at acute implantation (Fig. 18-25). The average threshold at implantation is about 1.05 V and 3.3 mA, measured at a pulse width of 0.5 msec. The average acute electrode impedance is 320 Ω. The steroid-eluting true epicardial or epimyocardial electrode is increasingly used as an atrial epicardial electrode and is becoming the dominant electrode for atrial epicardial pacing. Although implantation may be slightly more difficult, acute thresholds are comparable. In our institution, this type of electrode is currently used in more than 95%

406

SECTION 2  Clinical Concepts

4

Volts MA

3

2

1

0 Volts 4951

Current 4951M(P)

4965

Figure 18-25  Acute implantation voltage and current threshold values measured at a 0.5-msec pulse width for the original fishhook electrode (Medtronic Model 4951) compared with the newer platinized version (4951M[P]) and the steroid-eluting electrode (4965) when implanted on the atrium. Acute thresholds are not statistically different. Current at threshold for the steroid electrode is slightly higher, implying a lower impedance. Brackets represent 1 standard deviation around the mean. MA, milliamperes. (Data from Midwest Pediatric Pacemaker Registry.)

Endocardial Electrode Types As in the adult population, several general types of endocardial electrodes are in pediatric use: passive-fixation non-steroid-eluting electrodes, passive-fixation steroid-eluting electrodes, and active-fixation electrodes—both non-steroid-eluting and developed steroid-eluting models. However, the vast majority of electrodes used currently are steroid eluting. The most common endocardial electrode type in children continues to be the active-fixation screw-in electrode (Fig. 18-30). The use of this electrode has been advocated because of its better fixation qualities, given the tremendous range of anatomic variations in children with congenital heart disease. For implantation within the morphologic left ventricle in a child who has undergone an atrial switch repair for transposition of the great arteries, or in a child with ventricular inversion, the active-fixation electrode is almost universally used. Also, in a child whose right ventricle is greatly dilated, such that it is difficult to wedge the electrode into the trabecular recesses of the

ACUTE EPICARDIAL VENTRICULAR ELECTRODE THRESHOLDS 5

500

4

400

3

300

2

200

1

100

0

Ohms

of all atrial epicardial implants. The acute threshold average is 1.0 V at 0.50-msec pulse width, and somewhat higher for the bipolar version. The average impedance is 301 Ω for the unipolar Medtronic Model 4965 and 705 Ω for the bipolar 4968 electrode. We prefer the bipolar version because of the decreased far-field R-wave (FFRW) oversensing and increased impedance. More diversity exists in the choice of the electrode for ventricular pacing. A comparison of the original nonplatinized fishhook electrode (Medtronic Model 4951) with the screw-in electrode (Model 6917 or 5069) reveals essentially no difference in acute implantation thresholds. However, implantation thresholds for the currently available platinized fishhook electrode, 4951M(P), are slightly improved (Fig. 18-26). Both steroid-eluting electrodes tend to have slightly higher thresholds. Lead survival appears to be longer for the screw-in electrode than for the fishhook type, with 5-year lead survival rates of about 84% and 65%, respectively.55 Most failures were caused by exit block. Other studies, however, have found little difference in longevity between these two types of electrodes.53 Some of this interstudy discrepancy is believed to be related to different surgical modes of implantation for the fishhook electrode. Whether or not the lead was stabilized by being sutured to the myocardium was variable. Lack of such stabilization may cause more electrode movement in the myocardium and therefore increased fibrosis and risk for exit block develpoment54 (see Implantation Techniques). A key advance in epicardial pacing, as mentioned earlier, is the steroid-eluting electrode.55-58 This electrode consists of a platinized flat electrode that sits atop the epicardial surface, with a dexamethasoneimpregnated silicone plug to allow elution of the drug onto the area of myocardium being stimulated. About 1 mg of dexamethasone is present within the electrode. Both a unipolar version (Model 4965) and a bipolar version (4968) of this electrode are available (Medtronic). This electrode is affixed to the epicardial surface by sutures, with the active portion of the electrode not extending into the myocardium as with other epicardial electrodes. This is both advantageous and disadvantageous, depending on the patient. For patients whose epicardial surfaces are relatively nonfibrotic, this appears to be an advantage,

because there is less myocardial injury to provoke subsequent fibrosis. However, for patients with extremely fibrotic epicardial surfaces, as often occurs after multiple open-heart surgical procedures, these electrodes are difficult to use. In such patients, the surgeon must either find an area of myocardium with limited epicardial fibrotic reaction or strip away a fibrotic layer to expose the myocardium, which simply leads to further fibrosis. Initial experience with this steroid-eluting electrode is encouraging. Although acute thresholds appear to be comparable with those of other epicardial electrodes (see Fig. 18-26), the threshold rise is less over the first several months after implantation (Fig. 18-27).57 Midterm survival is also encouraging. For the Model 4968 lead placed on either the ventricle or the atrium, longevity is 85% at 75 months (Fig. 18-28). For the unipolar version (Model 4965), longevity is 75% at 75 months and 55% at 115 months for ventricular usage (Fig. 18-29). In select patients with limited myocardial fibrosis, epicardial electrodes that do not penetrate the myocardium appear to be beneficial; however, care must be taken to choose the most appropriate form of ventricular epicardial electrode to fit the individual patient. All three types of ventricular electrodes in current use have advantages and disadvantages, and no one type is ideally suited to all patients.

Volts current

ACUTE ATRIAL EPICARDIAL ELECTRODE THRESHOLDS

0 Volts 6917 (5069)

Current 4951

Impedance 4951M(P)

4965

Figure 18-26  Comparison of thresholds for Medtronic Model 6917 (now 5069) screw-in electrode, Model 4951 fishhook electrode, Model 4951M(P) platinized fishhook electrode, and steroid-eluting electrode (Model 4965), when implanted on the ventricle, shows no significant difference in voltage threshold, but impedance is slightly lower for steroid-eluting electrode, similar to findings for atrial use. Brackets represent 1 standard deviation around the mean. Current on Y axis is in milliamperes. (Data from Midwest Pediatric Pacemaker Registry.)



18  Pediatric Pacing and Defibrillator Use COMPARATIVE THRESHOLDS 2.5 - 2.7 VOLTS/IMPLANTATION TIME

407

4968 ELECTRODE PERFORMANCE ATRIUM

0.50

100

0.45 0.35

80

0.30 0.25 0.20

Survival (%)

Milliseconds

0.40

0.15 0.10 0.05 0.00

60 40

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52

20

Implantation time (weeks)

4951-P

10295A

0 0

• P <.05

50

75

100

125

100

125

Months

Figure 18-27  Comparative thresholds of Medtronic Model 4951-P platinized fishhook electrode versus the epicardial steroid-eluting electrode (Model 10295A, now 4965) show a lack of significant threshold rise in the first 3 months after implantation for the steroid-eluting epicardial electrode, with threshold improvement at 1 year after implantation. (From Karpawich PP, Harkini M, Arciniegas E, Cavitt DL: Improved chronic epicardial pacing in children: steroid contribution to porous platinized electrodes. Pacing Clin Electrophysiol 15:1152, 1992.)

VENTRICLE 100 80 Survival (%)

right ventricle, active-fixation electrodes are preferable. Alternate site RV pacing also requires an active-fixation electrode. A comparison of acute threshold data shows that active-fixation and passive-fixation electrodes have similar thresholds (Fig. 18-31). Both non-steroid-eluting passive-fixation electrodes and steroid-eluting passive-fixation electrodes have lower acute thresholds and do not differ from each other. The presence of the steroid does not influence the acute implantation threshold, although with increasing electrode age, this is no longer the case. Follow-up data indicate significantly lower electrode thresholds for the steroid-eluting electrode compared with other types.58 A comparison of steroid-eluting and non-steroideluting electrodes showed no difference in chronic thresholds at 5-V pulse amplitude but did show differences at 2.5 and 1.6 V (Fig. 18-32). Therefore, it appears that the strength-duration curve is shifted leftward for the steroid-eluting electrodes.

25

60 40 20 0 0

25

50

75 Months

Figure 18-28  Kaplan-Meier survival curve for Medtronic Model 4968 bipolar electrode shows 85% survival at 75 months for electrodes placed in both the atrium (top) and the ventricle (bottom).

4965 VENTRICULAR SURVIVAL ENDOCARDIAL ELECTRODE USE BY ELECTRODE TYPE

100

Survival (%)

80

Active 38%

60

Unknown 10%

40 20

Steroid 20%

0 0

25

50

75

100

125

150

Months Figure 18-29  Kaplan-Meier survival curve for Medtronic Model 4965 unipolar electrode placed in the ventricle shows 75% survival at 75 months and 55% at 115 months.

Passive 32%

Figure 18-30  Distribution of endocardial electrode types used: Active, active-fixation (screw-in) electrode; Passive, passive-fixation (tined) non-steroid-eluting electrode; Steroid, passive-fixation steroideluting electrode. (Data from Midwest Pediatric Pacemaker Registry.)

408

SECTION 2  Clinical Concepts

7

700

6

600

5

500

4

400

3

300

2

200

1

100

Ohms

Volts current

ENDOCARDIAL THRESHOLD CHARACTERISTICS AT IMPLANTATION

0

0 Volts

Current

Steroid

Impedance

Passive

Active

Figure 18-31  Acute thresholds for endocardial electrode types show a tendency toward lower thresholds in the passive-fixation and steroideluting electrodes compared with the active-fixation electrodes. However, the difference in voltage threshold is minimal. The changes become more evident in current and impedance values, with steroideluting electrodes having the lowest impedance and the highest current flow. Brackets represent 1 standard deviation around the mean. Current on Y axis is in milliamperes. (Data from Midwest Pediatric Pacemaker Registry.)

Such changes affect generator programming. In one study, only 33% of generators that used non-steroid-eluting electrodes could be programmed to 2.5 V of pulse amplitude, compared with 77% of generators that used steroid-eluting electrodes.58 The remainder required a pulse amplitude of 5 V or greater. Therefore, the use of steroid-eluting passive-fixation electrodes allowed chronically lower output settings for the pulse generator, thereby increasing generator longevity. The CHRONIC THRESHOLDS OF DIFFERING ELECTRODE TYPES 0.5

Pulse width (ms)

0.4 0.3 0.2 0.1 0 5

2.5

1.6

Pulse amplitude (volts) Active

Passive

Steroid

Figure 18-32  Chronic long-term electrode thresholds are significantly higher for active-fixation electrodes than for either passive-fixation or steroid-eluting electrodes. At low pulse amplitudes, steroid-eluting electrodes show significantly lower thresholds than the other types. Brackets represent 1 standard deviation around the mean. (Data from Serwer GA, Dorostkar PC, LeRoy S, Dick M II: Comparison of chronic thresholds between differing endocardial electrode types in children. Circulation 86:1-43, 1992.)

Figure 18-33  Chest radiograph showing placement of single-pass VDD system. Note the lead buckling in the atrium, which is necessary to place the atrial sensing electrodes (arrow) within the atrium.

follow-up averaged 3.3 years (median, 3.6 years). There are insufficient data to compare the steroid-eluting active-fixation electrodes with the older types. A smaller bipolar active-fixation electrode introduced in 2005 (Medtronic Model 3830) differs in many ways from other leads. It has an isodiametric design with diameter of 4.1 French and a fixed helix. With no central lumen, the electrode must be introduced through a guiding catheter (see Implantation Techniques). This makes the lead much smaller and thus more advantageous in children. It is steroid eluting, but instead of a steroid plug behind the helix, the steroid actually coats the helix. This electrode is particularly useful in patients with venous narrowing and should decrease the incidence of postimplant venous occlusion. Early data show excellent acute thresholds and low dislodgement rates comparable to stylet-placed leads.59 The catheter delivery system makes this an excellent choice for children with complex anatomy and alternate-site pacing. Single-lead VDD systems have been employed in children. These systems obviate the need for two electrodes yet maintain AV synchrony.60 However, a major problem is lack of atrial pacing capabilities when sinus node function is inadequate. Also, the spacing of the atrial electrodes from the electrode tip often is too great for use in children. The electrode must be buckled so that the atrial dipole is within the ventricle (Fig. 18-33), which could lead to ventricular electrode dislodgement. These problems, together with the increased complexity of the electrode construction, with a concomitant potential for increased electrode failure, combine to limit the usefulness of this approach in children, especially smaller children. Also, these are rather large leads, and with the development of smaller leads, utility of these leads is minimal. Summary We believe that the ideal pacing system in children is a dual-chamber system with the capacity for rate-responsive pacing, using endocardial atrial and ventricular bipolar electrodes, with active-fixation electrodes in the atrium and steroid-eluting active-fixation electrodes in the ventricle. The small, Medtronic Model 3830 electrode has become our first-line endocardial pacing lead, although it does require a relearning of implantation techniques. When the child’s size is marginal or endocardial pacing is contraindicated, we use epicardial pacing. In these



18  Pediatric Pacing and Defibrillator Use

patients, the preferred electrode is the steroid-eluting bipolar electrode for both the atrium and the ventricle or, in the presence of significant epicardial fibrosis, the platinized version of the fishhook electrode for the atrium and the helix (corkscrew) electrode for the ventricle.

Implantation Techniques In many ways, although differences exist, implantation techniques in children are similar to those used in adults. This section focuses on the important differences that clinicians must consider. EPICARDIAL IMPLANTATION TECHNIQUES The approach used for the placement of epicardial electrodes is highly variable, depending on the patient’s circumstances. Approaches to the epicardial surface have included thoracotomy, sternotomy, and subxiphoid incision. Regardless of the approach, an attempt should be made to place the electrode on the left ventricle rather than the right ventricle to minimize dyssynchrony and to preserve ventricular function. The subxiphoid approach requires the smallest incision. Through the same incision, both electrode implantation on the epicardial surface of the heart and pacemaker implantation in the abdomen can be accomplished.61-63 This approach has been used for both ventricular and atrial epicardial electrode implantation. The disadvantage of the subxiphoid approach is that it exposes only a limited ventricular and atrial surface, and in a patient who has extensive epicardial fibrosis from prior cardiac surgery, finding a suitable location for implantation of the electrode can be challenging. Such an approach requires a 6- to 7-cm skin incision from the xiphoid tip to a point superior to the umbilicus. The dissection is continued as deep as believed necessary to provide adequate tissue between the pacemaker and the skin surface. Depending on the depth of subcutaneous tissue, the pacemaker can be implanted above the rectus muscle, below the rectus muscle but above the peritoneum, or in some circumstances, intraperitoneally, housed in a Silastic pouch sutured to the underside of the peritoneum and anchored to the rectus fascia.62 The depth to which the incision is carried should be governed solely by the tissue available to cover the pacemaker. When only minimal tissue is present over the pacemaker, besides an unsightly bulge, the skin is more susceptible to trauma, with a resultant risk of pacemaker erosion and infection. A left thoracotomy approach is often used in the child who has had cardiac surgery and thus is at high risk for significant epicardial fibrosis.64 This approach affords an increased myocardial surface from which to choose an appropriate pacing site. The generator can be implanted in the abdomen, in the subclavicular region, or in rare settings, intrathoracically. However, for implantation of a dual-chamber system, the left thoracotomy approach affords less exposure of the atrium and requires left atrial pacing. Although this has been accomplished, it introduces complexity into the programming, because the postpace AV interval must be prolonged sufficiently to afford adequate time for RV filling, because of the time necessary for left-to-right atrial excitation spread. The postsense AV interval must be short to avoid an excessive AV interval. For this reason, we believe that right atrial pacing is preferable, but we use left atrial pacing if right atrial pacing is not possible. When the thoracotomy approach is used with abdominal placement of the generator, the electrode must be passed subcostally to a pocket created in the abdomen through a separate incision. The electrode must not be passed over a rib and must be tunneled from the thoracic cavity to the abdomen as medially as possible, to minimize the risk for traumatic electrode fracture. A median sternotomy approach can also be used, but this creates the largest and most obvious scar. However, it affords the best exposure of the epicardial surface of both the ventricle and the right atrium. In a patient with significant epicardial scarring and fibrosis, this provides the highest likelihood of finding an appropriate pacing site. After the electrode has been implanted, the device can be pulled through the subxiphoid region to the abdominal wall, where, through a separate

409

incision or an extension of the median sternotomy incision, an appropriate pocket can be created. Regardless of the electrode type chosen, appropriate anchoring of the electrode to the epicardial surface is crucial. Our approach is to insert the electrode into the myocardium and determine the threshold strength-duration curve. If it is acceptable, the electrode is sutured to the epicardial surface, and the thresholds are rechecked. Suturing the electrode to the surface theoretically reduces movement of the electrode tip within the myocardium, with less formation of fibrotic tissue and better long-term performance of the electrode. When the fishhook electrode is used and there is significant epicardial fibrosis, unbending of the barb to permit deeper penetration is often beneficial. Several types of myocardial electrodes should be available to the physician during implantation, to address any situation encountered. When the steroid-eluting electrode is used, a suitable position is found by holding the electrode in contact with the epicardial surface and quickly determining the voltage threshold at a single pulse width. If it is acceptable, the electrode is sutured to the epicardial surface, and a complete strength-duration curve is determined. Often, several sites must be tested before a suitable site is found. When using the bipolar version of this electrode, proper orientation of the two heads to each other is mandatory to achieve optimal sensing. For atrial implantation, the interelectrode axis should be perpendicular to the long axis of the ventricle, to minimize FFRW sensing. For ventricular use, however, the interelectrode axis should be parallel to the ventricular long axis, to maximize FFRW sensing. A gentle loop of the electrode should be left in the thoracic cavity to allow for some growth, but excessive loops should be avoided. Cases of entrapment of vascular structures by pacemaker electrodes have been reported.65,66 The extra length of the electrode is easily coiled and placed within the generator pocket; even this may allow for some growth, because the electrode wire slowly uncoils with growth of the patient. The exact placement of the abdominal pocket is generally left to the discretion of the surgeon. However, it should be placed away from the belt line and not in the right upper quadrant; placement there interferes with subsequent assessment of hepatic size, which may be important in children with structural cardiac disease. The electrodes should be tunneled from the thorax to the abdomen as near the midline as possible, to minimize the risk for electrode fracture. The placement of unused electrodes is not recommended. It was once believed that the placement of an unused electrode would provide a “spare” electrode that could be used if the primary electrode failed, thus precluding the need for a second thoracotomy. It was found, however, that if the primary electrode failed, the redundant electrode likely was also unusable.67 Therefore, the extra electrode provided no benefit to the child. ENDOCARDIAL IMPLANTATION TECHNIQUES Before endocardial implantation, echocardiography should be performed to make certain no contraindications to endocardial implantation exist—specifically, tricuspid valve dysfunction, right-to-left shunting, interatrial communications, or SVC obstruction. Whether the pacemaker is placed under the left or right clavicle is somewhat arbitrary but may be important for some patients, and the location should be discussed with them. Our general policy is to place the pacemaker on the side opposite the patient’s handedness (righthanded, pacemaker on left side). The endocardial approach used for implantation in children is similar to that in adults. Before beginning, transcutaneous pacing electrodes are placed to provide emergency pacing ability. A sudden decrease in intrinsic heart rate caused by the stress of the procedure or the general anesthesia, if administered, is not unusual. Although placement of a temporary transvenous pacing electrode can be done, the stress of this procedure alone can cause bradycardia. In addition, the risk for infection of the permanent system by the temporary electrode

410

SECTION 2  Clinical Concepts

must be considered. Transcutaneous pacing electrodes for all sizes of children are now available and function well. Next, venous angiography is performed to assess the anatomy and patency of the axillary and subclavian vein, as well as SVC patency. With a left-sided implant, presence of a left-sided SVC should be excluded. While introduction of electrodes through a left SVC can be done, we prefer to avoid this unless there is no option. Whether the electrode is introduced into the vascular system by a direct subclavian vein puncture,37,68,69 a cephalic vein cutdown procedure,9,38 or axillary vein puncture should be guided by the experience of the implanting physician. In our institution, direct vein puncture is used exclusively. Our approach is to enter the subclavian or axillary vein percutaneously and introduce a guide wire. An incision is then made laterally either along the deltopectoral groove or in the axilla,70 if the axillary vein approach is chosen. For the more common subclavian vein approach, the dissection is then carried down to the pectoral muscle. At this point, the depth of subcutaneous tissue is examined to determine whether tissue is sufficient to cover the generator. In many children, this tissue is inadequate, and placement of the generator above the pectoral muscle results in a significant pacemaker bulge as well as an increased risk for pacemaker erosion and trauma to the tissue covering the pacemaker.69 This is also psychologically important, because many children are self-conscious about a prominent bulge. If the tissue is believed to be inadequate, the dissection is carried through the pectoral, using blunt dissection to separate the muscle fibers, and a pocket is created in the subpectoral region. For the axillary approach, the pocket is always created under the pectoral muscle.71 After a pocket adequate to accommodate the pacemaker is created and the guidewire is incorporated into the pocket, a sheath and dilator are introduced into the subclavian vein over the previously positioned guidewire. The electrode is then passed into the right atrium, together with a new guidewire. The sheath is then removed. Retention of the guidewire allows for the introduction of a second electrode, in the case of a dual-chamber implant, or the option to remove the prior electrode and replace it without having to repuncture the subclavian vein. Some prefer to perform two separate vein punctures for introduction of two guidewires. This has the advantage of separating the entry sites of the electrodes such that manipulation of one is less likely to affect the other. Also, having two smaller holes in the vein rather than one larger hole may decrease bleeding. After the electrodes have been positioned and tested, any retained guidewire can be removed. The electrodes are then connected to the generator and placed in the pocket. For the lumenless Medtronic Model 3830 electrode, a slightly different technique is required. Rather than introduction of a sheath and dilator over the guidewire, a splittable guiding catheter and dilator are introduced and advanced over the guidewire into the desired chamber. The two styles of guiding catheters are deflectable and fixed curve. The deflectable catheter allows for fine control over tip position; however, current models are 9 French (9F) in diameter, requiring a hole in the vein much larger than the pacing electrode. The fixed-curve 7F catheter requires a smaller hole, but the curve style must be chosen before introduction. Several curve styles and sizes are available. Once the catheter tip is positioned at the point of electrode attachment, the wire and dilator are removed. The pacing electrode is then introduced through the catheter, emerging at the point of attachment. The pacing electrode is rotated 3 to 4 turns to affix the electrode tip in the endocardium. Electrode testing is then performed, and if adequate, a large loop of catheter is introduced. This is critical, because once the guiding catheter is removed, advancement of the electrode is difficult if not impossible. Once the catheter is removed, final position is achieved by carefully pulling back on the electrode. If two electrodes are to be placed, we often keep both guiding catheters in place until both electrodes are in place and tested. This reduces the chance of moving the first catheter with the second, necessitating repuncture of the vein; electrode repositioning is not possible once the guiding catheter has been removed. After removal of all guiding catheters, electrode sensing

Figure 18-34  Chest radiograph showing placement of endocardial electrode, which has been introduced through atrial wall, passed through atrioventricular valve, and secured to ventricular endocardial surface. The electrode is tunneled to the generator pocket in the abdominal wall.

should be retested because small changes in electrode orientation can affect the measured values. Another implantation approach is a hybrid of the epicardial and endocardial methods previously described. In some patients, transvenous implantation would be preferable but there is no venous access; the electrode can be inserted into the atrium through an incision in the atrial wall, then advanced into the ventricle across the AV valve.70 The atrial incision is closed with a purse-string suture after the electrode has been positioned in the ventricle. This provides the advantages of endocardial pacing with improved thresholds when venous access to the ventricle is not available. We have employed this approach in children with unacceptable epicardial electrode thresholds but with no venous access (Fig. 18-34). This can be especially useful after a right-sided heart bypass (Fontan) procedure, even though anticoagulation is necessary because of implantation within the systemic ventricle.45 The optimal site within the right ventricle for electrode placement has been questioned. Initially, the RV apex was used because it affords a stable site. However, the alteration of excitation sequence may lead to altered hemodynamics.72,73 Studies suggest that apical pacing may induce long-term changes in both RV and LV performance. Midseptal pacing may be more hemodynamically beneficial, but it is more difficult to achieve a stable electrode position with this approach.73 Use of the Medtronic 3830 using the guiding catheter makes midseptal positioning easier to obtain. ACUTE ELECTRODE EVALUATION After placement of the electrode, its electrical characteristics must be determined. For active-fixation or intramyocardial electrodes, 15 minutes should be allowed after placement of the electrode before threshold testing, to permit acute myocardial changes caused by electrode entry into the myocardium to subside. All changes do not subside in this period, but this short delay is warranted. Our initial approach



18  Pediatric Pacing and Defibrillator Use

411

+20 mV

+10 mV

–10 mV

A

–20 mV

+20 mV

+10 mV

–10 mV

B

–20 mV

Figure 18-35  Electrograms after acute endocardial placement of active-fixation electrode. A, Note the injury current present, making it impossible to determine waveform amplitude accurately. B, After 15 minutes, injury current (bar) has decreased, allowing accurate measurement of EGM amplitude. The true amplitude is much lower than the magnitude of the injury current in A. Also, thresholds may be adversely affected in the presence of injury current. All measurements should be postponed until it has resolved.

STRENGTH-DURATION CURVE OBTAINED AT IMPLANTATION 1.6 1.4 Current Volts

1.2 Volts MA

is to measure the electrode’s impedance and, if possible, the intrinsic EGM amplitudes. The impedance should be between 200 and 600 Ω for an epicardially placed electrode (values up to 1200 Ω can be acceptable with bipolar Medtronic 4968 electrode) and between 300 and 700 Ω for an endocardially placed electrode. The amplitude of the EGM should be sufficient to allow appropriate sensing by the generator being implanted. Care must be taken to avoid measurement of injury current rather than true signal amplitude (Fig. 18-35). Also, pacing thresholds can be adversely affected in the presence of injury current, and all measurements should be postponed until it resolves. The minimally acceptable spontaneous signal amplitude varies, depending on the specific generator. If these measurements are found to be acceptable, threshold testing is performed. It is our general practice to set a given pulse width and then determine the minimum pulse amplitude necessary to maintain capture. Multiple threshold determinations at differing pulse widths are performed to define the strength-duration curve adequately. It is important to determine the shape of the strength-duration curve to ensure that the minimum pulse width necessary to pace at any pulse amplitude and the minimum amplitude necessary to pace at any pulse width are sufficiently removed from the proposed generator settings, to allow for some movement in the strength-duration curve without risking loss of capture (Fig. 18-36). Data from the MPPR suggest that the ventricular threshold of a new electrode at a 0.5-msec pulse width is less than 1 V, and for the atrium, less than 1.5 V. Such threshold guidelines apply to both endocardial and epicardial electrodes.

1.0 0.8 0.6 0.4 0.2 0.0 0

0.2

0.4

0.6

0.8

1.0

Pulse width (msec) Figure 18-36  Example of strength-duration curve determined at implantation. From this curve, the minimum voltage needed to pace at any pulse width and the minimum pulse width needed to pace at any voltage can be determined.

412

SECTION 2  Clinical Concepts

A

B Figure 18-37  Posteroanterior (A) and lateral (B) chest radiographs from a patient who underwent endocardial electrode implantation after performance of an atrial switch (Senning) procedure for dextrotransposition of the great arteries. Note the electrode position in the left ventricle, away from the ventricular apex and the diaphragm, to avoid diaphragmatic stimulation.

Before the pulse generator is connected to the electrodes, it is advisable to pace the ventricle at the maximal output of the pacing system analyzer. In children, because the diaphragm is close to the electrode, diaphragmatic pacing can occur. If diaphragmatic pacing occurs at the maximal pacing system analyzer output, the electrode must be moved. This is particularly relevant for children with transposition of the great arteries, in whom a ventricular electrode is positioned within the left ventricle. Positioning of the electrode tip at the LV apex puts it close to the diaphragm, and there is a high incidence of diaphragmatic pacing. To prevent this, we position the electrode on the midposterior free wall at the approximate level of the papillary muscles (Fig. 18-37). This affords acceptable thresholds with a minimal risk for diaphragmatic pacing. This problem is more often seen in endocardial pacing than in epicardial pacing, but it can occur in either setting. Diaphragmatic stimulation can be seen with atrial pacing as a result of phrenic nerve stimulation. Thus, high-output atrial pacing must also be performed.

Follow-Up Methods for the Child with a Pacemaker Proper pacemaker programming and early recognition of inappropriate pacemaker performance require frequent, methodical, and appropriate follow-up. Pacemaker follow-up can be divided into three periods, based on time since implantation. The two most crucial periods are the first 2 months after implantation (early follow-up) and when the pacemaker approaches its theoretical life expectancy (late follow-up). Between these two periods, the functions of the pacemaker and electrode remain fairly stable, and the generator does not require frequent readjustment (intermediate follow-up). Problems can occur, however, particularly as a result of electrode breakage in the active child. This section discusses the major components of pacemaker follow-up—pacemaker clinic visit, 24-hour ambulatory ECG recordings, enhanced remote and transtelephonic monitoring, and treadmill

exercise testing—followed by a description of the differences among the three follow-up periods. PACEMAKER CLINIC VISIT During a pacemaker clinic visit, all patients undergo a complete history and physical examination, pacemaker interrogation, threshold testing, evaluation of electrode sensing, and routine ECG testing. When indicated, other tests, such as chest radiography and echocardiography, are also performed. Specific attention must be paid to obtaining a complete history as it relates to potential pacemaker malfunction. Symptoms suggesting pacemaker malfunction include sudden exercise intolerance, dizziness, nausea, and loss of consciousness. In particular, parents often note that their child has “less energy.” A common symptom in patients with intermittent atrial sensing malfunction is a sudden lack of energy or transient dizziness, related to loss of atrial sensing with a resultant acute drop in the pacing rate to the LRL of the pacemaker. This can often be a subtle finding and must be carefully sought, not only in the older child from whom a history can be obtained directly, but also from the parents of the younger child, who must be asked whether they have ever noted sudden changes in the child’s activity state or temperament, sudden interruptions of playtime, interruptions of eating, or sudden staring episodes suggestive of acute decrease in cardiac output. The physical examination should relate specifically to complications produced by the presence of pacemaker electrodes, such as AV valve incompetence, acute appearance of pericardial rubs (suggesting lead perforation), irregular heart rates, pocket infections, or in unusual situations, stenotic lesions, suggesting extracardiac compression of vessels by the epicardially implanted pacemaker electrodes. Pacemaker interrogation must include programmed settings and pacemaker performance data, comprising the electrode’s impedance, the generator battery’s voltage and cell impedance, the generator’s measured pulse amplitude, the electrode’s current flow, the energy



delivered, the pulse width, and the measured magnet rate. Such parameters can often reveal early signs of electrode dysfunction or approaching generator end-of-service life. Electrode impedance changes are of particular usefulness in indicating early exit block (manifested as increasing impedance) and insulation fracture or erosion of the electrode tip (manifested as a decline in electrode impedance). Interrogation of the pacemaker’s diagnostic counters is then performed to assess the extent of pacemaker use and the rate variability the patient is experiencing. Information provided by diagnostic counters is variable, depending on the pacemaker model. The most useful data are those collected over many months to assess degree of the pacemaker’s rate variability and the patient’s dependence on the pacemaker. This information is useful in assessing the appropriateness of the LRL in DDD pacing, the degree of AV conduction, and sinus node function (Fig. 18-38). Intracardiac EGMs are then recorded. The usefulness of such tracings is discussed later. Sensing thresholds are also performed to determine the least sensitive settings that still maintain appropriate sensing. Lastly, threshold determinations from both atrial and ventricular leads are obtained. Voltage thresholds both at a fixed pulse width and pulse width thresholds at a fix voltage are performed. All threshold determinations are performed in duplicate. Thresholds are reported as the minimum value that maintains 100% capture at each fixed setting. From these data, strength-duration curves are constructed and compared with previously obtained curves to detect shifts. After review of the data, appropriate programming decisions can be made. INTRACARDIAC ELECTROGRAM DETERMINATIONS Intracardiac EGMs should be obtained whenever possible. Electrograms are obtained both simultaneously with a surface electrocardiogram and with telemetered annotation markers that indicate the point during the EGM at which sensing or pacing occurs and the beginning and length of each refractory period. The relationship of programmed refractory periods to the waveform is shown. This is particularly useful for the atrial channel, to ascertain the appropriateness of the programmed settings. For example, if the atrial electrode has been implanted in the left atrium, a determination of the appropriate AV interval can be difficult because the spontaneous P wave on the body surface significantly precedes the time at which atrial sensing occurs (Fig. 18-39). This results in a prolonged PR interval, as determined from the surface ECG recording, which may raise concerns about appropriate generator function. Recording the annotation markers with the intracardiac EGM also permits minimization of refractory periods, to maximize the multiblock rate but not risk oversensing of ventricular depolarization or repolarization by the atrial channel (Fig. 18-40). This is an even greater concern in young children who experience high atrial rates and are at risk for multiblock, with a subsequent sudden decrease in the ventricular rate and a concomitant decrease in cardiac output if TARP is too long (see later discussion on results of exercise testing). We also find the intracardiac EGM to be helpful in determining decreasing atrial amplitudes over time, with the potential for loss of atrial sensing. As the electrode ages and the tip fibroses, recorded EGM amplitudes may decline, and appropriate changes in atrial sensitivity often need to be made. This is particularly relevant to exercise, during which atrial amplitudes may further decline. The intracardiac EGM is also useful in the diagnosis of atrial dysrhythmias. In the active child, presence of a high pace rate may not be unusual or may suggest an atrial tachycardia. An example of such a situation is in the presence of atrial flutter (Fig. 18-41). In the first example in the figure, the rapid atrial rate was apparent on the body surface ECG recording, and the ventricular pacing was at the URL. In the second example, the body surface ECG recording showed an apparently regular rhythm at a rate below URL; atrial EGM showed atrial flutter, with every other atrial beat in the refractory period.

18  Pediatric Pacing and Defibrillator Use 294–03 SN 011821 Ventricular rate histogram Range (BPM)

413

Apr. 28 ‘93 9:07 AM DDD Numbers of events

70

. . . . .24405 (1A)

80

. . . . .41265 (2A)

100

. . . . .34288 (3A)

120

. . . . .16113 (4A)

170

. . . . . . . .37 (5A)

300

A

Filled bars – percent actual events

Rate bins (PPM)

Total events/ term

% Total events

<55 55–64 65–74 75–84 85–94 95–104 105–114 >114 Total

0 0 0 21846 198 0 0 0 22044

0 0 0 99 1 0 0 0

% Paced 1 25 50 75 to to to to 0 24 49 74 99 100 * * * * * *

* *

B Diagnostic data (cardiac cycles) DDD mode Event counters last cleared... Sep. 9, 1:50 PM Number of: Premature ventricular events ..................57 Atrial pace events followed by ventricular sense event ....................13 Atrial pace events followed by ventricular pace event .............648,815 Atrial sense events followed by ventricular sense event ..................308 Atrial sense events followed by ventricular pace event ........16,777,215

0% 0% 4% 0% 96%

Percent paced – atrium ...........................................4% Percent paced – ventricle ....................................100%

C Figure 18-38  Examples of data obtained from generator diagnostic counters showing the number of beats occurring in each rate range.  A, Patient had acceptable heart rate variability with predominantly atrial pacing and ventricular sensing (intact AV conduction). B, Patient had minimal heart rate variability; reprogramming to a rate-responsive mode was required. C, Information about the types of atrial and ventricular beats occurring. This patient had mostly atrial and ventricular sensing. There was less than 20% atrial pacing, indicating an appropriate lower rate limit. The MVP feature has been enabled to promote AV conduction and minimize ventricular pacing (see Fig 18-11).

EXERCISE TESTING Exercise testing should be an integral part of all pacemaker follow-up in children old enough to undergo treadmill testing. Such testing often pinpoints inappropriate programming, manifested by inappropriate performance. In one series, 43% of patients had clinically significant inappropriate programming while exercising that was not apparent on routine pacemaker testing.74-75 Of these patients, 75% showed an inadequate heart rate increase with the stress of exercising. Although most

414

SECTION 2  Clinical Concepts

A

B Figure 18-39  Intracardiac electrogram from patient with left atrial pacing. In both panels, the top recording is the atrial EGM, and the bottom recording is the body surface electrocardiogram (ECG). A, During atrial pacing, the atrial EGM and the surface P wave occur close to each other. B, During atrial sensing, surface P wave now precedes the atrial EGM by a considerable time.

were paced in the VVIR mode, one patient in the DDD mode was shown to have an inadequate exercise response indicative of chronotropic incompetence. All such patients underwent reprogramming with subsequent appropriate heart rate increases. Other patients displayed spontaneous beats at maximal exercise, causing an automatic extension of the PVARP and acute multiblock, with an acute decline in the heart rate (Fig. 18-42). The development of multiblock was also seen with an acute decline in the heart rate from an inappropriately long TARP. The multiblock rate was only slightly above the URL, causing an abrupt decline in heart rate (Fig. 18-43). If decreasing the AV interval or the PVARP cannot adequately shorten TARP, use of the DDDR or VDDR mode may be helpful. When the multiblock rate is reached during either of these pacing modes, the ventricular rate falls to the sensor rate rather than the inappropriately sensed atrial rate, providing a smaller decline in the heart rate. Loss of capture at the maximal heart rate was also observed, even though there had been 100% capture at rest and programming of the pacemaker was believed to be appropriate, based on resting threshold testing (Fig. 18-44). Changes in pacing thresholds do occur and can worsen, as the previous example shows, or can improve.26,76 For fixed-rate pacing, thresholds decline after exercise, so resting thresholds are not necessarily indicative of those present during the stress of exercise (Fig. 18-45). However, these findings may not be applicable to the patient whose AP VP

pacemaker is in the rate-responsive mode, as the example in the patient who developed loss of capture at maximal exercise showed. This is a potentially serious problem that would not have been apparent had evaluation been performed only while the patient was at rest. Changes in P-wave amplitude were also documented at maximal exercise.77-79 A decrease in P-wave amplitude can result in loss of atrial sensing; in the DDD mode this can cause an immediate drop to the LRL of the pacemaker. The result can be syncope caused by a sudden decrease in cardiac output. Although DDDR pacing can minimize the magnitude of this heart rate drop, the physician should not rely on this mechanism, because the sensor rate may not be the same as the atrial rate, especially during activities such as swimming or cycling. Myopotential sensing by either channel can have similar effects.80,81 This is more evident in unipolar systems, but can occur in bipolar systems. AMBULATORY ELECTROCARDIOGRAPHIC MONITORING Ambulatory ECG monitoring is also essential in the appropriate follow-up of pediatric patients with pacemakers. This is particularly true for patients who are unable to exercise, because it may be the only method to evaluate high-rate performance. In many series, 24-hour ambulatory ECG monitoring was the only means by which pacemaker AS

VP

Figure 18-40  Intracardiac electrogram recorded in DDD mode. Annotation markers show the times of onset and termination of the various refractory periods. The dashed line after a denotation of atrial pacing (AP) or atrial sensing (AS) shows the duration of the total atrial refractory period (TARP), indicating it is of significant duration to prevent inappropriate sensing by the atrial amplifier of ventricular events. The dashed line after a ventricular pacing (VP) shows the duration of the ventricular refractory period but is of little use in this recording.



18  Pediatric Pacing and Defibrillator Use

AR

AS

AR

AS

MPR

AR

AR

MPR

AS

AR MPR

AS

AR

AR

AS

MPR

AR

415

AR MPR

A

AS

AR VP

AS

AR VP

AS

AR VP

AS VP

AR

AS VP

AR

AS VP

AR

AS VP

AR

B Figure 18-41  Atrial electrograms from two patients in atrial flutter. A, The time of atrial sensing (AS) is variable, as is the atrioventricular interval, because the pacemaker is at the upper rate limit (URL), or maximal paced rate (MPR). Many atrial beats are ignored as they fall in the atrial refractory period (AR). The changing total atrial refractory period (TARP) is a result of the Wenckebach behavior imposed by URL. B, There is a definite 2 : 1 block, and the pacemaker is not at the URL. The only suggestion of atrial flutter on the surface electrocardiogram was that the heart rate was completely regular. VP, Ventricular pacing.

malfunction was detected.82-84 Such monitoring is particularly valuable in evaluating atrial and ventricular sensing problems and intermittent lack of capture. This is important because myocardial characteristics and thus appropriate pacemaker programming may vary, depending on the activity state and time of day.30 Interactions between the patient’s intrinsic rhythm and the pacemaker are also more completely evaluated by ambulatory monitoring, potentially resulting in more optimal programming. REMOTE AND TRANSTELEPHONIC PACEMAKER MONITORING Transtelephonic pacemaker monitoring also plays an important role in pacemaker follow-up and has undergone major changes. Previously, transtelephonic monitoring consisted of only a real-time electrocardiogram with and without magnet application. This did provide some information, but was often difficult to perform in the uncooperative child. No stored data or trend data were available. Newer remote systems permit complete pacemaker interrogation of current and stored information, together with real-time EGMs and electrode threshold data performed automatically by the pacemaker in the ventricle,84 and more recently in the atrium.85 If interrogation is interrupted during data retrieval, it is halted until reception is again established, and retrieval resumes. This is particularly helpful in the young, uncooperative patient. When interrogation is complete, the data are transmitted in digital form to a central computer, eliminating the need for simultaneous data retrieval and telephone transmission. An example of such a system is the Medtronic CareLink system. Similar remote systems include Merlin.net (St. Jude Medical) and Biotronik Home Monitoring Service and also allow pacemaker follow-up. Benefits of such a system for early determination of potential problems have recently been evaluated.86 Other systems, such as

Latitude (Boston Scientific), allow remote follow-up of ICD devices but not pacemakers. In the protocol used at our follow-up clinic, the patient sends a transmission according to a predetermined schedule at a convenient time. If this is only a routine transmission, nothing further is required from the patient. If there are concerns, the patient calls the clinic and relates the concerns to the pacemaker nurse or technician. Each morning, the system is interrogated and new transmissions are retrieved. If problems are found, the patient is contacted. If the patient has concerns during nonbusiness hours, the on-call physician can be contacted and can retrieve the transmission from any computer. The data are reviewed, and the information is relayed to the patient and the responsible cardiologist. The information provided is summarized on the first page of the report. It indicates battery status, electrode thresholds and long-term trends, electrode impedances and long-term trends, counter data (percent paced and sensed in each chamber and number of high-rate episodes), and current programming. Subsequent pages provide a real-time EGM, magnet response, and stored EGMs from high-rate episodes. This information is equivalent to that obtained in a clinic visit. Although the system does not permit reprogramming or simultaneous recording of a surface ECG, it may otherwise obviate the need for a clinic visit if no problems are seen. For the standard transtelephonic system, longer rhythm strips must be run to assess pacemaker function if a motion artifact is present. Routinely, 60-second strips are run to ensure that adequate data are obtained. Both nonmagnet and magnet strips are obtained, as in adult patients. We allow the parents to choose the best time of day to call; they often vary the time they call, based on nap or school schedules. Transtelephonic monitoring is cost-effective, decreasing the number of outpatient visits needed, and also provides a method to address parent/child concerns about proper pacemaker function.87 The

SECTION 2  Clinical Concepts

05:40:00

05:20:00

05:00:00

04:40:00

04:20:00

04:00:00

416

Figure 18-42  Continuous ECG recording during exercise treadmill testing shows the development of spontaneous beats at maximal exercise. This resulted in automatic extension of the postventricular atrial refractory period (PVARP), with an overall decline in the heart rate from 167 to 141 bpm. This was associated with sudden fatigue and near-syncope and was corrected by elimination of automatic PVARP extension. Paper speed is 12.5 mm/sec, with each row representing 20 seconds. The time since onset of exercise is noted by the numbers in the left margin.

capability of the child or the parent to detect pacemaker malfunction is very limited.88 Use of transtelephonic ECG monitoring not only can confirm pacemaker malfunction but also can reassure the parent and child of proper function. EARLY FOLLOW-UP PERIOD Follow-up during the crucial early period must be frequent and thorough. This is especially true after a new electrode has been implanted. Our current protocol includes both pacemaker interrogation and noninvasive threshold determination at multiple pulse amplitudes performed at 1 day, 6 weeks, and 12 weeks after implantation. During this period, thresholds often vary, and the generator’s output may also need to be reprogrammed to maintain reliable pacing. Exit block, in particular, is common during this period, whereas little to no exit block is noted beyond 3 months.87 In another series, there appeared to be a slight increase in threshold after 3 months, but this occurred in only 24% of patients.88 It is important to determine thresholds at multiple pulse amplitudes, because the strength-duration curve can move in a horizontal direction, with thresholds at the higher outputs unchanging and thresholds at lower outputs showing marked increases (Fig. 18-46). In addition, 24-hour ambulatory ECG monitoring is performed within the first week after implantation to assess proper pacemaker function throughout the day, not only for a brief period during

pacemaker interrogation. For children old enough to undergo exercise testing, this is performed the first month after implantation. Remote or transtelephonic monitoring is done monthly during this period. INTERMEDIATE FOLLOW-UP During the intermediate follow-up period, defined as 3 months to 5 years after implantation, there tends to be only a small incidence of electrode or generator malfunction. Pacing systems tend to be more stable during this time and do not require as frequent reevaluation. Our current protocol is to see patients annually for pacemaker interrogation and threshold testing and to obtain 24-hour ambulatory ECG recordings if indicated. Remote or transtelephonic monitoring is done bimonthly unless complicating features are believed to require more frequent monitoring. In addition, patients and parents are encouraged to send transmissions whenever there is a question about proper pacemaker function. With the enhanced remote follow-up systems, fewer in-office follow-up visits may be needed. LATE FOLLOW-UP During the period from 5 years after implantation to pacemaker replacement, generator failure is more likely than electrode failure. Although electrode failure does occur, the thresholds, in general, tend

18  Pediatric Pacing and Defibrillator Use

417

11:40:00

11:20:00

11:00:00

10:40:00

10:20:00

10:00:00



Figure 18-43  Continuous ECG recording during exercise testing shows the development of multiblock with an acute decline in the heart rate, resulting in syncope. Patient’s upper rate limit was 180 bpm, with a multiblock rate of 187 bpm. This lack of difference between URL and multiblock rate provided no gradual heart rate decline but rather an acute decline in heart rate and cardiac output. The multiblock rate was increased by shortening the postventricular atrial refractory period. Paper speed is 12.5 mm/sec, with each row representing 20 seconds. The time since onset of exercise is noted by the numbers in the left margin.

to be stable, and most electrode failures during this period are a consequence of acute lead fracture and not exit block. There usually is no warning of lead fracture, and no current follow-up method has been useful in predicting such events. However, depletion of the generator’s battery can be adequately detected early through the use of monthly transtelephonic ECG monitoring. Ambulatory ECG recordings are still obtained yearly.

single-center experience with 11 children age 4 to 16 years,90 use of nonthoracotomy electrode systems in 17 children age 12 to 20 years,91 and a larger single-center experience with 27 patients.91 The issues surrounding the use of ICDs in children involve appropriate patient selection, selection of epicardial versus endocardial implantation and the techniques involved, appropriate tachyarrhythmia detection and therapy programming, and appropriate follow-up.

Antitachycardia Devices in Children with Congenital Heart Disease

PATIENT SELECTION

IMPLANTABLE DEFIBRILLATOR USE The use of ICDs in children had been limited by many factors, including uncertainty of the indications for use, device size, and the difficulty initially of implanting the epicardial electrodes. Randomized studies are lacking in patients with structural heart disease to determine those at highest risk who would receive the greatest benefit from ICD placement. With additional experience in the adult population and smaller devices and electrodes, both epicardial and endocardial, the pediatric use of ICDs has increased. Studies include a large multicenter experience with initial use of ICDs in children age 1.9 to 20 years,89 a

The only current class I indication for ICD placement is for secondary prevention in patients who have sustained an aborted sudden cardiac death (aSCD) episode not amenable to surgery or ablation. In all the series mentioned, all patients had experienced a syncopal or sudden cardiac death (SCD) episode documented to be a ventricular arrhythmia or had an inducible ventricular arrhythmia at electrophysiologic study after their syncopal or SCD event. Silka et al.89 found that 76% of children were survivors of an SCD episode, whereas 10% had experienced a syncopal episode with inducible sustained ventricular tachycardia; the remainder had drug-refractory VT. The underlying diagnoses were hypertrophic cardiomyopathy, long QT syndrome (LQTS), dilated cardiomyopathy, or repaired congenital heart disease.

SECTION 2  Clinical Concepts

07:40:00

07:20:00

07:00:00

06:40:00

06:20:00

06:00:00

418

Figure 18-44  Continuous ECG recording during exercise testing in a patient who developed acute intermittent loss of capture at maximal exercise. Threshold testing at rest indicated excellent thresholds, with the minimal pulse width necessary to pace being 0.15 msec at 5.4-V amplitude. Programmed settings were pulse width of 0.5 msec and amplitude of 5.4 V. At rest and during early exercise, there was 100% capture; loss of capture occurred only at maximal exercise. Pulse width was subsequently increased to 1.0 msec, with no loss of capture on repeat testing. Paper speed is 12.5 mm/sec, with each row representing 20 seconds. The time since onset of exercise is noted by the numbers in the left margin.

Fewer than one-half the children had depressed ventricular function. In general, any child who has survived an SCD episode or has a condition that can result in SCD should be considered for ICD implantation. Medical therapy should always be employed, but one must decide whether medical therapy alone will completely eliminate the likelihood of a repeat episode. By example, the patient with LQTS who has experienced an aSCD episode should be treated medically and should also undergo ICD placement. Conversely, a child with congenital complete heart block and a documented episode of ventricular fibrillation (VF) may require only permanent pacing. Although cardiomyopathies and primary electrical diseases constitute the most common diagnoses requiring ICD placement, children who have undergone repair of congenital heart disease are beginning to present with malignant ventricular arrhythmias. Patients with tetralogy of Fallot, aortic stenosis, and transposition of the great arteries after atrial switch repair have been identified as higher-risk patients.89 In our experience, 15% of all patients receiving ICDs had undergone prior repair of tetralogy of Fallot. Children with this diagnosis accounted for 22% of patients in one report.92 Any child who has undergone a ventriculotomy or repair of a coronary artery abnormality is at risk for ventricular arrhythmias. There are fewer data to support guidelines for which pediatric patients would benefit from an ICD for primary prevention. The most

recent guidelines list implantation for high-risk patients without syncope as a class IIb indication (class IIb defined as probably useful but less well established by evidence).19 Patients with inherited arrhythmias such as the malignant types of LQTS, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT) are often considered for ICD placement for primary prevention. Minimal data support ICD use in patients based solely on QRS duration. In tetralogy of Fallot, QRS duration is caused mostly by RV enlargement, and risk of VF is unknown. Our practice has been to place an ICD for episodes of documented VT or VF, syncope with an unknown etiology, or inducible VT at electrophysiologic testing. Placement for primary prevention is rare in our hands. IMPLANTATION APPROACHES Two decisions affect ICD implantation: epicardial versus endocardial electrode placement and subclavicular versus abdominal device placement. Each can be made independently of the other. Initially, only epicardial electrode placement was used in children because of the large size of the transvenous electrode and the inappropriate shocking coil spacing, or the need to place a second electrode. Even with transvenous electrode improvements (discussed later), epicardial placement



18  Pediatric Pacing and Defibrillator Use STRENGTH-DURATION CURVE SHIFT WITH EXERCISE

Pulse width (msec)

1.2

0.9 Pre-exercise Post-exercise

0.6

0.3

0.0 0

1

2

3

4

5

6

Pulse amplitude (volts) Figure 18-45  Data from a patient with fixed-rate VVI pacing who demonstrated a decrease in thresholds after termination of exercise compared with pre-exercise values. At higher pulse amplitudes, there was a minimal change, but marked changes were noted at lower pulse amplitudes. This denotes a shift of the strength-duration curve leftward, implying increased excitability of the heart with exercise. (Data from Serwer GA, Kodali R, Eakin B, et al: Changes in pacemaker threshold with exercise in children and young adults. J Am Coll Cardiol 17:207A, 1991.)

remains the preferred method for smaller children. The smallest child to receive an endocardial system in the study of Kron et al.91 weighed 32 kg, and the smallest in Hamilton et al.90 weighed 27 kg. In our center, the smallest child weighed 15 kg. Historically, we used epicardial patches in children who weigh less than 15 kg or in whom there is no venous access to the ventricle. When used, patches are usually placed to maximize the distance between them and to maximize exposure of the myocardium to the defibrillation energy. Patches are sutured to the pericardium rather than the epicardial surface, to minimize growth effects and patch distortion (Fig. 18-47). With time, distortion can develop, but it does not necessarily have an adverse effect on the defibrillatory thresholds. The

STRENGTH-DURATION CURVE CHANGES WITH TIME

Pulse width (msec)

2/14/93 3/12/93

1.0

0.5

0.0 0

1

2

3

4

leads are then tunneled to the abdomen, and the pocket is created, as for implantation of an epicardial pacemaker system. In one case of a child with absent abdominal musculature, the device was placed intrathoracically. In some patients, even the small patch electrodes may be too large. Recently, we have begun to use coils placed in the posterior mediastinal space medially and along the lateral LV wall laterally or posteriorly behind the ventricular mass. Defibrillatory energy is delivered between these electrodes, traversing the heart in an anterolateral direction (Fig. 18-48). Such an arrangement has resulted in acceptable defibrillatory thresholds, using a multiple coil or a single coil and an active can.93-96 Such systems have shorter longevity than traditional transvenous systems but still afford adequate defibrillation.96 With the development of smaller-diameter transvenous electrodes and use of the device can as the second defibrillation electrode, a transvenous system can be used in most children. The currently available electrodes, both single and dual coil, can be introduced with a 7F to 9F introducer depending on the type of electrode used. However, the intercoil spacing in the dual-coil electrode is usually too large to be used in children. Positioning the second coil properly requires buckling of the electrode within the right atrium, potentially dislodging the electrode tip (Fig. 18-49). Use of the single-coil electrode eliminates this problem. Even with electrode buckling, the SVC coil remains close to the clavicle, placing it at risk for fracture. In addition, the second coil may make extraction more difficult. The second coil may also increase the risk of an extraction procedure later, because it may cause more fibrosis around the SVC coil in an area that is narrow and potentially at the innominate vein–SVC junction, where the lead makes a sharp bend, unlike in the larger child or adult, where the coil seats entirely in the SVC. Use of a single-coil electrode requires that the device can serves as the second electrode; alternatively, a second intravascular coil or a subcutaneous array can be used as the second electrode, if initial defibrillatory thresholds are not satisfactory. Initially, use of the active can was restricted to implantation of the device under the left clavicle. However, we have implanted the device in a left upper quadrant abdominal pocket, with the single-coil, bipolar-pacing, steroid-eluting electrode introduced into the left subclavian vein and tunneled subcutaneously to the device pocket97 (Fig. 18-50). This technique is similar to the method proposed by Molina et al.98 for transvenous pacemaker implantation in small patients. Defibrillatory thresholds have been less than 10 J in all cases, even though the electrode area is reduced.99 No patient has required an additional electrode (subcutaneous array or second transvenous electrode). PROGRAMMING CONSIDERATIONS

2.0

1.5

419

5

Pulse amplitude (volts) Figure 18-46  Example of change with time in strength-duration curve. In this patient, the strength-duration curve shows changes that would not have been apparent if thresholds had been determined only at pulse amplitudes greater than 2.5 V.

The issues of appropriate pediatric programming are similar to those in the adult patient. The major concern is the higher sinus rates that can occur in a child. Initially, β-blockers were employed to reduce the maximal sinus rate. However, this approach often resulted in significant exercise intolerance. Although β-blockers may be indicated to treat the underlying disease (e.g., LQTS), their use solely to reduce the maximal sinus rate is no longer necessary. Current devices can now be programmed to very high rates as a criterion of VT and can also employ other markers, such as increased QRS duration or altered QRS morphology and sudden onset. For most children, however, use of high rate alone is usually sufficient to detect fibrillation. Also, many children have wide QRS complexes as a result of prior cardiac surgery, making the QRS morphology a difficult criterion to use. In practice, we program the device to a detection cycle interval that is 50 msec greater than the documented fibrillation cycle interval, consistent with the approach of Hamilton et al.90 QRS duration is used only if cycle interval alone has been unable to prevent inappropriate therapy delivery. In patients with LQTS, the physician must consider the prolonged T-wave interval and possible T-wave oversensing that can result in double counting of the ventricular rate and inappropriate therapy delivery. Careful testing for T-wave oversensing must be performed at

420

SECTION 2  Clinical Concepts

A

B

Figure 18-47  A, Chest radiograph taken after acute placement of epicardial defibrillation patches in a child. B, Chest radiograph in same child 4 years after implantation shows buckling of the patches, although the defibrillatory thresholds remain low. Note the placement of a transvenous atrial electrode, which was tunneled to the device in the abdomen using a lead extender, because the device had been upgraded to a dual-chamber pacemaker-defibrillator. The epicardial ventricular pacing and sensing electrodes placed originally continue to be used.

implant and at each interrogation. One may also want to consider evaluation of this during exercise testing. FOLLOW-UP PROCEDURES At our center, all children initially underwent induction of VF at implant and 1 week after implantation to ensure that detection and therapy were appropriate. However, if no problems were suspected clinically, defibrillatory thresholds proved to be acceptable in all cases.

Determination of thresholds beyond implantation is now reserved for patients in whom there is a suspicion of system malfunction. At each clinic visit, the device is interrogated, and each recorded event is inspected for cycle length and QRS morphology. Pacing thresholds are also determined, as for pacemaker patients. Transtelephonic systems have been developed to permit interrogation of ICD status remotely. Such systems allow for determination of battery voltage, charge time, electrode impedance, and viewing of event counters, recent events, and real-time EGMs. These systems allow for better

*

Figure 18-48  Anteroposterior (left) and lateral (right) chest radiographs after placement of dual-coil intrathoracic defibrillator system; one coil is in the inferoposterior mediastinum (arrow) and the other in the left lateral chest. Star indicates the pace-sense epicardial electrodes.



18  Pediatric Pacing and Defibrillator Use

421

within 4 years.100 Also, the medical therapy is reevaluated to ensure that it does not require alteration. Finally, the psychological aspects of the child’s reaction to the therapy are evaluated, and support is offered as needed. Assessing the need for long-term support is extremely important, as discussed later. ANTITACHYCARDIA PACING

Figure 18-49  Chest radiograph shows placement of dual-coil singlelead transvenous defibrillator system, with the lead tunneled to the abdomen. Note the buckling of the lead within the atrium, which was necessary to place the distal coil properly within the innominate vein. This could potentially dislodge the right ventricular coil and still leave the distal coil near the clavicle/first rib space.

and more frequent ICD follow-up without the need for repeated clinic visits in otherwise asymptomatic patients. After each therapy delivery, the child is seen in the clinic and the device interrogated, or a remote transmission is sent to evaluate the event and to ensure the therapy was appropriate. This is particularly crucial because inappropriate therapies are not rare. Up to 50% of patients have been found to receive at least one inappropriate therapy

Pace termination of atrial arrhythmias is often used in patients with congenital heart disease.101 This has become possible with the development of a dual-chamber antitachycardia pacemaker with a rate response suitable for use in some patients. Although it does not have defibrillator capabilities and therefore is not suitable for pace termination of VTs, the device has proved useful for treatment of atrial flutter, particularly in postoperative patients, in whom atrial flutter is often seen but is difficult to treat with medication or ablative techniques. The Medtronic AT500 has been used in a series of patients with congenital heart disease and atrial tachycardias.101 The most recent version (Medtronic EnRhythm) has improved functionality and allows enhanced remote follow-up; it successfully terminated the tachycardia in 54% of episodes. Success is influenced by many factors, including proximity of the electrode to the reentrant circuit, atrial size, and the potential for multiple reentrant circuits. It does require placement of both atrial and ventricular electrodes, even if only atrial pacing is anticipated, because ventricular sensing is needed to prevent pacing in 1 : 1 AV rhythms. In addition, these electrodes must be bipolar in configuration, and close electrode spacing is required to minimize far-field oversensing, especially of the atrial electrode. Proper electrode placement and selection are more critical for antitachycardia pacing (ATP) than for routine pacemaker placement. Proper programming of the tachycardia sensing and termination parameters increases its complexity, but these devices provide an important adjunct for patients with drug-resistant atrial tachyarrhythmias, especially when there are indications for bradycardia pacing. However, inherent limitations in this device restrict its use in children (e.g., maximum URL of 150/min, lack of automated threshold determination).

Cardiac Resynchronization Therapy in Patients with Structural Cardiac Disease

Figure 18-50  Chest radiograph shows placement of a single-coil transvenous defibrillator system, with the lead tunneled down the lateral chest wall to the device. This also serves as the second defibrillation electrode and is placed in a left upper quadrant abdominal pocket. Because of small patient size, defibrillation threshold was good, even though the defibrillatory vector is less than ideal.

Cardiac resynchronization therapy (CRT) has the potential to improve function in the patient with structural heart disease. The major issues with the recent use of CRT in this patient population are similar to those in the adult population, including the approach to measure dyssynchrony and to assess improvement.102 However, unique issues exist. Most children being considered for CRT are already paced; they rarely have left bundle branch block unless being paced from the right ventricle, often have right bundle branch block (RBBB), have often had ventricular surgery, may have a systemic right ventricle rather than systemic left ventricle, or only one ventricle, and have multiple anatomic variants, making group comparisons difficult. Indications also continue to vary among patients, making evaluation of efficacy difficult. Therefore, implantation criteria developed for patients with ischemic or even nonischemic disease and LV conduction delays have little relevance. Guidelines for this patient population comparable to adult patients do not exist. Results of initial series on the long-term benefits of biventricular pacing for LV function appear promising.103-106 However, nonresponders continue to be seen in all series, ranging from 10% to 15%, even though available series are small and selection criteria varied. Patients with univentricular hearts in particular appear to have a high number of nonresponders.104 Patients with RV failure and RBBB pose unique problems, with variable results.104,106,107 Dubin et al.107 found an acute improvement in RV dP/dT with RV pacing in patients with intact AV conduction, suggesting a possible role for improved RV function with CRT or multisite pacing. Also, the question of CRT versus combined CRT/ICD remains unanswered.104

422

SECTION 2  Clinical Concepts

Preimplant assessment remains crucial. In our institution, this consists of assessment of the degree of heart failure, including ejection fraction, and assessment of mechanical dyssynchrony using electrocardiographic techniques.108,109 Use of regional measures of velocity and strain by speckle tracking techniques quantitatively measures dyssynchrony by time to maximal velocity or strain of multiple wall segments and calculation of the average time and standard deviation (SD) for each segment about the mean (Fig. 18-51). An SD above 35 msec is considered significant dyssynchrony. This method also allows for identification of the site of the latest mechanical activation to use in determining the optimal LV lead position. This is simplified by epicardial placement over transvenous placement by allowing easier access to a much larger portion of the left ventricle. LV pacing through a coronary sinus electrode in small children can be problematic because of the small size of the coronary sinus, anatomic variation (especially presence of left SVC draining to sinus), and possible long-term need for such therapy. Given the coronary sinus electrodes currently available, most LV pacing may need to be accomplished through the epicardial route. Intraoperative or body surface ECG mapping has also been proposed to indentify the site

of latest LV activation to determine the optimal site for LV pacing.110 This does narrow the QRS width, but further work is required to see if this has a long-term beneficial effect on LV function. Acute use of multisite pacing in the postoperative patient has also been investigated as a means to improve cardiac function acutely. Zimmerman et al.111 placed temporary pacing leads on the atrium, midanterior RV free wall (ground or positive pole of ventricular pacing), diaphragmatic surface of right ventricle, and distal RV outflow tract. The latter two leads were connected to the negative ventricular pacing pole. With such pacing, blood pressure improved compared with no pacing, and cardiac index improved as well. Although patient numbers were small, the authors concluded that multisite pacing improved RV synchrony and cardiac performance. Pacing sites were chosen specifically to address RV dyssynchrony because many patients had RBBB. Proper programming parameters are largely unknown for CRT in patients with structural cardiac disease. Acute adjustment with measurement of select hemodynamic parameters may be of some help, but long-term benefits may not be predicted by acute measurements. Although it is anticipated that CRT will prove beneficial, much work

DYSSYNCHRONY QUANTIFICATION PRE-CRT

SD = 98 msec

POST-CRT

SD = 42 msec

Figure 18-51  Measurement of mechanical dyssynchrony before and after cardiac resynchronization therapy (CRT). Time from QRS onset (left edge of graph) to peak velocity of select points, indicated by the dots on the curves, is measured with an average and standard deviation (SD) of the values around the calculated average. Before CRT the SD was 98 msec, decreasing to 42 msec after CRT.



18  Pediatric Pacing and Defibrillator Use

remains before it becomes an established therapy for this patient population.112

Prophylactic Medication Significant controversy has surrounded the need for prophylactic antibiotic agents in the prevention of subacute bacterial endocarditis in children with pacemakers. The current recommendations of the American Heart Association do not suggest the use of antibiotics in children with pacemakers.113 However, this is influenced by the underlying structural disease that may require such therapy. Prophylactic anticoagulation has not proved useful in children with endocardial pacing systems. Only children with chronic atrial flutter or atrial fibrillation are routinely anticoagulated. We believe that the risk to the active child from chronic anticoagulation is significant, and that the benefit is minimal.

Psychosocial Adjustments CHILDREN WITH PACEMAKERS Comprehensive care of the child with a pacemaker requires awareness of the psychosocial issues faced by children and families. Although there are issues specific to having a pacemaker, such as dependence on a mechanical device and the certainty of periodic surgeries throughout life, the overall challenges are similar to those faced by children with other types of chronic illness. Treatment goals include facilitation of positive child and family adjustments and prevention of avoidable negative psychosocial outcomes. Important illness-related tasks for parents of children with pacemakers include participating in the treatment plan, preserving emotional well-being for themselves and their children, and preparing for an uncertain future.114 Children who are at high risk for emotional or behavioral adjustment problems may benefit from early identification and intervention.115 Because they require lifelong device therapy, these children, by definition, have a chronic illness.116 Because of the underlying disease and permanent need for a device, the children and their families are chronically subjected to stressful experiences, including repeated surgeries, body image changes, and exposure to the possibility of death.117 Although disease severity varies, most patients can anticipate many fruitful adult years, and many are anticipated to have a normal or nearly normal life span. When examining psychosocial outcomes in this population, no significant differences were found between children with pacemakers and comparison children on standardized measures of trait anxiety, selfcompetence, and self-esteem.118 Children with pacemakers were more external in their locus of control orientation than healthy controls, but not significantly different from children with comparable heart disease who did not have a pacemaker.119 Interview data suggested that comparison children were likely to report negative stereotypes about children with pacemakers. However, most chronically ill children make positive adjustments, although an increased risk for psychosocial problems suggests that up to 30% of children with chronic illness demonstrate secondary psychosocial impairment by 15 years of age.120,121 The risk for psychosocial problems in the pediatric pacemaker population can be understood as a response to chronic stress that challenges the adaptive capacities of children and families.122,123 Consistent with this model, negative adjustments are likely to occur when stress exceeds the child’s adaptive capacities. Certainly, there is wide variation in children’s adaptations, and some children are able to make positive adaptations despite extremely stressful circumstances.124,125 Many of the factors linked with children’s adjustments reflect a continuum, with one end representing a protective factor and the other a risk factor. Families who are cohesive and supportive are associated with positive adaptations in children, whereas family functioning that is disengaged and rigid is associated with emotional and behavioral problems in the children.126 Disease-related biomedical factors anticipated to affect children’s adjustments include diagnosis (disease severity, prognosis, treatment),

423

functional impairment, cognitive abilities, and visibility (physical changes).127,128 For children with a chronic illness, diagnosis and disease severity are less important predictors of adjustment than other factors.127 However, the diagnosis of heart disease during childhood may pose particular challenges, for reasons not well understood.129 Biomedical factors that may negatively influence psychosocial outcomes for children with heart disease include early mother-infant attachment problems, neuropsychological changes, learning disabilities, and exclusion from competitive sports.130-132 Inherent childhood factors that may affect adjustment include temperament, developmental stage, and competency.127 For example, an academically gifted child may experience opportunities for self-esteem, socialization, and social recognition that ameliorate the negative effects of having a chronic illness, whereas the child with a learning disability who has a chronic illness is at increased risk for serious adjustment problems.133 Social-environmental factors linked with children’s adjustments include family environment, maternal psychological functioning, family economic resources, and children’s peer relationships. Adaptive, cohesive families who communicate effectively support positive adjustments for children.134,135 Maternal adjustment may play a particularly important role in children’s adjustment,136,137 and persistent maternal distress (e.g., symptoms of anxiety or depression) warrants intervention.127 Economic resources appear to be powerful moderators of children’s adjustment to stressful life circumstances.125,138,139 The quality of children’s friendships is also important, because positive peer relationships are linked with prosocial behavior, academic achievement, stress resistance, and later, adolescent competence.140-142 Conversely, negative child peer relationships are associated with academic failure, aggressive behavior,139,143 and general psychopathology, which persists during adulthood.144 Social isolation and feelings of loneliness are potential sources of emotional distress for chronically ill children and family members.135 Coping methods are the processes used by children and families to accomplish disease-related tasks, maintain normal function, and minimize family disruption. Adaptive parental coping strategies include maintaining family integrity through cooperation and maintenance of an optimistic outlook; maintaining social support, self-esteem, and psychological stability; and understanding the medical situation through communication with other parents and health care providers.145 Coping is a dynamic process that may promote or hinder positive adjustments. Coping methods can be categorized as problem focused or emotion focused; in general, both methods are used by individuals responding to stress.146 Problem-focused coping methods involve actions taken to address a stressful situation, whereas emotion-focused methods are those coping methods that change the emotional reaction to an event, such as altering the perception of the experience, blunting, or denial. The different coping strategies employed by fathers and mothers may be a source of distress in the marriage.147 Children’s coping strategies reflect their developmental stage, and problemfocused strategies precede emotion-focused strategies during childhood.148 Implications for Health Care Providers Knowledge of the factors associated with child and family adjustments, illness-related tasks, and coping methods guide comprehensive treatment for the child with a pacemaker and may be used by providers to clarify what can be realistically influenced within their practices. Comprehensive management of the child with a pacemaker is based on assessments of the child and family, with identification of areas of strength and vulnerability. As described previously, considerable data suggest that key areas to include in the assessment are child functional impairment, school achievement and peer relationships, maternal distress, family functioning, and socioeconomic status. If these factors are favorable, it is highly likely that the child will make a positive adjustment to having a pacemaker. Significant problems in any of these areas suggest the need for further assessment, intervention, and possible referral to a mental health professional.

424

SECTION 2  Clinical Concepts

Provider-Family Interactions Provider-family interactions afford key opportunities for education, support, and intervention aimed at facilitating positive child adjustments. Initial implantation and pacemaker replacement are stressful times for children and families, when many questions and concerns arise. Families are generally more relaxed during routine follow-up visits, making this an optimal time to further the provider-family relationship, explore lifestyle issues, and affirm successes in the child’s life. Because questions often arise between visits, it is important to provide ready access to experienced pacemaker professionals. Communication with providers about the child’s prognosis, appropriate activities, and restrictions is necessary for parents and children to adjust to life with a pacemaker. At initial implantation, many parents are unfamiliar with the use of pacemakers in children and may assume that the child “won’t live long, because only old people get pacemakers.” Conversations with the child and family about what the pacemaker means for the child’s future are important, because emotional well-being is predicated on a hopeful outlook—one that permits belief in a personal and meaningful future.148 As identified previously, feelings of loneliness and social isolation are potential sources of emotional distress for children with pacemakers and family members. Providers can furnish opportunities for social support, both informally, by introducing families in the clinic or hospital, and formally, by sponsoring support groups. Providers can also link families with state and national family support networks and reputable online support groups. Children may benefit from meeting other children with pacemakers in the clinic or from having a “pacemaker pen pal.” One child who attends our clinic was feeling isolated because he “never met other kids who have pacemakers.” A one-time social gathering was arranged with the child, his parents, and three other families who agreed to participate. A pediatric psychologist facilitated the discussion, and the distressed child experienced a more positive mood after the meeting. Education is necessary so that parents can adhere to monitoring protocols, use medical resources effectively, and provide appropriate activities for their children. Areas to be addressed include the symptoms of pacemaker malfunction, appropriate use of transtelephonic monitoring systems, precautions, activity recommendations, and the need for periodic pacemaker replacement. It is our practice to recommend cardiopulmonary resuscitation (CPR) training for all parents with pacemaker-dependent children. Education of the child varies based on developmental stage and other factors. Children who undergo initial pacemaker implantation in infancy or early childhood need ongoing education regarding their disease and treatment to fill age-related gaps in their understanding. When developing a teaching plan, it is important to remember that children’s social network may include nontraditional family members, school personnel, and extended family members. Initial pacemaker placement, or at replacement, is a stressful time for children and families. Parents often have questions about when to talk to their child about the upcoming procedure and what content to include. The aim of preoperative education is to facilitate the child’s ability to cope with the stress of surgery. The timing, content, and methods used to educate children vary with developmental stage and must be individualized. In general, upcoming surgery should be discussed with young children soon before the surgery (24-48 hours). Young children often respond enthusiastically to short play sessions during the preoperative visit, with hospital articles such as anesthesia masks and plastic syringes. An important functional outcome for children with pacemakers is successful integration into the school community. Although there is realistic concern about negative stereotyping by school personnel, some data suggest that parents believe school personnel should be informed about their child’s illness, and that health professionals are the most appropriate people to provide this education.149 To facilitate school integration, we have used a variety of interventions, including participation in parent-teacher meetings at the child’s school, visiting

the child’s classroom, and making pacemaker models and other materials available to the child for school presentations. CHILDREN WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS Minimal data are available regarding the adjustments of children and adolescents after ICD implantation. In nine patients age 13 to 49 years, Vitale and Funk150 reported difficulty sleeping, low energy, and interruptions in planned activities. Problems reported for older patients after ICD implantation include increased anxiety levels, excessive anger, psychological disturbances, sexual abstinence, and restricted physical and social activities.151,152 Some studies emphasize that most older adults appear to make positive adjustments after ICD implantation.153 The pediatric ICD population would also appear to be at risk for the development of psychosocial problems from disease-related factors, including disease severity, functional impairment, and body image changes. Disease severity is significant, because these children have survived, or are at high risk for, a lethal arrhythmia. Many are survivors of out-of-hospital cardiac arrests, with the accompanying fear, drama, and exposure to death. The incidence of anoxic encephalopathy after cardiac arrest is not insignificant; if it does occur, it can be anticipated to affect later adjustment. Visibility is becoming less of an issue; devices are becoming smaller, yet remain large in relation to a child’s body mass. The treatment delivered by the device is another source of distress for patients, with ramifications exceeding the pain and potential embarrassment at therapy (see later discussion). Also, many children who require ICD implantation have inherited diseases, such as LQTS, familial dilated cardiomyopathy, or hypertrophic cardiomyopathy. Therefore, health-related concern extends beyond that child to other family members who may be affected. Because of the hereditary nature and severity of these diagnoses, many families have experienced the death of one or more family members, which adds to feelings of grief, anxiety, and guilt. In our experience, the potential for a life-threatening arrhythmia and receiving a shock are sources of considerable anxiety, particularly for adolescents. Conscious shocks, particularly repeated conscious shocks, can be extremely traumatic. Three adolescent patients with ICDs experienced conscious (appropriate) shocks, and two experienced repeated conscious shocks. After these events, all three patients experienced severe anxiety that persisted longer than 1 month. In two patients, school phobias developed. The other patient was home for summer vacation and, uncharacteristically, would not participate in usual summer activities, preferring to stay at home. One young patient demonstrated classic symptoms of posttraumatic stress disorder, including intrusive reexperiencing of the traumatic event, suicidal thoughts, feelings of detachment, and high levels of anxiety. All three patients required professional counseling, and one was treated with antidepressant medication and biofeedback. All have since returned to school; two are now in college and one in high school. It is important to note that none of these adolescents had a history of psychiatric problems before the ICD. It is known that repeated unpredictable aversive stimuli, in addition to producing fear and avoidance behavior, can have long-term debilitating effects.154 Many of the experiments done on the effects of aversive conditioning actually used unpredictable electrical shocks as the source of the stimuli. Maier and Seligman155 proposed that, in such circumstances, people may develop the expectation that their behavior has little effect on their environment, and this expectation may generalize to a wide range of situations. This behavior mode, referred to as learned helplessness, has been linked with human depression. Complicating the situation for patients with tachyarrhythmias is the catecholamine release that occurs secondary to anxiety. The increased heart rate is often perceived as the possible onset of the arrhythmia, leading to increased anxiety and feelings of loss of control. Relaxation under these conditions can present a challenge for young people. Potential therapies, in addition to counseling, include relaxation methods and biofeedback.156



18  Pediatric Pacing and Defibrillator Use

Support groups have been helpful in promoting positive adjustments to chronic illness in family members.157 Factors associated with support group participation that may be therapeutic for patients and family members include sharing of information, instilling of hope, universality, altruism, and interpersonal learning. Although this is an effective intervention, the use of support groups by this population thus far appears limited. Professionals working with these patients report that many younger patients do not participate in ongoing ICD patient support groups, because the groups do not address issues of personal concern, such as work, intimate relations, childbirth, school, friends, and dating. Also, the relatively small numbers of young defibrillator patients in any one geographic area have limited the ability to initiate support groups specifically for this population. In an attempt to address the needs of this unique population, we have collaborated with the adult electrophysiology service at the University of Michigan to have an annual “Youth and Young Adult Support Seminar” for ICD patients in their 30s and younger. In addition to educational workshops on topics of interest to young patients, professionally facilitated support groups were provided, according to age, gender, and role (patient, spouse, or parent). It is our belief that the

425

children and adolescents benefited from their interactions with young adult ICD patients, because they could see firsthand that a meaningful future is possible for them. Evaluations revealed that many of the patients had never met another young person with a defibrillator before the conference. School reentry after ICD implantation has been a source of considerable concern for parents and school professionals. Education of school personnel by clinic staff regarding the child’s arrhythmia, how the device works, what to do if therapy is given, and development of an emergency plan for school personnel is routine after implantation. Parental permission is always obtained before the school is contacted, and parents are included as important participants in all school-based meetings. During the meetings, it has been helpful to emphasize the protection afforded by the device and that the purpose of undergoing device implantation is to permit the child to live, as much as possible, a normal life. The long-term outlook of children requiring either ICD or pacemaker implantation continues to improve. Therefore, a positive attitude must be conveyed to the child, the parents, and the caregivers to allow the child to lead as normal a life as possible.

REFERENCES 1. Moquin PM, Vaysse J, Durand M, et al: Implantation d’un stimulateur interne pour correction d’un bloc auriculoventriculoventriculaire chirurgical chez une enfant de 7 ans. Arch Mal Coeur Vaiss 55:241, 1962. 2. Gillette PC, Wampler DG, Shannon C, Oth D: Use of cardiac pacing after the Mustard operation for transposition of the great arteries. J Am Coll Cardiol 7:138, 1986. 3. El-Said G, Rosenberg HS, Mullins LE, et al: Dysrhythmias after Mustard’s operation for transposition of the great arteries. Am J Cardiol 30:526, 1972. 4. Shearn RPN, Flemming WH: Fourteen years of implanted pacemakers in children. Ann Thorac Surg 25:144, 1978. 5. Simon AB, Dick M, II, Stern AM, et al: Ventricular pacing in children. Pacing Clin Electrophysiol 5:836, 1982. 6. Walkens JJS: Cardiac pacemakers in infants and children. Pediatr Cardiol 3:337, 1982. 7. Ector H, Dhooghe G, Daenen W, et al: Pacing in children. Br Heart J 53:541, 1985. 8. Serwer GA, Mericle JM: Evaluation of pacemaker pulse generator and patient longevity in patients aged 1 day to 20 years. Am J Cardiol 59:824, 1987. 9. Walsh CA, McAlister HF, Anders CA, et al: Pacemaker implantation in children: a 21-year experience. Pacing Clin Electrophysiol 11:1940, 1988. 10. Brownlee JR, Serwer GA, Dick M, II, et al: Failure of electrocardiographic monitoring to detect cardiac arrest in patients with pacemakers. Am J Dis Child 143:105, 1989. 11. McCue CM, Mantakas ME, Tingelstad JB, Ruddy S: Congenital heart block in newborns of mothers with connective tissue disease. Circulation 56:82, 1977. 12. Kangos JJ, Griffiths SP, Blumenthal S: Congenital complete heart block: a classification and experience with 18 patients. Am J Cardiol 20:632, 1967. 13. Dorostkar P, Serwer GA, LeRoy S, Dick M, II: Long-term course of children and young adults with congenital complete heart block. J Am Coll Cardiol 21:295A, 1993. 14. Michaelsson M, Riesenfeld T, Jonzon A: Natural history of congenital complete atrioventricular block. Pacing Clin Electrophysiol 20:2098, 1997. 15. Kugler JD, Danford DA: Pacemakers in children: an update. Am Heart J 117:665, 1989. 16. Karpawich PP, Gillette PC, Garrison A, et al: Congenital complete atrioventricular block: clinical and electrophysiologic predictors of need for pacemaker insertion. Am J Cardiol 48:1098, 1981. 17. Winkler RB, Freed MD, Nadas AS: Exercise-induced ventricular ectopy in children and young adults with complete heart block. Am Heart J 99:87, 1980. 18. Eldor M, Griffin JC, Abbott VA, et al: Permanent cardiac pacing in patients with long QT syndrome. J Am Coll Cardiol 3:600, 1987. 19. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices). Circulation 117:e350, 2008. 20. Rishi F, Hulse LE, Auld DO, et al: Effects of dual-chamber pacing for pediatric patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 29:734, 1997. 21. McGrath LB, Gonzalez-Lavin L, Morse DP, Levett JM: Pacemaker system failure and other events in children with surgically induced heart block. Pacing Clin Electrophysiol 11:1182, 1988.

22. Serwer GA, Mericle JM, Armstrong BE: Epicardial ventricular pacemaker electrode longevity in children. Am J Cardiol 61:104, 1988. 23. Serwer GA, Uzark K, Dick M, II: Endocardial pacing electrode longevity in children. J Am Coll Cardiol 15:212A, 1990. 24. Serwer G, Dick M, II, Eakin B: Cardiac output response to treadmill exercise in children with fixed-rate pacemakers. Circulation 84:II-514, 1991. 25. Karpawich PP, Perry BL, Farooki ZQ, et al: Pacing in children and young adults in nonsurgical atrioventricular block: comparison of single-rate ventricular and dual-chamber modes. Am Heart J 113:316, 1987. 26. Karpawich PP, Justice CD, Cavitt DL, Chang CH: Developmental sequelae of fixed-rate ventricular pacing in the immature canine heart: an electrophysiologic, hemodynamic, and histopathologic evaluation. Am Heart J 119:1077, 1990. 27. Karpawich PP, Rabah R, Haas JE: Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block. Pacing Clin Electrophysiol 22:1372, 1999. 28. Kaltman JR, Ro PS, Zimmerman F, et al: Managed ventricular pacing in pediatric patients and patients with congenital heart disease. Am J Cardiol 102:875, 2008. 29. Horenstein MS, Karpawich PP: Pacemaker syndrome in the young: do children need dual chamber as the initial pacing mode? Pacing Clin Electrophysiol 27:600, 2004. 30. Preston TA, Fletcher RD, Luechesi BR, et al: Changes in myocardial threshold: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235, 1967. 31. Lau C, Cameron DA, Nishimura SC, et al: A cardiac evoked response algorithm providing threshold tracking: a North American multicenter study. Pacing Clin Electrophysiol 23:953, 2000. 32. Cohen MI, Buck K, Tanel RE, et al: Capture management efficacy in children and young adults with endocardial and unipolar epicardial systems. Europace 6:248, 2004. 33. Bauersfeld U, Nowak B, Molinari L, et al: Low-energy epicardial pacing in children: the benefit of autocapture. Ann Thorac Surg 68:1380, 1999. 34. Serwer GA, Uzark K, Beekman R, Dick M, II: Optimal programming of rate altering parameters in children with rate-responsive pacemakers using graded treadmill exercise testing. Pacing Clin Electrophysiol 13:541, 1990. 35. Yabek SM, Wernly J, Check TW, et al: Rate-adaptive cardiac pacing in children using a minute ventilation biosensor. Pacing Clin Electrophysiol 13:2108, 1990. 36. Gillette PC, Shannon C, Blair H, et al: Transvenous pacing in pediatric patients. Am Heart J 105:843, 1983. 37. Ward DE, Jones S, Shinebourne EA: Long-term transvenous pacing in children weighing ten kilograms or less. Int J Cardiol 15:112, 1982. 38. Spotnitz HM: Transvenous pacing in infants and children with congenital heart disease. Ann Thorac Surg 49:495, 1990. 39. Kammeraad JAE, Rosenthal E, Bostock J, et al: Endocardial pacemaker implantation in infants weighing ≤10 kilograms. Pacing Clin Electrophysiol 27:1466, 2004. 40. Gillette PC, Zeigler V, Bradhaus GB, Kinsella P: Pediatric transvenous pacing: a concern for venous thrombosis? Pacing Clin Electrophysiol 11:1935, 1988. 41. Yakvevich V, Alogen D, Papo J, Vidne BA: Fibrotic stenosis of the SVC with widespread thrombotic occlusion of its major tributaries. J Thorac Cardiovasc Surg 85:632, 1983. 42. Sunder SK, Ekong EA, Sevalingram K, Kumar A: SVC thrombosis due to pacing electrodes. Am Heart J 123:790, 1992.

43. Wilkoff BL, Byrd CL, Love CJ, et al: Pacemaker lead extraction with the laser sheath: results of the Pacing Lead Extraction with the Excimer Sheath (PLEXES) trial. J Am Coll Cardiol 33:1671, 1999. 44. Kantharia BK, Kutalek SP: Extraction of pacemaker and implantable cardioverter-defibrillator leads. Curr Opin Cardiol 14:44, 1999. 45. Sharifi M, Sorkin R, Lakier JB: Left heart pacing and cardioembolic stroke. Pacing Clin Electrophysiol 17:1691, 1994. 46. Levin AR, Spach MS, Boineau JP, et al: Atrial pressure-flow dynamics in atrial septal defects (secundum type). Circulation 37:476, 1968. 47. Serwer GA, Armstrong BE, Anderson PAW, et al: Use of contrast echocardiography for evaluation of right ventricular hemodynamics in the presence of ventricular septal defects. Circulation 58:327, 1978. 48. Westerman CR, Van Revanter SH: Surgical management of difficult pacing problems in patients with congenital heart disease. J Cardiovasc Surg 2:351, 1987. 49. Scheffer M, van Gelder B: Transvenous implantation of a ventricular pacing lead in a patient with an artificial tricuspid valve prosthesis. Neth Heart J 11:359, 2003. 50. Shah MJ, Nehgme R, Carboni M, Murphy JD: Endocardial atrial pacing lead implantation and midterm follow-up in young patients with sinus node dysfunction after the Fontan procedure. Pacing Clin Electrophysiol 27:949, 2004. 51. Moak JP, Friedman RA, Motfat D, et al: Dual-chamber pacing in children: the optimal lead configuration-unipolar or bipolar? J Am Coll Cardiol 17:208A, 1991. 52. Michalik RE, Williams WH, Zorn-Chelten S, Hotches CR: Experience with a new epimyocardial pacing lead in children. Pacing Clin Electrophysiol 7:83, 1984. 53. Kugler J, Minsour W, Blodgett C, et al: Comparison of two myoepicardial pacemaker leads: follow-up in 80 children, adolescents, and young adults. Pacing Clin Electrophysiol 11:2216, 1988. 54. DeLeon SY, Ilbawi MN, Becker CL, et al: Exit block in pediatric cardiac pacing: comparison of the suture-type and fishhook epicardial electrodes. Thorac Cardiovasc Surg 99:905, 1990. 55. Hamilton R, Gow R, Bahoric B, et al: Steroid-eluting epicardial leads in pediatrics: improved epicardial thresholds in the first year. Pacing Clin Electrophysiol 14:2066, 1991. 56. Karpawich PP, Harkini M, Arciniegas E, Cavitt DL: Improved chronic epicardial pacing in children: steroid contribution to porous platinized electrodes. Pacing Clin Electrophysiol 15:1151, 1992. 57. Johns JA, Fuh FA, Burger JD, Hammon JW, Jr: Steroid-eluting epicardial pacing leads in pediatric patients: encouraging early results. J Am Coll Cardiol 20:395, 1992. 58. Serwer GA, Dorostkar PC, LeRoy S, Dick M, II: Comparison of chronic thresholds between differing endocardial electrode types in children. Circulation 86:1-43, 1992. 59. Chakrabarti S, Morgan GJ, Kenny D, et al: Initial experience of pacing with a lumenless lead system in patients with congenital heart disease. PACE 32:1428, 2009. 60. Rosenthal E, Bostock J: VDD pacing in children with congenital complete heart block: advantages of a single pass lead. Pacing Clin Electrophysiol 20:2102, 1997. 61. Robertson JM, Hillel L: A new technique for permanent pacemaker implantation in infants and children. Ann Thorac Surg 44:209, 1987. 62. Ulicny KS, Jr, Detterbeck FC, Starek PJK, Wilcox BR: Conjoined subrectus pocket for permanent pacemaker placement in the neonate. Soc Thorac Surg 53:1130, 1992.

426

SECTION 2  Clinical Concepts

63. Ott DA, Gillette PC, Cooley DA: Atrial pacing via the subxiphoid approach. Tex Heart Inst J 9:149, 1982. 64. Lawrie GM, Seale JP, Morris GC, Jr, et al: Results of epicardial pacing by the left subcostal approach. Ann Thorac Surg 28:561, 1979. 65. Brenner JI, Gaines S, Cordier J, et al: Cardiac strangulation: twodimensional echo recognition of a rare complication of epicardial pacemaker therapy. Am J Cardiol 61:654, 1988. 66. Perry JC, Nihill MR, Ludomirsky A, et al: The pulmonary artery lasso: epicardial pacing lead causing right ventricular outflow obstruction. Pacing Clin Electrophysiol 14:1018, 1991. 67. Serwer GA, Dick M, II, Uzark K, et al: The value of redundant ventricular epicardial electrode placement in children. Pacing Clin Electrophysiol 9:531, 1988. 68. Hoyer MH, Beerman LB, Ettedgui JA, et al: Transatrial lead placement for endocardial pacing in children. Ann Thorac Surg 58:97, 1994. 69. Hayes DC, Holmes DR, Jr, Maloney JD, et al: Permanent endocardial pacing in pediatric patients. J Thorac Cardiovasc Surg 85:618, 1983. 70. Gillette PC, Edgerton J, Kratz J, Zeigler V: The subpectoral pocket: the preferred implant site for pediatric pacemakers. Pacing Clin Electrophysiol 14:1089, 1991. 71. Lee JC, Shannon K, Boyle NG, et al: Evaluation of safety and efficacy of pacemaker and defibrillator implantation by axillary incision in pediatric patients. Pacing Clin Electrophysiol 27:304307, 2004. 72. Karpawich PP: Chronic right ventricular pacing and cardiac performance: the pediatric perspective. Pacing Clin Electrophysiol 27:884, 2004. 73. Karpawich PP, Horenstein MS, Webster P: Site-specific right ventricular implant pacing to optimize paced left ventricular function in the young without and without congenital heart disease. Pacing Clin Electrophysiol 25:566, 2002. 74. Serwer GA, Dorostkar PC, LeRoy S, et al: Evaluation of ratevariable pacemaker function at maximal exertion in children and young adults. Pacing Clin Electrophysiol 16:899, 1993. 75. Serwer GA, Kodali R, Eakin B, et al: Changes in pacemaker threshold with exercise in children and young adults. J Am Coll Cardiol 17:207A, 1991. 76. Gillette PC, Zinner A, Kratz J, et al: Atrial tracking (synchronous) pacing in a pediatric and young adult population. J Am Coll Cardiol 9:811, 1987. 77. Frohlig G, Blank W, Schwerdt H, et al: Atrial sensing performance of AV universal pacemakers during exercise. Pacing Clin Electrophysiol 11:47, 1988. 78. Ross BA, Zeigler V, Zinner A, et al: The effect of exercise on the atrial electrogram voltage in young patients. Pacing Clin Electrophysiol 14:2092, 1991. 79. Bricker JT, Barison A, Traveek MS, et al: The use of exercise testing in children to evaluate abnormalities of pacemaker function not apparent at rest. Pacing Clin Electrophysiol 8:656, 1985. 80. Jain P, Kaul U, Wasir HS: Myopotential inhibition of unipolar demand pacemakers: utility of provocative manoeuvres in assessment and management. Int J Cardiol 34:33, 1992. 81. Strathmore NF, Mond HG: Noninvasive monitoring and testing of pacemaker function. Pacing Clin Electrophysiol 10:1359, 1987. 82. Kerstjens-Frederikse MWS, Bink-Boelkens MTE, de Jongste MJL, Homan van der Heide JN: Permanent cardiac pacing in children: morbidity and efficacy of follow-up. Int J Cardiol 33:207, 1991. 83. Jarosik DL, Redd RM, Buckingham TA, et al: Utility of ambulatory electrocardiography in detecting pacemaker dysfunction in the early postimplantation period. Am J Cardiol 60:1030, 1987. 84. Cohen MI, Buck K, Tanel RE, et al: Capture management efficacy in children and young adults with endocardial and unipolar epicardial systems. Europace 6:248, 2004. 85. Sperzel J, Milasinovic G, Smith TW, et al: Automatic measurement of atrial pacing thresholds in dual-chamber pacemakers: clinical experience with atrial capture management. Heart Rhythm 2:1203, 2005. 86. Crossley GH, Chen J, Choucair W, et al: Clinical benefits of remote versus transtelephonic monitoring of implanted pacemakers. J Am Coll Cardiol 54:2012, 2009. 87. Vincent JA, Cavitt DL, Karpawich PP: Diagnostic and cost effectiveness of telemonitoring the pediatric pacemaker patient. Pediatr Cardiol 18:86, 1997. 88. Shepard RB, Kam J, Colvin EC, et al: Pacing threshold spikes months and years after implant. Pacing Clin Electrophysiol 14:1835, 1991. 89. Silka MJ, Kron J, Dunnigan A, Dick M, II: Sudden cardiac death and the use of cardioverter-defibrillators in pediatric patients. Circulation 87:800, 1993. 90. Hamilton RM, Dorian P, Gow RM, Williams WG: Five-year experience with implantable defibrillators in children. Am J Cardiol 77:524, 1996. 91. Kron J, Silka MJ, Ohm O-J, et al: Preliminary experience with nonthoracotomy implantable cardioverter-defibrillators in young patients. Pacing Clin Electrophysiol 17:26, 1994. 92. Stefanelli CB, Bradley DJ, Leroy S, et al: Implantable cardioverterdefibrillator therapy for life-threatening arrhythmias in young patients. J Interv Card Electrophysiol 6:235, 2002. 93. Berul CI, Triedman JK, Forbess J, et al: Minimally invasive cardioverter-defibrillator implantation for children: an animal

model and pediatric case report. Pacing Clin Electrophysiol 24: 1789, 2001. 94. Luedemann M, Hund K, Stertmann W, et al: Implantable cardioverter-defibrillator in a child using a single subcutaneous array lead and an abdominal active can. Pacing Clin Electrophysiol 27:117, 2004. 95. Stephenson EA, Batra AS, Knilans TK, et al: A multicenter experience with novel implantable cardioverter-defibrillator configurations in the pediatric and congenital heart disease population. J Cardiovasc Electrophysiol 17:41, 2006. 96. Radbill AE, Triedman JK, Berul CI, et al: System survival of nontransvenous implantable cardioverter-defibrillators compared to transvenous cardioverter-defibrillators in pediatric and congenital heart disease patients. Heart Rhythm 7:193, 2009. 97. Fischbach PS, Law IH, Dick M, II, et al: Use of a single-coil transvenous electrode with an abdominally placed implantable cardioverter-defibrillator in children. Pacing Clin Electrophysiol 23:884, 2000. 98. Molina LE, Dunnigan AC, Crosson JE: Implantation of transvenous pacemakers in infants and small children. Ann Thorac Surg 59:689, 1995. 99. Halperin BD, Reynolds B, Fain ES, et al: The effect of electrode size on transvenous defibrillation energy requirements: a prospective evaluation. Pacing Clin Electrophysiol 20:893, 1997. 100. Korte T, Koditz H, Niehaus M, et al: High incidence of appropriate and inappropriate ICD therapies in children and adolescents with implantable cardiovertor-defibrillators. Pacing Clin Electrophysiol 27:924, 2004. 101. Stephanson EA, Casavant D, Tuzi J, et al: ATTEST Investigators. Efficacy of atrial antitachycardia pacing using the Medtronic AT500 pacemaker in patients with congenital heart disease. Am J Cardiol 92:871, 2003. 102. Janousek J: Cardiac resynchronization in congenital heart disease. Heart 95:940, 2009. 103. Strieper M, Karpawich P, Frias P, et al: Initial experience with cardiac resynchronization therapy for ventricular dysfunction in young patients with surgically operated congenital heart disease. Am J Cardiol 94:1352, 2004. 104. Dubin AM, Janousek J, Rhee E, et al: Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study. J Am Coll Cardiol 46:2277, 2005. 105. Janousek J, Vojtovic P, Hucin B, et al: Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects. Am J Cardiol 88:145, 2001. 106. Cecchin F, Frangini PA, Brown DW, et al: Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: five years experience in a single institution. J Cardiovasc Electrophysiol 20:58, 2009. 107. Dubin AM, Feinstein JA, Reddy M, et al: Electrical resynchronization: a novel therapy for the failing right ventricle. Circulation 107:2287, 2003. 108. Vannan MA, Pedrizzetti G, Li P, et al: Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography 2:8265, 2002. 109. Freidberg MK, Silverman NH, Dubin AM, Rosenthal DN: Mechanical dysschrony in children with systolic dysfunction secondary to cardiomyopathy: a Doppler tissue and vector velocity imaging study. J Am Soc Echocardiogr 20:756, 2007. 110. Silva JNA, Ghosh S, Bowman TM, et al: Cardiac resynchronization therapy in pediatric congenital heart disease: insights from noninvasive electrocardiographic imaging. Heart Rhythm 6: 1178, 2009. 111. Zimmerman FJ, Starr JP, Koenig PR, et al: Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery. Ann Thorac Surg 75:1775, 2003. 112. Serwer GA: Cardiac resynchronization therapy in the young patient: current status and future directions. J Cardiovasc Electrophysiol 17:1072, 2006. 113. Wilson W, Taubert KA, Gewitz M, et al: Prevention of infective endocarditis: guidelines from the American Heart Association. Circulation 116:1736, 2007. 114. Moos RH, Tsu UD: The crisis of physical illness: an overview. In RH Moos, editor: Coping with Physical Illness, New York, 1977, Plenum, p 3. 115. Satin W, LaGreca AM, Zigo MA, Skyler JS: Diabetes in adolescence: effects of a multifamily group intervention and parent simulation of diabetes. J Pediatr Psychol 14:259, 1989. 116. Eiser C: Growing Up with a Chronic Disease, London, 1993, Jessica Kingsley. 117. Gamble WJ, Owens JP: Pacemaker therapy for conduction defects in the pediatric population. In Roberts N, Gelband H, editors: Cardiac Arrhythmias in the Neonate, Infant, and Child, New York, 1977, Appleton-Century-Crofts, p 469. 118. Alpern D, Uzark K, Dick M, II: Psychosocial responses of children to cardiac pacemakers. J Pediatr 114:494, 1989. 119. Wallander JL, Thompson RJ: Psychosocial adjustment of children with chronic physical conditions. In Roberts MC, editor: Handbook of Pediatric Psychology, ed 2, New York, 1995, Guilford Press, p 124. 120. Pless IB, Roghmann KJ: Chronic illness and its consequences: observations based on three epidemiologic surveys. J Pediatr 79:351, 1971.

121. Rolland J: Chronic illness and the life cycle: a conceptual framework. Fam Proc 26:203, 1987. 122. Wallander JL, Vami JW: Adjustment in children with chronic physical disorders: Programmatic research on a disability-stresscoping model. In LaGreca AM, Siegal L, Wallander JL, Walker CE, editors: Stress and Coping with Pediatric Conditions, New York, 1992, Guilford Press, p 279. 123. Garmezy N, Tellegen A: Studies of stress-resistant children: methods, variables, and preliminary findings. In Morrison F, Lord C, Keating D, editors: Advances in Applied Developmental Psychology, vol 1, New York, 1984, Academic Press, p 231. 124. Werner EE, Smith RS: Vulnerable but Invincible: a Longitudinal Study of Resilient Children and Youth, New York, 1982, McGraw-Hill. 125. Wallander JL, Varni JW, Babani L, et al: Family resources as resistance factors for psychological maladjustment in chronically ill and handicapped children. J Pediatr Psychol 14:157, 1989. 126. Thompson R, Gustafson K: Adaptations to Chronic Childhood Illness, Washington, DC, 1996, American Psychological Association. 127. Stein RE, Jessop DJ: A noncategorical approach to chronic childhood illness. Public Health Rep 97:354, 1982. 128. Lavigne JV, Faier-Routman J: Psychological adjustment to pediatric physical disorders: a meta-analytic review. J Pediatr Psychol 17:133, 1992. 129. Goldberg S, Simmons RJ, Newman J, et al: Congenital heart disease, parental stress, and infant-mother relationships. J Pediatr 119:661, 1991. 130. Miller G, Tesman JR, Ramer JC, et al: Outcome after openheart surgery in infants and children. J Child Neurol 11:49, 1996. 131. Wright M, Nolan T: Impact of cyanotic heart disease on school performance. Arch Dis Child 71:64, 1994. 132. Gutgesell HP, Gessner IH, Better VL, et al: Recreational and occupational recommendations for young patients with heart disease. Circulation 74:1195A, 1986. 133. Werner ME, Smith R: Kauai’s Children Come of Age, Honolulu, 1982, University of Hawaii Press. 134. Hamlett KW, Pellegrini DS, Katz KS: Childhood chronic illness as a family stressor. J Pediatr Psychol 17:33, 1992. 135. Blechman EA, Delamater AM: Family communication and type 1 diabetes: a window on the social environment of chronically ill children. In Cole RE, Reiss D, editors: How Do Families Cope with Chronic Illness? Hillsdale, NJ, 1993, Lawrence Erlbaum. 136. Demaso D, Campis L, Wypij D, et al: The impact of maternal perceptions and medical severity on the adjustment of children with congenital heart disease. J Pediatr Psychol 16:137, 1991. 137. Lyons-Ruth K, Zoll D, Conell D, Grunebaum HV: The depressed mother and her one year old infant: environment, interaction, attachment and infant development. In Field T, Tronick E, editors: Maternal Depression and Infant Disturbance, San Francisco, 1986, Jossey-Bass, p 61. 138. Masten AS, Garmezy N, Tellegen A, et al: Competence and stress in school children: the moderating effects of individual and family qualities. J Child Psychol Psychiatry 29:745, 1988. 139. Green KD, Forehand R, Beck SJ, Vosk B: An assessment of the relationship among measures of children’s social competence and children’s academic achievement. Child Dev 51:1149, 1980. 140. Masten AS, Morison P, Pellegrini DS: A revised class play method of peer assessment. Dev Psychol 21:523, 1985. 141. Morison P, Masten AS: Peer reputation in middle childhood as a predictor of adaptation in adolescence: a seven year follow-up. Child Dev 62:991, 1991. 142. Pelham WE, Milich R: Peer relationships in children with hyperactivity/attention deficit disorder. J Learn Disabil 17:560, 1984. 143. Cowen EL, Pederson A, Babigian H, et al: Long-term follow-up of early detected vulnerable children. J Consult Clin Psychol 41:438, 1973. 144. McCubbin HI, McCubbin MA, Patterson JM, et al: CHIP: Coping-Health Inventory for Parents. An assessment of parental coping patterns in the care of the chronically ill child. J Marr Fam 45:359, 1983. 145. Lazarus RS, Folkman S: Stress, Appraisal, and Coping, New York, 1984, Springer. 146. Affleck G, Tennen H, Rowe J: Mother, fathers, and the crisis of newborn intensive care. Infant Mental Health 11:12, 1990. 147. Compas BE, Worsham NL, Ey S: Conceptual and developmental issues in children’s coping with stress. In LaGreca AM, Siegal LJ, Wallander JL, Walker CE, editors: Stress and Coping in Child Health, New York, 1992, Guilford Press, p 7. 148. Yarcheski A, Scoloveno MA, Mahon N: Social support and wellbeing in adolescents: the mediating role of hopefulness. Nurs Res 43:288, 1994. 149. Andrews SG: Informing schools about children’s chronic illness. Pediatrics 88:306, 1991. 150. Vitale MB, Funk M: Quality of life in younger persons with an implantable cardioverter-defibrillator. Dimens Crit Care Nurs 14:100, 1995. 151. Cooper DK, Luceri RM, Thurer RJ, et al: The impact of the automatic implantable cardioverter-defibrillator on quality of life. Clin Prog Electrophysiol Pacing 4:306, 1986.



152. Kuiper R, Nyamathi A: Stressors and coping strategies of patients with automatic implantable cardioverter-defibrillators. J Cardiovasc Nurs 5:65, 1991. 153. Luderitz B, Jung W, Deister A, Manz M: Patient acceptance of implantable cardioverter-defibrillator devices: changing attitudes. Am Heart J 1994;127:1179.

18  Pediatric Pacing and Defibrillator Use 154. Mazur JE: Learning and Behavior, Upper Saddle River, NJ, 1998, Prentice Hall, p 187. 155. Maier SF, Seligman M: Learned helplessness: theory and evidence. J Exp Psychol Gen 105:3, 1976. 156. Stoyva JM, Carlson JG: A coping/rest model of relaxation and stress management. In Goldberger L, Breznitz S, editors:

427

Handbook of Stress: Theoretical and Clinical Aspects, New York, 1993, Free Press, p 724. 157. Teplitz L, Egenes KJ, Brask L: Life after sudden death: the development of a support group for automatic implantable cardioverter-defibrillator patients. J Cardiovasc Nurs 4:20, 1990.

428

SECTION 2  Clinical Concepts

19  19

Subcutaneous Implantable Cardioverter-Defibrillators WARREN M. SMITH  |  GUST BARDY  |  MARGARET HOOD  |  ANDREW A. GRACE

In the almost four decades since Michel Mirowski implanted the first

automatic defibrillator, these devices have transitioned from controversial to a routine facet of patient care.1,2 At that pivotal moment in 1972, Dr. Mirowski was under tremendous scrutiny and heavy skepticism.3,4 The original device that he implanted was rudimentary by present standards, with a crude, probability-density detection algorithm for sensing ventricular fibrillation (VF) and the requirement of thoracotomy for placement of an epicardial electrode system. Nevertheless, this device performed reasonably well, despite its simple imperative of shocking VF using a coil in the superior vena cava and a patch over the cardiac apex. We remember Dr. Mirowski arguing passionately at the scientific meetings, when more complex devices were introduced, that his original device, a shock-only defibrillator, was all that was needed. Although no clinician currently would argue that a shock-only device is sufficient in the care of patients with diverse diseases, Mirowski’s passionate adherence to that premise should not be summarily dismissed in an age when the basic technology of an implanted defibrillator has become subservient to many, less critical functions. This chapter revisits Dr. Mirowski’s vision after almost 40 years, with some technologic twists along the way.

Background Successive waves of technologic advances have created the modern, sophisticated device comprising a modest-sized, electrically active generator (i.e., active can) implanted pectorally, utilizing defibrillationefficient biphasic waveforms, one to three transvenously inserted leads, and antibradycardia/antitachycardia and biventricular pacing capability, as well as programmable detection algorithms and defibrillation energy strengths. The success of this technology is mirrored by the estimated 200,000 devices implanted worldwide in 2009. Despite these remarkable achievements, implantable cardioverter-defibrillators (ICDs) still generate controversy, particularly in the United States, where both physicians and the public are questioning ICD reliability and safety. This peaked in 2009 with the withdrawal of the Fidelis lead from the market amid extensive and often critical publicity.5-11 Further complaints over lead reliability continue, together with concerns over engineering reliability.6,11 The growing number of lead failures has exposed the Achilles heel of ICDs: the need to attach an electrode directly to the heart via the vascular system. The complicated path that the lead must follow, the hostile environment of the body, and the requirement that leads be supple combine to threaten lead integrity. Moreover, the necessary adherence of the electrode tip to the myocardium and potential attachment of the body of the lead to the veins traversed result in an appreciable risk of injury and death if lead extraction becomes necessary. Reported ICD lead “survival” rates vary from 85% to 98% at 5 years and 60% to 72% at 8 years; Figure 19-1 plots data from 10 studies.10 Table 19-1 summarizes the reported incidence of complications when lead extraction is judged necessary, with mortality ranging from zero to 2.7%, the latter figure relating to associated overwhelming sepsis.12-19 These concerns, along with the well-known complications of routine transvenous lead insertion (perforation, tamponade, pneumothorax, hemothorax, sepsis, endocarditis), indicated the need to develop an ICD that would not require transvenous leads.

428

Early Investigation Experience with Subcutaneous Defibrillation The first efforts to explore subcutaneous defibrillation broke new ground in understanding of energy requirements and the type and location of electrodes. A major corollary was whether a defibrillation threshold of sufficiently low magnitude could be achieved, and if batteries and capacitors then could be small enough to be inserted into a generator of reasonable size. Without these answers, the issue of reliable sensing from an extracardiac location would prove moot. In August 2001 a collaborative research group explored the index question of how much energy was needed for subcutaneous defibrillation. With appropriate ethics committee approval and patient consent, the first test of subcutaneous defibrillation was performed in humans at Green Lane Hospital in Auckland, New Zealand.20 The original test was conducted in a 56-year-old man undergoing transvenous ICD implantation because of a recent cardiac arrest. A small incision was made over the low lateral chest wall to permit tunneling of an anteriorly and posteriorly situated subcutaneous oval disk electrode of approximately 5 cm2 in surface area. A standard transvenous right ventricular lead was used to induce ventricular fibrillation, which was terminated, to the team’s satisfaction, with the first shock, chosen at a strength of 70 joules using a biphasic waveform with a 50% tilt and 100-µF capacitance. This shock resulted in success at an energy level that was much less than was then known possible with transthoracic defibrillation, using two large surface pad electrodes. At that time, the lower limit of average defibrillation threshold efficacy was presumably 100 to 115 J. Clearly, avoiding the resistive effect of the skin was surprisingly beneficial. As discussed later, the energy requirements proved to be even more remarkable. Although defibrillation with our initial configuration was successful, the posterior space proved too difficult to access and therefore was subsequently abandoned. Attempting to access a posterior subcutaneous space from an anterior approach with a supine patient clearly was impractical, regardless of how low the defibrillation energy would prove to be. Four more patients were tested using various anterior/ anterolateral configurations in the latter half of 2001, and defibrillation was successful in all. Each of these pilot explorations led to a more definitive and sequential approach to vector and electrode selection. Our original intention had been to develop a curved generator, resembling a flattened banana, which would mold to the natural contour of the intercostal space (Fig. 19-2). In fact, early prototypes with this shape were tested, but unfortunately it proved too difficult to accommodate the necessary components of the generator to this design and was reluctantly abandoned. Subsequent studies undertaken with additional help (Johannes Sperzel, Jorg Neuzner, and Stefan Spritzer in Germany; Andrew Grace at Papworth Hospital in the United Kingdom; Andrei Ardashev at Burdenko Hospital in Moscow, as well as at Green Lane; Jon Hunt of Cameron Health) allowed rapid progress in identifying a practical lead system.

Optimal Defibrillation Configuration Having demonstrated proof of concept, the research aim was then to evaluate systematically which of many electrode configurations would



19  Subcutaneous Implantable Cardioverter-Defibrillators

429

ICD lead survival (%)

100 90 80 70 60 50

0

2

4

6

8

10

Years post implant Aass (2002), n = 80 Aass (2002), n = 72 Dorwarth (2003), n = 261 Eckstein (2008), n = 1317 Ellenbogen (2003), n = 76

Hauser (2002), n = 521 Kitamura (2006), n = 249 Kleemann (2007), n = 990 Kron (2001), n = 474 Luria (2001), n = 391

Figure 19-1  Results of 10 studies of implantable cardioverterdefibrillator (ICD) lead performance selected according to ≥18 months’ follow-up available, publication in a peer-reviewed journal after 1999, and statistical inclusion of patients who died or were lost to follow-up. The size of the data point/circle is proportional to the total number of patients in the study. Data box shows primary author, year of publication, and patient number (n) for the 10 studies. (Modified from Maisel WH, Kramer DB: Implantable cardioverter-defibrillator lead performance, Circulation 117:2721-2723, 2008.)

be most effective, as well as most practical from a surgical perspective. Although multiple systems were examined and abandoned, four viable configurations were eventually chosen for detailed study. In this next phase of development, these four defibrillation systems compared the utility of retaining the conventional pectoral generator site versus a novel, left lateral placement of the generator. In addition, a variety of electrode shapes, lengths, and positions were examined. The specific four combinations chosen were as follows (Fig. 19-3): • Left lateral canister that would simulate an electrically active pulse generator, coupled to an 8-cm coil electrode placed parasternally, adjacent to the sternal midline. • Electrically active canister in the standard left pectoral (infraclavicular) position, with a 4-cm coil electrode positioned beneath the left inframammary fold near the rib margin, starting from the xiphoid process. • Left pectoral, electrically active canister with an 8-cm coil electrode passing from the left inferior sternum across to the inferior margin of the left rib cage as an L-shaped linear coil electrode. • Lateral thoracic, electrically active canister with a lower left parasternal, 5-cm2 oval disk electrode. Defibrillation testing of these temporary lead configurations was completed immediately before permanent transvenous ICD

TABLE

19-1 

Figure 19-2  Torso model showing original curved electrode designed to mold to the lateral intercostal space.

implantation in a total of 78 patients in a number of centers, most at Green Lane and Papworth Hospitals. These data have been published previously.21 A Latin Square design was used for testing with analysis of variance (ANOVA). A step-up/step-down protocol was used to determine defibrillation thresholds (DFTs) using a 50%-tilt biphasic waveform. An initial test shock of 40 J was delivered after 10 seconds of induced VF, incrementing to a maximum of 80 J or decrementing to a minimum of 10 J. Bardy et al.21 fully describe the DFT testing protocol. Unsuccessful shocks were followed by prompt, transthoracic rescue defibrillation. For the four configurations just described, the mean DFT (±SD) was as follows, respectively (Fig 19-4): • 32.5 ± 17.0 J (95% CI: 27.8-37.3) • 40.4 ± 13.7 J (95% CI: 35.4-45.4) • 40.1 ± 14.9 J (95% CI: 33.7-46.5) • 34.3 ± 12.1 J (95% CI: 28.8-39.8) These data suggested the optimal configuration was a left lateral canister placement and an 8-cm parasternal electrode with both a low DFT and a relatively narrow standard deviation range (±SD; CI, confidence interval; ANOVA P = .07). Despite being a novel location, the left lateral position proved to be “user friendly,” with easy tissue planes to dissect and good visibility for electrode and generator placement. With meticulous attention to hemostasis, no pocket hematomas were

Complications with Pacemaker and ICD Extraction

Patients (N) Leads extracted (N) Complete extraction (%) Partial extraction (%) Failure (%) Major complications (%) Death (%)

Smith et al.19 1299 2195 86.8 7.4 5.8 2.5 0.6

Byrd et al.12 2338 3540 93 5 2 1.4 0.04

Jones et al.17 498 975 97.5 1.6 0.9 0.4 0.0

Kennergren et al.18 292 383 90.9 3.4 5.7 5.1 0.0

Hamid et al.16 183 369 90.7 7.6 1.7 2.2 2.7

430

SECTION 2  Clinical Concepts

1. LGen-S8

2. PGen-S4

WC

3. PGen-C8

4. LGen-S5 disk

Figure 19-3  Four lead systems acutely tested for the “optimal” system. 1, Left lateral pulse generator with 8-cm coil electrode at left parasternal margin, designated LGen-S8. 2, Left pectoral pulse generator with left parasternal 4-cm coil electrode positioned at the inferior sternum, designated PGen-S4. 3, Left pectoral pulse generator with 8-cm coil electrode curving from left inferior parasternal line across to inferior margin of left sixth rib, designated PGen-C8. 4, Left lateral pulse generator with left parasternal 5-cm2 oval disk, designated LGen-S5 (disk). (Modified from Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter-defibrillator, N Engl J Med 363:36-44, 2010.)

encountered, and the incisions healed soundly, even during these early years and with relatively limited procedural experience. The next phase of the research involved a comparison between DFTs with the “optimal” subcutaneous system just identified and a standard transvenous system. The purpose was not only to examine relative efficacy in terminating VF in the same patients, but also to ensure that there would be a comparatively parallel degree of energy reserve in any design of a subcutaneous-only ICD (S-ICD). 100 Delivered energy

Total n = 78 80 60 40 20

32.5 n = 61

40.4 n = 31

40.1 n = 23

34.3 n = 21

LGen-S8

PGen-S4

PGen-C8

LGen-disk

0 Configuration Figure 19-4  Delivered defibrillation threshold energies. Defibrillation threshold data (mean ± SD) for four practical lead/electrode configurations (see Fig. 19-3) in acute human trials (total of 78 patients). (Modified from Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter-defibrillator, N Engl J Med 363:3644, 2010.)

Figure 19-5  Chest radiograph of patient in the permanent implant pilot study. White arrow shows location of parasternal electrode of subcutaneous ICD with a laterally placed generator. An episode of induced ventricular tachycardia and its termination is shown along bottom of radiograph. The patient (WC) is a 46-year-old, 114-kg, secondary prevention male patient with coronary disease, NYHA Class I, and ejection fraction of 30% to 35%. The transvenous lead was implanted 9 years earlier through the right subclavian vein because left-sided venous access was not possible and no right cephalic vein was present. At this (second) generator replacement, the transvenous lead showed noise and R-wave oversensing.

For the direct, Paired Transvenous Defibrillation Efficacy Trial a total of 49 patients were enrolled between April 2004 and June 2005. Importantly, the subcutaneous electrode was placed using only anatomic landmarks, and its position documented by fluoroscopy only after testing was complete. A typical electrode position is shown in Figure 19-5. After both systems were in place and both pockets closed, DFTs were compared in a randomized and interleaved manner, using the same protocol previously described.21 The mean DFT for transvenous and subcutaneous ICD systems, respectively, was 11.1 ± 8.5 J (95% CI: 8.6-13.5) and 36.6 ± 19.8 J (95% CI: 31.1-42.5), P < .001. Only one patient failed to defibrillate with the subcutaneous system, and subsequent screening showed that the electrode was grossly malpositioned laterally, with the coil electrode outside the left lateral margin of the cardiac silhouette (Fig. 19-6). As part of this study, it should also be noted that one patient also failed to defibrillate with the transvenous system, although with appropriate electrode location. In summary, the data derived from these preliminary trials helped the engineers determine battery and capacitor requirements, as well as lead system design, to ensure that the device would work with the same degree of efficacy in terminating VF as transvenous leads. Without this work, the next phase of the development process, a reliable detection algorithm, could not be undertaken.

Other Investigator Approaches to Subcutaneous Defibrillation Before reviewing the steps leading up to the development of the Cameron Health S-ICD detection algorithm, it is appropriate to acknowledge the efforts made by others who have explored the need for avoiding transvenous lead systems. In 2005, Burke et al.22 evaluated the defibrillation energy requirement of a hybrid left chest anterior cutaneous patch to a pectoral



19  Subcutaneous Implantable Cardioverter-Defibrillators

431

with the lateral implant site. Completing a questionnaire before explant, three patients preferred either the subcutaneous left lateral thoracic site or the standard infraclavicular ICD location. One cited no difference. Serial recordings from the subcutaneous electrode over the duration of the implant maintained the quality of sensed myocardial electrograms. These data suggest that generator size, although larger to accommodate the need for higher energies, and device conformation were not concerns with respect to the left lateral thoracic location, and presented no more of a comfort issue than infraclavicular devices. SENSING WITH A SUBCUTANEOUS LEAD

Figure 19-6  Fluoroscopy image of the malpositioned parasternal electrode in the one patient who failed to defibrillate in the Paired Transvenous Defibrillation Efficacy Trial.

subcutaneous emulator canister. With this can-to-patch shocking vector, they reported 78% success in nine patients starting with 70 J and 91% success in a further 11 patients starting with 50 J. Seven of nine patients in this second group (78%) were successfully defibrillated with a 30-J shock. Further efforts to develop a subcutaneous ICD system seemed warranted. In 2008, Lieberman et al.23 reported an 81% success rate in 32 patients using a step-down protocol beginning at 35 J. Although our group had abandoned a posterior approach, their defibrillation configuration consisted of an electrically active generator emulator with a surface area of 60 cm2 implanted in a low pectoral position, together with a 25-cm coil electrode tunneled around the back of the left thorax between the sixth and tenth intercostal spaces, with the lead tip as close to the spine as possible. Postshock pacing by the subcutaneous electrode was not attempted. No complications were reported. Isolated case studies in the pediatric population also demonstrated the feasibility of shocking the heart between an abdominally sited generator and a subcutaneous array, or an electrode variably positioned toward the left axilla.24-28 Each of these patient-specific adaptations, however, still required some form of transvenous or epicardial sensing electrodes. Also, these were primarily adapted to developments in patient clinical status, surgical limitations or lead failures, and the clinically limited options to repair the previously implanted intrathoracic defibrillation lead system. TOLERABILITY AND COMFORT OF LATERAL GENERATOR SITE Although surgical access seemed reasonable at implant for the novel, lateral generator site we were considering, there was no information about how “tolerable” a generator in this position would prove for patients chronically implanted. It might prove awkward and a cause of repetitive minor trauma; experience with generators in the lateral thorax was nonexistent, although earlier, nonthoracotomy ICD systems would often place a subcutaneous patch in the subscapular position. To help answer these concerns, Smith and Hood29 conducted a small study in 2007 of seven patients, in whom a mock generator, with sensing capability only, was left in situ after the completion of acute testing, together with the subcutaneous electrode. The patients also received a standard transvenous ICD, and over the next 6 to 12 months, were asked to compare the pectoral and lateral implant sites for any inconvenience or concerns. Only one patient reported any discomfort

The subcutaneous electrode has two sensing electrodes, one positioned distally adjacent to the manubrium-sternal junction and one positioned in the vicinity of the xiphoid (Fig. 19-7). Electrograms may be detected either between the two electrodes or between either sense electrode and the pulse generator. The S-ICD system automatically selects the vector optimal for rhythm detection and avoidance of double QRS counting or T-wave oversensing. The need for treatment is predicated by feature analysis of signals followed by rate detection. Also, a conditional discrimination zone can be programmed at 170 to 240 beats per minute (bpm) to identify and exclude supraventricular tachycardia (SVT). Extensive testing of these sensing algorithms in the studies conducted to date and in-vitro showed an excellent capability to correctly identify VF and rapid ventricular tachycardia (VT).30 The capability exists to screen patients by comparing the QRS/T-wave amplitudes from the surface electrocardiogram at chest wall locations with a simple ruler, to confirm myocardial sensing will be adequate for a subcutaneous device. Figure 19-8 shows the programmer screen with the parameters available for programming.

Prelude to First Use of Stand-Alone Subcutaneous Defibrillator The substantial body of research completed over 8 years showed that defibrillation could reliably be achieved with a laterally situated,

A C B

Figure 19-7  Locations of the subcutaneous implantable cardioverterdefibrillator (S-ICD) system components in situ. A and B designate the distal and proximal sensing electrodes, respectively; C, shock coil electrode. (Modified from Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter defibrillator, N Engl J Med 363:36-44, 2010.)

432

SECTION 2  Clinical Concepts

Overview of Experience to Date

Figure 19-8  Programmer screen for the subcutaneous ICD shows the four parameters available for programming: device on/off, postshock pacing on/off, supraventricular tachycardia (SVT) discrimination zone on/off, and if on, the upper rate of its use.

electrically active canister and a parasternal subcutaneous electrode. The required energy levels proved as such to allow a reasonably sized generator, and patient comfort seemed acceptable. A pilot study of a chronically implanted generator in the new lateral site had been satisfactory in terms of patient acceptability and comfort. The subcutaneous electrode had proved surprisingly easy to position reliably using only anatomic landmarks. This latter feature obviated the need for x-ray screening. Cardiac capture was feasible, so temporary postshock backup pacing was possible with the subcutaneous device. However, because the large stimulus strength required for cardiac capture resulted in a global excitation of all thoracic musculature, chronic pacing or antitachycardia pacing (ATP) was impractical for this system. In addition, accurate sensing of myocardial electrograms and reliable discrimination from noise and stray electric currents, a critical aspect of defibrillator performance, had been carefully validated with the new system. The time seemed appropriate for definitive human implants. The first permanent implant of a subcutaneous-only ICD was in Auckland, New Zealand, on July 28, 2008, by the authors, Gust Bardy, Margaret Hood, and Warren Smith. A schematic of the S-ICD system in place is shown in Figure 19-7. Thereafter, implants were also performed at Christchurch Hospital (by Ian Crozier and Iain Melton), resulting in a total of six patients with class I indications for ICD treatment implanted with a subcutaneous system in New Zealand for the initial pilot experience. Patients were excluded if they required antibradycardia pacing or were known to have VT slower than 170 bpm or monomorphic VT, known to be reliably terminated with ATP. The primary endpoint was two successful conversions from VF with 65 J in a maximum of four attempts. An example of a successful conversion is shown in Figure 19-5. All patients underwent implantation as planned, and after 33 months’ follow-up, the system has been well tolerated without complication. The full detail of this experience has previously been reported.21 Since this initial experience, the S-ICD has undergone successful completion of a European regulatory trial, the details of which are reported earlier.21 Of 55 patients, 52 satisfied implant criteria of two successive VF conversions at 65 J; 12 episodes of spontaneous VT were treated in three patients in that early experience, with only one death, in an 85-year-old man with end-stage renal failure who asked that his S-ICD be turned off in the weeks before his death from kidney disease. The subcutaneous defibrillator is currently released for clinical use in Europe. A U.S. Food and Drug Administration (FDA) trial is also currently underway, with the experience to date proving that S-ICD therapy has a growing role to play in prevention of sudden cardiac death.

A totally subcutaneous ICD system bodes to be a valuable extension to the options presently available to treat patients who present with, or are at risk of, malignant ventricular rhythms. Although a substantial experience has established the standard subpectoral pocket as a safe and convenient generator location, the novel lateral pocket has also proved user friendly, with easy-to-establish tissue planes resulting in a short learning curve for operators experienced in conventional implantation techniques. Long-term follow-up and larger patient numbers will be necessary for clinicians to become completely comfortable with this approach; however, the preliminary experience is very encouraging. The early experience of some lead dislodgments has emphasized the need for adequate anchorage of the distal tip. This experience also led to the introduction of an anchoring sleeve at the xiphoid, essentially eliminating the problem of dislodgment in subsequent experience, even in novice implanters. Implementation of these new anchoring techniques minimized lead dislodgment in more than 600 subsequent cases. No chronic lead extractions have yet been necessary, but any future removals could reasonably be anticipated to be straightforward and certainly safe. As potential limitations, one must be cognizant that there will be a few patients in whom body habitus may render myocardial sensing marginal. Fortunately, this is readily identifiable before implant with the use of a special surface electrocardiographic (ECG) template that mimics the S-ICD sensing algorithm and easily identifies those few patients who might have difficulty with subcutaneous sensing. There are several more definitive exclusions to use of the S-ICD. The absence of a chronic pacing capability presently excludes patients requiring antibradycardia pacing, and a transvenous device is more appropriate for patients with relatively slow VT or who demonstrated reliable antitachycardia termination of VT. There is no substantive evidence to demonstrate that empiric ATP is superior to shock-only therapy in patients not demonstrating monomorphic VT before implant. Indeed, the only randomized trial to date shows increased mortality and shock rates with ATP. This is consistent with recent observations showing that a majority of primary prevention patients have polymorphic nonsustained VT, which would easily be accelerated into VF with empiric ATP during charging.31,32 Consequently, we remain conservative in this domain. One of the less obvious advantages of the S-ICD will be its role in the preservation of the intravascular system for later use, especially in younger patients. The 30-year-old patient with hypertrophic cardiomyopathy at increased risk for sudden death would be fortunate not to need one or more lead extractions in his lifetime. For such patients, the subcutaneous ICD has the potential to confer a long-term morbidity and mortality benefit separate from that intrinsic to its treatment of ventricular tachyarrhythmias. In other patients, being able to defer the possible need for transvenous access by starting with the subcutaneous system is likely to be a clinically useful strategy. Children are another group likely to benefit substantially. Present technology in children requiring ICDs is associated with a disturbing frequency of serious complications, which reflects their smaller veins and more rapid growth rates24,25 (see Chapter 18). Also, we are currently exploring the value of the S-ICD in women because it is unlikely to interfere with mammography; neither the lead nor the generator is within the breast tissue.

Future of Subcutaneous Defibrillators The advent of a viable subcutaneous defibrillation option has implications beyond a mere technical advance. The financial pressure from the need to contain health care costs is constant and growing. The savings from being able to implant devices in a sterile but otherwise “low-tech” room (no expensive lead lining, lead-lined jackets, or fluoroscopy) will be important to all health care administrators, but especially those in third world countries where limited capital is best prioritized to devices



19  Subcutaneous Implantable Cardioverter-Defibrillators

rather than expensive support infrastructure. Physicians and nurses will also be grateful for the freedom from radiation exposure and from the heavy jackets with resulting back problems. In addition, the simple, predictable surgery allows for reliable scheduling of cases. The transvenous ICD that is more complex and takes longer than anticipated will have a cascade effect on the timing of subsequent procedures. Often, this type of delay “bumps” the last patient to the next day. This has cost implications largely hidden from the physician but readily apparent to the administration of any hospital complex. Also, because programming is so simple with the S-ICD, manufacturer representatives are not required. Removal of corporate liaisons in health care will help simplify the care of patients. Since the first device implanted by Mirowski, a progressive increase in complexity may have ultimately become counterproductive, if a substantial proportion of patients do not need or are unlikely to benefit from excessive sophistication, and a few are actually harmed by physicians confused by the plethora of programming options. There is a virtue in simplicity, as exemplified in the limited subcutaneous device options, provided this translates over longer-term follow-up to lives saved with minimal inappropriate shocks. Appropriate trials should be designed to compare transvenous to subcutaneous defibrillation and confirm the population best served by each device. Parallel with such trials is the issue of routine defibrillation testing at implantation. Once essential, such testing is now of debatable utility; it certainly seems time to test its value in randomized trials. Abandoning routine testing would abbreviate an already-short implant time for subcutaneous devices, likely with further cost savings and elimination of the occasional adverse outcome related to failure to terminate VF. Perhaps the most controversial issue is deciding which physicians are best suited to implant such devices. The very real risks and uncertainties associated with the early years of ICDs mandated that a fully trained electrophysiologist join the cardiac surgeon, whose expertise

433

was also desirable for placement of epicardial patches. The simplification of transvenous device placement has eliminated the cardiac surgeon from most implanting centers. It may also be time for electrophysiologists, expensive to train and relatively limited in number, to surrender some jurisdiction to other colleagues. Given the increasing numbers of heart failure patients in most societies, many of whom will be candidates for prophylactic defibrillation, workforce issues suggest that devolvement of uncomplicated implants to less highly trained individuals would be highly desirable to meet demand at a sustainable societal cost. Perhaps this is a further parameter for those contemplating future trials to consider.

Conclusion The journey over 9 years from the unknown feasibility of a novel approach to the availability of a commercial device has been a gratifying experience for those involved. In particular, the collaboration between clinicians and engineers as data were acquired and the research advanced has been a rewarding experience. We gratefully acknowledge the altruism of the many patients who selflessly agreed to allow research testing at the implant of a standard device in order that future patients might benefit. We believe their commitment has not been in vain and that subcutaneous defibrillation will enhance the treatment options available to patients with serious heart rhythm disorders. The advent of ICD technology began in 1961 with Zacuoto and de Boissoudy33 using automated antiarrhythmia therapy through temporary transvenous catheters in hospitalized patients. Subsequently, Schuder et al.34 and then Mirowski et al.1 developed a fully implantable defibrillator for animal use by 1970. Prototype human implants by Mirowski et al.2 in 1980 were followed by the advances of biphasic waveforms, transvenous leads, and active generator technology. Where an entirely subcutaneous ICD fits in this history, and whether or not it proves a significant advance, awaits further evidence.

REFERENCES 1. Mirowski M, Mower MM, Staewen WS, et al: Standby automatic defibrillator: an approach to prevention of sudden coronary death. Arch Intern Med 126:158-161, 1970. 2. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322-324, 1980. 3. Lown B, Axelrod P: Implanted standby defibrillators. Circulation 46:637-639, 1972. 4. Lown B, Axelrod P: Implanted standby defibrillators: the authors’ reply. Circulation 47:1136, 1973. 5. Burton T: Medtronic says wires may have had role in 13 deaths, Sprint Fidelis, March 14, 2009. http://online.wsj.com/article/ SB123697437188922919.html. 6. Faulknier BA, Traub DM, Aktas MK, et al: Time-dependent risk of Fidelis lead failure. Am J Cardiol 105:95-99, 2010. 7. Feder BJ: Patients warned as maker halts sale of heart implant, New York Times, Oct 15, 2007. http://www.nytimes.com/2007/ 10/15/business/15device.html?_r=1&oref=slogin. 8. Feder BJ: Defibrillators are lifesaver, but risks give pause, New York Times, Sept 13, 2008. http://www.nytimes.com/2008/09/13/ business/13defib.html?_r=1&oref=slogin. 9. U.S. Food and Drug Administration: Statement on Medtronic’s voluntary market suspension of their Sprint Fidelis defibrillator leads. Oct 15, 2007. http://www.fda.gov/bbs/topics/NEWS/2007/ NEW01724.html. 10. Maisel WH, Kramer DB: Implantable cardioverter-defibrillator lead performance. Circulation 117:2721-2723, 2008. 11. Morrison BT, Rea RF, Hodge DO, et al: Risk factors for implantable defibrillator lead fracture in a recalled and a nonrecalled lead. J Cardiovasc Electrophysiol 21:671-677, 2010. 12. Byrd CL, Wilkoff BL, Love CJ, et al: Intravascular extraction of problematic or infected permanent pacemaker leads: 1994-1996. U.S. Lead Extraction Database, MED Institute. Pacing Clin Electrophysiol 22:1348-1357, 1999. 13. Corrado A, Gasparini G, Raviele A: Lead malfunctions in implantable cardioverter-defibrillators: where are we and where should we go? Europace 11:276-277, 2009.

14. Duray GZ, Schmitt J, Cicek-Hartvig S, et al: Complications leading to surgical revision in implantable cardioverterdefibrillator patients: comparison of patients with singlechamber, dual-chamber, and biventricular devices. Europace 11:297-302, 2009. 15. Eckstein J, Koller MT, Zabel M, et al: Necessity for surgical revision of defibrillator leads implanted long-term: causes and management. Circulation 117:2727-2733, 2008. 16. Hamid S, Arujuna A, Ginks M, et al: Pacemaker and defibrillator lead extraction: predictors of mortality during follow-up. PACE 33:209-216, 2009. 17. Jones SO, Eckart RE, Albert CM, Epstein LM: Large, single-center, single-operator experience with transvenous lead extraction: outcomes and changing indications. Heart Rhythm 5:520-525, 2008. 18. Kennergren C, Bucknall CA, Butter C, et al: Laser-assisted lead extraction: the European experience. Europace 9:651-656, 2007. 19. Smith HJ, Fearnot NE, Byrd CL, et al. Five-years experience with intravascular lead extraction. U.S. Lead Extraction Database. Pacing Clin Electrophysiol 17:2016-2020, 1994. 20. Bardy GH, Cappato R, Smith WM, et al: The totally subcutaneous ICD system (the S-ICD) [abstract]. Pacing Clin Electrophysiol 24:II-578, 2002. 21. Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 363:36-44, 2010. 22. Burke MC, Coman JA, Cates AW, et al: Defibrillation energy requirements using a left anterior chest cutaneous to subcutaneous shocking vector: implications for a total subcutaneous implantable defibrillator. Heart Rhythm 2:1332-1338, 2005. 23. Lieberman R, Havel WJ, Rashba E, et al: Acute defibrillation performance of a novel, non-transvenous shock pathway in adult ICD indicated patients. Heart Rhythm 5:28-34, 2008. 24. Alexander ME, Cecchin F, Walsh EP, et al: Implications of implantable cardioverter-defibrillator therapy in congenital heart disease and pediatrics. J Cardiovasc Electrophysiol 15:72-76, 2004.

25. Friedman RA, Garson A Jr: Implantable defibrillators in children: from whence to shock. J Cardiovasc Electrophysiol 12:361-362, 2001. 26. Gradaus R, Hammel D, Kotthoff S, Bocker D: Nonthoracotomy implantable cardioverter-defibrillator placement in children: use of subcutaneous array leads and abdominally placed implantable cardioverter-defibrillators in children. J Cardiovasc Electrophysiol 12:356-360, 2001. 27. Jolley M, Stinstra J, Pieper S, et al: A computer modeling tool for comparing novel ICD electrode orientations in children and adults. Heart Rhythm 5:565-572, 2008. 28. Nanthakumar K: Trying to make “sense” of extra thoracic implantable defibrillator. Heart Rhythm 5:35-36, 2008. 29. Smith WM, Hood MA: Comfort/tolerability test results for a subcutaneous ICD compared to a standard transvenous lead [abstract]. Heart Rhythm 4:S210-PO3-30, 2007. 30. Gold MR, Theuns DA, Knight BP, et al: Comparison of arrhythmia discrimination by subcutaneous versus dual-chamber ICD systems: primary results From START [abstract]. Circulation 120:S649, 2009. 31. Chen J, Poole JE, Johnson GW, et al: Implications of rapid nonsustained ventricular tachycardia in ICD heart failure patients in the Sudden Cardiac Death in Heart Failure Trial [abstract]. Heart Rhythm 7:S54-AB26-5, 2010. 32. Wathen MS, Degroot PJ, Sweeney MO, et al: Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 110:2591-2596, 2004. 33. Zacouto F, de Boissoudy P: On an electronic device allowing the determination of the mechanism of cardiac syncope and starting corresponding reanimation in mammals. CR Seances Soc Biol Fil 155:1257-1260, 1961. 34. Schuder JC, Stoeckle H, Gold JH, et al: Experimental ventricular defibrillation with an automatic and completely implanted system. Trans Am Soc Artif Intern Organs 16:207-212, 1970.

434

SECTION 2  Clinical Concepts

20  20

Leadless Pacing Concepts KATHY L. LEE  |  CHU-PAK LAU

A

ll pacing leads are associated with complications, including infection, fracture, failure, and dislodgement1,2 (see Chapter 19 for problems associated with transvenous pacing leads). Also, extraction of a chronically implanted lead is a high-risk procedure. Access to the left ventricle is achieved with a pacing lead advanced into the coronary sinus and positioned in a coronary vein branch. Implantation of the left ventricular lead may be technically challenging and associated with a significant incidence of failure to access and implant the lead, implantation in a suboptimal location, and complications.3,4 With new device systems that require implantation of multiple leads, and with patients living longer, the incidence of lead complications increases over time. Therefore, efforts are ongoing to develop a pacing system that eliminates the pacing lead as a conduit for energy transfer.

Pacing in Cardiac Resynchronization Therapy Compared with epicardial pacing, endocardial left ventricular (LV) stimulation minimizes the conduction delay from the epicardium to the endocardium and may result in more physiologic conduction, with greater hemodynamic benefit. An animal experiment of eight anesthetized dogs with induced left bundle branch block (LBBB) studied the acute hemodynamic effects of endocardial and epicardial LV pacing. Electrical activation and repolarization were evaluated with 122 epicardial and endocardial electrodes. Compared with epicardial pacing, endocardial pacing doubled the degree of electrical resynchronization and increased the LV dP/dtmax by 90% and stroke work by 50% (Fig. 20-1). During single-site LV pacing, the range of atrioventricular (AV) intervals with more than 10% increase in LV resynchronization and LV dP/dtmax was significantly longer for endocardial than epicardial pacing. Epicardial pacing, but not endocardial pacing, was associated with a transmural dispersion of repolarization.5 Randomized clinical trials on cardiac resynchronization therapy (CRT) have demonstrated its clinical benefits. The acute hemodynamic response to CRT in patients with nonischemic dilated cardiomyopathy depends on the pacing site, with major interindividual and intraindividual variations. In 35 patients with heart failure of nonischemic etiology referred for CRT implantation, the acute hemodynamic response to DDD-LV pacing was systematically assessed at 11 predetermined LV pacing sites. Pacing at the endocardial LV site with the best hemodynamic response doubled the increase in dP/dtmax compared to epicardial coronary sinus pacing6 (Fig. 20-2). CRT with endocardial LV pacing maximizes hemodynamic benefit and may be associated with fewer nonresponders. In a retrospective study comparing chronic epicardial and endocardial pacing, 23 patients with severe heart failure and wide QRS were implanted with CRT devices. Fifteen patients underwent conventional epicardial LV pacing, and eight underwent endocardial LV pacing by atrial transeptal approach because of unfavorable coronary sinus anatomy. Six months after implant, echocardiography and Doppler tissue imaging were performed during right ventricular (RV) and biventricular (BiV) pacing to evaluate LV function, LV wall velocities, and regional electromechanical delay. The septal wall (21.3% vs. 11%) and lateral wall (54% vs. 41%) electromechanical delay was reduced more by endocardial than epicardial CRT compared with RV pacing.7

434

Endocardial LV pacing improves LV function better than epicardial pacing when measured by standard echocardiographic parameters such as aortic and mitral time-velocity integral (40% vs. 2%) and lateral LV wall systolic motion (31% vs. 14%).7 Endocardial CRT appears to provide more homogeneous intraventricular resynchronization than epicardial CRT and is associated with better LV filling and systolic performance. Cardiac resynchronization therapy with multisite LV stimulation has been associated with better LV remodeling and a higher left ventricular ejection fraction (LVEF) than conventional BiV stimulation.8 Forty patients with permanent atrial fibrillation undergoing implantation of CRT device were enrolled in a multicenter randomized singleblind crossover study. Each patient had one lead implanted in the right ventricle and two LV leads implanted in two separate coronary veins. Echocardiographic parameter of resynchronization, reverse remodeling, quality of life, and 6-minute walking distance with triple-site (one RV and two LV) versus dual-site (one RV and one LV) stimulation were compared. Triple-site stimulation was associated with a higher LVEF and smaller LV end-systolic volume and diameter. Leadless pacing will enable endocardial LV stimulation without the risks of systemic thromboembolism and mitral regurgitation. It will also avoid diaphragmatic stimulation and RV apical pacing, enable multisite pacing, and allow almost free choice of stimulation location within the left or right ventricle.

Totally Self-Contained Intracardiac Pacemaker After the first clinical use of implantable pacing system in 1960, a totally self-contained leadless intracardiac pacemaker had been developed as a new concept of pacing technology. The intracardiac pacemaker was as small as a capsule 8 mm in diameter and 18 mm long, with integral electrodes and an attachment mechanism.9 It was small enough to be implanted entirely within the heart when delivered with a catheter guided by a transvenous sheath (Fig. 20-3). The attachment mechanism consisted of radially directed spiral barbs, with the stimulation electrodes located away from the attachment site. In an animal study of three dogs implanted with the prototype of this “capsule” intracardiac pacemaker, after several weeks of implant, the stimulation threshold was stable and less than 1 microjoule per pulse. The first functioning investigational model of the intracardiac pacemaker used a mercury battery as the power source for asynchronous electronic pacing. The system was implanted in a dog with induced heart block and provided asynchronous pacing for 66 days with no complications, because the capsule was in the right ventricle. Chemical batteries, biologic fuel, kinetic energy, and nuclearpowered energy have been evaluated for incorporation into the capsule intracardiac pacemaker as power sources. Betacel, a family of betavoltaic nuclear batteries (Douglas Laboratories, McDonnell-Douglas Astronautics, St. Louis) had been developed and incorporated into the first nuclear-powered intracardiac pacemaker.9 The investigational system had been implanted in a dog for asynchronous pacing at 100 beats per minute (bpm) to demonstrate the feasibility of this pacing technology. It was once thought that such technology might enable the battery life of a pacemaker to be extended to several decades. However, results of safety and feasibility on further testing were not reported.



40

40 *

30

20

#

EPI ENDO

#

#

10

Best Worst CS pacing

* *

*

10

* *

*

0 Dp/dtmax

0 LVopt

Dp/dtmin

–10

LVshort

–10

ESP Pulse pressure

–20

30

Increase in LV dP/dtmax (%)

* *

20

*

BiV

*

*

25 #

*#

*

20 *

*

Figure 20-2  Acute hemodynamic changes of DDD-LV pacing. Comparison of the magnitude of change of increase in dP/dtmax, pulse pressure, end-systolic pressure (ESP) at the best endocardial LV site, the worst LV site, and the coronary sinus (CS) in 35 CRT candidates; *P <.01. (Data from Derval N, Steendijk P, Gula LJ, et al. Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. J Am Coll Cardiol 55:566-575, 2010.)

15

ACOUSTIC (ULTRASOUND) ENERGY

10 5 0

B

30

Change (%)

LV resynchronization (%)

*

A

435

20  Leadless Pacing Concepts

BiV

LVopt

LVshort

Figure 20-1  Acute hemodynamics of epicardial and endocardial CRT. Percentage increase in A, electrical left ventricular (LV) resynchronization (percent reduction in LV activation time), and B, LV dP/dtmax during epicardial (EPI) and endocardial (ENDO) pacing, compared with baseline atrial pacing in canine heart with left bundle branch block. BiV, Biventricular pacing; LVopt, LV pacing with optimal fusion resulting in the greatest effect of resynchronization; LVshort, LV pacing with short AV interval; *P <.05 versus baseline; #P <.05 ENDO versus EPI. (Data from Van Deuren C, van Geldorp IE, Rademakers LM, et al. Endocardial left ventricular pacing improves cardiac resynchronization therapy in canine LBBB hearts. Circ Arrhythm Electrophysiol 2:580-587, 2009.)

The next development in alternative energy sources for pacing to replace the pacing lead was the use of ultrasound (ultrasonic, acoustic) energy. The use of ultrasound-mediated energy to drive a remotely positioned electrode for direct myocardial stimulation was first reported in 2006.11 This new technology uses the mechano-electrical properties of piezoelectric materials for transformation of energy. The experimental setup used in the acute study included an ultrasoundtransmitting transducer connected to an ultrasound generator and a steerable bipolar electrophysiology (EP) catheter incorporating a receiver-electrode near the distal end (Fig. 20-4). Ultrasound energy

KINETIC ENERGY Many concepts have been patented for the development of a leadless pacing system. More than a decade ago, the automatic energygenerating system for quartz watches had been used as a leadless pacemaker power source in an experimental animal model.10 A mechano-electrical energy conversion system developed for quartz watches that converted kinetic energy into electrical energy was used as the power source of a commercially available pulse generator circuit and directly sutured on the epicardial surface of the canine heart. After a full charge, adequate energy was generated for continuous overdrive pacing of the heart for 60 minutes. The stroke motion of the myocardium generated pulses of energy that were stored in a capacitor. The charging and discharging results suggested that the automatic powergenerating system might supply enough energy for use in a cardiac pacemaker. It was thought that this might be developed into a buttontype cardiac pacemaker to be implanted by a thoracoscopic procedure. The invasive nature of the procedure precluded further development of this innovative technology in humans.

A

Insertion

B

Attachment

C

Implanted

Figure 20-3  Intracardiac pacemaker implantation procedure. A, Insertion of intracardiac pacemaker attached to a delivery catheter inside a guiding sheath. B, Attachment of the pacemaker endocardially. C, Intracardiac pacemaker detached from the catheter and implanted endocardially.

436

SECTION 2  Clinical Concepts

Figure 20-4  Investigational equipment of ultrasound pacing. Upper left, Ultrasound transducer. Lower left, Enlarged view of receiver-electrodes incorporated in distal end between bipoles used for sensing and electrical pacing. Right, Electrophysiology catheter.

was amplitude adjusted and transmitted at about 330 kHz. The low frequency used in this application enables better tissue penetration. Ultrasound pulses generated from the transmitting transducer travel through the chest wall to reach the receiver-electrode, with circuitry to transform the pulses into electrical energy for myocardial stimulation. The feasibility and safety of this novel technology was first demonstrated acutely in animals.11 In the acute safety study, histologic examination was performed in pigs exposed to continuous ultrasound transmission from the investigational system for 2 hours. No mechanical or thermal biologic effect was identified in the sacrificed animals. In the acute feasibility study, the receiver-electrode incorporated into a transvascular catheter was selectively positioned and in contact with various porcine heart chambers. Ultrasound energy was then transmitted from the external transducer placed on the chest wall through the chest to reach the receiver. Acoustic energy was converted to electrical energy, delivered from the receiver-electrode in contact with the myocardium for pacing stimulation. Proximal connections on the EP catheter allowed either direct electrical pacing using a pacing system analyzer (PCA) or monitoring of the receiver output during ultrasoundmediated pacing. The catheter itself was not directly involved in or

required for ultrasound-mediated pacing. The acute porcine study demonstrated feasibility of leadless ultrasound-mediated pacing in five animals at 30 select sites in the right atrium, right ventricle, left ventricle, and simultaneously in both left and right ventricles. After the animal experiments, an acute human study demonstrated for the first time that the transfer of energy from an external source to stimulate the heart was feasible without a pacing lead.12 The experimental setup was similar to that used in the animal study. A steerable EP catheter with the receiver-electrode incorporated near the distal end was used for introduction into a cardiac chamber and selective positioning at the endocardial pacing location. An external transmitter connected to an ultrasound generator was positioned on the anterior chest wall, and ultrasound gel was used for coupling (Fig. 20-5). The 12 male and 12 female patients age 48 ± 12 years and weighing 75.2 ± 15.7 kg (range, 50-116 kg) were evaluated during or after completion of clinical EP procedures. One patient each had a history of aortic regurgitation, hypertrophic cardiomyopathy, heart failure (HF), hypertension, coronary artery disease, and cerebrovascular accident (stroke). In the HF patient, preexisting AV conduction abnormality was present, and a dual-chamber pacemaker (Philos, Biotronik) had been implanted. No other cardiovascular condition was present in 18 patients. A total Figure 20-5  Experimental setup of first study of leadless pacing in humans. PSA, Pacing system analyzer.

Electrode catheter

Ultrasound transmitter console

External ultrasound transmitter

PSA

Data collection instrumentation



20  Leadless Pacing Concepts

of 82 sites were evaluated with the investigational pacing system; two sites were excluded because electrical pacing capture was inconsistent. Of the 80 sites analyzed, 12 were in the right atrium, 35 in the right ventricle, 31 in the left ventricle, and two were LV sites accessed epicardially from a coronary vein. A mean of 3.3 and range of 2-6 sites were evaluated per patient. Electrical and ultrasound-mediated pacing was performed at 460 to 600–msec pacing cycle length and 0.5-msec pulse width. Ultrasound was transmitted at a mean frequency of 350 ± 25 kHz (range, 313-385 kHz). Ultrasound-mediated pacing was successful at all 80 sites, with consistent pacing capture achieved at 77 sites. Beat-to-beat variation in the receiver-electrode output voltage during pacing ranged from 1.04 ± 0.67 V to 2.16 ± 1.10 V. The ultrasoundmediated pacing threshold, attempted at 59 sites in 18 patients, was 1.01 ± 0.64 V. The electrical pacing threshold, obtained at 70 sites in 21 patients, was 1.60 ± 1.12 mA. Assuming a tissue impedance of 605 ohms, the electrical pacing threshold was 0.97 ± 0.67 mA, similar to the ultrasound-mediated pacing threshold (Fig. 20-6). The mechanical index (MI) at the site during ultrasound-mediated pacing was 0.51 ± 0.31 MI (range, 0.12-1.50 MI). In the 18 patients with calculated ultrasound-mediated pacing thresholds, MI at the site was 0.45 ± 0.30. The mean electrical output energy per pacing pulse was 2.68 ± 3.04 microjoules (µJ), while the mean ultrasound energy burst was 12.86 ± 15.70 millijoules (mJ). The transmitter to receiver distance was 11.3 ± 3.2 cm. Ultrasound-mediated pacing was achieved at all 80 sites with consistent capture at 77 sites. No adverse event was related to ultrasound-mediated pacing. No patient experienced discomfort during pacing. A major target of this novel technology is CRT. Leadless pacing with ultrasound-mediated energy was also tested in HF patients.13 Ten patients with advanced HF and LVEF ≤35% were studied. With the same experimental setup, a receiver-electrode to deliver ultrasoundmediated pacing was positioned endocardially in the lateral or posterior LV wall after a clinically indicated left-sided heart catheterization. Ultrasound-mediated pacing thresholds were determined. The acoustic windows on the chest wall that allowed consistent capture were determined with the patient lying supine, titled 30 degrees leftward, 30 degrees rightward, and 30 degrees upward. The acoustic windows were also determined with computed tomography (CT) and transthoracic echocardiography. Three-dimensional thoracic CT reconstruction was obtained with the patient in supine position during end-inspiration and right lateral position during both end-inspiration and endexpiration. The area on the chest wall mapping the transmission path to the heart without any intervening lung tissue was defined as the CT-determined acoustic window (Fig. 20-7). The receiver-electrode location and the standard transmitter location were simulated on the 3D reconstruction, and the horizontal and vertical movements of the

Transmit marker

Recorded threshold voltage

Electrode output

Transmit delay Figure 20-6  Oscilloscope recording during ultrasound-mediated pacing. Upper trace (blue) recorded the marker of ultrasound transmission. Bottom trace (yellow) recorded electrode output waveform. The threshold voltage was measured at the lower boundary of the trailing edge of the output waveform. Transmit delay was the actual time taken for acoustic wave to travel from the transmitter to the receiver.

437

Figure 20-7  Acoustic window. Example of acoustic window (outlined in black) defined on three-dimensional reconstruction of CT image taken at end-inspiration when patient was lying supine.

receiver relative to the transmitter were determined in all three scanning conditions. Transthoracic echocardiography using a commercially available ultrasound imaging system and a vascular transducer operating at frequency range of 3-11 MHz was performed to determine the echocardiographic acoustic window. The measurement was acquired with the patient lying in multiple positions, as with those tested during ultrasound-mediated pacing. The echocardiographic acoustic window on the chest wall that allowed clear visualization of the near-field endocardium was measured. Ultrasound-mediated pacing was successful in all patients. The acoustic window measured 39.6 ± 18.2 cm2. The window size decreased with rightward tilt and increased with leftward and upward tilt. The values correlated with measurements made by transthoracic echocardiography and CT. Target receiver movement of 1.2 ± 1.4 cm horizontally and 1.3 ± 0.8 cm vertically were estimated by CT. In these patients, the acoustic window on the chest wall that allows efficient ultrasound transmission was large and sufficient for subcutaneous implantation of the ultrasound generator, even after accommodating changes with respiratory movement and body positioning. Implantable Leadless Pacing System Incorporating this novel technology, the future implantable leadless pacing system (wireless cardiac stimulation, WiCS) is being developed with the following components: 1. Delivery catheter system: a catheter-based system used for implanting the electrode. 2. Electrode: an ultrasound energy receiver and energy converter implanted in the endocardium to pace the heart. 3. Pulse generator: an ultrasound energy pulse transmitter implanted subcutaneously in the thorax, consisting of two connected modules, the transmitter, and the battery (Fig 20-8). 4. Programmer: the external communication instrument used for implant and follow-up. The implantable electrode is an ultrasound energy converter in a titanium can 1 cm long and 2.67 mm in diameter, with an activefixation anchor mechanism with five active barbs (Fig. 20-9). The tip of the anchor functions as the cathode while the body functions as the anode. Preliminary short-term results (6-95 days) on use of the endocardial LV pacing system (WiCS, EBR Systems, Sunnyvale, Calif) on eight goats showed no dislodgement, thrombus formation, or embolization.14 The pacing electrodes were fully endothelialized at 90 days, with a fibrous capsule of 0.36-mm mean thickness and mean implant depth of 2.65 mm into the endocardium.

438

SECTION 2  Clinical Concepts

Box 20-1 

CHALLENGES IN DEVELOPMENT OF LEADLESS PACING TECHNOLOGY WITH ULTRASOUND ENERGY • Low efficiency of energy conversion significantly shortens battery longevity. • Problem with consistent capture with a constantly changing pacing window. • Long-term safety of prolonged exposure to ultrasound, with possible heating effect and tissue injury. • Reliability of a leadless sensing circuit. • Operation and integration of multiple sensing and pacing sites for CRT. • Potential interference from external environment. • Unconventional parasternal site for implanting the pacemaker generator. • Development of a reliable delivery and anchoring system for implanting the endocardial receiver-electrode. • Integration with an implantable defibrillator. Figure 20-8  Pulse generator in leadless pacing system. Wireless cardiac stimulation (WiCS). Top, Ultrasound transmitter (13 cc, 25 g) to be implanted in thoracic pocket within acoustic window. Bottom, Battery unit (42 cc, 90 g) to be implanted in abdominal pocket.

The transmitter (13 cc, 25 g) will be implanted subcutaneously in the acoustic window of the chest wall while the cable is being tunneled, and the battery (42 cc, 90 g) implanted in the abdominal pocket. The receiver and transmitter are programmed to operate at the same frequency of ultrasound pulses. The ultrasound beam will be optimized and focused onto the receiver-electrode to improve the efficacy of energy transfer (Fig. 20-10). The estimated device longevity will need to be comparable to that of a conventional pacemaker to make it commercially viable. The acoustic window suitable for implant on the patient’s chest wall can be localized preoperatively by conventional echocardiography, a convenient method that can predict efficient ultrasound transmission for leadless pacing.13,15

CRT, Cardiac resynchronization therapy.

A novel method was developed to distinguish right ventricular, right atrial, or left ventricular pacing output to enable the leadless system to provide LV pacing synchronized to the RV pacing of a co-implanted pacemaker or defibrillator to provide CRT16 (Fig. 20-11). Addition of the leadless LV stimulation system to a conventional dual-chamber pacemaker or defibrillator for CRT is the current state of development and clinical research. Although this leadless technology provides thus far the most developed system, many will doubt the long-term safety and feasibility of continuous ultrasound stimulation (Box 20-1).17,18 Although the lack of effect of short-term ultrasound-mediated pacing has been shown histologically in animal experiments, tissue injury secondary to heating with continuous exposure is theoretically possible. A novel method developed for calibration of acoustic energy transfer in the wireless

Figure 20-9  Implantable leadless intracardiac electrode. An ultrasound energy converter with five active barbs for anchoring.



20  Leadless Pacing Concepts

439

the sensing circuit of the stand-alone leadless pacemaker will operate. The sensing mechanism used in the investigational subcutaneous defibrillator may provide some insight.20 There are certainly many challenging issues to be resolved before this concept can be turned into a commercially available implantable pacing device. INDUCTION TECHNOLOGY

Figure 20-10  Transmission and focusing of ultrasound. Crosssectional CT scan of the thorax shows the range of ultrasound transmission from the subcutaneous transmitter positioned within acoustic window of anterior chest wall, focusing onto (blue lines) the endocardial receiver electrode (red spot).

pacing system may improve its long-term safety.19 Interference from ubiquitous environmental sources may also be hazardous, although precise formatting and fine-tuning of the device can be done to minimize this, which is certainly a major safety issue that requires extensive evaluation. A user-friendly delivery system with a reliable anchoring mechanism is essential for a safe and optimal implantation. Regarding the risk of infection, the receiver-electrode is small and embedded in the endocardium, and complete endothelialization was seen in animal studies. The risk of infection should be low and comparable to that of implanting a coronary stent or an atrial septal defect–occluding device. In addition to energy delivery, transmission of a sensed signal is an important function of a pacing lead. There is little information on how

Figure 20-11  Co-implant of leadless and conventional pacemakers for CRT. A conventional dual-chamber pacemaker implanted in the left pectoral region, with leads in the right atrium and the right ventricle. The leadless LV pacing system with an intracardiac electrode in the LV, a transmitter implanted in the lower chest wall connected to a battery implanted in the upper abdomen.

Besides kinetic and acoustic energy sources, electric pulses transformed from an alternating magnetic field have recently been tested in a porcine model for leadless cardiac stimulation.21 The system consists of two components, a subcutaneous transmitter unit and an endocardial receiver unit. The subcutaneous primary coil generates an alternating magnetic field, which is converted by the secondary coil inside the heart to a voltage pulse for pacing stimulation. In the porcine experiment described, an alternating magnetic field of approximately 0.5 mT was generated by the transmitter unit in a distance of 3 cm. Voltage pulses with a duration of 0.4 msec and voltage amplitude of 0.6 to 1.0 V were generated. Continuous stimulation of the porcine heart was demonstrated for 30 minutes. The advantage of this technology is that the efficiency of energy conversion is relatively high, making device longevity less of a problem. However, both the transmitter coil and the receiver are of considerable size and weight. The long-term safety with heat production in the receiver unit generated with continuous exposure is uncertain. Potential external interference by environmental electromagnetic fields is also cause for major concern.

Biologic Pacemaker Genetically engineered pacemakers may become a viable alternative to implantable electronic devices for the treatment of bradyarrhythmias in the future (see Chapter 7). Gene-based approaches involve beta-2 adrenergic receptor (β2-AR),22 repolarizing current (IK1),23,24 and funny current (If ),25-28 as prime targets for gene transfer that allow nonpacemaker cardiomyocytes to generate rhythmic action potentials such as the genuine, electrically active nodal pacemaker cells. The earliest attempt in enhancing cardiac chronotropy (but not inducing pacemaker activity) was made with transient, overexpressing β2-ARs in the right atrium of swine.22 Because the pacemaker activity of the native sinoatrial (SA) node is modulated by the autonomous nervous system, β2-AR regulates cardiomyocyte chronotropic responses through a G protein and cAMP-mediated pathway. Stimulation of β2-AR increases the If in cardiomyocytes and subsequently leads to an increased rate of depolarization. Upregulation of β2-AR by overexpressing the cloned receptor has been shown to increase the response of the heart rate to adrenergic stimulation. Although If is most abundant in the SA node, overexpression of wild-type hyperpolarization-activated cyclic nucleotide (HCN)—modulated channel alone does not suffice to induce automaticity in quiescent adult LV cells.29,30 Unlike SA nodal cells, adult atrial and ventricular cells are normally electrically quiescent because of the intense expression of the cardiac inward-rectifier K+ current, IK1 (encoded by the Kir2 gene family), that stabilizes a negative resting membrane potential, about −80mV, and thus suppresses excitability or any latent spontaneous pacemaker activity. By contrast, IK1 is virtually absent in the SA nodal cells. In fact, it has been convincingly demonstrated that latent pacemaker activity of normally quiescent cardiomyocytes can be unleashed to produce spontaneous firing activity by genetic inhibition of Kir2-encoded IK1, although the induced firing is approximately threefold slower than normal.23,24 In addition, the inability to induce automaticity by overexpression of wild-type HCN channels may also be related to the complex molecular identity of endogenous If. Instead, employing protein-engineering technology to create mutant HCN channels with more favorable biophysical properties, two engineered HCN channels, mE324A25,26 and HCN 235-7,27,28 have been reported to reduce the pacemaker dependence in a large, animal bradycardia model. Apart from conversion of myocytes into pacemaker

440

SECTION 2  Clinical Concepts

cells, other strategies include stem cell transplantation.29 Unresolved issues include longevity and stability of pacemaker genes, as well as limitations in adenoviral and stem cell therapy. Research in this area will provide insight on whether a biologic pacemaker will become clinical reality and outperform electronic pacemaker in terms of safety, reliability, and longevity.

Conclusion With improvement and sophistication, one or some of these technologies may eventually enable safe, long-term leadless pacing and open up

a new arena for CRT. Some nonresponders may be converted to responders with optimization of the left ventricular stimulation site. Multisite pacing will no longer be limited by problems in vascular access or coronary venous anatomy. Responders may obtain maximal benefit from CRT with endocardial LV stimulation. Although leadless pacing is only in the proof-of-concept stage, a subcutaneous implantable defibrillator has been developed and tested in clinical trial. The preliminary result is encouraging. The integration of leadless pacemaker and subcutaneous implantable defibrillator is important because heart failure patients frequently require CRT in combination with an implantable defibrillator.

REFERENCES 1. Baddour LM, Epstein AE, Erickson CC: Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 121:458-477, 2010. 2. Borek PP, Wilkoff BL: Pacemaker and ICD leads: strategies for long-term management. J Interv Card Electrophysiol 23:59-72, 2008. 3. Bax JJ, Abraham T, Barold SS, et al: Cardiac resynchronization therapy. Part 2. Issues during and after device implantation and unresolved questions. J Am Coll Cardiol 46:2168-2184, 2005. 4. Barold SS, Herwerg B: Pacing in heart failure: how many leads and where? Heart 94:10-13, 2008. 5. Van Deuren C, van Geldorp IE, Rademakers LM, et al: Endocardial left ventricular pacing improves cardiac resynchronization therapy in canine LBBB hearts. Circ Arrhythm Electrophysiol 2:580-587, 2009. 6. Derval N, Steendijk P, Gula LJ, et al: Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. J Am Coll Cardiol 55:566-575, 2010. 7. Garrigue S, Jais P, Guillaume E, et al: Comparison of chronic biventricular pacing between epicardial and endocardial left ventricular stimulation using Doppler tissue imaging in patients with heart failure. Am J Cardiol 88:858-862, 2001. 8. Leclercq C, Gadler F, Kranig W, et al: A randomized comparison of triple-site versus dual-site ventricular stimulation in patients with congestive heart failure. J Am Coll Cardiol 51:1455-1462, 2008. 9. Spickler JW, Rasor NS, Kezdi P, et al: Totally self-contained intracardiac pacemaker. J Electrocardiol 3:325-331, 1970. 10. Goto H, Sugiura T, Harada Y, et al: Feasibility of using the automatic generating system for quartz watches as a leadless pacemaker power source. Med Biol Eng Comput 37:377-380, 1999.

11. Echt DS, Cowan MW, Riley RE, et al: Feasibility and safety of a novel technology for pacing without leads. Heart Rhythm 3: 1202-1206, 2006. 12. Lee KL, Lau CP, Tse HF, et al: First human demonstration of cardiac stimulation with transcutaneous ultrasound energy delivery: Implications for wireless pacing with implantable devices. J Am Coll Cardiol 50:877-883, 2007. 13. Lee KL, Tse HF, Echt DS, et al: Temporary leadless pacing in heart failure patients with ultrasound-mediated stimulation energy and effects on acoustic window. Heart Rhythm 6:742-748, 2009. 14. Echt DS, Moore D, Cowan M, et al: Chronic implantation of leadless pacing electrodes in the left ventricle of a goat model [abstract]. Heart Rhythm 7(5 suppl):451-452, 2010. 15. Yeh DD, Fu DK, Kwan D, et al: Acoustic window for ultrasoundmediated leadless cardiac pacing [abstract]. Heart Rhythm 6(5 suppl):315-316, 2009. 16. Liem LB, Mead RH, Fowler R, et al: A novel method for synchronizing leadless pacing to a co-implanted pacing system [abstract]. Heart Rhythm 7(5 suppl):309, 2010. 17. Sweeney MO: In a footnote, at least. Heart Rhythm 3:1207-1209, 2006. 18. Benditt DG, Goldstein M, Belalcazar A: The leadless ultrasound pacemaker: a sound idea? Heart Rhythm 6:749-751, 2009. 19. Willis NP, Brisken A, Echt DS, et al: Novel method for calibration of acoustic energy transfer in a wireless pacing system [abstract]. Heart Rhythm 7(5 suppl):373, 2010. 20. Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 363:36-44, 2010. 21. Wieneke H, Konorza T, Erbel R, et al: Leadless pacing in the heart using induction technology: a feasibility study. Pacing Clin Eletrophysiol 32:177-183, 2009.

22. Edelberg JM, Huang DT, Josephson ME, Rosenberg RD: Molecular enhancement of porcine cardiac chronotropy. Heart 86(5): 559-562, 2001. 23. Miake J, Marban E, Nuss HB: Gene therapy: Biological pacemaker created by gene transfer. Nature 419:132-133, 2002. 24. Miake J, Marban E, Nuss HB: Functional role of inward rectifier current in heart probed by Kir2.1 overexpression and dominant-negative suppression. J Clin Invest 111:1529-1536, 2003. 25. Bucchi A, Plotnikov AN, Shlapakova I, et al: Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker. Circulation 114(10):992-999, 2006. 26. Rosen MR, Brink PR, Cohen IS, et al: Genes, stems cells, and biological pacemakers. Cardiovasc Res 64:12-23, 2004. 27. Xue T, Siu CW, Lieu DK, et al: Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels. Circulation 115:1839-1850, 2007. 28. Tse HF, Xue T, Lau CP, et al: Bioartificial sinus node constructed via in vivo gene transfer of an engineered pacemaker HCN channel reduces the dependence on electronic pacemaker in a sick-sinus syndrome model. Circulation 114:1000-1011, 2006. 29. Plotnikov AN, Shlapakova I, Szabolcs MJ, et al: Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 116:706-713, 2007. 30. Qu J, Barbuti A, Protas L, et al: HCN2 overexpression in newborn and adult ventricular myocytes: distinct effects on gating and excitability. Circ Res 89:E8-E14, 2001.

21  21

Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation PETER H. BELOTT  |  DWIGHT W. REYNOLDS

The approach to cardiac pacemaker implantation has evolved during

the past half century.1 From the initial epicardial implants of Senning2 and transvenous implantation by Furman and Schwedel,3 cardiac pacemaker implantation has undergone radical changes not only in the implanted hardware but also in the preoperative planning, anatomic approach, personnel, and implantation facilities. The early trend from the epicardial approach to the simpler transvenous cutdown led to the percutaneous technique developed by Littleford and Spector.4 Previously simple preoperative planning, in particular device selection, has become complex. The pacemaker system, both device and electrodes, must be individualized to the patient’s particular clinical and anatomic situation. The implantation procedure, previously the exclusive domain of the cardiovascular surgeon, has also become the purview of the invasive cardiologist. Similarly, the procedure has undergone a transition from the operating room to the cardiac catheterization laboratory or special procedures room. Except in special instances, the luxury of an anesthesiologist has disappeared, with the implanting physician assuming additional responsibilities. Finally, because of concerns about cost containment, the usual in-hospital postoperative observation period has been dramatically reduced or replaced by an ambulatory approach to pacemaker implantation. Similarly, since Mirowski et al.5 implanted the first implantable cardioverter-defibrillator (ICD) in 1980, its evolution has been comparable with that of the cardiac pacemaker. The initial epicardial ICD placement with an abdominal pocket has given way to a transvenous approach and a pectoral pocket. The surgery initially performed in the operating room exclusively by a cardiovascular surgeon is now carried out by nonsurgeons in the catheterization or electrophysiology laboratory. Also, protracted hospital stays have been replaced by much shorter hospital stays, even outpatient situations. The once-simple ICD device is now much more complex, offering total arrhythmia control as well as backup dual-chamber rate-adaptive pacing. The advent of cardiac resynchronization therapy (CRT) has added a new level of complexity to pacemaker and defibrillator implantation. Not only is a third lead required, but reliable left ventricular stimulation also is essential for positive clinical results. CRT has brought new challenges to device implantation with respect to venous access, coronary sinus cannulation, lead positioning, effective stimulation, and new complications. Further, the new popularity of selective or alternative-site pacing for optimal hemodynamics and arrhythmia management has challenged the traditional sites of lead placement. All these changes have had a price: new techniques have created new challenges as well as new problems. This chapter explores all aspects of modern pacemaker and ICD implantations from a practical point of view as it addresses these new challenges and concerns.

Pacemaker Implantation PERSONNEL Implanting Physician or Surgeon Traditionally, pacemaker implantation procedures were performed exclusively by a thoracic or cardiac surgeon. The skills were acquired

during a residency or fellowship. Early pacemaker implantations involved more extensive surgery and, at times, an open-chest procedure for placement of epicardial electrodes. The pulse generator and electrodes were large, requiring considerable dissection and surgical skill. Since 1980, diminishing pacemaker size has limited the more extensive surgery previously required. At present, the knowledge and skills required for dual-chamber pacing are well suited for the physician trained in cardiac catheterization. It is generally accepted that the pacemaker-implanting physician may be either a thoracic surgeon or an invasive cardiologist.6 At times, the two may even act as a team, with the surgeon isolating the vein and the cardiologist positioning the electrodes. With the current reimbursement structure and the changing economic environment, however, this team approach is rapidly becoming burdensome; in any event, it is frequently unnecessary. Currently, the credentialing for pacemaker implantation procedures poses a dilemma. The trainee in thoracic surgery has ever-diminishing exposure to pacemaker implantation as the procedure becomes more the responsibility of the cardiologist. At the same time, the cardiologist has little or no exposure to proper surgical technique, the use of surgical instruments, and preoperative and postoperative care. Although controversy surrounds the appropriate implantation experience and its length, physicians with limited training and ongoing experience apparently have higher complication rates.7 To remain proficient, the physician should perform a minimum of 12 procedures per year. In a single-center study of more than 1300 permanent pacemaker implants, Tobin et al.8 reported complications in 4.2% of patients. The economic impact was substantial. Most importantly, there was an inverse relationship between the incidence of acute complication and implanter experience and case volume. Similarly, complications associated with elective generator replacements, revisions, and upgrades have been directly related to operator experience. Harcombe et al.9 found a higher rate of late complications after elective replacements (6.5%) compared with initial implants (1.4%). This higher rate was clearly related to operator inexperience. There is a definite need for formal training programs specifically designed to teach cardiac pacing.10-12 Such programs should be offered to both cardiologists and surgeons interested in cardiac pacing. The ideal program should be comprehensive and integrated, involving not only all implantations but also follow-up and troubleshooting. To be an effective implanter, the physician must understand the problems of follow-up and troubleshooting. Formal didactic experience and hands-on exposure are necessary. Although a formal, year-long, comprehensive, integrated training program is ideal, consideration of physicians who are out of formal training programs sometimes requires combining more intensive didactic programs with extended, supervised hands-on experience. Training is important for the implantation and nonimplantation aspects of pacing. We see substantially less enthusiasm for the presurgical and postsurgical aspects of pacing. We ardently believe such mastery is crucial to becoming an effective implanter. Regardless of how physicians have been trained to implant pacemakers, careful review of their training and experience by those granting privileges at the institution will help prevent inadequately trained individuals from performing independent, unsupervised pacemaker

443

444

SECTION 3  Implantation Techniques

implantation. Criteria for adequate training and experience should involve a minimum number of pacemaker procedures, including single-chamber and dual-chamber implantations, lead replacements, pulse generator replacements, and upgrades to dual-chamber from single-chamber systems. Also, some documentable experience in an active pacemaker service clinic should be required.13 An electrophysiology (EP) fellowship is one way of obtaining these skills, and physicians trained as surgeons, pediatricians, radiologists, and cardiologists have access to this training. Credentials can include the EP boards under the jurisdiction of the American Board of Internal Medicine, the Certified Cardiac Device Specialist examination by the International Board of Heart Rhythm Examiners, and cardiothoracic (CT) surgical boards, but only for pacemakers, not ICDs. Support Personnel Support personnel are crucial to the success and safety of any pacemaker procedure. Historically, whether in a large medical center or a small community hospital, the procedure was performed in the operating room (OR). This had its drawbacks because each case could be a first-time experience for the OR staff. Pacemaker procedures were often added at the end of a busy OR schedule and were assigned to the first available room with support personnel, who changed from procedure to procedure. Personnel not familiar with the procedure can interrupt the flow of the case. Even with the transition to the cardiac catheterization laboratory (CCL) for pacing procedures, the same problems can apply. Conversely, depending on the volume of procedures in the OR and CCL, there may be more opportunity for consistent, recurrent availability of cardiovascular technicians, nurses, and radiography personnel in the CCL. These more focused staff members tend to have a certain appreciation for the procedure and are better equipped to deal with the unique problems that may be encountered during pacemaker implantation. Whether implantation takes place in the OR or CCL, the minimal personnel required are the same, as follows: • A scrub nurse or technician familiar with each operator’s surgical preferences. • A circulating nurse to support the personnel who have scrubbed. This support generally involves delivery of supplies and equipment to the sterile field as needed and patient monitoring and medication administration, although this latter function is somewhat limited in the OR when an anesthesiologist is present. • A clinician responsible for electrical testing. It is also useful to have access to an experienced cardiovascular radiology technician, which generally is more easily accomplished in the CCL than the OR. The presence of an anesthesiologist or nurse anesthetist (CRNA) is inconsistent. Initially an essential member of the implantation team, an anesthesiologist in many centers is now involved only in special situations requiring airway support in an unstable or otherwise problematic patient. As ICDs, biventricular devices, extraction procedures, and other patients with unstable hemodynamics have become more common, each patient should be assessed for the need for support before the procedure. Anesthesiology staff should always be available for emergency situations and consulted if problems are anticipated. The participation of the manufacturer’s representative as support personnel has always been a subject of debate. This person’s role varies from center to center.14 At one extreme, the representative merely delivers the device and leads to the hospital. At the other extreme, the person is a vital member of the support team, retrieving threshold data, filling out registration forms, and at times, offering technical advice. The latter extreme is particularly true in smaller institutions with less pacemaker activity and in-house support of ICD implantation. A welltrained manufacturer’s representative can be an important member of the support team. An experienced representative dedicated to cardiac pacing and ICD implantation typically has broad experience and a knowledge base in problems unique to the company’s products. Although such a representative of industry can be helpful, this person, no matter how experienced or knowledgeable, should not be

considered an acceptable alternative to a knowledgeable, skilled, and experienced physician implanter. If an industrial representative is to be used during implantations for support, hospital approval is advisable. Comparing OR and CCL support personnel requirements, besides the CCL’s previously noted general advantages, another important concern is sterile technique. The regular OR personnel tend to be more keenly aware of sterile technique and are scrupulous in this regard. In contrast, CCL personnel are not routinely trained in OR and sterile techniques, and if not strongly reinforced, these procedures can be disastrously neglected. IMPLANTATION FACILITY AND EQUIPMENT The cardiac catheterization laboratory and special procedures room appear well suited for permanent pacemaker and ICD procedures.15,16 Early concerns about safety and sterility were unfounded, if these issues are appropriately addressed prospectively. Radiologic capabilities are invaluable; high-resolution images, unlimited projections, and angiographic capabilities assist in venous access and electrode placement, as well as in variable image magnification, digital image acquisition, and image imposition techniques and storage. In addition, these facilities tend to be equipped for ready access with all the catheters, guidewires, sheaths, and angiographic materials for special situations. The implantation facility also typically has the most sophisticated physiologic monitoring and recording equipment (Fig. 21-1), offering continuous, surface and endocardial electrical recordings, as well as extensive hemodynamic monitoring capabilities. Again, staffing with qualified cardiovascular nurses and technologists is essential. Concerns about the potential for infection must be addressed. These facilities are designated as intermediate-sterile areas. The sterile precautions tend to be less rigid than in the OR. The CCL also tends to be a high-traffic area. A rigid protocol for sterile technique must be established, and the room sealed from traffic after cleaning for the surgical procedure. Everyone entering this area must wear scrub clothing, a hat, and a mask. The ventilation system should also meet the standards for an intermediate-sterile area. The CCL and special procedures room generally have another drawback. Many do not allow the patient to be placed in the Trendelenburg position, which can be important in the percutaneous approach to pacemaker implantation. However, using a wedge under the legs early in the procedure can obviate this problem. The ideal room or suite would be dedicated to pacemaker and ICD procedures, with all the capabilities and skilled staffing previously

Figure 21-1  Cardiac catheterization laboratory. The patient is surrounded by sophisticated monitoring equipment, including a pulse oximeter, a physiologic recorder, an external defibrillator, an automatic blood pressure cuff, and an emergency “crash” cart.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

described, although this is clearly the exception at present. As the number of transvenously implanted defibrillators, biventricular systems, and extraction procedures increases, however, more rooms will likely be dedicated to pacemaker and ICD implantation. The strongest arguments for implanting a pacemaker in the operating from are sterility and patient control. The OR is typically the area of best sterility and sterile technique. A pacemaker represents a foreign body, so a prime concern is infection. An OR procedure generally offers the maximum protection against infection. Also, patient control is better because policy in most ORs requires that an anesthesiologist be available for any procedure. Presence of the anesthesiologist allows for more effective airway control and ventilation in the unstable or uncooperative patient. The anesthesiologist is available to intubate the patient and even administer general anesthesia, if necessary. The OR has a wide range of available surgical instruments and supplies and arguably is better than the CCL should a catastrophe occur requiring more extensive surgery, such as an open-chest procedure, although this rarely occurs and the advantage is usually theoretical. The main pitfall of the OR is the inconsistent quality of the fluoroscopy equipment. It is usually of lesser quality and of limited capability compared with that available in the CCL. In addition, the OR equipment is frequently shared with other services, such as orthopedics, and scheduling conflicts can arise. The lack of immediate access to angiographic materials and catheterization equipment is another drawback to using the OR for pacemaker procedures. Unless device implantation is given special consideration and is performed in a specific OR with equipment and supplies under the control of a device physician and staff, there is a tendency for lack of technical preparation, which disrupts the procedural flow and can adversely affect the outcome. However, this same caveat holds for a busy CCL. The monitoring equipment used for the device procedure is variable. A multichannel electrocardiographic (ECG) recording system is frequently recommended; such systems are able to monitor and record a minimum of three surface electrocardiograms and one intracardiac electrocardiogram.17 From a more practical view, the only requirement is continuous ECG monitoring on an oscilloscope. The ECG pattern need only be clear. Selection of ECG leads should demonstrate adequate atrial and ventricular morphology for defining underlying rhythm, arrhythmias, and atrial and ventricular capture. However, multiple and particularly orthogonal ECG leads are useful to confirm the lead position by ECG morphology. Threshold information can be obtained from the combined use of a pacing system analyzer (see later) and the recording system. Sensing data can be obtained from a reliable analyzer alone. Multichannel recorders provide more thorough evaluation and documentation and occasionally are extremely valuable in discerning arrhythmias, capture, capture morphology, timing, and so on. The multichannel recorder also allows retrieval of intracardiac signals, precise waveform analysis, and assessment of ventriculoatrial (VA) conduction. High-quality hard copy for analysis is also generally available with these more sophisticated recording devices, which tend to be ubiquitous in the CCL but uncommon in the OR. Patient monitoring should also include reliable blood pressure and arterial oxygen saturation (Sao2) determinations, usually obtained with an automatic noninvasive blood pressure cuff and a transcutaneous Sao2 monitor. Arterial catheter pressure monitoring is rarely required; it is useful for patients with potential hemodynamic instability but can also be associated with morbidity. These devices are of particular value when an anesthesiologist is not in attendance. Continuous Sao2 monitoring can detect hypoventilation from sedation, pneumothorax, and air embolization. A direct current (DC) biphasic defibrillator and complete emergency cart should be in the room where the pacemaker procedure is performed. The cart must include an Ambu bag and intubation equipment. The surgical instruments for a pacemaker procedure are usually found in a “minor surgical” setup (Fig. 21-2). Depending on the institution, the contents of a minor surgery setup can be overwhelming, particularly for the nonsurgeon implanting physician. The rows of

445

Figure 21-2  Minor surgery tray with minimum required surgical instruments and supplies. From top left and clockwise, Needle holder, scalpel, four sizes of curved hemostats and clamps, Goulet retractor, two Senn retractors, Weitlaner self-retaining retractor, Metzenbaum scissors, suture scissors, nontoothed forceps, and toothed forceps. The four packages are one of “free needles” and three of resorbable and nonresorbable sutures.

unnamed clamps and retractors would suggest the need to enter a major body cavity. Actually, a pacemaker procedure can be performed efficiently with only a few, well-selected instruments,18 and there are many acceptable variations and personal preferences. Problems can occur, however, with the nonsurgeon implanting physician who is unfamiliar with the instruments and their appropriate use. Box 21-1 lists the contents of an acceptable basic surgical tray for pacemaker implantations. The Gelpi and Weitlaner retractors can be used throughout the procedure for improved visual exposure (see Fig. 21-2). The Senn retractor is used for more delicate retraction of tissue edges; one end is L shaped, and the other has tiny claws. Another useful retractor, the Goulet retractor (see Fig. 21-2), can be replaced with a Richardson retractor and is extremely helpful in retraction when creating the pacemaker pocket. Unlike other large retractors, the smooth, scalloped ends of these retractors are gentle to the tissues while Box 21-1 

PACEMAKER SURGICAL INSTRUMENT TRAY 2 1 1 1 1 2 1 4 5 1 2 1 1 1 2 1 1 1 1 1 1 1

Adson forceps with teeth mouse-tooth forceps smooth forceps medium blunt Weitlaner retractor small Weitlaner retractor Senn retractors Army-Navy retractor baby towel clips curved mosquito clamps Peers clamp curved Kelly clamps small Metzenbaum scissors curved Mayo scissors No. 3 knife handle small needle holders Goulet retractor Bozeman uterine dressing forceps pkg 1-0 silk 18-inch suture material pkg 2-0 polyglactin mesh nonabsorbable suture material pkg of 4-0 polyglactin mesh nonabsorbable suture material No. 3 or 4 French (3F or 4F) eye needle No. 10 scalpel blade

446

SECTION 3  Implantation Techniques

affording a generous area of exposure. Army-Navy retractors can also be helpful for this purpose. Other instruments, such as forceps (with or without “teeth”), hemostats, scissors (tissue and other), needle holders, and clamps, are necessary, but their use does not require explanation here. Proper use and care of the instruments are crucial, and replacement of worn-out instruments is mandatory for avoiding frustration, delays, and suboptimal work. Device procedures performed in the OR typically benefit from excellent lighting. Multiple high-intensity lamps light the surgical field. However, this is not the case for procedures in the CCL or special procedures room, where lighting is frequently marginal. One solution is a high-intensity headlamp, which is extremely useful when creating the pocket and inspecting for bleeders, particularly when one’s head blocks out other light (Fig. 21-3). Using the headlamp can initially be frustrating and requires practice, but once facile, it will become the major light source for creating the pocket. Even in the OR, despite all the lighting, the headlamp can be very helpful. The electrocautery device can be useful, and some experienced implanters consider it essential to any pacemaker procedure. Its use, however, is controversial.19-21 Historically, using electrocautery equipment for cutting or coagulation during a pacemaker procedure was taboo, with concerns about causing burns at the myocardium-electrode interface, destroying the pulse generator, and damaging the pacemaker leads. The general consensus, however, is that an appropriately grounded electrocautery device is safe when two precautions are taken: (1) active cautery should never touch the exposed proximal pin of the electrode, and (2) use of all electrocautery should cease when the pulse generator is in the surgical field. Cutting with electrocautery expedites pulse generator changes while avoiding the risk of cutting the lead. At times, even in the most experienced hands, a tedious dissection ends with the scalpel or scissors nicking or cutting the electrode insulation. Use of rapid strokes with cautery avoids the buildup of heat, preventing injury to leads. Although experience indicates no important untoward effects on the myocardium if the cautery touches the pulse generator, there is a risk of causing a permanent no-output situation by destroying the pulse generator. This appears particularly true in certain pulse generators or when the battery voltage is well below the replacement indicator. The risk to the patient of a sudden lack of output can be eliminated by placing a temporary pacemaker in pacemaker-dependent patients; this consideration is fundamental to all pacemaker procedures whether or not electrocautery is used.

Figure 21-3  High-intensity headlamps optimize visualization in situations of limited lighting experienced frequently in the catheterization laboratory and sometimes in the operating room.

Figure 21-4  Multifunction Medtronic 2090 pacemaker system analyzer. This device determines the pacing and sensing functions of the electrode and the pulse generator as well as the electrical integrity of the electrode. (From Barold SS: Modern cardiac pacing. Armonk, NY, 1985, Futura, p 444.)

The pacing system analyzer (PSA) is extremely valuable during pacemaker procedures. PSA circuitry (especially sensing) mimics that of the planned pulse generator and more accurately predicts the performance of the pulse generator, even when stimulators and recorders are available. The early PSAs were simple and designed to measure the pacing and sensing thresholds for single-chamber ventricular pacing. PSAs were unable to perform (or cumbersome performing) the tasks required for atrial and dual-chamber pacing.22 Previously, PSA devices were designed to test both the lead function and the pulse generator. Currently, PSAs can test lead function and usually can adjust the pacing mode so that both the atrial and the ventricular leads can be tested without risking asystole. Modern PSAs can function in any mode and should measure from either chamber, offering a clear digital display as well as extensive programmability. PSAs provide emergency capabilities, including high output, high rate, and often antitachycardia pacing. In addition, hard copy and electronic transfer of data is useful for documentation. An example of a PSA is the Medtronic model 2090 (Fig. 21-4); Table 21-1 summarizes its desirable features. Some of the pacemakers driven by sensors, (e.g., temperature, oxygen) require special additional sensor analysis by a specialized PSA tool. Whether supplied by the institution or the manufacturer, a good PSA is essential. There never seem to be enough spare parts during a pacemaker procedure. Most manufacturers offer service kits containing splice kits, stylets, lead adapters, wrenches, lubricant, lead caps, wire cutters, and so on (Box 21-2). It is advisable to set up a pacemaker cart stocked with all the supplies likely to be needed. This cart should hold (1) a temporary pacemaker tray that contains the materials for venous insertion, as well as the temporary pulse generator and leads, (2) an assortment of sheath sets, dilators, and guidewires, (3) the service kits from the manufacturers of the most commonly used pacemakers, (4) the equipment for lead retrieval, and (5) if they are used, a supply of polyester (Parsonnet; C. R. Bard) pouches (Fig. 21-5). A designated person should make sure supplies are reordered and up to date. Other, lesser used supplies can be obtained from the OR or central supply facility, such as a Jackson-Pratt drain for managing hematomas (Fig. 21-6) and various-sized Penrose drains for tunneling.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

TABLE

21-1 

447

Operating Features of the Medtronic CareLink Programmer 2090 Pacing System Analyzer (Medtronic)

Parameter Models Lower rate:   AOO, AAI, VOO, VVI, DOO   DDD, VDD Upper rate Amplitudes (A and V) Pulse width (A and V) AV interval:   Sensed   Paced Rapid atrial stimulation Atrial refractory Ventricular refractory Atrial sensitivity Ventricular sensitivity Polarity (A and V) Atrial Blanking After atrial pace After atrial sense After ventricular pace:   VVI/VOO   DDD/VDD After ventricular sense Ventricular Blanking After atrial pace After ventricular sense After ventricular pace Measurement Parameters P-wave amplitude R-wave amplitude Impedance (A and V) Slew rate Pacing current Special Features Rapid stimulation Rates Emergency pacing

Range VOO, VVI, AOO, AAI, DOO, DDD, VDD, ODO 30-220 30-110 80-220 0.1-10.0 V 0.02-1.5 msec 20-350 msec 20-350 msec 200-800 min. (ppm) 200-500 msec 250 msec 0.25-20 mV 0.5-20 mV Unipolar/bipolar 160-300 msec 160-300 msec 150-350 msec 200-220 msec 150 msec 40 msec 125 msec 200 msec 0.3-30 mV 0.6-30 mV 200-2499 2500-4000 0.1-4.0 V/s 0.1-25 Max AOO, VOO, DOO modes 180-800 ppm VVI rate at 70 at 10 V and 1.5 msec

A, Atrium/atrial; AV, atrioventricular; V, ventricle/ventricular.

Figure 21-5  Polyester (Dacron) Parsonnet pouch. The pouch is useful in patients with little subcutaneous tissue and is usually soaked in povidone-iodine (Betadine) before the pacemaker is inserted into the pouch, which is then inserted into the pacemaker pocket. (Courtesy C.R. Bard, Billerica, Mass.)

key preoperative consideration is documentation of the bradyarrhythmia, through 12-lead electrocardiogram (ECG), Holter monitor, event recordings, or inhospital critical care unit or telemetry unit monitoring. Supporting laboratory data, such as digitalis levels, thyroid parameters, and blood chemical analysis, provide documentation that the bradycardia is not secondary to another condition. The patient evaluation should substantiate the indications outlined by the American College of Cardiology (ACC), American Heart Association (AHA), and North American Society of Pacing and Electrophysiology (NASPE)

PREOPERATIVE PLANNING Planning a pacemaker procedure is important if the case is to proceed smoothly, starting with patient evaluation, including symptoms, medications, and associated conditions. The physical examination may demonstrate the effects of bradycardia, including altered vital signs, evidence of cardiac decompensation, and neurologic deficits. Anatomic issues potentially affecting the implant can also be uncovered. A Box 21-2 

SUPPLIES AND SPARE PARTS FOR PACEMAKERS Lead stylets: varying lengths, varying stiffness Straight and variable J-shaped retention wire curve Silicone oil Helical coil adaptor with 5-mm pin Sterile medical adhesive Wire crimper-cutter Lead connector caps: 3.2, VS-1, and 5-mm sizes Step-up and step-down adapters Adapter sleeves Screwdriver kit and torque wrenches One set of connecting cables Introducer sets of all sizes

Figure 21-6  Jackson-Pratt drainage system. The system allows for sterile closed-wound drainage. The negative-pressure squeeze bulb has a one-way valve that prevents drainage from returning to the wound.

448

SECTION 3  Implantation Techniques

joint task force.23 The documentation should be readily available and is usually affixed to the patient’s chart.

TABLE

21-2 

Analysis of Ambulatory Pacemaker Procedures, 1983-1995

Inpatient Versus Outpatient Procedure With all documentation obtained and indications met, the next step is scheduling the procedure. Pacemaker and ICD surgery can be performed on either an inpatient or an outpatient basis. Traditionally, even pacemaker procedures were done on an inpatient basis, which involves formal admission of the patient to the hospital for the procedure. The preoperative evaluation (in most cases), the device procedure, and early postoperative care are carried out in the hospital. Generally, the patient has already been admitted to the hospital because of symptoms (e.g., syncope) and the diagnosis of a bradyarrhythmia subsequently established. The device procedure is then scheduled. Alternatively, the evaluation is mostly or partly completed before admission; after the need for a pacemaker is determined, the patient is admitted for the pacemaker procedure and postoperative care. In some cases, this inpatient approach is inefficient and not cost-effective. The early pacing systems were large, had brief longevity, and were prone to catastrophic complications, such as lead dislodgement, perforation, and wound infection. Postoperatively, therefore, patients were managed with extreme caution; an abbreviated hospital stay seemed radical, and an ambulatory procedure was unthinkable. Currently, complications are rare; pacemakers and even ICDs are small; venous access is easy and quick with the introducer technique; and the procedure is relatively minor. Refinements of the electrode systems with active and passive fixation have reduced the dislodgement rate to near zero. In addition, the indications have been expanded to include more patients who are less pacemaker dependent and for prophylactic purposes. Lastly, and perhaps most directly, there is a growing mandate for cost containment. The very technologies that have made cardiac pacing and ICDs physiologic, reliable, and safe have resulted in higher cost. For all these reasons, it seems logical that an ambulatory approach for device procedures could be safe and effective as well as less expensive. There is a trend toward performing pacemaker procedures on an ambulatory basis. The experiences at several centers, in both Europe and the United States, have clearly supported the safety and efficacy of this approach.24,25 Concerns about potential complications continue to be expressed.26-28 Questions about lead selection, the timing of discharge, and the intensity of follow-up are frequently raised. In addition, the economic impact has yet to be fully appreciated. Although more ambulatory pacemaker procedures are being performed, this has not been reflected well in the pacing literature. Since the original reports of Zegelman et al.24 and Belott,25 Haywood et al.29 have reported a randomized controlled study of the feasibility and safety of ambulatory pacemaker procedures. Although the study group was small (50 patients), the results were similar to those of one of the authors (PHB). There was good patient acceptance, no evidence of a higher complication rate, and cost savings of £540 (at that time, about $810 U.S.). Since the initial report of 181 new pacemaker implants in 1987, our own ambulatory experience continues to be gratifying. During a 13-year span reported in 1996, that experience comprised 1474 pacemaker procedures, 1043 (69%) of which were performed on an ambulatory basis.30 The experience also included pulse generator changes, all of which we have performed on an outpatient basis since 1987. Our experience indicates that 60% to 75% of new pacemaker implantations can be successfully performed as ambulatory procedures (Table 21-2). There have been no additional ambulatory failures, pacemaker-related emergencies, or deaths in the ambulatory procedures. (An ambulatory failure is an implantation that is initiated as an ambulatory procedure, but for which the hospital stay is extended to admitting the patient because of a complication.) The complications encountered in ambulatory cases included one hemothorax detected 2 weeks after discharge, successfully managed by hospitalization and chest tube drainage. Three hematomas were managed on an ambulatory basis with reoperation, control of bleeding, and drain placement. Two small pneumothoraces that did not require chest tubes occurred fortuitously in hospitalized patients who had no planned ambulatory procedure.

Year 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 total

Total No. Patients 99 102 112 110 112 123 100 107 135 119 145 113 97 1474

No. Patients Ambulatory 34 34 56 60 78 87 70 87 124 94 128 104 87 1043

No. Patients Discharged on Day of Procedure 8 16 44 56 78 86 68 83 124 90 125 102 87 967

No. Patients Discharged <24 hr after Procedure* 26 18 12 4 0 1 2 4 0 4 3 2 0 76

Percentage of Ambulatory Procedures 34 34 50 60 69 70 70 77 91 78 88 92 88 69

*Patients were hospitalized overnight.

These experiences underscore the safety of the ambulatory approach. At present, almost all elective pacemaker procedures (new implantations, electrode repositioning, upgrade procedures, electrode extractions, and pulse generator changes) are done on an ambulatory basis. A simple protocol is used, and the patients often go home 1 to 2 hours after the procedure. They are seen the following day in the pacemaker clinic. Box 21-3 outlines a simple outpatient protocol. In most institutions, patients can remain in the hospital overnight and still be considered outpatients. This practice conforms to the present U.S. Health Care Financing Administration (HCFA) definition of ambulatory surgery for reimbursement in the United States, as follows: “When a patient with a known diagnosis enters a hospital for a specific minor surgical procedure or treatment that is expected to keep him or her in a hospital for only a few hours (less than 24) and this expectation is realized, he or she will be considered an outpatient regardless of the hour of admission, whether or not he or she occupied a bed, and whether or not he or she remained in the hospital past midnight.”31 An important caveat of ambulatory pacemaker procedures is that if there is any doubt or concern about the patient’s wellbeing, the hospital stay can be extended. In the United States, the primary instrument for reimbursement is Medicare, administered by the Centers for Medicare and Medicaid Services. To limit fraud and abuse, a recovery system of private contractors was implemented, called the Medicare Recovery Audit program. With respect to pacemakers and defibrillators, the program has brought pressure to bear on hospitals to perform these procedures on an outpatient basis. Hospitals have been denied reimbursement on the basis of insufficient and inaccurate documentation of medical Box 21-3 

OUTPATIENT PROTOCOL 1. Surgery scheduled as an outpatient procedure with outpatient number assigned. 2. Preoperative blood analyses, electrocardiogram, and chest x-ray study performed on an outpatient basis within 24 hours before admission. 3. Patient instructed to fast after midnight of the evening before the procedure. 4. Patient instructed to report to the outpatient department on the morning of the day of procedure. 5. Postoperative electrocardiogram and chest x-ray study performed. 6. Patient discharged when fully awake and vital signs stable. 7. Patient instructed to report to the pacemaker center the next morning.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

necessity as well as incomplete and improper coding. The denial of reimbursement has been challenged and reversed on a number of occasions. The fundamental issue is documentation. For this purpose and for all other regulatory and reimbursement purposes, clear documentation of indications for the device and the need for inpatient or outpatient procedures is essential. Preoperative Patient Assessment The preoperative patient assessment consists of the synthesis of all patient information, including history, physical findings, old records, cardiac rhythm strips, and laboratory data. With this information, appropriate decisions can be made about the pacemaker mode, leads, and general approach. The first such decision is whether the patient requires a singlechamber or dual-chamber pacemaker. With the expansion of options in devices, physicians also need to consider whether the patient’s condition would be better served with an ICD or a cardiac resynchronization device. As a rule, if the patient has intact atrial function, every effort is made to preserve atrial and ventricular relationships. Singlechamber ventricular pacing is usually reserved for the patient with chronic atrial fibrillation or atrial paralysis. A device is selected with appropriate size, longevity, and programmability. If the heart is chronotropically incompetent, a device that offers some form of rate adaptation is considered. Lead selection is equally important. One necessary decision is whether to use passive-fixation or active-fixation leads. Generally, an active-fixation electrode is selected when problems of dislodgement are expected, such as in the patient with a dilated right ventricle or amputated atrial appendage. Active-fixation leads are one of several factors that enhance removability of the lead, if it is necessary in the future. Also important is the pacing configuration (unipolar vs. bipolar). This decision relates to both electrodes and the pulse generator. Although the use of bipolar pacing and sensing has definite advantages, bipolar leads have historically been more complicated and prone to more problems. Bipolar leads are also larger in diameter. The compatibility of electrodes and the pulse generator is extremely important, particularly when using an original electrode with a modern pulse generator. If these are incompatible, an appropriate adapter must be obtained. Directly related to the device selection process is whether an ICD or CRT system should be placed. These decisions also affect the type of device selected and the lead systems employed. If an ambulatory approach is being considered, the patient is assessed with respect to the risk of this approach. An unstable patient should always be admitted to the hospital. If the patient is critically ill, pacemaker dependent, or unstable, a temporary pacemaker is considered. It is usually better to take the few extra minutes and place a temporary pacemaker. Doing so can avoid moments of “terror” during the procedure if asystole occurs. This statement is particularly true in patients with complete atrioventricular block, in whom an apparently stable escape rhythm can suddenly disappear, a common situation after initial pacing has been established. The timing of the procedure usually relates to the stability of the patient. In the critically ill patient in whom there are concerns about the stability of the cardiac rhythm or temporary pacemaker, an early permanent procedure is in order. Conversely, in a patient whose survival is in doubt, the clinician may appropriately decide to wait for stabilization. At times, the procedure is delayed because of systemic infection or sepsis. A permanent pacemaker implantation performed in a septic patient may lead to the seeding of bacteria on the pacemaker or electrode. If there is active infection, our approach is to defer the procedure until the patient is afebrile and no longer septic, to reduce the risk of pacemaker system infection. Decisions with regard to the implantation site are not as important at present as when only large pulse generators were available. The currently available devices, weighing less than 30 grams, make the site, in most situations, moot. Devices tend to be tolerated well in almost any location. However, special circumstances deserve men­ tion, including hobbies, recreational/occupational activities, cosmetic

449

issues, and previous medical conditions. In the patient who hunts, for example, the pacemaker should be placed on the side opposite that of the rifle butt. Similar considerations are appropriate for the tennis enthusiast or golfer (although our experience with golfers indicates that placing the pacemaker on the backswing or followthrough side varies). In a young person, placement of the pacemaker under the breast (women) or in the axilla may be more desirable from a cosmetic point of view. Medical conditions, such as previous surgery, radiation therapy, and skeletal or other anatomic abnormalities, should also be considered. In the patient who is small with little subcutaneous tissue, a subpectoralis muscle (subpectoral) implantation may be required. This calls for the use of a bipolar system to avoid stimulation of skeletal muscles. Preoperative Orders The preoperative orders for pacemaker implantation are generally simple. The patient fasts for at least 6 hours before the procedure. If the implantation is an ambulatory procedure, the patient reports to the hospital on the day of the procedure, with enough time to obtain the necessary preoperative testing, generally 2 hours. The preoperative procedures consist of posteroanterior (PA) and lateral chest radiographs, an ECG, a complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), and measurements of serum electrolytes, blood urea nitrogen (BUN), and serum creatinine. Because the patient is fasting, adequate hydration is maintained with a stable intravenous (IV) line. Hydration is extremely important for subsequent venous access and prevention of air embolization during the procedure. It can be frustrating and dangerous to try to gain venous access in a patient who is dehydrated after prolonged fasting without IV hydration. We generally request that the IV line be started on the side of the planned procedure, so as to facilitate venography during attempts at venous access if this becomes a problem. The management of pacemaker surgery in the patient taking anticoagulants is controversial. Little information is available regarding management of a patient who requires anticoagulation. Clearly, however, the patient receiving anticoagulants, including heparin and platelet antagonists, is at risk for hematoma formation. It is generally held that in patients who require oral anticoagulants, PT should be normalized before implantation. Anticoagulant therapy can be resumed between 24 and 48 hours after pacemaker implantation. Reducing the PT to normal in a patient requiring anticoagulants (e.g., with artificial heart valve) creates a serious risk for thromboembolic complications. To address this issue, many operators choose to admit the patient to the hospital and start IV heparin while the warfarin is withheld and PT normalized. This process, called bridging, often takes several days. When the PT has reached the control value, the patient is scheduled for surgery. On the day of surgery, the heparin is stopped, and in some situations, the anticoagulation is reversed and the procedure carried out. Several hours postoperatively, the heparin is resumed. After 24 to 48 hours with no evidence of significant hematoma, the warfarin is then resumed; when therapeutic levels are reached, the heparin is stopped, and the patient is discharged with oral warfarin therapy. In 2008 the American College of Chest Physicians (ACCP) published evidence-based practice guidelines for the perioperative management of patients receiving antithrombotic therapy,32 including vitamin K antagonists (VKAs) and antiplatelet drugs. ACCP recommends temporary cessation of VKAs and use of perioperative bridging anticoagulation with low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) for patients at moderate to high risk for thromboembolism and for those with a mechanical heart valve, atrial fibrillation, or venous thrombosis. There is no mention of uninterrupted VKA therapy. For the patient taking antiplatelet drugs who has bare-metal or drug-eluting stents and requires surgery within 6 weeks of stent placement, uninterrupted antiplatelet therapy is recommended. In patients who require temporary interruption of antiplatelets, treatment is stopped 7 to 10 days before surgery. It is recommended that antiplatelet drugs be resumed approximately

450

SECTION 3  Implantation Techniques

24 hours postoperatively. Frequently with pacemaker and ICD procedures, however, antiplatelet therapy cannot be suspended. Cost controls and managed care can make this process problematic. In addition, despite vigorous attempts at hemostasis, significant hematomas have resulted from the use of heparin. This problem is anecdotal, but in our general experience, the greatest risks for bleeding complications, hemorrhage, and hematoma occur with the use of heparin or platelet antagonists such as aspirin. Having encountered a patient with a devastating thromboembolic complication caused by withdrawal of warfarin, as well as multiple large hematomas from the use of heparin, one of us (PHB) has chosen to perform pacemaker and ICD procedures with the patient still undergoing anticoagulation with oral warfarin. As a rule, patients taking oral anticoagulants have their international normalized ratio (INR) reduced to about 2. With this policy in effect more than 22 years, there have been no devastating hematomas or thromboembolic events. In a recent 13-year retrospective review of 458 device procedures on patients receiving continuous uninterrupted VKA therapy, there were only eight hematomas and no catastrophic hemorrhages or VKA-related deaths.33 This gratifying experience underscores the safety and cost-effectiveness of continuous uninterrupted VKA therapy, which unfortunately remains unaddressed by current guidelines for cardiac implantable electronic device (CIED) procedures. We believe that pacemaker and ICD procedures can be performed safely with the patient anticoagulated as previously described. Supporting this approach in a 4-year experience, Goldstein et al.34 found no difference in incidental bleeding complications between patients receiving warfarin and those without anticoagulation. No wound hematomas, blood transfusions, or clinically significant bleeding occurred in any patients receiving warfarin. In a later, large series of patients, Giudici et al.35 further substantiated the safety and efficacy of CIEDs without reversing warfarin therapy. More recently, Ahmed et al.36 demonstrated that interrupting anticoagulation is associated with increased thromboembolic events, and cessation of VKAs with bridging was associated with a higher rate of pocket hematoma and prolonged hospital stays. The authors concluded that continuous uninterrupted VKA therapy with a therapeutic INR was safe and cost-effective. Thal et al.37 compared the incidence of hematoma formation among patients receiving continuous warfarin, aspirin, and clopidogrel therapy. Hematoma formation was rare, even among anticoagulated patients, although an increased incidence was seen in patients receiving dual-antiplatelet therapy. Dreger et al.38 found CIED procedures to be safe in patients on dual-antiplatelet therapy but recommended the use of a drainage system. In patients requiring CRT, Ghanbari et al.39 found uninterrupted warfarin therapy to be a safe alternative to routine bridging therapy, reducing risk of bleeding and shortening hospital stay. More recently, continuing warfarin in patients with a therapeutic INR was shown to be a safe, costeffective approach compared with cessation of warfarin and bridging anticoagulation. A new strategy is developing with the release of dabigatran in the United States. This direct thrombin inhibitor has the advantage of a short half-life and obviates the need for INR tracking. The RE-LY study demonstrated its efficacy and safety for patients with atrial fibrillation in comparison to warfarin.40 At this time, no data are available on the impact of dabigatran on perioperative hematomas or the most appropriate perioperative management. However, witholding the medication for 24 hours before the procedure and restarting 24 hours later seems a reasonable initial approach. The risks of interrupting continuous anticoagulant therapy with a resultant thromboembolic event can be substantial. Although hemorrhage is possible during and after pacemaker procedures in patients with therapeutic levels of anticoagulation, the risk seems minimal. The bleeding can generally be treated with local measures, such as the placement of drains or reoperation. Risk of bleeding is greatly outweighed by risk of thromboembolism after withdrawal of anticoagulant therapy. Pacemaker and ICD surgery in the patient receiving anticoagulant therapy is becoming more prevalent as more patients are

prescribed these therapies for atrial fibrillation. The patient is instructed to continue maintenance oral medications, which may be taken with small sips of water. Patients taking a hypoglycemic agent are instructed to reduce the preoperative dose by 50%. The administration of prophylactic antibiotics is controversial. We prefer intraoperative administration of a broad-spectrum cephalosporin (e.g., cefazolin). Others use vancomycin, which covers all grampositive organisms. Approximately 50% of device infections are caused by methicillin-resistant staphylococci. Screening for Staphylococcus aureus nasal colonization helps in identifying patients at highest risk. The patient should scrub the chest, neck, shoulders, and supraclavicular fossae with a povidone-iodine (Betadine) sponge the evening and the morning before the procedure; the surgical area usually is shaved in the procedure room. Also, the patient should empty the bladder before coming to the procedure room. PACEMAKER IMPLANTATION: GENERAL INFORMATION On arrival at the procedure room, the patient is transferred to a radiography table. In the catheterization laboratory or special procedures area, the table’s radiolucent properties are standard. In the operating room, prior arrangements are made for a special radiolucent operating table; it is advisable to test the fluoroscopy equipment’s ability to penetrate the table. It is also helpful to establish proper x-ray tube orientation. Attention to these details can avoid later problems, when it is discovered that the patient is on the wrong table, the radiographic equipment is inoperative, or the image is upside down, backward, or both. Almost immediately, the patient is connected to physiologic monitoring (ECG, pulse oximetry, blood pressure cuff). If not already done, a reliable venous line is established, preferably on the side of the operative site. The circulating nurse must have easy access to the IV line for drug administration and introduction of radiographic materials. Oxygen can be administered by nasal cannula or mask. With a temporary pacemaker, the appropriate site is shaved and prepared, and the temporary pacemaker is placed using the Seldinger technique. It is important to secure the lead and sheath adequately to maintain accessibility and allow easy removal at the end of the procedure. Site Preparation and Draping When effective patient support has been established, focus turns to the operative site. If not already accomplished, shaving and skin cleansing should include the neck, supraventricular fossae, shoulders, and chest. The operative site, shaved and cleansed, is now formally prepared and draped. A povidone-iodine (Betadine) scrub may be followed by alcohol, then povidone-iodine solution, with skin drying before applying the final povidone-iodine solution. Alternately, povidone-iodine gel is spread liberally over the operative site. Within 30 seconds, an optimal bactericidal effect is achieved. With this approach, scrubbing the area is not required. For patients allergic to povidone-iodine, a chlorhexidine (Hibiclens) or hexachlorophene (pHisoHex) scrub can be used. Currently, many traditional scrubs have been replaced by either a povidone-iodine or a chlorhexidine and alcohol combination. These preoperative skin preparations have the benefit of a single, rapid application. DuraPrep is iodine povacrylex and isopropyl alcohol; ChloraPrep is 2% chlorhexidine and 70% isopropyl alcohol; both offer rapid-acting broad-spectrum protection. Because alcohol-based antiseptic solutions can act as fuel for surgical fires, the skin preparation must be allowed to dry, strictly observing recommended drying times. In addition, it is important to remove the fuel; surgical fires in the OR can result in patient burns and even death.41 The draping process is a matter of personal preference. One of the authors (DWR) applies a sterile, see-through plastic adhesive drape (impregnated with an iodoform solution) over the entire operative area. The other (PHB) uses one or more sterile plastic drapes with adhesive along one side (Fig. 21-7); the adhesive surface is applied from shoulder to shoulder at the level of the clavicle, which serves to create



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

A

451

B

Figure 21-7  A, Application of a 3M (Minneapolis) 10/10 drape to create a sterile barrier. B, The drape folds over the support of common house (Romex) wire, creating an effective sterile barrier and preventing patient claustrophobia.

a sterile barrier from the shoulder level down. Depending on the situation, other barriers can be created. In both cases, the plastic drape is used to optimize sterility. After some form of sterile barrier is established, the operative site is draped with sterile towels, and one or more large, sterile surgical sheets are applied. Care is taken to avoid smothering the patient and causing claustrophobia, best achieved by keeping the drapes off the patient’s face and maintaining the cephalic aspect of the main drape perpendicular to the patient’s neck. This arrangement allows unrestricted access to the patient’s head and neck. The main drape is clipped to some form of support on both sides of the patient. The support can consist of IV poles placed on each side of the patient. Such an arrangement may not be possible in laboratories, where it interferes with radiographic equipment. Alternatively, the drape may be fixed to the C-arm or image intensifier. This solution is less than optimal; the drapes pull away whenever the C-arm or radiographic table is repositioned, increasing the risks of contamination and breaks in sterile technique. A simple, cost-effective solution consists of a

A

length of common house wire (8/3-gauge Romex) shaped into an arc over the patient’s neck. The ends of the wire are bent at right angles to the arc and tucked under the x-ray table padding at the level of the patient’s shoulders (Fig. 21-8). The weight of the patient’s shoulders supports the wire arc. The wire positioned under the shoulder is checked with fluoroscopy to avoid interference with the radiographic field of view. The house wire is strong enough to keep its shape under the weight of the surgical drape, offering optimal patient comfort and a reliable sterile barrier. There is no interference with the C-arm, and claustrophobia is avoided. The traditional use of a Mayo stand over the patient’s face is problematic because it can cause claustrophobia, makes access to the patient’s airway difficult in an emergency, and may interfere with the x-ray equipment. From the moment the catheterization laboratory or special studies room is cleaned, it must be treated as a surgical suite. All personnel must wear surgical clothing, hats, and masks. There should be an attempt to seal the room, limiting traffic and restricting access to personnel participating in the procedure.

B

Figure 21-8  A and B, House (Romex) wire shaped to form an arch over the patient’s head is positioned under the patient’s mattress and bent to accommodate differences in patients and circumstances.

452

SECTION 3  Implantation Techniques

Anesthesia, Sedation, and Pain Relief

TABLE

Most pacemaker procedures are performed with local anesthesia and some form of sedation and pain reliever.42 Local anesthesia alone is inadequate for optimal patient comfort; its effect does not prevent the discomfort associated with creation of the pacemaker pocket. Therefore, the additional combination of a narcotic and sedative is recommended; use of sedation alone is frequently inadequate. The challenge to the physician in charge is to achieve patient comfort without risking oversedation or respiratory depression. If an anesthesiologist or nurse anesthetist is part of the implantation team, patient comfort is usually achieved easily and safely. In this situation, if respiratory depression occurs, the patient can easily be ventilated. When the implanting physician orders the sedation and narcotics, however, the patient must be carefully monitored by the circulating nurse. The medications should be administered slowly. The selection and dose of local anesthetic are also important considerations. A local agent in therapeutic concentration that provides rapid onset of action and sustained duration is desirable. Local agents can be used in combination to achieve the desired effect, such as lidocaine for its rapid onset and bupivacaine for its sustained action. Also, the upper limit of total local anesthetic dose should not be exceeded. Toxic blood levels of local anesthetics can result in profound neurologic abnormalities, including obtundation and seizures. Table 21-3 lists the pharmacologic properties of common local anesthetic agents. The selection of sedative and narcotic depends on personal preference. We use midazolam and fentanyl. The operator should become familiar with one or more sedative agents as well as an analgesic, preferably a narcotic. Many newer agents are available. The selection of a benzodiazepine in combination with a semisynthetic narcotic can achieve ideal sedation, amnesia, and analgesia. A cooperative, relaxed, and pain-free patient is fundamental to the success of the procedure and the avoidance of complications. Pentothal and nitrous oxide have been used to effect brief periods of complete sedation at times of anticipated maximum discomfort, but the use of these drugs requires the expertise of an anesthetist because temporary respiratory support is frequently needed. The U.S. Joint Commission on Accreditation of Healthcare Organizations mandates that institutions establish a policy and protocol for patients receiving IV sedation, which would include pacemaker procedures. In essence, the protocol requires formal patient assessment before sedation. Resuscitation equipment must be present at all times in the sedation and recovery areas, and patients undergoing IV sedation must be monitored with pulse oximetry, continuous ECG rhythm monitoring, and automatic blood pressure recordings. Monitoring of the patient should continue for at least 30 minutes after the last IV sedative dose and for at least 90 minutes after intramuscular (IM) sedative administration. There are also strict discharge criteria. Table 21-4 lists common intravenous sedation drug protocols. A North American Society of Pacing and Electrophysiology (NASPE;

TABLE

21-3 

Pharmacologic Properties of Common Local Anesthetic Agents

Agent Esters Chloroprocaine (Nesacaine) Procaine (Novocain) Tetracaine Amides Bupivacaine (Marcaine) Lidocaine (Xylocaine)

Onset (min) Slow (5-10) Fast (5-15) Slow (20-30) Moderate (10-20) Fast (5-15)

Duration (hr)

Protein Binding (%)

Max Adult Dose

Short (0.5-1.5) Short (0.5-1.5) Long (3-5)

5

800 mg (11 µg/kg)

—

800 mg (11 µg/kg)

85

200 mg

Long (3-5)

82-96

100 mg

Moderate (1-3)

55-65

300 mg (4 µg/kg)

21-4 

Drug Protocols for Conscious Sedation

Drug Name Meperidine Morphine Fentanyl Valium Droperidol Midazolam Nitrous oxide Thiopental Ketamine

Route of Administration IM or IV IM or IV IM or IV IV IV IV Inhalation IV IV

Dosage 25-100 mg 1.5-15 mg 50-100 µg 2-10 mg 8-17 mg/kg 1-2.5 mg 30%-50% 1-4 mg/kg 0.5 mg/kg

Maximum 100 mg 20 mg 100 mg 10 mg 17 mg/kg 5 mg 50% — 0.5 mg/kg

Comments Long acting Long acting Very short acting — — — — Temporary LOC Temporary LOC

IM, intramuscular; IV, intravenous; LOC, loss of consciousness.

now Heart Rhythm Society) Expert Consensus developed recommendations and specified minimum training requirements on the use of IV sedation/analgesia by nonanesthesia personnel in patients undergoing arrhythmia-specific diagnostic, therapeutic, and surgical procedures.43 Antibiotic Prophylaxis and Wound Irrigation The use of prophylactic antibiotics to reduce the incidence of postoperative wound infection in a pacemaker procedure is controversial.44 Importantly, antibiotics are not a substitute for good infection control practices, an adequate surgical environment, and good surgical technique. The use of antibiotics in a pacemaker procedure follows the principle of prophylaxis, in which the risk for infection is low but the morbidity is high.45-47 The selection of antibiotics is based on sitespecific flora for wound infection and the spectrum, kinetics, and toxicity of the antimicrobial agent. The risk factors for infection have been well defined. The National Research Council for Wound Classification places the risk for infection from an elective procedure with primary closure at less than 2%. One important consideration is the higher risk for infection in procedures lasting longer than 2 hours. Now more formally studied, the use of prophylactic antibiotics in the low-risk, high-morbidity group, such as patients receiving pacemakers and defibrillators, appears justified. A meta-analysis of antibiotic prophylaxis showed a significant reduction in the incidence of infection.48 The spectrum of the antibiotic prophylaxis only needs to cover the gram-positive skin flora, primarily Staphylococcus epidermidis and S. aureus. In the case of pacemakers and cardiac procedures, the cephalosporins appear ideal (e.g., 1-2 g of cefazolin IV, preanesthesia). Because many institutions have a high incidence of methicillin-resistant S. aureus or S. epidermidis, vancomycin should be considered (e.g., 1 g IV slowly preoperatively). Postoperative doses are left to clinical judgment. Generally, 1 g of either drug may be given intravenously (IV) up to 8 hours postoperatively. Occasionally, the postoperative doses of cephalosporin are given orally for several days.49 A large, prospective, randomized double-blind placebo-controlled trial (RCT) recently validated the efficacy of antibiotic prophylaxis before implantation of pacemakers and defibrillators.50 The trial planned to enroll 1000 patients, but enrollment was terminated at 649 patients by the safety committee. The study demonstrated a significant reduction in infectious complications with antibiotic prophylaxis with 1 g of cefazolin administered before the procedure. Pretreatment with cefazolin reduced the incidence of postprocedural infection (0.64% cefazolin vs. 3.28% placebo; P = .016). The utility of prophylactic antibiotic has now been well established. Studies have shown that a single preoperative dose of antibiotics is as effective as a 5-day course of postoperative therapy. The prophylaxis should target the anticipated organisms. With complicated or contaminated procedures, additional postoperative coverage is indicated. During prolonged procedures, antibiotics should be readministered every 3 hours. Most importantly, prophylactic antibiotics should be administered within 1 hour before incision and should not be given more than 24 hours after the procedure.51-53



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

TABLE

21-5 

453

Common Antimicrobial Irrigation Protocols

Agent Bacitracin Cephalothin Cefazolin Cefuroxime Vancomycin Povidone-iodine

Concentration 50,000 units in 200 mL of saline 1 g/L of saline 1 g/L of saline 750 mg/L of saline 200-500 mg/L of saline Concentrated or diluted in aliquots of saline

Xiphisternal Upper abdominal

An additional strategy in the prevention of infection is topical antibiotic prophylaxis or antibiotic wound irrigation.54 Controlled trials evaluating the benefit of antibiotic irrigations are lacking. The concept of irrigation is to provide a high concentration of antibiotic at the site of potential infection at the time of contamination. The technique has proved most efficient in the absence of established infection and uses nonabsorbable antibiotics. Historically, aminoglycosides and bacitracin combinations have been used, but regimens vary in number, type, concentration, and duration of antibiotic use. Systemic toxicity with antibiotic irrigation is a major concern. Using large volumes of irrigating solutions with systemic antibiotics can greatly exceed the therapeutic range. The superiority of irrigation over systemic antibiotic administration has never been proved, and given the potential toxicity, caution in its use is recommended. Table 21-5 lists common antibiotic irrigation protocols. Recently, a novel antibacterial pouch (AIGISx, TyRxPharma) was developed to inhibit biofilms of S. aureus on CIEDs. It consists of a controlled–release polypropylene envelope impregnated with the antibiotics rifampin and minocycline. Its purpose is to reduce the incidence of pocket infections associated with pulse generator changes and other CIED procedures in the patient at high risk for infection; it is not recommended for all patients. An in vitro study demonstrated that the envelope significantly reduced the ability of S. aureus to form biofilms on mock CIEDs.55 Such patients at high risk for infection include the immunocompromised patient with renal failure patients receiving oral anticoagulants, and those undergoing CIED replacement/ revision procedures. Bloom et al.56 reported on use of the antibacterial pouch in 624 consecutive CIED procedures of high-risk patients. Device implantation was successful in 621 procedures, with only three major infections. There were no deaths related to the pouch. Use of the pouch was associated with high CIED implantation success with low infection rate in a population at high risk for CIED infection. No data show that the antibiotic pouch reduces the rate of clinical infection in any population. Despite the controversial nature of prophylactic systemic antibiotics and topical irrigation, the experience of one of the authors (PHB) at the Pacemaker and Arrhythmia Center, El Cajon, California, has been very gratifying. A protocol of intravenous antibiotics and wound irrigation has been followed at this facility since 1978. In each case, 1 g of cefazolin was given intraoperatively, followed by cefadroxil monohydrate, 500 mg, twice daily for 4 days. Previously a sponge soaked in povidone-iodine was placed in the pacemaker pocket just after pocket formation and removed at wound closure. To avoid the risk of leaving a sponge in the pocket, the pocket is flushed with povidone-iodine administered by 10-cc syringe. In more than 1500 pacemaker procedures, there have been two wound infections. A similar low incidence of infection has occurred at the other author’s (DWR) institution, University of Oklahoma College of Medicine. Since 1980, this institution’s regimen has consisted of a preoperative dose of cefazolin, 1 g IV, followed by 1 g IV for one to five more doses every 8 hours (depending on length of stay), as well as pocket irrigation with a solution of bacitracin, gentamicin, and polymyxin. Although the issue is admittedly controversial, the implanting physician needs to experience only one pacemaker infection with its many problems to become convinced that infection should be avoided at all cost.

Left anterolateral thoracotomy Left subcostal

Figure 21-9  Location of surgical incisions for the placement of epimyocardial systems.

Anatomic Approaches for Implantation There are two basic anatomic approaches to the implantation of a permanent pacemaker.57,58 Historically, the first is the epicardial approach, and the second the transvenous approach. The epicardial approach calls for direct application of pacemaker electrodes on the heart. This requires general anesthesia and surgical access to the epicardial surface of the heart. The transvenous approach is usually performed with local anesthesia and IV sedation. Each approach can be accomplished by several unique techniques. Currently, 95% of all pacemaker implantations are performed transvenously. The epicardial approach is generally reserved for patients who cannot undergo safe or effective pacemaker implantation by the transvenous route. The major epicardial techniques involve either applying the electrode(s) directly to a completely exposed heart or performing a limited thoracotomy through a subxiphoid incision (Fig. 21-9). A third technique places the leads by mediastinoscopy. There is even a fourth technique, which combines epicardial and endocardial lead placement. The several techniques used for the transvenous approach involve a venous surgical cutdown, percutaneous venous access, or a combination of both (Box 21-4). The pros and cons of the various approaches and techniques are reviewed here. A thorough knowledge of the anatomic structures of the neck, upper extremities, and thorax is essential for cardiac pacing (Fig. 21-10). The precise location and orientation of the internal jugular, innominate, subclavian, and cephalic veins are important for safe venous access.59,60 Their anatomic relations to other structures is crucial to avoiding complications. The venous anatomy of interest, from a cardiac pacing point of view, starts peripherally with the axillary vein.60 This large venous structure represents the continuation of the basilic vein and starts at the lower border of the teres major tendon and latissimus dorsi muscle. The axillary vein terminates immediately beneath the clavicle at the outer border of the first rib, where it becomes the subclavian vein. The axillary vein is covered anteriorly by the pectoralis minor and pectoralis Box 21-4 

TECHNIQUES FOR AXILLARY VENOUS ACCESS • Blind percutaneous puncture using surface landmarks • Blind puncture through the pectoralis major muscle using deep landmarks • Direct cutdown on the axillary vein • Fluoroscopy: needle the first rib for reference • Contrast venography • Doppler guidance • Ultrasound guidance

454

SECTION 3  Implantation Techniques

Common carotid artery Internal jugular

Clavicle

Lesser supraclavicular fossa

Subclavian artery Subclavian vein Clavicular head

Sternal head

Sternocleidomastoid muscle Figure 21-10  Anatomic relationship of the vascular structures in the neck and superior mediastinum.

major muscles and the costocoracoid membrane. The axillary vein is anterior and medial to the axillary artery, which it partially overlaps. At the level of the coracoid process, the axillary vein is covered only by the clavicular head of the pectoralis major muscle (Fig. 21-11). At this juncture, the axillary vein receives the more superficial cephalic vein. The cephalic vein terminates in the deeper axillary vein at the level of the coracoid process beneath the pectoralis major muscle. The cephalic vein often used for pacemaker venous access is classified as a “superficial vein of the upper extremity.” This vein, which actually commences near the antecubital fossa, travels along the outer border of the biceps muscle and enters the deltopectoral groove, an anatomic structure formed by the deltoid muscle and clavicular head of the pectoralis major. The cephalic vein traverses the deltopectoral groove and superiorly pierces the costocoracoid membrane, crossing the axillary artery and terminating in the axillary vein just below the clavicle at the level of the coracoid process. The subclavian vein is a continuation of the axillary vein. The subclavian vein extends from the outer border of the first rib to the inner

Trapezius muscle Clavicle Subclavius muscle Cephalic vein Pectoralis major muscle (cut) Pectoralis minor muscle Latissimus dorsi muscle Digitations of serratus anterior muscle

Lateral and medial pectoralis nerve

end of the clavicle, where it joins with the internal jugular vein to form the brachiocephalic trunk or innominate vein. The subclavian vein is just inferior to the clavicle and subclavius muscle. The subclavian artery is located posterior and superior to the vein. These two structures are separated internally by the scalenus anticus muscle and phrenic nerve. Inferiorly, the subclavian vein is associated with a depression in the first rib and on the pleura. The brachiocephalic trunks or innominate veins are two large, venous trunks located on each side of the base of the neck. The right innominate vein is relatively short. It starts at the inner end of the clavicle and passes vertically downward to join with the left innominate vein just below the cartilage of the first rib to form the superior vena cava (SVC). The left innominate vein is larger and longer than the right, passing from left to right for approximately 2.5 inches (6 cm), where it joins with the right innominate vein to form the SVC. The left innominate vein is in the anterior and superior mediastinum. The internal and external jugular veins have also been used for pacemaker venous access. The external jugular vein is a superficial vein of the neck that receives blood from the exterior cranium and face. This vein starts in the substance of the parotid gland, at the angle of the jaw, and runs perpendicular down the neck to the middle of the clavicle. In this course, the external jugular crosses the sternocleidomastoid muscle and runs parallel to its posterior border. At the attachment of the sternocleidomastoid to the clavicle, the external jugular vein perforates the deep fascia and terminates in the subclavian vein just anterior to the scalenus anticus muscle. The external jugular is separated from the sternocleidomastoid muscle by a layer of deep cervical fascia. Superficially, it is covered by the platysma muscle, superficial fascia, and skin. The external jugular vein can vary in size and may even be duplicated. Because of its superficial orientation, the external jugular vein is less frequently used for cardiac pacing venous access (Fig. 21-12). The internal jugular vein is an unusual site for pacemaker venous access. Because of its larger size and deeper and more protected orientation, however, the internal jugular vein is used more frequently than the external jugular vein. The internal jugular vein starts just external to the jugular foramen at the base of the skull. It drains blood from the interior of the cranium as well as superficial parts of the head and neck. This vein is oriented vertically as it runs down the side of the neck. Superiorly, the internal jugular is lateral to the internal carotid and inferolateral to the common carotid. At the base of the neck, the internal jugular vein joins the subclavian vein to form the innominate vein. The internal jugular vein is large and lies in the cervical triangle, defined by the (1) lateral border of the omohyoid muscle, (2) inferior border of the digastric muscle, and (3) medial border of the sternocleidomastoid muscle. The superficial cervical fascia and platysma

Subclavian artery and vein Brachial plexus Acromion Coracoid process Axillary artery and vein External intercostal muscles Body and xiphoid process of sternum Superior thoracic artery Thoracoacromial artery

Figure 21-11  Detailed anatomy of the anterolateral chest demonstrating the axillary vein with the pectoralis major and pectoralis minor muscles removed.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Anterior belly of digastric muscle

455

Hyoid bone Exterior carotid

Stylohyoid muscle Anterior jugular vein Thyroid cartilage

Mylohyoid muscle Sternohyoid muscle

Internal jugular vein Thyroid gland

Sternocleidomastoid muscle

Figure 21-12  Detailed anatomy of the neck demonstrating the relationship of  venous anatomy to the superficial and deep structures.

External jugular vein

Trapezius muscle

muscle cover the internal jugular vein, which is easily identified just lateral to the easily palpable external carotid artery. From a venous access perspective, the location of the subclavian vein may vary from a normal lateral course to an extremely anterior or posterior orientation in elderly patients. Byrd61 has described the subclavian venous anatomy of two distinct deformities, both of which

Posterior clavicle

Trachea

make venous access more difficult and hazardous. The first deformity involves a posteriorly displaced clavicle (Fig. 21-13). This is usually seen in patients with chronic lung disease and anteroposterior chest enlargement. Such patients can be identified from the presence of a horizontal deltopectoral groove and the posteriorly displaced clavicle. The second deformity is an anteriorly displaced clavicle (Fig. 21-14),

Posterior clavicle

Figure 21-13  Posterior displacement of clavicle. The deltopectoral groove is in a horizontal rather than an oblique position. (From Byrd CL: Current clinical applications of dual-chamber pacing. In Zipes DP, editor: Proceedings of a symposium. Minneapolis, 1981, Medtronic, p 71.)

Figure 21-14  Anterior displacement of clavicle. The deltopectoral groove is nearly vertical. (From Byrd CL: Current clinical applications of dual-chamber pacing. In Zipes DP, editor: Proceedings of a symposium. Minneapolis, 1981, Medtronic, p 71.)

Anterior clavicle

456

SECTION 3  Implantation Techniques

Right atrium Left ventricle (posterior)

Plane of tricuspid valve

Right ventricle (anterior)

Figure 21-15  Spatial orientation of the right ventricle as an anterior structure in relationship to the left or posterior ventricle or coronary sinus, which is also posterior.

which is found occasionally, especially in elderly women. In this situation, the clavicle is anteriorly bowed or actually displaced anteriorly. It is important that the implanting physician recognize such variations so as to avoid complications such as pneumothorax and hemopneumothorax when using the percutaneous approach. It is assumed that the implanting physician is also completely familiar with the anatomy of the heart and great vessels.62 However, their spatial orientation is at times confusing, particularly with respect to the right atrium (RA) and right ventricle (RV). In the frontal plane, the border of the right side of the heart is formed by the RA. The border of the left side of the heart is composed of the left ventricle. Importantly, the RV is located anteriorly (Fig. 21-15) and is triangular. The apex of the RV is the generally accepted initial “target” for ventricular lead placement, although its location can vary. Its normal location, distinctly to the left of midline, depends on the rotation of the heart, which is affected by various pathologic and anatomic conditions. At times, the apex may be located directly anterior to or even to the right of midline. A lack of appreciation of these variations can lead to considerable difficulty in electrode placement. The choice of site for pacemaker implantation is also occasionally important anatomically. This decision is typically made most appropriately on the basis of the patient’s dominant hand, occupation, recreational activities, and medical conditions. The decision should not be made according to the dominant hand of the implanting physician. However, some fundamental differences exist between the anatomy of the right and left sides, which can be frustrating when passing a pacemaker electrode. It seems to be easier for many right-handed implanters to work on the right side of the patient, and vice versa, but from a surgical point of view, catheter manipulation from the right can be a frustrating experience. When entering the central venous circulation from the left upper limb, the pacemaker electrode tracks along a smooth arc to the RV. There are generally no sharp angles or bends (Fig. 21-16, A). Conversely, when approaching from the right, the electrode is forced to negotiate a sharp angle or bend at the junction of the right subclavian and internal jugular veins, where the innominate vein is formed (Fig. 21-16, B). This acute angulation can make the manipulation of the pacemaker electrode difficult when a curved stylet is fully inserted. Another anatomic pitfall occurs when there is a persistent left SVC, making passage to the heart from the left more difficult and, if there is no right SVC, makes passage from the right impossible. These situations are considered later, in the discussion of ventricular electrode placement.

A

B

Figure 21-16  A, Smooth course of an electrode entering from the left side. B, Acute angulation of the catheter course when the lead enters the venous system from the right.

TRANSVENOUS PACEMAKER PLACEMENT Cephalic Venous Access The right or left cephalic vein is the most common vascular entry site for insertion of pacemaker electrodes by the cutdown technique.63 The cephalic vein is located in the deltopectoral groove (Fig. 21-17), which is formed by the reflections of the medial head of the deltoid and the lateral border of the greater pectoral muscles. The groove can be precisely located by palpating the coracoid process of the scapula. The dermis along the deltopectoral groove is infiltrated with local anesthetic, encompassing the anticipated length of the incision. A vertical incision is made adjacent to and at the level of the coracoid process. It is extended for about 2 to 5 cm. Care is taken to keep the scalpel blade perpendicular to the surface of the skin. One can create smooth skin edges by making an initial single stroke that carries through the dermis to each corner of the wound. The subcutaneous tissue is infiltrated with local anesthetic along the edges of the incision. The Weitlaner retractor is applied to the edges of the wound, and the subcutaneous tissue is placed under tension. The tension is released by light strokes of the scalpel from corner to corner of the wound in the midline. As the subcutaneous tissue falls away, tension is restored by reapplication of the Weitlaner retractor. This process is continued down to the surface of the pectoral fascia. The fascia is left intact. At this level, the borders of the pectoral and deltoid muscles forming the deltopectoral

Cephalic vein Coracoid process

Axillary vein

Figure 21-17  Anatomy of deltopectoral groove.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

groove are identified. A Metzenbaum scissors is used to dissect along the groove by separating the muscles’ fibrous attachments. The Weitlaner retractor is reapplied more deeply to retract the muscle. Gradual release of the fascial tissue between the two muscle bodies will expose the cephalic vein. At times, the cephalic vein is diminutive or atretic and unable to accommodate a pacemaker lead. In this case, the cephalic vein can be dissected, centrally, to the axillary vein, and this larger vein catheterized. Once the vein to be catheterized is localized, it is freed of all fibrous attachments. Ligatures are applied proximally and distally (Fig. 21-18, A). The distal ligature is tied and held by a small clamp. The proximal ligature is not tied but is kept under tension with another clamp. An arbitrary entry site is chosen between the two ligatures. The anterior one half of the vein at this site is grasped with a smooth forceps, and the vein is gently lifted. A small, horizontal venotomy is made with iris scissors (Fig. 21-18, B) or a No. 11 scalpel blade. The vein is continuously supported by the forceps. The venotomy is held open by any of several means: a mosquito clamp, forceps, or vein pick. Gentle traction is applied on the distal ligature while tension is released on the proximal ligature. With the venotomy held widely open, the electrode or electrodes are inserted and advanced into the central venous circulation (Fig. 21-18, C). Subclavian Venous Access For many years, vascular access has been achieved for many purposes through the use of the Seldinger technique. This simple approach calls for the percutaneous puncture of the vessel with a relatively long, largebore needle; passage of a wire through the needle into the vessel; removal of the needle; and passage of a catheter or sheath over the wire into the vessel with removal of the wire. An 18-gauge, thin-walled needle 5 cm in length is typically used, although smaller needles are available. These needles come prepackaged with most introducer sets

457

Figure 21-19  Prepackaged introducer set with 18-gauge needle, guidewire, and sheath with rubber dilator.

(Fig. 21-19), but an extra supply should be available. The historical problem limiting the use of this technique in cardiac pacing was the inability to remove the sheath from the pacemaker lead. The development of a peel-away sheath by Littleford solved this problem.64-67 Use of the percutaneous approach requires a thorough knowledge of both normal and abnormal anatomy to avoid complications. The subclavian vein is generally the intended venous structure used for percutaneous venous access in cardiac pacing. Given the previously discussed anatomic variations, the subclavian vein puncture is typically made near the apex of the angle formed by the first rib and clavicle.68 This defines the “subclavian window” (Fig. 21-20). At this puncture

A

B

C Figure 21-18  A, Introduction of a lead into the cephalic vein, which is isolated and tied off distally. B, Venotomy performed with iris scissors. C, Lead inserted while venotomy is held open with a vein pick.

Figure 21-20  The subclavian window. (From Barold SS, Mugica J: New perspectives in cardiac pacing. Armonk, NY, 1988, Futura, p 257.)

458

SECTION 3  Implantation Techniques

External jugular vein

Costoclavicular fibers: Posterior

Subclavius

Transverse cervical vein Acromion

Anterior (cut)

Internal jugular vein Cla

1 Rib

Manubrium

2 Rib

Subclavius m

vicle 1 Rib

Costoclavicular ligament

Cephalic vein 2 Rib

Sternum Axillary vein

A

B

3R

ib

Superior vena cava

Cephalic catheter

Lateral catheter

C

Medial catheter

site (and after both skin infiltration with local anesthetic and a 1-cm incision at the site, which generally is 1 to 2 cm inferolateral to the point where the clavicle and first rib actually cross), the needle is aimed in a medial and cephalic direction. It is important to make the puncture with the patient in a “normal” anatomic position. The infraclavicular space or costoclavicular angle should not be artificially opened by maneuvers such as extending the arm or placing a towel roll between the scapulae. These maneuvers can open a normally closed or tight space and lead to undesirable puncture of the costoclavicular ligament or subclavius muscle, which in turn can result in lead entrapment and crush. With the patient in the normal anatomic position, access to the subclavian window is medial yet usually avoids the costoclavicular ligament. The more medial puncture and needle trajectory of this approach vastly improves the success rate and dramatically reduces the risks of pneumothorax and vascular injury compared with a more lateral approach. With this medial position, the vein is a much larger target, and the apex of the lung is more lateral. This safer approach is a departure from the conventional subclavian venous puncture, which calls for introduction of the needle in the middle third of the clavicle. There are legitimate concerns that this medial approach, although safer, results later in higher complication rates and failure rates from conductor fracture and insulation damage.69 It is postulated that the extreme medial position results in a tight fit, subjecting the lead to compressive forces and causing binding between the first rib and the

Figure 21-21  A, Musculoskeletal anatomy of the infraclavicular space. B, Relationship of the venous structures to clavicle, first rib, and costoclavicular ligaments. C, Course of leads through the venous structures shows how the pacemaker electrode can become entrapped. (From Jacobs DM, Fink AS, Miller RP, et al: Anatomical and morphological evaluation of pacemaker lead compression. Pacing Clin Electrophysiol 16: 434, 1993.)

clavicle. Occasionally, this binding can even crush the lead, now called the subclavian crush phenomenon. This phenomenon is more common in larger, complex leads of the in-line bipolar, coaxial design. Fortunately, the incidence of this complication is low. Fyke70,71 first reported insulation failure of two leads placed side by side with use of the percutaneous approach through the subclavian vein, where there was a tight costoclavicular space. This issue has now been addressed thoroughly by two independent groups. Jacobs et al.72 analyzed a series of failed leads for the mechanism of failure, using autopsy studies to correlate the anatomic relationship of lead position to compressive forces (Fig. 21-21). These autopsy data demonstrated generation of significantly higher pressure when leads were inserted in the costoclavicular angle than with a more lateral puncture. The authors concluded that the tight costoclavicular angle should be avoided. Magney et al.73 derived similar data from cadaveric studies and suggested that lead damage is caused by soft tissue entrapment by the subclavius muscle rather than bony contact. This soft tissue entrapment causes a static load on the lead at that point, and repeated flexure around the point of entrapment may be responsible for the damage. Concern about subclavian crush has also been communicated by pacemaker manufacturers in company literature.74,75 Reduction in lead diameter and perhaps modification of lead technology may be required to eliminate this problem. In the meantime, technique modification appears to be effective at reducing its occurrence. In our experience, if



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

a pacemaker lead feels tight in the costoclavicular space, it is more susceptible to being crushed; it has become our practice at the University of Oklahoma (DWR) to remove the lead from the vein in this situation and repuncture the vein in a slightly different location with reintroduction of the lead. We believe that this practice has reduced the incidence of crush, although more substantial modifications in technique, described later, may be indicated. Addressing this issue, along with other introducer- or percutaneousrelated complications, Byrd76 has described a “safe introducer technique.” This technique consists of a “safety zone” associated with precise conditions ensuring a safe puncture. Byrd also describes a new technique for cannulating the axillary vein if this safety zone cannot be entered. Byrd’s safety zone is defined as a region of venous access between the first rib and the clavicle, extending laterally from the sternum in an arc (Fig. 21-22, A). As a condition for puncture, the site of access must be adequate for ease of insertion to avoid friction and puncture of bone, cartilage, or tendon. With this technique, subclavian vein puncture should never be made outside the safety zone or in violation of the preceding conditions. If the safety zone is inaccessible, or the preceding conditions are not met, an axillary vein puncture is recommended. As previously

459

Coracoid process Axillary vein

Deltoid

Pectoralis major muscle

Pectoralis minor muscle

Figure 21-23  Anatomic relation of axillary vein to pectoralis minor muscle. The pectoralis major muscle has been removed. Note the cephalic vein draining directly into the axillary vein at approximately the first intercostal space. (From Belott PH et al: Unusual access sites for permanent cardiac pacing. In Barold SS, Mugica J, editors: Recent advances in pacing for the 21st century. Armonk, NY, 1998, Futura, p 139.)

40°

0°

A

Lateral

Medial

B Figure 21-22  A, Anatomic orientation of the “safety zone” for intrathoracic subclavian vein puncture. B, Safe access to the extrathoracic portion of the subclavian vein as described by Byrd. (A from Barold SS, Mugica J: New perspectives in cardiac pacing 2, Armonk, NY, 1991, Futura, p 108; B from Byrd CL: Recent developments in pacemaker implantation and lead retrieval. Pacing Clin Electrophysiol 16:1781, 1993.)

mentioned, the axillary vein is actually a continuation of the subclavian vein after it exits the superior mediastinum and crosses the first rib. The axillary vein is also frequently referred to as the extrathoracic portion of the subclavian vein (Fig. 21-23). Axillary Venous Access (see Box 21-4) The axillary vein approach is actually not new. In 1987, on the basis of cadaveric studies that established reliable surface landmarks, Nichalls77 and Taylor and Yellowlees78 reported this approach as an alternative safe route of venous access for large, central lines. The axillary vein has a completely infraclavicular course (Fig. 21-24). The needle path must always be anterior to the thoracic cavity, avoiding risks of pneumothorax and hemothorax. The axillary vein starts medially at a point below the aspect of the clavicle where the space between the first rib and the clavicle becomes palpable. The vein extends laterally to a point about three fingerbreadths below the inferior aspect of the coracoid process. The skin is punctured along the medial border of the smaller pectoralis muscle at a point above the vein as it is defined by the surface landmarks. One punctures the axillary vein by passing the needle anterior to the first rib, maneuvering posteriorly and medially corresponding to the lateral to medial course of the axillary vein. The needle never passes between the first rib and the clavicle, but stays lateral to this juncture. Some implanters have found it useful to abduct the arm 45 degrees when using this approach. In the technique described by Byrd, the axillary vein puncture is performed as a modification of the standard subclavian vein procedure without repositioning of the patient (Fig. 21-25; see also Fig. 21-20, B). The introducer needle is guided by fluoroscopy directly to the medial portion of the first rib. The needle is held perpendicular to, and touches, the first rib. The needle, held perpendicular to the rib, is “walked” laterally and posteriorly, touching the rib with each change of position. Once the vein is punctured, as indicated by aspiration of

460

SECTION 3  Implantation Techniques

Internal jugular vein

Coracoid process Pectoralis minor muscle

Lateral landmark (A)

Medial landmark (B)

Axillary vein Axillary artery

Figure 21-24  Nichalls’ landmarks for axillary venipuncture. (From Belott PH, Byrd CL: Recent developments in pacemaker implantation and lead retrieval. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing. Armonk, NY, 1991, Futura.)

venous blood into the syringe, the guidewire and the introducer are inserted with use of standard technique. This approach essentially guarantees a successful and safe venipuncture without compromising the leads if the conditions for entering the safety zone are adhered to and if the first rib is touched to maintain orientation. The only complication not prevented by this approach is inadvertent puncture of the axillary artery. Byrd79 has reported success in a series of 213 consecutive cases in which the extrathoracic portion of the subclavian vein (axillary vein)

Cephalic vein Axillary vein First rib

Pectoralis muscle

Figure 21-25  Byrd’s technique for access to extrathoracic portion of subclavian vein. Sequential needle punctures are walked posterolaterally along the first rib. (From Belott PH, Byrd CL: Recent developments in pacemaker implantation and lead retrieval. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing. Armonk, NY, 1991, Futura.)

was successfully cannulated as a primary approach. Magney et al.80 subsequently reported a new approach to percutaneous subclavian venipuncture to avoid lead fracture. This technique is very similar to Byrd’s and uses extensive surface landmarks for venipuncture (Fig. 21-26). It involves puncture of the extrathoracic portion of the subclavian vein. Magney et al.80 define the location of the axillary vein as the intersection with a line drawn between the middle of the sternal angle and the tip of the coracoid process. This is generally near the lateral border of the first rib. Belott81 described blind axillary venous access using a modification of the Byrd and Magney recommendations. In this technique, the deltopectoral groove and coracoid process are primary landmarks and are palpated, and the curvature of the chest wall is noted (Fig. 21-27). An incision is made at the level of the coracoid process. It is carried medially for about 6.25 cm (2.5 inches) and is perpendicular to the deltopectoral groove (Fig. 21-28). The incision is carried to the surface of the pectoralis major muscle. The deltopectoral groove is visualized on the surface of the muscle. The needle is inserted at an angle 45 degrees to the surface of the pectoralis muscle and parallel to the deltopectoral groove and 1 to 2 cm medial (Fig. 21-29). At present, the blind venous access approach has been abandoned (PHB) for this first rib approach, because it reduces the risk of pneumothorax to zero.82 Critical to its success is the ability to identify the first or second rib on a radiograph. In addition, if the first rib is poorly visualized or set too far under the clavicle, one can always use the second rib in a similar fashion. To access the axillary vein using the first rib, the image intensifier is pulled over to the incision. The first rib is then identified, usually the most superior U-shaped rib (Fig. 21-30, A). The ribs seen traversing medial to lateral in an inferior direction are posterior. Identifying the first rib fluoroscopically is critical. If the operator misinterprets a posterior rib as the first rib, a percutaneous stick will result in a pneumothorax or access of undesired cardiopulmonary structures. The first step in accessing the axillary vein using the first rib is to place the 18G percutaneous needle and syringe on top of the pectoralis major muscle in the superior aspect of the incision. Using fluoroscopy, the needle tip is placed in the middle of the first rib (Fig. 21-30, B). The angle of the syringe and needle is gradually increased as the needle is advanced through the pectoralis major muscle. The foreword motion of the



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Cp

x V M

R1

461

Ax

St

A

Cp

V M

St

Figure 21-27  Superficial landmarks of deltopectoral groove. Palpation of the deltopectoral groove and coracoid process. Ax

B Figure 21-26  Deep (A) and superficial (B) anatomic relationships of the Magney approach to subclavian venipuncture. Point M indicates the medial end of the clavicle. X defines a point on the clavicle directly above the lateral edges of the clavicular/subclavius muscle (tendon complex) (R1). V indicates the center of the subclavian vein as it crosses the first rib. The arrow indicates the center of the subclavian vein as it crosses the first rib. Ax, Axillary vein; Cp, coracoid process; St, center of the sternal angle; *, costoclavicular ligament. Arrow in B points to Magney’s ideal point for venous entry. (From Magney JE, Staplin DH, Flynn DM, et al: A new approach to percutaneous subclavian needle puncture to avoid lead fracture or central venous catheter occlusion. Pacing Clin Electrophysiol 16:2133, 1993.)

percutaneous needle and syringe should allow the tip of the needle to be maintained fluoroscopically over the body of the first rib. To maintain first rib orientation, a rather steep angle is generally required. The needle advancement is continued until the first rib is struck. In essence, this maneuver is attempting to pin the axillary vein to the first rib (Fig. 21-31). Once the first rib is touched, the needle and syringe are slowly withdrawn under suction until the vein is entered, as indicated by a flash of blood in the syringe. If the first pass is unsuccessful, the needle and syringe are moved medially or laterally, and the maneuver is repeated until successful. Once the vein is entered, the guidewire is passed and the sheath applied per standard technique. If the needle is advanced toward the first rib through tissue or muscle without the needle tip initially visualized fluoroscopically directly over the first rib, this shallow angle may result in the needle passing between an intercostal space. This will result in a pneumothorax. It is recommended

Pectoralis major

B Angle of deltopectoral groove

Pectoralis major

A

Angle of deltopectoral groove Figure 21-28  A, Incision perpendicular to the deltopectoral groove at the level of the coracoid process. B, Close-up view of incision demonstrating the plane of the deltopectoral angle and the plane of the deltopectoral groove and pectoralis muscle.

462

SECTION 3  Implantation Techniques

Deltopectoral groove

1.5 to 2 cm

Spencer et al.84,85 reported the use of contrast material for localizing the axillary vein in 22 consecutive patients. Similarly, Ramza et al.86 demonstrated the safety and efficacy of using the axillary vein for placement of pacemaker and defibrillator leads when guided with contrast venography. They successfully accomplished lead placement in 49 of 50 patients using this technique. Access to the axillary vein can also be guided by Doppler flow detection and ultrasound techniques. Fyke87 describes use of an extrathoracic introducer insertion technique in 59 consecutive patients (total of 100 leads) with a simple Doppler flow detector. A sterile Doppler flow detector is moved along the clavicle. Once the vein is defined, the location and angulation of probe are noted, and the venipuncture is carried out (Fig. 21-33). Care is taken to avoid directing the Doppler beam beneath the clavicle. Gayle et al.88 have developed an ultrasound technique that directly visualizes the needle puncture of the axillary

45°

Figure 21-29  Needle and syringe trajectory and angle with respect to the deltopectoral groove and chest wall.

that a figure-of-eight stitch be applied around the needle puncture for hemostasis and the retained-guidewire technique used for multiple lead placement. Occasionally, in a thin patient, the axillary artery can be easily palpated. This makes the axillary vein stick easy, because the percutaneous puncture can be made just medial and inferior to the palpable axillary pulse. Because it cannot always be palpated, the axillary pulse is not a reliable landmark. The axillary artery and brachial plexus are usually much deeper and more posterior structures. This simple technique, which uses basic anatomic landmarks of the deltopectoral groove and a blind venous stick, has been used successfully in 168 consecutive pacemaker and ICD procedures. There have only been three failures requiring an alternative approach. With a thorough knowledge of the regional anatomy, the physician can safely use the axillary vein as a primary site for venous access. Access to the axillary vein may also be achieved by direct cutdown. With Metzenbaum scissors, fibers of the pectoralis major muscle are separated adjacent to the deltopectoral groove at the level of the coracoid process. This is just above the level of the superior border of the pectoralis minor. If the pectoralis major is split in this area and the fibers are gently teased apart in an axis parallel to the muscle bundle, the axillary vein can be found directly beneath the pectoralis major muscle. A purse-string stitch is applied to the axillary vein, which can then be cannulated by a direct puncture or cutdown technique. The purse-string stitch will serve for hemostasis and ultimately assists in anchoring the electrodes after positioning. A number of techniques can facilitate access to the axillary vein. Varnagy et al.83 describe a technique for isolating the cephalic and axillary veins by introduction of a radiopaque J-tipped polytetrafluoroethylene guidewire through a vein in the antecubital fossa under fluoroscopic control (Fig. 21-32). The metal guidewire is then palpated in the deltopectoral groove or identified with fluoroscopy. This guides the subsequent cutdown or puncture of the vessel with fluoroscopy. A cutdown can be performed on a vein, and the intravascular guidewire pulled out of the venotomy to allow the application of an introducer. If a percutaneous approach is used, the puncture can always be extrathoracic, using fluoroscopy to guide the needle to the guidewire. This technique offers the benefit of rapid venous access while avoiding the risk of pneumothorax associated with the percutaneous approach. Contrast venography, described subsequently, can also be used for axillary venous access. The venous anatomy can be observed with contrast fluoroscopy in the pectoral area and, if possible, recorded for repeat viewing. The needle trajectory and venipuncture are guided by the contrast material in the axillary vein. Laboratories with sophisticated imaging capabilities can create an image “mask” (see later).

Posterior ribs

A

B Figure 21-30  A, Radiograph showing location of the first rib. Arrows point to the rib’s anterior border. B, Radiograph of needle over the first rib. The needle tip is maintained in this position as the needle and syringe are advanced. This is accomplished increasing the steepness of the needle angle.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

463

SCM

1st rib Steep

CCL

P CI AV SCV

90° Shallow

R1 45°

Figure 21-31  Needle trajectory in relationship to first rib. The superior needle is piercing the axillary vein. The needle tip is touching the first rib. The lower needle with the shallow angle runs the risk of entering the intercostal space, causing pneumothorax.

vein.89 A portable ultrasound device with sterile sleeve and needle holder are used. The ultrasound head is placed over the skin surface in the vicinity of the axillary vein. Once the vein is visualized, the puncture technique can be used. This technique has been used with considerable success for both pacing and defibrillator electrodes. There have been no reports of pneumothoraces. This technique can be carried out transcutaneously or through the incision on the surface of the pectoralis muscle (Figs. 21-34 and 21-35). In summary, the axillary vein has become a common venous access site for pacemaker and defibrillator implantations, because of concerns about subclavian crush and the requirement for insertion of multiple electrodes for dual-chamber pacing and at least one large complex electrode for transvenous defibrillation. A number of reliable techniques are available for axillary venous access (see Box 21-4). Given the recent interest in the axillary vein, it is recommended that the implanting physician become thoroughly familiar with the relevant anatomy. The interested physician must visit the anatomic laboratory to refresh and review the regional anatomy and surface landmarks.

R2

Figure 21-33  Doppler ultrasound location of the axillary vein crossing the first rib. AV, Axillary vein; CCL, costoclavicular ligament; Cl, clavicle; P, Doppler probe; R1, first rib; R2, second rib; SCM, subclavius muscle; SCV, subclavian vein.

There is also some concern that lateral access of the axillary vein can result in acute bends in the lead. This can result in increased lead stress and potential for fracture or lead damage, because in its lateral aspect, the axillary vein is a much deeper structure as it transitions to the subclavian vein. It is this deeper venous access that results in acute lead angulation. This is particularly true for those who use the second rib as a landmark for axillary venous access. For a more conventional subclavian vein approach, Lamas et al.90 have even recommended fluoroscopic observation of the needle trajectory for achieving a successful and safe subclavian vein puncture. They initially identify the clavicle on the side of the puncture, noting its

Axillary vein

Figure 21-32  Percutaneous access to the axillary vein using a J wire introduced by means of the antecubital vein for reference.

Figure 21-34  Ultrasonic image of the axillary vein.

464

SECTION 3  Implantation Techniques

Subclavian vein

Axillary vein

First rib

Figure 21-35  Ultrasound-guided puncture of the axillary vein with use of the Site-Rite device (Site Rite Ultrasound System, Salt Lake City, Utah).

course and landmarks. The skin is entered about 2 cm inferior to the junction of the medial and lateral halves of the clavicle, aiming with fluoroscopic guidance for the caudal half of the clavicular head. The various techniques of transvenous pacemaker lead placement— the subclavian window, the safety zone, the axillary vein puncture, or fluoroscopic guidance—have some common features. Needle orientation is always medial and cephalad, almost tangential to the chest wall. All needle probing should use a forward motion. Lateral needle probing should be avoided because it could lacerate important structures. Anatomic landmarks are defined, and the puncture is made, with rare exception, with the patient in the anatomic position. The costoclavicular angle is not artificially opened by maneuvers. Although the essence of the nonaxillary approaches is medial placement to avoid the lung, the undesirable puncture of the costoclavicular ligament should be avoided. In the obese patient, the tendency is to orient the needle more perpendicular to the chest wall in an attempt to pass between the clavicle and first rib. This perpendicular angle is to be avoided with the medial approaches because it is associated with a higher incidence of pneumothorax. In this circumstance, a more inferior skin puncture is recommended, allowing the needle to slip between the first rib and clavicle. The needle is therefore kept almost tangential to the chest wall, avoiding the lung. Some implanters bend the needle in an attempt to slip under the clavicle. We do not recommend this maneuver because it is associated with a higher incidence of pneumothorax and vascular trauma. We instead recommend that in the morbidly obese patient, the subclavian puncture be carried out after direct visualization of the pectoral muscle. This can be done only by making an initial skin incision and carrying it down to the pectoral muscle. Once the anatomic landmarks are defined, the needle is slipped between the first rib and the clavicle with a trajectory that is nearly tangential to the chest wall and directed cephalad and medial. This last recommendation raises the question whether the skin incision should routinely be made first, with percutaneous venous access carried out through the incision, or whether an initial percutaneous venous puncture should be performed, followed by the incision. It is

arguably better for one not to commit to an initial pocket-length incision and subsequent venipuncture. Doing so avoids the embarrassment of having to explain matching incisions if venous access could not be achieved through the initial incision and one is forced to move to the patient’s other side. It is difficult enough explaining multiple unsuccessful skin punctures. As an acceptable alternative, regularly used at the University of Oklahoma, a 1-cm-long stab wound can be made initially, through which the venipunctures can be accomplished. This approach allows easy incorporation of the puncture sites (especially if two separate punctures are used for a dual-chamber pacing system) into a single incision that is extended after successful venipuncture. A full incision is made to the greater pectoral fascia before one gains access to the vein. As with axillary vein access techniques, the subclavian puncture can be facilitated by the use of contrast venography.91 It is helpful in patients with potentially difficult venous access. Venography should be considered before any puncture in which venous patency is in doubt or abnormal anatomy is suspected. As described by Higano et al.,91 a venous line is established in the arm on the side of planned pacemaker venous access. The line should be reliable and 20 gauge or larger. One must ensure that the patient does not have an allergy to radiographic contrast material. The contrast injection is performed by a nonsterile assistant. From 10 to 50 mL of contrast material (nonionic or ionic) is injected rapidly into the IV line in the forearm, followed by a saline bolus flush. The contrast medium moves slowly in the peripheral venous system and can be moved along by massage of the arm through or under the sterile drapes. The venous anatomy is observed with fluoroscopy in the pectoral area and, if possible, recorded for repeated viewing (Fig. 21-36). The needle trajectory and venipuncture are guided by the contrast material in the subclavian vein. In more sophisticated radiologic laboratories, a mask or map can be made for guidance after the contrast medium has dissipated. The process can be repeated as necessary. The actual percutaneous puncture is carried out with a syringe attached to the 18-gauge needle. A common practice is to fill the syringe partially with saline. The theory behind this practice is that if a pneumothorax occurs, it will be detected by air bubbles aspirated through the saline. In addition, the saline can be used to flush out tissue plugs that may obstruct the needle and prevent aspiration. We avoid this practice because we believe that one does not need air bubbles to detect an inadvertent pneumothorax. More important, the syringe

Figure 21-36  Contrast venography–guided venipuncture. With contrast material, the needle is guided under fluoroscopic guidance directly to the vein.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

even partially filled with saline makes it difficult to differentiate between arterial and venous blood, because when blood (arterial or venous) mixes with the saline, it takes on the color of oxygenated blood. If saline is not used, which vascular structure has been entered is more readily apparent. When proceeding with a percutaneous venipuncture, one should hold the syringe in the palm of the hand with the dorsal aspect of the hand resting on the patient. This gives support and control as the needle is advanced. With the needle held this way, tactile sensation is enhanced, and one can frequently feel the needle enter the vein. Once the vessel is entered, the guidewire is inserted, and the tip advanced to a position in the vicinity of the right atrium (Fig. 21-37). We prefer to use J-shaped or curved-tip guidewires for safety reasons. If resistance is encountered, the wire is withdrawn slightly and advanced again. If the resistance persists, the wire position is checked with fluoroscopy. If the wire just outside the tip of the needle appears coiled, it is probably extravascular. In this case, the wire and needle are removed, and

A

B Figure 21-37  A, Once venous access is achieved, the needle is supported with one hand, and the guidewire with tip occluder is advanced with the other hand. B, Guidewire tip advanced to the middle right atrium. (A from Belott PH: Retained guide wire introducer technique, for unlimited access to the central circulation. Clin Prog Pacing Electrophysiol 1:59, 1983.)

465

a new venous puncture is carried out. Extremely rarely, one may not be able to re-enter the vein. This may be due to collapse of the vein by a resultant hematoma caused by a small tear in the vein from the misdirected guidewire. In this case, one should probably proceed to an alternative approach or site of venous access, to avoid an unnecessary waste of time and a higher risk of pneumothorax with multiple subsequent unsuccessful percutaneous punctures. Occasionally, the guidewire tracks up the internal jugular vein. Changing the angle of the needle slightly to a more medial and inferior direction while the guidewire is still in the internal jugular vein, withdrawing the guidewire back into the needle, and then advancing again usually results in passage of the guidewire through the innominate vein and SVC into the right atrium. This maneuver may have to be repeated several times with varying needle angulations. Care must be exercised to avoid tearing the vein. The application of a 5-French (5F) or 6F dilator can sometimes help steer the guidewire in the right direction. In rare cases, the guidewire and needle must be removed and a new puncture site selected. The key point is that once venous access has been achieved, every effort is made to retain it. When air is withdrawn through the needle during attempted venipunctures, suggesting lung puncture and raising the possibility of a pneumothorax, our practice is to withdraw the needle, wait to ensure a rapid-onset, large, symptomatic pneumothorax is not occurring, and then proceed with a different needle trajectory and further attempts at venipuncture. In our experience, most lung punctures occurring with forward (not lateral!) needle motion do not result in a clinically apparent (on chest radiography) pneumothorax. If a pneumothorax does develop, it may do so in this setting over a matter of hours and may not even be apparent radiographically at the end of the procedure. If a lung puncture has occurred, obtaining another upright chest radiograph 6 hours after completion of the procedure is advisable. If a pneumothorax has developed, a chest tube or catheter evacuation procedure may be necessary, although frequently, a small to moderate pneumothorax that is not expanding can be managed conservatively without evacuation. Similarly, if an arterial puncture occurs inadvertently, our approach consists of removal of the needle and compression at the puncture site for about 5 minutes, followed by repeated venipuncture attempts with a different needle path. It is rare for such arterial punctures to result in a hemothorax, provided that no tearing of the artery has occurred (avoidance of lateral needle motion is crucial here as well). Follow-up chest radiographs are recommended 6 to 18 hours after the procedure, and postoperative hemoglobin and hematocrit measurements are suggested. The most important problem to avoid if the artery has been punctured is nonrecognition and placement of a sheath into the artery. If there is any doubt about whether the artery has been punctured, a blood sample withdrawn through the needle and subjected to oximetric analysis should clarify the situation. Once the wire is successfully positioned in the vein, some implanters place a purse-string suture in the tissue around the point of entry of the wire into the tissue. Alternatively, a figure-of-eight stitch can be applied (Fig. 21-38). This step can be helpful later for hemostasis.92 Such sutures require that an incision be made beginning at the needle and extending inferiorly to the depth of the pectoral fascia. Once the guidewires are in the subclavian vein, it is usually a simple procedure to advance the appropriate-sized dilator and peel-away sheath over the wire into the venous circulation. Occasionally, there is substantial resistance to dilator-sheath advancement, and repetitive dilation with progressively larger dilators is necessary. Alternatively, a 15- to 20-degree bending of the tip of the full-sized introducer may facilitate advancement over the wire. If difficulty with advancement occurs, we generally remove the sheath from the dilator and use only the dilator initially to dilate the track into the vein. This protects the rather delicate sheaths from damage. After successful advance of the dilator alone over the wire, the dilator can be withdrawn, the sheath added, and both then advanced over the wire. We have found that gentle back-pressure on the guidewire while the dilator-sheath is advanced also facilitates advancement in difficult or tortuous vessels.

466

SECTION 3  Implantation Techniques

Figure 21-38  Placement of the figure-eight stitch to enhance hemostasis. (From Belott PH: Retained guide wire introducer technique, for unlimited access to the central circulation. Clin Prog Pacing Electrophysiol 1:59, 1983.)

After the sheath has been successfully passed over the guidewire to the vicinity of the SVC, the dilator and guidewire can be removed, and the lead advanced through the sheath. Problems can be encountered when the lead is passed through the sheath. Occasionally, in the process of introduction, the sheath buckles at a point in the venous system where there is a bend93 (Fig. 21-39). This usually occurs after the removal of the dilator. It can also occur if the sheath is advanced against the lateral wall of the SVC; if a buckle occurs, the lead will not pass this point. Forcing the lead can result in damage to the cathode and insulation. This kink can usually be observed on fluoroscopy. There are several solutions to this problem. If the guidewire and dilator have both been removed, both can be replaced down the sheath. The dilator with wire inside is now functioning not only as a way to stiffen the sheath, but also as a tip occluder, and both can be passed back down the sheath. The tapered tip of the dilator will straighten the buckle.

Figure 21-39  Buckling of the introducer sheath prevents the passage of the electrode.

One can change the position of the buckle point by slightly advancing or retracting the sheath. The dilator is removed, but the guidewire can be retained. It is hoped that the retained guidewire will act as a stent, preventing the buckle from recurring and thus allowing the electrode to pass completely down the sheath. Another option when buckling of sheath occurs is to advance the lead to within a couple of centimeters of the buckle and then slowly withdraw the sheath, holding the lead position stationary. The sheath, including the buckle point, may occasionally be easily withdrawn over the tip of the lead, and the lead can be cautiously advanced. In this situation, it is sometimes necessary to withdraw the stylet from the tip of the lead to allow easy advancement of the lead beyond the buckle point. Inexperienced implanters should be cautious with this latter technique, however, because it may damage the distal electrodes. If these maneuvers fail, the guidewire and dilator are reinserted and the sheath and dilator are removed, leaving the guidewire in the vein. Tissue compression or traction is applied to the purse-string suture for hemostasis. The sheath is inspected for buckling. At this point, the implanter should consider advancing a sheath of the next larger size over the retained guidewire, because application of the same-sized sheath usually results in recurrence of the same problem. The important point is that despite this frustrating experience, one must be reluctant to relinquish the vein once it has been catheterized. Generally, the larger sheath is less likely to buckle, especially if the guidewire is retained to act as a stent. With successful electrode introduction, the sheath is briskly pulled back out of the circulation, and skin compression or traction is applied to the purse-string or figure-of-eight suture for hemostasis. The risk of air embolization is substantial with the percutaneous approach; using the Trendelenburg position is recommended. With the shift of the pacemaker procedure to the CCL or special procedures room, however, it is often impossible to place the patient in Trendelenburg position. Consequently, the patient is at greater risk for air embolization if the percutaneous approach is used. It is most important that the implanting physician be aware of the danger and take steps necessary to avoid this potential catastrophe (Box 21-5). The physician must be aware that removal of the sheath dilator in a patient who is fasting and somewhat volume depleted can rapidly cause aspiration of large quantities of air. Because the luxury of the Trendelenburg position is unlikely to be available in the CCL, other steps must be taken. Contrary to some practices, the patient about to undergo pacemaker implantation should be kept in a euvolemic or even a relatively volumeoverloaded state if there is no contraindication. Instead of IV fluids at a restricted rate, adequate hydration should be maintained. We routinely place a large, wedge sponge under the patient’s legs to enhance blood return and increase central venous pressure.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Box 21-5 

467

A

PREVENTION OF AIR EMBOLISM DURING PERMANENT PACEMAKER PROCEDURES Normal-Risk Patient Remember that air embolism is possible. Ensure good hydration; no long periods without oral intake. Be aware of increased risk (i.e., with open sheath in vein). Assess hydration by observing central venous pressure. High-Risk Patient Increase hydration (i.e., with wide-open intravenous lines). Ensure that patient is awake and cooperative. Elevate patient’s lower extremities and place wedge under legs. Use Trendelenburg position (if available). Plan for expeditious lead placement and sheath removal. Check for introduction of air. Monitor patient continuously (blood pressure, heart rate/rhythm, O2 saturation).

A

Extremely High-Risk, Uncooperative Patient Provide intubation, deep sedation or general anesthesia.

An assessment of the state of hydration can be carried out during the procedure. With the sheath in the central venous circulation, careful withdrawal of the dilator from the sheath can allow the state of hydration and venous pressure to be observed: After the dilator is withdrawn in the hydrated patient with adequate venous pressure, there is continuous blood flow out of the sheath despite the cycle of respiration. In the dehydrated patient, withdrawal of the dilator results in little or no blood flow. The blood meniscus is barely visible. More important, on inspiration, the blood meniscus is observed to move substantially inward. If this is seen, the dilator can be rapidly advanced back into the sheath; alternatively, the sheath can be pinched and additional precautions taken to avoid air embolization. If a wedge has not been placed under the patient’s legs, this can be done now and is frequently helpful. Also, at this point, it is most important to have the cooperation of the patient. If sleeping, the patient should be aroused. The patient should be coached to reduce the depth of respirations and avoid the sudden, large inspiration that can result in the aspiration of a lethal volume of air into the vein. At the same time, IV fluid administration is increased to enhance hydration. Having the patient hold the breath after maximal inspiration offers the greatest latitude in time, because the patient will have to exhale before inhaling, thereby causing negative intrathoracic pressure and aspiration of air into the vein. This gives the implanter time to insert the lead. Pinching of the sheath with the lead going through it to avoid air embolization is ineffective and gives a false sense of security. A peel-away sheath with a hemostasis valve would be useful. In the patient who is substantially sedated or uncooperative, adequate hydration and elevation of the lower extremities are the only solutions. Careful planning of the lead insertion procedure also helps. Expeditious lead insertion is important. For example, positioning the electrodes with the sheath in situ is unwise, because it may result in air embolism or unnecessary blood loss. Once the lead has been inserted, the introducer should be rapidly withdrawn. The practice of peeling away the sheath while part of it is in an intravascular location should be avoided; doing so is a waste of time and increases the risk for air embolization and blood loss. In this regard, the actual peeling away of the sheath is not even a necessity at this point as long as it is completely extravascular. It can be peeled away later at one’s convenience. In fact, the tabs of the unpeeled sheath can be used to pin the lead to the drapes during threshold testing, preventing inadvertent dislodgement of the lead onto the floor. With the sheath withdrawn completely from the circulation, hemostasis is achieved by applying tension to the purse-string or figure-of-eight suture or by applying skin compression over the entry site. A variation of the introducer technique involves retaining the guidewire. Instead of being removed together with the dilator, the guidewire

B Figure 21-40  A, Guidewire with dilator removed remains in the sheath. The lead has been inserted and advanced (inset) alongside the guidewire. B, Both the guidewire and the lead are advanced to the vicinity of the middle right atrium. Additional introducers can be advanced over this retained guidewire to place additional leads. (A from Belott PH: Retained guide wire introducer technique, for unlimited access to the central circulation. Clin Prog Pacing Electrophysiol 1:59, 1983.)

is left in place so that the lead is passed through the sheath alongside it. The sheath is subsequently removed and peeled away (Fig. 21-40). Occasionally, the size of the electrode and the sheath precludes the passage of the lead alongside the guidewire. In this case, the guidewire is removed, the lead passed down the sheath, and the guidewire reinserted behind the electrode. This maneuver succeeds because it is the electrode that will not pass alongside the guidewire, whereas the lead body is thinner and leaves enough room in the sheath to accommodate the guidewire. Certain leads (especially those with bipolar electrodes) and sheath combinations are too tight to allow passage of both the electrode and guidewire. In this case, a larger sheath can be used. When the guidewire is reintroduced, the tip occluder is not used because it can wind up in the central circulation fairly easily. Reusing the dilator as a tip occluder during reinsertion of the guidewire works well. The retained guidewire may provide unlimited venous access and

468

SECTION 3  Implantation Techniques

the ability to exchange or introduce additional electrodes by simply applying another sheath set to the guidewire. The retained guidewire should be held to the drape with a clamp to avoid inadvertent dislodgement. The retained guidewire can serve as a ground for unipolar threshold analysis instead of a grounding plate. It can also be used as an intracardiac lead for recording of the atrial electrogram (to confirm atrial capture) or as an electrode for emergency pacing. We routinely retain an intravascular guidewire in both single-chamber and dualchamber procedures until a satisfactory lead position is obtained. Occasionally, difficulty may be encountered with the standardlength sheath. Venous tortuosity, obstruction, and anomalies may preclude the advancement of the lead to the right side of the heart. This problem is usually solved by advancing a 24-cm-long sheath over the guidewire directly to the right atrium. This is also advisable when an extraction has been done during the procedure because of the weakening of the venous wall. An appropriate length .035-inch guidewire is recommended. It is important that the guidewire be placed well distal to the problem area. Most long sheaths are prepackaged with a long guidewire. If an exchange is required, it is critical not to lose venous access. The original, short .035-inch guidewire should be retained, and a standard 6F sheath advanced over it. The dilator is removed and a long .035-inch guidewire passed down the 6F sheath alongside the shorter guidewire. The 6F sheath is removed, the short guidewire retained, and the long sheath passed over the long guidewire. Methods of Dual-Chamber Venous Access The percutaneous approach is particularly useful in dual-chamber pacing. It has eliminated the earlier dilemma of needing to introduce two leads into a vein exposed by cutdown that may barely accommodate a single lead, with the resultant need for a second venous access site. Box 21-6 lists the options for dual-chamber venous access. For dual-chamber pacing, at least four methods that involve the percutaneous approach are described here. The first three can be used with any of the previously described percutaneous approaches. Two Separate Percutaneous Sticks and Use of Two Sheath Sets.  Parsonnet et al.94 described the insertion of two sets of permanent electrodes, with a third set for a cardiac venous lead. Two separate punctures raise the risk of complications related to the venipuncture process, and not finding the vessel the second time is also possible. The advantage of this method is that even relatively large bipolar leads can be easily and independently manipulated after introduction, with little risk of unwanted and frustrating movement of the other lead. One Percutaneous Puncture and Use of Large Sheath with Passage of Both Electrodes.  The passage of two electrodes down one sheath reduces the risk of making two separate punctures.95,96 However, the large sheath may increase the risk of substantial air embolism and blood loss. In our experience, there is also frequent frustration from lead interaction, entanglement, and dislodgement. Retained-Guidewire Technique.  The retained-guidewire technique can be used alone as a method for the introduction of two leads or can be incorporated into any of the other techniques for the introduction Box 21-6 

VENOUS ACCESS OPTIONS FOR SINGLE- AND DUAL-CHAMBER PACING Venous Cutdown Isolation of one or two veins With cephalic vein guidewire (Ong-Barold technique) Percutaneous Two separate sticks and sheath applications Two electrodes down one large sheath Retained guidewire (Belott’s technique) Extrathoracic access to subclavian vein (Byrd’s technique)

Electrode stylet is not removed but rather positioned in the lower right atrium Figure 21-41  Ventricular lead has been placed first. The guidewire has been retained, and the lead stylet is positioned in the lower right atrium for stability.

of two leads.97,98 One of the authors (PHB) uses this technique alone, preferentially for dual-lead introductions, and the other (DWR) uses it as backup in combination with the two separate puncture techniques described previously. This approach is most desirable because it provides unlimited access to the central circulation. The implanter using this technique can easily add and exchange leads, an important advantage in dual-chamber pacing, in which the initially chosen atrial lead is occasionally unacceptable for a given anatomic situation. Less frequently, it is also helpful to be able to exchange ventricular leads. When using the retained-guidewire technique for dual-chamber implantation, one usually positions the ventricular electrode first, a practical and safe step. The ventricular electrode can be more easily stabilized and is less susceptible to dislodgement from positioning of the second electrode. One can then stabilize the ventricular electrode by leaving the stylet pulled back in the lead in the vicinity of the lower right atrium (Fig. 21-41). A stitch should be placed proximally around the lead and suture sleeve and secured about 1 to 2 cm from the puncture site in the subcutaneous tissue on the surface of the pectoral muscle. After ventricular electrode stabilization, a second sheath can be advanced over the retained guidewire. The atrial electrode is introduced, positioned, tested, and secured. Alternatively, the retainedguidewire technique can be employed to introduce both leads into the SVC, right atrium, or inferior vena cava (IVC) areas before positioning either electrode. This procedure may reduce risk of dislodgement of the initially positioned electrode caused by introduction of the second sheath. Regardless of variation, the guidewire is removed only after all leads have been placed and tied down (Fig. 21-42). A purse-string or figure-of-eight suture can be tied loosely to achieve hemostasis around the puncture site. Sheath Set Technique with Cutdown Approach.  Ong et al.99 described a modified cephalic vein guidewire technique for the introduction of one or more electrodes. The Ong-Barold technique appears to be a safe and reasonable alternative to the percutaneous subclavian vein introducer technique.100 It is particularly recommended for the



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

469

Sacrificed vein Retained guidewire 2nd Introducer Retained guidewire

Figure-of-8 stitch

Guidewire

1st Lead Electrode 1st Introducer

Suture sleeve

A

Figure 21-43  Cephalic vein guidewire technique uses the guidewire as access to the vein for one or more electrodes. The distal connection of the cephalic vein is sacrificed (Ong-Barold technique). (From Barold SS, Mugica J, editors: New perspectives in cardiac pacing 2. Armonk, NY, 1991, Futura, p 112.)

inexperienced implanter. It is also recommended for use in patients at high risk of complications with the percutaneous approach, as well as when the percutaneous approach is anticipated to be difficult if not impossible. This technique requires an initial cutdown to the cephalic vein as previously described. For a single-lead introduction, the size of the vein is irrelevant. All that is necessary is the introduction of the guidewire, which is accomplished with needle puncture under direct visualization. The cephalic vein is sacrificed because it seems to invaginate into the subclavian vein with advancement of the sheath set over the guidewire (Fig. 21-43). Hemostasis is achieved with pressure or the application of a figure-of-eight stitch. Despite the sacrifice of the cephalic vein, no venous complications have been reported. When two leads are required, the retained-guidewire technique and sheath set technique can be used in this approach. COMPLICATIONS OF PERCUTANEOUS VENOUS ACCESS AND BLIND SUBCLAVIAN PUNCTURE The safety and efficacy of the blind subclavian puncture remain controversial with respect to the incidence of serious complications and even death (Box 21-7). Parsonnet and Bernstein101 reported a 0.4% incidence of serious complications in a survey of 11 implanting physicians in a review of 2500 cases. Furman102 showed the remarkable efficiency of the cutdown approach for single-chamber and dualchamber pacing, particularly with unipolar leads. The cutdown technique, however, was less useful for the introduction of bipolar leads via a single cephalic vein. Furman103 reported no vascular or pleural

B Figure 21-42  A, Ventricular electrode and retained guidewire are demonstrated in the main drawing. The inset demonstrates the ventricular lead anchored by suture around its suture sleeve and the second sheath advancing over the retained guidewire. A hemostat on the figure-eight suture maintains hemostasis. B, The atrial and ventricular electrodes have been positioned, yet the guidewire is still retained.   (A from Barold SS, Mugica J: New perspectives in cardiac pacing 2. Armonk, NY, 1991, Futura, p 110.)

Box 21-7 

COMPLICATIONS OF PERCUTANEOUS VENOUS ACCESS AND SUBCLAVIAN PUNCTURE • Pneumothorax • Hemothorax • Hemopneumothorax • Laceration of subclavian artery • Arteriovenous fistula • Nerve injury • Thoracic duct injury • Chylothorax • Lymphatic fistula

470

SECTION 3  Implantation Techniques

complications in a large series of 3500 cases in which the cutdown approach was used for single-chamber and dual-chamber pacemaker implantations. Parsonnet et al.7 analyzed the pacemaker implantation complication rates with respect to contributing factors. They reviewed 632 consecutive implantations over a 5-year period performed by 29 implanting physicians at a single institution. There were 37 perioperative complications. Complications were analyzed in regard to experience of the implanting physician. Percutaneous venous access was associated with the highest complication rate and contributed significantly to a 5.7% overall complication rate. When the complications related to the percutaneous approach were excluded, the complication rate dropped to a more acceptable 3.5%. The highest complication rate was among physicians implanting fewer than 12 pacemakers a year and with the least pacing experience. In reviewing complications of pacemaker insertion, Sutton and Bourgeois104 noted an overall 1% incidence of subclavian vein puncture leading to pneumothorax. Arterial puncture occurred more often, at a rate of about 3%, but generally was not associated with any morbidity. Similarly, in their analysis of thrombotic complications, axillary vein thrombosis was rare, occurring in 0.5% to 1% of cases. Interestingly, partial venous obstruction in the great veins was almost the rule and occurred to some degree in up to 100% of cases. Clinical pulmonary embolism, however, was extremely rare. As a rule, partial or silent inconsequential thrombosis is considered extremely common but generally of no clinical significance.105 PLACEMENT OF THE VENTRICULAR ELECTRODE Many techniques for placing the ventricular electrode are described throughout the published pacing literature,105 essentially reflecting the approach with which any particular clinician has facility. There is no one correct technique. Ventricular electrode placement is largely independent of the route of venous access. The implanting physician must draw on experience to deal with the variety of situations that will be encountered in any given patient. In time, implanters develop their own technique. The fundamental principles and maneuvers are common to all: (1) simultaneous manipulation of lead and stylet, (2) documentation of passage into the right side of the heart, and (3) manipulation of the electrode into the apex or other desired location in the right ventricle. One must grasp the concept that pacemaker placement involves a “symphony” of lead and stylet movements. Without the two working together, proper electrode positioning is impossible. The lead without stylet resembles a limp piece of spaghetti. During positioning of the ventricular electrode, the lead must negotiate a course through the chambers of the right side of the heart and, ultimately, to the right ventricular (RV) apex. This is typically accomplished through preforming of the lead stylet. Preforming enables easier manipulation of the lead and is probably the best way to position a pacemaker electrode effectively. A curve is applied to the distal aspect of the stylet. The size or tightness of the curve and how it is created are personal preferences. As a rule, a curve that is too gentle will fail to negotiate the tricuspid valve, making passage into the pulmonary artery difficult. Conversely, a curve that is too tight may fail to negotiate the venous structures in the superior mediastinum, such as the innominate vein and SVC. At times, however, unusual circumstances call for extremes of wire curvature for effective positioning of the electrode. In every case, the ideal curve for the stylet is slightly different. There are several ways to form the curve on the stylet. Some implanters choose to use a blunt instrument, such as the tip of a clamp or scissors. The stylet is pulled between the thumb and the blunt instrument with a rotary motion of the wrist, forming the curve. Another method is to form the curve by pulling the guidewire between the thumb and index finger, gently shaping the curve. Whatever method is used, the curve should be a bend that is not sharp, because a sharp bend in a stylet generally precludes its passage through the lead. The aim of the curve is to enable the curved stylet to direct the electrode to the appropriate position.

Unlike diagnostic catheters, the pacemaker lead cannot be steered or torqued into position. Positioning of a pacemaker electrode solely depends, therefore, on the manipulation of lead and stylet together. The basic technique of lead positioning involves advancing the electrode, with curved stylet in place, through the chambers of the right side of the heart. A more sophisticated variation of this technique involves simultaneously advancing the electrode while retracting and readvancing the stylet. The retraction of the stylet renders the lead tip floppy. With the use of a slightly retracted, but curved stylet and pointing the electrode body in the proper direction, the lead, with 1 to 2 cm of its floppy tip, usually allows for more precise and expeditious electrode placement. An alternative related technique that can expedite ventricular lead implantation, although more difficult to master, involves the use of a straight stylet. The stylet is retracted to allow the floppy lead tip to “catch” on a structure in the right atrium, with subsequent advancement of the lead. The lead body then prolapses through the tricuspid valve into the right ventricle. The stylet can then be cautiously advanced to stiffen the lead body and, generally, free the tip from the catch. It is possible, even likely, that these techniques involving prolapse of the leads across the tricuspid valve present less likelihood of damaging the valve or entangling subvalvular structures than techniques involving direct advancement of stiff-tipped leads. The fluoroscope should be used for the entire lead positioning process and can be used initially in the posteroanterior (PA) projection or in the right anterior oblique (RAO) projection. The latter helps delineate the RVA to the left of the spine and toward the left lateral chest wall. The RAO projection creates the illusion that the “mind’s eye” expects, with respect to the location of the RVA, specifically, that the RV apex is near the apex of the cardiac silhouette. In many patients, however, the RVA tends to be more anterior than leftward. Much time can be wasted trying to position a ventricular electrode to the left of the spine toward the apex of the cardiac silhouette (in the PA projection) when, in reality, the RV apex is directly anterior to the spine. This anterior position results in an electrode position that is over the spine or nearly so and appears in the PA projection to be erroneously placed in the right atrium or in the less desirable proximal aspect of the right ventricle. Rotating the image intensifier unit into the RAO projection in this situation superimposes the RV apex over the apex of the cardiac silhouette in the left side of the chest, confirming the appropriate position (Fig. 21-44). Whether or not the initial choice of projection is the RAO, it should be used freely to facilitate ventricular lead placement. Fluoroscopy is also important for confirmation of the final lead position, whether RVA or some septal location. It is important to rule out inadvertent passage of the lead across a patent foramen ovale and placement in the left ventricle. This can be very deceiving in the

AP

RAO

Figure 21-44  Wire frame demonstrating the orientation of the lead in the right ventricular apex in the anteroposterior (AP) and right anterior oblique (RAO) projections. Note that in the AP projection, the electrode appears to be vertical, whereas in the RAO, the lead is horizontal from right to left.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

anterior projection. A clue is a very high lead takeoff from the right atrium to the apical position. There is often a “chair sign” in which the lead plateaus from the right to the left ventricle. Correct RV apical lead placement versus patent foramen ovale to left ventricular (LV) lead placement can easily be confirmed by use of the RAO and left anterior oblique (LAO) fluoroscopic projections. The RAO projection helps determine how apical the lead is in the right ventricle. The LAO projection will determine whether the lead is in the right or left ventricle. In LAO projection if the lead is in the left ventricle it will be seen going from left to right across the spine. In the lateral projection, RV lead placement is confirmed with the lead tip anterior, whereas if the lead is in the left ventricle, the lead tip will be posterior (see Fig. 21-72). Right ventricular leads are now being placed on the septum to avoid deleterious hemodynamic effects of the RV apical lead position. Location on the RV septal wall reduces the opportunity for myocardial perforation and diaphragmatic stimulation. RV septal positions result in a more physiologic pattern of ventricular activation. However, it is impossible to distinguish RV free wall (anterior) location from RV septal (posterior) without fluoroscopic confirmation. A new technique has been developed for rapid and consistent lead placement on the right ventricular outflow tract (RVOT) septum.106 The technique uses active-fixation leads and a specially shaped stylet. A generous distal curve is applied to the stylet.107 The distal 2 cm of the stylet is bent to produce a swan neck deformity. The terminal straight end is forward Fig. 21-45, A). If the stylet is placed in reverse, the terminal bend faces posteriorly for easy septal access. Once the lead is place on the septum,

Posterior angulation

A

B

PA

LAO

Figure 21-45  Lead placement on right ventricular outflow tract septum. A, The prepared stylet with a generous curve. 2-cm terminal bend and posterior angulation. B, Posteroanterior (PA) and left anterior oblique (LAO) fluoroscopic images of a dual-chamber pacing system with an active-fixation lead attached to the mid-RV septal wall (arrows). (From Rosso R, Medi C, Teh AW, et al: Right ventricular septal pacing: the success of stylet-driven active-fixation leads. Pacing Clin Electrophysiol 33:49-53, 2010.)

471

final position is confirmed by the PA and 40-degree LAO projections (see Fig. 21-45, B). A high success rate is reported, but the optimal position on the RVOT septum remains to be determined. We recommend that the electrode be passed initially across the tricuspid valve and then out into the pulmonary artery (Fig. 21-46, A to C). This maneuver confirms passage into the right side of the heart and precludes erroneous placement in the coronary sinus (CS). The RAO projection is also helpful in making certain the lead is not in the CS. If the lead is appropriately placed in the RV apex, there will be no posterior component in the course of the lead on the RAO projection. If the lead is in the CS, it will have a posterior course on this projection. If it courses down the middle cardiac vein, the lead will have a posterior course as it traverses the CS, then an anterior course as it traverses this branch. Techniques for placement of the electrode into the RV apex involve the combined manipulation of the lead stylet and electrode body. If one chooses to pass the electrode to the pulmonary artery as an indicator of being across the tricuspid valve, the next maneuver is to advance the stylet to the tip of the electrode. With the stylet advanced to the electrode tip and the electrode tip in the pulmonary artery, the electrode is slowly withdrawn from the pulmonary artery, dragging the tip down along the interventricular septum. This may result in premature ventricular contractions or runs of nonsustained ventricular tachycardia. When the electrode tip has reached the lower third of the septum, the stylet may be retracted about 2 to 3 cm, making the tip floppy; this can be done with a curved or straight stylet (Fig. 21-46, D). The lead tip can be observed to move up and down with the flow of blood, the motion of the tricuspid valve, and RV contractions. As it does so, it will intermittently point toward the RV apex. If one coordinates advancing the lead body (with or without the stylet fully inserted, although generally only straight stylets should be fully inserted at this point) with the appropriate lead trajectory, one can gently seat the tip in the RV apex. This maneuver can be repeated by withdrawal and readvance of the electrode until the desired fluoroscopic location is achieved for threshold testing. After satisfactory electrode tip placement, the curved stylet is withdrawn and replaced with a straight stylet if a curved stylet was initially used and if it was not already replaced (some implanters replace the curved stylet with a straight one while the lead tip is still in the pulmonary artery). The straight stylet is advanced to the electrode tip, and the electrode with stylet in place is gently advanced toward the RVA until it is fully inserted and resistance is encountered. Care should be taken not to dislodge the electrode tip with the straight stylet. Dislodgment is a common occurrence, especially in patients with an enlarged right atrium. In the process of being advanced to the electrode tip, the straight stylet can force the electrode body inferiorly to the lower right atrium and IVC, consequently dragging the tip of the electrode out of the RV apex and back into the right atrium. Ways to avoid this extremely frustrating phenomenon include using a more flexible stylet, which will be guided more easily by the electrode coil than the stiff stylet. Also, before advancing the stylet, one can straighten the lead body as it crosses the tricuspid valve by gently pulling back on the lead; this usually avoids the looping of the lead in the lower right atrium. Lead fixation in the right ventricle can be validated with a gentle pull on the electrode until resistance, both tactile and visual, is encountered. This is a good method for ensuring reliable fixation if a tined or other passive-fixation lead is being used. With an active-fixation lead, the best method for determining that reliable fixation is accomplished is a subject of debate. Some believe that threshold measurements, not retraction of the lead tip to the point of resistance, is a better way of validating fixation. It is argued that the strength of fixation in the tissue with a screw-in electrode is impossible to gauge from the sensation of resistance on retraction and that, all too often, the bond is disrupted when one pulls back on the screw-in electrode to the point of resistance. Conversely, others argue that the same gentle lead retraction, coupled with achievement of acceptable thresholds, is more appropriate validation for achievement of active fixation. The argument here is that acceptable thresholds may be achieved without adequate fixation,

472

SECTION 3  Implantation Techniques

A

B

C

D

Figure 21-46  A, Lead with curved stylet approaching the tricuspid valve. B, Lead being pushed against the tricuspid valve. C, Lead snapping across the tricuspid valve into the right ventricle. D, Lead passed to the pulmonary artery, then withdrawn to the right ventricular apex.

and that adequate fixation easily prevents the disruption of an acceptable bond by gentle retraction. If the initial stylet choice was straight, or after the electrode with the curved stylet has been passed to the pulmonary artery and is replaced with a stiff, straight stylet, the tip of the straight stylet can be positioned just across the tricuspid valve. It usually points to the RV apex. Simultaneous advancement of the stylet and retraction of the electrode drags the electrode tip down the interventricular septum to the end of the stylet, which is tracking toward the RV apex. Once the electrode tip has snapped into a straight position, now in line with the trajectory of the stylet, both are advanced to the RV apex. In both cases, when one is seating the electrode in the RV apex, one can more easily avoid perforations by simultaneously advancing the electrode body while

retracting the stylet. Thus, the stylet is not acting as a battering ram but is merely pointing the way. In all cases, if there is any doubt about the location of the electrode in the RV apex, the fluoroscope is merely rotated into the steep RAO or lateral projection. As previously noted, a correctly placed electrode is observed to curve anteriorly, with the electrode tip appearing almost to touch the sternum. If the electrode curves posteriorly toward the spine, it is likely in the coronary sinus. Although the means of venous access has little bearing on electrode placement, there is some difference between the left and right sides. Placement of the ventricular electrode after venous access has been achieved from the left side generally appears to be more expeditious. The ventricular lead with a curved stylet in place will track in a gentle curve from the point of venous entry through to the SVC, right atrium



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

A

473

B

Figure 21-47  A, Acute bends encountered with right venous access orient the lead to the lateral wall of the right atrium when a stylet with a modest curve is inserted into the electrode. B, The lead must be backed into the right ventricle, across the tricuspid valve, when a right-sided approach is used. Rotation or partial withdrawal of the stylet is sometimes helpful in moving the electrode across the valve.

(RA), right ventricle (RV), and pulmonary outflow tract (see Fig. 21-16, A). Typically, little or no difficulty is encountered. There are generally no acute bends or angles. The only occasional impediment is the tricuspid valve, which can be negotiated with one of several techniques. One may be able to advance the tip across the valve without hang-up. If the lead tends to hang up on the valve, retracting the stylet and using the floppy-tip technique already described frequently solves this impasse. In another technique, the curved tip of the electrode is pushed across the valve by creating a loop. Whatever technique is used, because of the anatomic configuration, passage from the left typically presents minimal difficulty. The elderly patient with an extremely tortuous left subclavian–innominate venous system is an exception; the venous structure may have one or more sharp angles or bends in the superior mediastinum before entry into the RA. It would be a truly extreme case for such tortuosity to preclude passage of the electrode from the left. Passage and placement of the ventricular electrode after right venous access may be much more challenging. Intrinsic to this approach is one acute angle or bend in the venous system (see Fig. 21-16, B). This bend occurs at the junction of the right subclavian vein and internal jugular vein, where the innominate vein is formed. More importantly, this bend is clockwise; therefore, when a lead with a curved stylet is placed in the vein from the right, the electrode is typically directed clockwise or to the lateral RA wall (Fig. 21-47, A). In this situation, routing the tip across the tricuspid valve, which is in the other direction, requires skill and ingenuity. One method involves building a loop in the RA in an attempt to prolapse the lead and to back the electrode across the valve, with the tip ultimately flipping into the right ventricle (Fig. 21-47, B). If the lead has tines, they may be caught on the tricuspid valve and may prevent transit to the right ventricle. Another, somewhat more successful method of crossing the tricuspid valve is the floppy-tip technique. If the curved stylet is withdrawn to the high RA, with the lead tip in the lower RA, the lead will no longer point to the lateral atrial wall. Its trajectory may now be medial, toward the tricuspid valve. Advancing the body of the lead, even though the tip is floppy, allows the lead tip to cross the tricuspid valve into the right ventricle. With this approach, it is important to avoid extreme stylet curves, which increases the tendency of the lead tip to move toward the lateral RA

wall. Future lead designs need to incorporate some steering mechanism in either the stylet or the lead. A benefit of modern lead design is the various fixation mechanisms that have resulted in a near 0% dislodgment rate. The implanting physician should become familiar with the lead-handling characteristics of the various active-fixation and passive-fixation designs. It is especially important to gain experience with the passive-fixation mechanism of tines. Learning to recognize when tines are stuck on an endocardial structure, and not be intimidated by the resistance encountered when traction is applied, is essential. There has yet to be a reported case of endocardial trauma from a tined electrode, even though one may occasionally think the tines have permanently attached themselves to an endocardial structure during attempts at lead placement. It is this same feeling of resistance that ensures us that the electrode will not dislodge once an ideal location is found. When the tip of a tined lead becomes caught on a structure in an undesirable position, it is usually impossible to advance the lead. The lead must be pulled free and usually withdrawn to the RA, no matter what force must be applied. Sometimes, it may take multiple electrode advances and withdrawals with the tines hanging up and preventing placement in the RV apex. Subtle adjustments in the stylet manipulation, as well as persistence, will ultimately overcome this problem. The active-fixation leads offer a new set of problems. Some unique problems in placement are directly related to design. There are basically two types of active-fixation leads in use, both involving a helix or “screw” as the fixation mechanism. First, there is the fixation tip design with an exposed or fixed screw. Because the screw is continually exposed, its tip may catch onto any endocardial structure. As one would expect, this type of helix has a high propensity for being caught, particularly on the chordae of the tricuspid valve. Unlike tines, the screw, when caught, cannot be pulled free without some concern of damaging endocardial structures. It can usually be freed easily with counterclockwise rotation of the lead body, which results in unscrewing of the tip (the available screws are made with a clockwise helix). Some manufacturers have attempted to resolve this problem by coating the exposed screw with a sugar compound that ultimately dissolves, exposing the screw. This can work well, provided that one is consistently able to place the lead in an optimal position quickly; doing so

474

SECTION 3  Implantation Techniques

requires significant skill and experience. Once the coating has dissolved, the screw can hook endocardial structures if there is a difficult positioning or a need to reposition or withdraw to the RA. The exposed screw does, however, offer a reliable fixation mechanism. The second type of active-fixation lead employs an extendableretractable screw that is mechanically extended from its “resting” retracted position. This lead is generally easier to work with because the problem of helix hang-up is avoided. In fact, the extendableretractable screw-in type leads may be the easiest of all leads to position. Placement of both types of fixation mechanisms uses the stylet techniques previously described. Care should be used to avoid overtorque of the screw fixation mechanism. Each lead has a characteristic appearance when the helical mechanism is fully engaged. Further rotation of the mechanism only causes trauma to the myocardium, increased acute injury, and interferes with assessment of the sensing and capture functions. Usually the acute injury resolves within 2 to 3 minutes, but if the lead is overtorqued, the time to stabilization of the threshold measurements increases. If too much torque is applied, chronic threshold elevation can be seen and potentially an increased rate of myocardial perforation. When the implanting physician is satisfied with electrode placement, the stylet may be withdrawn to the vicinity of the lower RA108 (Fig. 21-48). Alternatively, the stylet can be completely removed. Threshold testing is then carried out. If thresholds are acceptable, the ventricular electrode may be secured. Some implanters leave the stylet in the lead with the tip in the lower RA and secure the lead with the anchoring sleeve. This practice reduces the risk for ventricular lead dislodgement during placement and positioning of the atrial lead. Other implanters remove the stylet completely for testing and securing the lead, but not for atrial lead placement and positioning, because there is general agreement that the stylet helps stabilize the ventricular lead during atrial lead manipulation, which otherwise can frequently dislodge the ventricular lead. The suture sleeve is advanced down the shaft of the lead body to the vicinity of venous entry. One to three ligatures are applied around the suture sleeve and lead, incorporating a generous amount of pectoral muscle (Fig. 21-49). In our experience, multiple ligatures that are not

Lead stylet

Figure 21-48  The stylet of the ventricular electrode is left in the lead but is withdrawn to the lower right atrium to permit threshold testing and assessment of the appropriate amount of lead redundancy.

Figure 21-49  Using the suture sleeve to secure the ventricular electrode to the pectoral muscle.

excessively tight make lead slippage as well as lead damage less likely than a single, tightly applied ligature. Securing the ventricular electrode immediately after satisfactory positioning is important. Early securing helps prevent inadvertent dislodgement whether or not an atrial electrode is to be placed. The ventricular electrode should be oriented somewhat horizontally in a plane roughly parallel to the clavicle. This orientation avoids excessive bending of the lead at the point where it exits the vein. PLACEMENT OF ATRIAL ELECTRODES Atrial electrode placement can be extremely easy but has been the nemesis of many implanting physicians. It has even been responsible for the resistance of many implanters to the dual-chamber approach to cardiac pacing. This, we believe, is largely because the clinician has not been exposed to proper placement technique. Once again, it must be appreciated that the proper placement of any pacemaker electrode is a symphony of lead and stylet. The lead, by itself, cannot be steered or twisted into place. Two fundamental techniques relate directly to lead design. The first is placement of an electrode with a preformed curve or atrial J electrode.109 This electrode can have either active-fixation or passivefixation mechanisms. More often, a lead with passive-fixation tines is used. After insertion into the venous system, the lead tip is positioned with a straight stylet fully inserted in the middle to lower RA. The preformed J has been straightened with the straight stylet. Fluoroscopy can be applied in either the PA or the RAO projection. Under fluoroscopic observation, the straight stylet is withdrawn several centimeters. The atrial lead tip can be observed to begin assuming its J configuration, with the tip beginning to point upward. The lead body is then slowly advanced at the venous entry site (Fig. 21-50). On fluoroscopy, the lead tip is observed to continue its upward motion, eventually seating in the atrial appendage. If the lead tip is too low in the RA, it may catch on or cross the tricuspid valve as the stylet is withdrawn. In this case, the lead is simply withdrawn slightly and the maneuver repeated slightly higher in the RA. If the lead tip is too high in the RA or is in the SVC, the tip will not move upward adequately. In this case, the electrode is repositioned more inferiorly. After gaining experience with this maneuver, one can use it repeatedly and deftly perform the act of retracting the stylet slightly. This brisk move “snaps” the lead tip into the atrial appendage, at times resulting in better electrodeendocardium contact. Frustration and failure may occur if one attempts atrial placement by briskly removing the entire stylet and



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

475

mechanism must be activated. This step usually involves the extension of a screw or helix. The exposed or fixed screw described previously is not available in a preformed atrial J configuration. The second fundamental technique of atrial electrode placement involves the use of a straight or non-preformed lead. This lead is positioned in the atrium using a stylet preformed into a J shape that can be modified to other configurations. The stylets typically come with the lead already preformed into the J shape, or if desired, a straight stylet can be shaped into the J or other configurations using the same technique described for curving the ventricular lead stylet. The stylet can then be positioned in the atrium, frequently in the atrial appendage, although it has become increasingly evident that other locations in the atrium, especially the anterior and lateral free walls, can be easily and safely targeted.112 Manipulation of the stylet is required to gain access to the various atrial locations. At times, modification of the preformed stylet shape is required. At the University of Oklahoma (DWR), the modification of the J stylet into a shape similar to that of an Amplatz coronary artery catheter (several varieties) has been helpful in gaining access to a number of positions in the RA. The principal advantage of the non-preformed leads (which use stylets of various shapes) with active-fixation mechanisms is that one is not restricted to the atrial appendage, as discussed later. With a straight or nonpreformed active-fixation lead, either a fixed screw or an extendableretractable screw can be used. Reports have detailed successful placement of a straight, tined lead in the atrial appendage without dislodgement. Because of the risk for dislodgement and the high success rate of both active-fixation and preformed atrial J leads, however, this is not recommended, especially early in one’s experience. The use of an active-fixation lead in the atrium is ideal in patients who have undergone open-heart surgery during which the atrial appendage was amputated. Other advantages to using an active-fixation lead in the atrium include, as already noted, the ability to choose the placement site and map the atrium for optimal electrical threshold. By extending and retracting an extendable-retractable screw or attaching and detaching Figure 21-50  Positioning a preformed atrial J electrode by partial withdrawal of the lead stylet.

expecting the electrode to jump into the atrial appendage. This maneuver usually results in the electrode coiling on itself in the SVC or RA. With the stylet so coiled, further attempts at positioning are impossible until it has been reinserted and the process restarted. Good atrial positioning consists of a generous J loop, with the tip moving from medial to lateral in a to-and-fro manner in the PA radiographic projection110,111 (Fig. 21-51). In the lateral projection, the tip should be anterior and observed to “bob” up and down. With the firmly seated tip in the atrial appendage, the lead body should be twisted or torqued to the left and right to establish a position of neutral torque. Sometimes, in the process of positioning, torque can build up. If it is not released, electrode dislodgement could result. This same maneuver of twisting can also result in better electrode-myocardium contact. With experience, one gains a sense of the proper J or loop size, which can be a source of frustration. Too much or too little loop can result in dislodgement, depending somewhat on the lead model. Another frustrating event can occur in relation to conformational changes in the vasculature with postural movement. With the patient supine, just the right loop appears to have been created, but as soon as the patient is upright, the conformational change occurs, and the mediastinal vasculature appears to shift inferiorly, pulling up on the lead and obliterating the loop. Unfortunately, this situation may not be discovered until the postimplantation chest radiograph is reviewed. Attempts at gauging the loop size by having the patient take deep inspirations are frequently unrewarding. As a general rule, it is better to create a more generous loop. Positioning the preformed J lead with an active-fixation screwin mechanism uses the same basic technique described earlier. After positioning in the atrial appendage, however, the active-fixation

Figure 21-51  The to-and-fro, medial-to-lateral motion of a wellplaced atrial lead in the atrial appendage when viewed in the posteroanterior projection.

476

SECTION 3  Implantation Techniques

a fixed screw, one can analyze multiple positions. The straight activefixation lead can be placed essentially anywhere in the atrium. On the other hand, the preformed atrial J lead can typically and easily be placed only in the atrial appendage. A second advantage of the activefixation lead is its ease of retrievability. The ability to remove a lead implanted for long-term function, if removal becomes necessary in the future, is probably more easily accomplished with an active-fixation lead. Proper or adequate placement of active-fixation leads is reflected by good electrical threshold measurements. Adequate active lead fixation has been related to a current of injury. Development of a current of injury indicates that within 10 minutes of fixation, pacing thresholds return to acceptable limits and indicate good fixation.113 As discussed in the section on ventricular electrode placement, opinions differ about whether, in addition to the achievement of optimal electrical parameters, a gentle tug on the lead after fixation is helpful in determining whether good mechanical fixation is achieved. Although some implanters use a floppy-tip technique for unusual or precise lead placement, some types of active-fixation leads (especially of the extendableretractable variety) require full insertion of the stylet to activate the screw-in mechanism. The floppy-tip approach is not effective in this situation. This problem is not encountered with the fixed screw and some of the extendable-retractable screws. Occasionally, one encounters difficulty while attempting to place leads in the atrial appendage with the preformed atrial J stylet. In certain situations, the lead with J stylet in place does not assume an adequate J shape to enter the atrial appendage or make contact with atrial muscle. The reason may be that the stylet is too limp or does not have enough curve, or that the atrium is large. One may need to use a stiffer stylet and preform it with an exaggerated curve or J shape. One may also have difficulty trying to maneuver stiffer stylets down through the electrode, as well as during negotiation of the venous system in the superior mediastinum. A trial-and-error approach using multiple stylet configurations ultimately leads to success. The side of venous access has little effect on trial electrode placement. Whether placement is from the right or the left, the preformed J electrode or the straight electrode with preformed J stylet can generally provide easy access to the atrial appendage. Venous access may affect placement of the electrode in unusual atrial positions. Precise placement through the use of stylet and electrode manipulation may be more difficult from the right side. As discussed for ventricular lead placement, the electrode, depending on the shape of the stylet curve, may seek a right lateral orientation. Securing the atrial lead is similar to securing the ventricular lead. After percutaneous venous access and placement, the atrial lead also should be oriented in a generally horizontal plane, roughly parallel to the clavicle. If the pocket has not already been made, the infraclavicular space is opened by means of dissection with Metzenbaum scissors. Dissection is carried to the surface of the greater pectoral muscle near its attachment under the clavicle. The fibers of the platysma muscles are severed. A 1-0 silk suture is placed in a generous “bite” of the pectoral muscle under the anticipated site of attachment. The suture sleeve is advanced down the lead to the vicinity of the suture. Care should be taken not to dislodge or change the atrial lead position in the process. Occasionally, the suture sleeve binds to the electrode, making it difficult to position. One can best manage this difficulty by lubricating the lead with sterile saline or other fluid, then using smooth forceps to slide the sleeve into position. Once the suture sleeve is in position, the suture is secured around it. Many implanters first put a knot in the suture on the surface of the muscle. The two ends of the suture are then wrapped around the suture sleeve and tied. This second tie is directly around the lead and is designed to prevent lead slippage. Some implanters use multiple sutures rather than a single suture, as discussed for ventricular electrode placement. Care must be taken to make the tie snug and yet avoid injury to the lead. It is important to orient the electrode horizontally. As with ventricular leads, doing so orients the lead in a plane similar to that of the axillary vein, reduces the bend

of the lead, and may decrease the likelihood of the crush phenomenon or other stress-related lead damage. If venous access and electrode placement have been achieved with venous cutdown, there is essentially no risk of the classic crush injury. Generally, the suture sleeve and lead are anchored to the pectoral muscle parallel to the vein. Similar precautions concerning lead injury should be observed. The securing process is the same, and one should avoid acute angulation of the lead and the creation of points of lead stress. UPGRADING TECHNIQUES An upgrading procedure is necessary in patients with the pacemaker syndrome. With the growing acceptance of dual-chamber pacing, all patients who have been implanted with VVI systems and who have intact atrial function are now being considered for a pacemaker system upgrade with the addition of an atrial lead. In addition, some patients with an existing pacemaker system need an upgrade to an automatic ICD or a biventricular system for resynchronization. Such patients also need a pacing and shocking electrode and/or a left ventricular lead. Generally, this change is deferred until the time of pulse generator power depletion, but greater awareness of the pacemaker syndrome or the need for an ICD or resynchronization has resulted in earlier pacemaker system upgrades. The upgrade procedure requires new venous access for the introduction of one or more new leads. It may also involve the introduction of a new ventricular lead because of problems with the existing lead. Most pacemaker system upgrades require the replacement of the pulse generator, although occasionally, the existing pulse generator used in the ventricle can be used for atrial pacing. Upgrade procedures usually involve a conventional approach using one of the previously described percutaneous techniques or a venous cutdown. If the first ventricular lead was placed through the cephalic vein, the percutaneous approach is almost mandatory for the upgrade. Conversely, in patients treated with an initial percutaneous subclavian approach, the new lead can be introduced either by cutdown of the cephalic vein or through percutaneous venous access. In the case of an initial percutaneous approach, the ventricular electrode can serve as a map. Using fluoroscopy, one can use the existing ventricular lead as a target to guide the percutaneous needle. Care should be taken not to touch or damage the first lead with the needle. The lead should be used as a reference landmark for the expected location of the subclavian vein. Bognolo et al.114,115 have described a technique to reestablish venous access using the original ventricular lead. The patency of the venous structures can be assessed as previously described with the injection of radiographic contrast material.91 If access to the subclavian vein cannot be obtained by following the axioms of the safe introducer technique previously described by Byrd,76 an extrathoracic puncture of the axillary vein can be done. The puncture of the vein can be expedited with a simple technique: a guidewire or catheter is passed to the vicinity of the subclavian vein through a vein in the arm. The guidewire or catheter can be palpated or viewed fluoroscopically, thus serving as a reference for venous access. In the case of a cutdown on a previously unused cephalic vein, the OngBarold percutaneous sheath set technique can be used.99 Lead compatibility is important when considering a pacemaker system upgrade. To avoid embarrassment, one must be aware of the new pulse generator’s compatibility with the chronic lead system. Occasionally, ipsilateral venous access is impossible. Either the vessel is thrombosed, or some form of obstruction precludes the placement of a second (atrial) lead from the same side. In this case, contralateral venous access can be achieved, and the lead tunneled back to the original pocket (Fig. 21-52). Early injection of radiographic contrast material may expedite the decision to use this approach. The use of the contralateral subclavian (rather than cephalic) vein is recommended for this approach.116 The distance to the original pocket is less, and the new lead is not as susceptible to dislodgement. The same percutaneous techniques and precautions are used as previously described for the



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

2nd Electrode

1

477

2

Pulse generator removed 2nd Incision

Atrial lead tunneled to original pocket

3 Dual chamber pulse generator implanted

Figure 21-52  Pacemaker upgrade using the contralateral subclavian vein. 1, Pacemaker pocket is opened, and the original pulse generator and lead are dissected free, externalized, and disconnected. 2, Second lead is inserted by means of the contralateral subclavian vein. 3, Second lead is tunneled back to the initial pocket. (From Belott PH: Use of the contralateral subclavian vein for placement of atrial electrodes in chronically VVI paced patients. Pacing Clin Electrophysiol 6: 781, 1983.)

percutaneous approach. The only difference is the size of the skin incision, which is limited to about 1 to 1.5 cm. The incision need only be large enough to allow anchoring of the lead and securing of the suture sleeve. As in an initial implantation, the incision should be carried down to the pectoral fascia. Once the lead has been positioned and secured, it can be tunneled to the original pocket. The maneuver of passing an electrode or catheter through tissue from one location to another is referred to as tunneling. It always involves the passage of a catheter from one wound through tissue to a second wound remote from the first. An example is the placement of a pacemaker lead through the internal jugular vein. The lead is passed from the jugular incision through the tissue over (or under) the clavicle to the pacemaker pocket in the pectoral area. With the development

A

of implantable defibrillator lead and patch systems that do not require thoracotomy, tunneling has become popular and necessary. A number of techniques are available for tunneling. They differ in level of trauma to the tissue and lead. As a rule, the least traumatic technique is desirable. A popular technique is to place the proximal end of the lead or leads to be tunneled in a 14-inch Penrose drain (Fig. 21-53, A). A gentle, nonconstricting tie is applied around the drain just distal to the lead connector (see Fig. 21-52, B). The track of the tunnel, from the satellite wound to the pocket, is infiltrated with local anesthesia by means of an 18-gauge spinal needle. The free end of the Penrose drain is then brought to the receiving wound from the satellite wound in the subcutaneous tissue. This can be accomplished with several techniques. The first technique involves the use of a Kelly clamp

B

Figure 21-53  A, Penrose drain and lead grabbed by a clamp that has been passed from the recipient wound to the donor site. Penrose drain and lead(s) are pulled back to the recipient wound. B, Tunneling from one wound to another by placing the electrode(s) in a Penrose drain. The lead(s) are placed in a 14-inch Penrose drain and tied. The Penrose drain is then grabbed with a long clamp.

478

SECTION 3  Implantation Techniques

or uterine packing forceps. The tip of the clamp is pushed bluntly in the subcutaneous tissue from the receiving wound directly to the satellite wound. Care is taken to keep the tunnel as deep as possible, usually on the surface of the muscle. The free end of the Penrose drain is grasped and pulled back from the satellite wound to the receiving wound. The remainder of the Penrose drain containing the electrode connector pin is pulled through the track to the receiving wound. The tie is released, and the Penrose drain is removed. A second technique delivers the Penrose drain to the receiving wound by use of a “passer,” usually a knitting needle or dilator. In this technique, the free end of the Penrose drain is fixed to the back end of the passer with a tie. The pointed tip of the passer is inserted into the satellite wound and pushed to the receiving wound. The tip of the passer is grasped and pulled into the receiving wound with the Penrose drain attached. The remainder of the Penrose drain with the lead is then pulled into the receiving wound. A variation of this technique uses the percutaneous technique to establish the tunnel. After the track of the tunnel is infiltrated with an 18-gauge spinal needle, the needle is passed from the wound of origin to the receiving wound. A guidewire is passed through the needle into the receiving wound. A standard peel-away introducer is then passed over the guidewire from the satellite incision to the receiving wound. The sheath can then be used to pass the lead, and the sheath is eventually removed and peeled. Another variation uses the dilator of the sheath set to tunnel and the guidewire to pull the Penrose drain from wound to wound. After the dilator is used to create the tunnel from one wound to the other, the guidewire is passed through the dilator. The dilator is removed, and the guidewire is attached to the loose end of the Penrose drain. The implanter then brings the Penrose drain to the receiving wound by pulling the guidewire. A technique that is similar in principle to the use of the Penrose drain, but that may be more traumatic, involves the use of a small chest tube and a Pean clamp. The size of the chest tube is determined by the size and number of leads to be tunneled at one time. The length is determined by the distance from the initial wound to the receiving wound. The tube may be cut to size and the end beveled to a point. The leads at the wound of origin are placed in the back end of the chest tube. The Pean clamp is bluntly passed from the receiving wound to the wound containing the leads. The pointed end of the chest tube is grasped by the Pean clamp and is pulled into and through the receiving wound. Although more traumatic to tissue, this technique is protective of the electrodes. Another related technique involving the use of a chest tube requires blunt passage of the chest tube, with the trocar in place, through the subcutaneous tissue from the site of origin to the receiving wound with the lead or leads placed in the “back end” of the tube after removal of the trocar. The tube can then be pulled through into the receiving wound. Lastly, new tunneling tools have been developed for use with implantable defibrillators. These tools may be used for pacemaker lead tunneling as well. The preceding techniques and principles are used whenever tunneling is required. Tunneling with a clamp and directly grasping the lead should always be avoided because of the risk of damage to the lead. Recently, venoplasty has been introduced as an alternative approach to venous access in situations of subtotal or total venous obstruction. This alternate approach is intended to avoid tunneling techniques or lead extraction as a means of gaining repeat venous access. The tools and techniques of venoplasty are described in Chapter 22. PLACEMENT OF EPICARDIAL ELECTRODES Epicardial pacemaker implantation was the earliest, and once the most common, implantation technique, but it has limited use and usefulness today, largely because of the unparalleled success of transvenous implantation. Today, epicardial implantation is reserved mainly for patients undergoing cardiac surgery. In fact, in many centers, even in

patients needing permanent pacing who are undergoing cardiac surgery, temporary epicardial electrodes are applied, with subsequent implantation of permanent transvenous pacing systems. Modern transvenous leads have largely eliminated the problems of exit block and dislodgement. These leads have proved more reliable than epicardial leads. In addition, the abdominal pacemaker location of epicardial systems may cause more discomfort than a prepectoral location. Currently, only unusual circumstances dictate an epicardial implantation, including (1) patients undergoing cardiac surgery for another indication (with the preceding caveat), (2) patients with recurrent dislodgements of transvenous systems, (3) patients with prosthetic tricuspid valves or congenital anomalies, such as tricuspid atresia, and (4) more recently, patients undergoing CRT in whom coronary sinus (CS) lead placement has been unsuccessful. There are multiple reasons for unsuccessful CS lead placement, including unsuccessful CS cannulation, poor branch anatomy location, poor lead stability, unacceptable capture thresholds, and diaphragmatic or phrenic nerve stimulation. This chapter has dealt extensively with transvenous electrode placement, but epicardial placement is treated more superficially. There are several surgical approaches for epicardial lead placement. The most common is probably the median sternotomy performed as a secondary procedure at the time of other, related cardiac surgery. In this case, both the atria and ventricles are mapped for optimal pacing thresholds and other electrophysiologic parameters. The electrodes are attached directly to the epicardium. The electrode is tunneled via the chest tube technique to a subcutaneous pocket in the upper abdomen. For epicardial electrode placement performed as a primary procedure, there are three distinct approaches: the subxiphoid approach, the left subcostal approach, and the left anterolateral thoracotomy. The first two avoid a “formal” thoracotomy. The pericardium is entered through an abdominal incision that is supradiaphragmatic. The subxiphoid approach exposes the diaphragmatic surface of the heart and mainly the right ventricle. The right ventricle can be thin, and care should be taken to avoid laceration, which can require urgent thoracotomy and, possibly, cardiopulmonary bypass. The left subcostal approach exposes more of the left ventricle. The left lateral thoracotomy favors LV electrode placement. With this approach, an incision is made in the fifth intercostal space. The incision extends from the left parasternal border to the left anterior axillary line. Care must be taken to avoid the phrenic nerve. All the epicardial pacemaker implantation techniques require general anesthesia. The median sternotomy and left lateral implantation procedures generally require chest tube placement. The epicardial procedures are performed in an operating room by a thoracic surgeon trained specifically in epicardial pacemaker implantation. Epicardial lead placement has also been accomplished by additional, minimally invasive techniques, such as the same small-incision techniques used for coronary or valve surgery. In addition, thoracoscopic and robotic surgical techniques are now more frequently attempted for LV lead placement. Also, as with the techniques used for ablation, techniques for percutaneous access to the pericardium are under development. These leads will probably be placed without general anesthesia. SECURING LEADS, CREATING POCKETS, AND CLOSURE When all electrodes are in position, it is time to establish permanent venous stasis and secure the leads. These maneuvers pertain to the transvenous approach only. In the epicardial procedures, the electrodes have already been secured directly to the heart, and no vascular structure has been entered that requires comparable attainment of venous stasis. In the case of the transvenous approach, one or more leads must be secured and the venous port of entry permanently sealed. If the cutdown approach has been used, the proximal and distal ligatures must be tied. One should take care not to injure or cut the lead when securing the ligature around the vein containing the lead. The venous



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Figure 21-54  Secured atrial and ventricular electrodes with the suture sleeves. When necessary, hemostasis is ensured at the puncture site with a loose, nonconstricting tie.

ties are merely to effect hemostasis, not to secure the lead. These ties should be gentle and as nonconstricting as possible. The securing process using the anchoring sleeves has already been described. We reiterate here that the leads should be secured and oriented in a plane that is roughly parallel to the subclavian or axillary vein to reduce the risk for subclavian crush injury. As with the ligatures around the leads, the suture sleeves should be secured snugly but not overtightened (Fig. 21-54). If the figure-of-eight or purse-string suture has been used in conjunction with the percutaneous approach, it can be tied after all leads are in position and no further venous entry is desired. Also at this time, the retained guidewire can be removed, although this is not essential. The retained guidewire can be removed later, just before wound closure; in this case, if the figure-of-eight or purse-string suture has been tied properly, there will be no back-bleeding. In any case, the guidewire should be retained until the last moment, when no further venous access is required. It should be removed only after the implanter is completely satisfied with electrode placement and there is no need for replacement or exchange. As with the venous ligatures used in the cutdown technique, the figure-of-eight or purse-string suture requires only enough tension to collapse the vein or the tissue surrounding the leads near their point of entry into the vein. It is not intended to anchor the leads. If tied too tightly, it may injure the lead or leads. Again, the retained guidewire need not be removed before the figure-of-eight stitch is tied. The retained guidewire can be removed much later, just before wound closure. Once the leads have been secured, it is time to create the pacemaker pocket if this step has not already been accomplished. Traditionally, the step is performed at the end of the procedure. The actual timing of the pocket creation, however, is at the discretion of the implanting physician. Some implanters prefer to create the pocket early in the procedure, even as the initial step in a pacemaker implantation. In this case, a rudimentary pocket is created and packed with gauze, allowing time for natural hemostasis. Toward the end of the procedure, the packing is removed, and the pocket is reinspected for hemostasis and surgically modified as necessary. The alternative approach involves creation of the pacemaker pocket after the leads have been secured.

479

There are arguments for both approaches. Proponents of early pocket creation argue that bleeding is more easily controlled with less risk of damage to leads. Proponents of late pocket creation argue that making the pocket early is “putting the cart before the horse” and that the highest priority is to establish pacing early to protect the patient. Creation of the pacemaker pocket is of lower priority. In addition, early creation of the pocket may result in embarrassment if the pocket is not used because venous access was unsuccessful. A reasonable modification of the early pocket approach avoids the risk of embarrassment if the vein on that side is not used for access. It involves percutaneous venous access with placement and maintenance of an intravenous guidewire before pocket creation, which, in turn, precedes placement of the leads using the guidewire. This approach ensures venous access before formation of the pocket and achieves the advantages of early pocket formation noted previously. Before the pacemaker pocket is created, the area is generously infiltrated with a local anesthetic agent, assuming that local anesthesia is used. If an earlier incision has been made to facilitate lead placement and securing, anesthesia is best achieved through infiltration along the edge of the incision directly into the subcutaneous tissue. The incision is carried down to the anterior surface of the pectoral fascia. The pacemaker pocket is best formed predominantly inferior and medial to the incision, although many implanters also form a small portion of the pocket superior and lateral to an incision directed from the venipuncture site in an inferolateral vector. The advantage of this approach is that the pulse generator, with leads coiled deep, can then be placed directly under the incision, making subsequent pacing procedures, such as pulse generator replacement, both easy and safe with an incision at the same site. A plane of dissection is created at the junction of the subcutaneous tissue and pectoral fascia. This is best achieved by putting the subcutaneous tissue under slight tension with some form of retraction, to better define the plane of dissection. The Senn retractor can be used initially and then is replaced by the Goulet retractor. The plane of dissection can be started with either the Metzenbaum scissors or the cutting function of electrocautery. After a plane of dissection has been established, the remainder of the pocket can be created with blunt dissection. Some argue that blunt dissection is less traumatic to the tissues. The problems with blunt dissection are the lack of adequate visualization and the lack of control with respect to tissue depth. Optimally, the pacemaker pocket should be as deep as possible, right on top of the fascia of the pectoral muscle. This arrangement offers the optimal subcutaneous tissue thickness necessary to avoid erosion. Unfortunately, with blunt dissection, this ideal plane can be lost, creating inconsistent pocket thickness with greater risk of erosion. The current pacemaker is small, limiting the amount of dissection required and the pocket size needed. The pocket can easily be created with direct visualization instead of blindly. As previously noted, the subcutaneous tissue is held under gentle tension, defining the plane of dissection. Sharp dissection with Metzenbaum scissors or the cutting function of electrocautery (or both) is then used to form the pocket. This technique is less traumatic than blunt dissection. The pocket created by precise dissection over the pectoral muscle provides optimal tissue thickness. Thus, the pocket is created under direct vision, and the plane of dissection is well controlled. The headlamp as a light source can be helpful here. There is less risk for hematoma because all bleeding is directly visualized and managed with electrocautery. Occasionally, the patient has little or no subcutaneous tissue. In this situation, a subpectoral implantation should be considered. Fortunately, with the dramatically reduced size of pacemakers and the availability of the Parsonnet pouch (see Fig. 21-5), this approach is rarely necessary.117 If required, placement of the pacemaker under the pectoral muscle represents only a slight departure from the techniques already described. The one major concern is the increased risk of bleeding and hematoma formation. However, if one understands the anatomy and performs the procedure correctly, little or no bleeding is encountered when the subpectoral space is entered, although typically an increased risk for hematoma formation is observed. In subpectoral

480

SECTION 3  Implantation Techniques

implantation, the incision has already been carried down to the surface of the pectoral muscle, and the leads secured. The pectoralis major muscle is inspected for a separation or seam between parallel muscle fibers. Metzenbaum scissors are used to open the fascia over the seam. Using the blunt ends of two Senn retractors, one can gently separate the muscle bellies and lift the pectoralis major muscle off the chest wall. The chest wall is usually identified from its yellow fatty tissue. Once the space is entered, one can insert an index finger and gently lift the pectoralis major muscle, bluntly creating a space under the muscle and on top of the pectoralis minor muscle. Occasionally, a vascular pedicle is seen, which can be moved to one side. If this pedicle is inadvertently torn, hemostasis is easily achieved with vascular staples. If one is careful to avoid tearing of the muscle and tissue, little or no bleeding is encountered. If bleeding is encountered, it is most effectively managed with electrocautery. Incisions should be made through the muscle parallel to the muscle fibers. The muscle is separated, and a plane of dissection is established on the chest wall. This pocket is best created with blunt dissection. As already described, considerable bleeding can be encountered with subpectoral implantations. This bleeding is best controlled with electrocautery. Careful visual inspection using a Goulet retractor and good lighting is important. All bleeding sources should be identified and either sutured, stapled, or electrocoagulated. Pocket drainage is rarely required. As discussed earlier, use of electrocautery has been a traditional taboo in cardiac pacing. It can cause fibrillation or burns at the myocardium-electrode interface and can reprogram or even irreparably damage the pulse generator. However, electrocautery can be extremely useful in a pacemaker procedure in both coagulation and cutting modes. It is the surest and most expeditious way to control bleeding and create the pacemaker pocket. It can be used safely, provided that one is aware of the dangers and takes a few precautions. Current electrocautery systems are extremely safe from an electrical hazard point of view. Built-in mechanisms protect against improper grounding. Three simple rules should be followed that are specific to the use of electrocautery systems in pacemaker implantation procedures. First, the use of electrocautery should be avoided when the pulse generator is in the surgical field. Second, the cautery must never touch the exposed pin of the pacemaker lead. Third, the cautery must never touch the retained guidewire if the wire is in the heart. A new electrosurgical instrument, the Plasmablade (Peak Surgical, Palo Alto, Calif), is now being used in cardiac implantable electronic device (CIED) procedures. This instrument offers the precision of a scalpel and bleeding control without the collateral tissue or lead damage. Pacemaker and defibrillator leads are very susceptible to heat buildup of conventional electrocautery, which can damage and even breech the insulation. The Plasmablade delivers pulsed plasma radiofrequency energy delivered through a highly insulated electrode. This device cuts tissues at an average temperature less than half that of conventional electrocautery, dramatically reducing thermal injury to tissue and leads by up to 75%. This is particularly important for polyurethane leads that are prone to thermal damage. This electrosurgical device is particularly useful in pulse generator changes when dissecting out leads encased in dense, encapsulating scar. Early experience with pacemaker and defibrillator leads has been successful and promising. An alternate energy source for both dissection and cauterization is the carbon dioxide (CO2) laser (e.g., Aesculite and Light scalpel). When used for surgery, this laser operates in a noncontact fashion; the tip of the laser is held close to but does not touch the target tissue. The CO2 laser is also an effective tool for hemostasis. The laser offers the benefit of improved visibility of the surgical field, reduced procedure time, precision cutting, pinpoint accuracy, and control in pocket creation. Also, patient discomfort, risk of infection, and hematoma are reduced, with improved recovery time. The use of electrocautery and laser in surgery creates varying amounts of surgical smoke. It is well known that the smoke plume is carcinogenic and can carry pathogens that can be directly inhaled.118,119 Surgical smoke has been associated with numerous risks, from airway

Box 21-8 

RISKS ASSOCIATED WITH SURGICAL SMOKE • Airway inflammation • Hypoxia and dizziness • Cough • Tearing • Nausea and vomiting • Hepatitis • Asthma • Pulmonary congestion • Chronic bronchitis • Carcinoma • Emphysema • Human immunodeficiency virus (HIV) infection

obstruction to HIV (Box 21-8). The simplest way to reduce the risk of smoke inhalation is to have the scrub assistant hold the standard suction apparatus close to the source, usually the tip of the cautery or laser pencil. Several smoke evacuator systems attach directly to the cautery pencil. Wound drainage is required in patients who manifest excessive bleeding. The term wet pocket has been used to describe this condition. This situation is being encountered more frequently with the growing use of anticoagulants. In patients taking aspirin, warfarin, or heparin, a wet pocket often occurs, and medical indications often preclude cessation of such drugs. If a patient is taking warfarin, a prothrombin time that is 1 to 1.5 times the control level is less likely to cause a problem than a value greater than 1.5 times the control level. In the latter situation, the procedure should be postponed until PT reaches a more reasonable level. Heparin and platelet antagonists appear to cause the greatest problem. Despite diligent efforts to establish hemostasis, the pockets may continue to ooze diffusely. In this circumstance, some implanters have resorted to the topical application of thrombin. The patient taking anticoagulants whose pacemaker pocket appears wet should be considered for some form of drainage. As a general rule, if reasonable hemostasis cannot be achieved, the pacemaker pocket should be drained (although drainage should not be considered an alternative to adequate attempts to attain hemostasis). This is accomplished by placing a Jackson-Pratt drain or Blake drain. A trocar connected to the drainage tubing is passed from the inferior aspect of the pacemaker pocket to a satellite exit wound remote from the pacemaker pocket. The distal end of the tubing in the pacemaker pocket is specially designed with soft rubber and multiple drainage ports. This end can be cut to the desired size to avoid excessive tubing in the pocket. After the pacemaker pocket is closed, the proximal end of the drainage tubing is connected to a closed-suction system. The Jackson-Pratt system is preferred because it has a one-way valve that allows emptying yet prevents inadvertent flushing of drained fluids back into the pocket. It is small and of little encumbrance to the patient. To avoid infection, the drainage system is removed within 24 hours. If drainage is copious, a longer period may be required. In the case of persistent bloody drainage, the wound should be reexplored and the culprit bleeding vessel ligated or cauterized. Wound irrigation is largely a matter of personal preference, with no clearly established mandate by investigations to perform it. Drainage options range from simple saline lavage to concentrated solutions of multiple antibiotics; such solutions likely are unnecessary, especially if systemic antibiotics are used (see previous discussion). In addition to irrigation of the wound, some implanters place antibiotic-soaked gauze pads in the pocket early to achieve not only antibiosis but also hemostasis through compression with the pads. Closure of the pacemaker pocket consists of initial approximation of the subcutaneous tissues and subsequent skin closure. The subcutaneous tissue can be approximated by single or multiple layers of interrupted or running sutures. The number of layers is a function of



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

the thickness of the subcutaneous tissue. The suture material used by most implanters for subcutaneous closure is an absorbable semisynthetic product that is fairly strong, usually 2-0 or 3-0. The choice of the several techniques of skin closure relates to the desired cosmetic effect and time spent. An ideal cosmetic effect can be achieved with the subcuticular suture. This is best accomplished with 4-0 semisynthetic absorbable suture material, which does not require removal. The use of interrupted sutures has the least pleasing cosmetic result, and the sutures must be removed. The resulting scar may have visible crosshatches. Many skin closures are performed with surgical staples or clips, which are cosmetically appealing and extremely fast. The only drawback to the use of staples is that they require removal in 7 to 10 days. Skin closure can also be achieved without sutures by using surgical glue. Cyanoacrylate, commonly known as SuperGlue and Crazy Glue, has been developed for closure of small surgical wounds. It is a tenacious adhesive that is very good for bonding body tissue. Several medical-grade glues (2-octyl cyanoacrylate) have been developed for sutureless surgery. These glues can be used to close the skin after pacemaker implantation or pulse generator change. Their use for the largerincision defibrillator implants is usually not recommended. This closure is waterproof and requires no dressing. It is essential that the incision be completely dry and closed, even to use the adhesive, which is for external use only. Surgical glue occasionally causes a violent inflammatory skin reaction. There is also concern that skin bacteria are sealed in and can travel to the device pocket, resulting in a pocket infection. After closure of the skin, the wound is coated with an antiseptic ointment, and a dry sterile dressing is applied. Because a pocket has been created that can fill with blood, some form of pressure dressing may be used, although it is often not easy to maintain the pressure in an ambulatory or otherwise active patient. IMMEDIATE POSTOPERATIVE CARE The intensity of monitoring after implantation varies from center to center, although there is general agreement that postoperative intensive care monitoring is not usually required. Patients who were in the intensive care unit before implantation may be transferred to a bed on a nursing unit for continuous cardiac rhythm monitoring, unless another reason exists for their intensive care. Other patients electively admitted to the hospital specifically for pacemaker implantation are also returned to a cardiac monitoring area. Basic rhythm monitoring appears sufficient. The activity level allowed the patient in the immediate postoperative period is subject to the implanter’s preference. In the early days of pacing, the patient was kept on strict bed rest with restricted activity for many days. Current lead systems with both active-fixation and passive-fixation mechanisms offer a new dimension of security. The historic dislodgement rates of almost 20% have been dramatically reduced. In most centers, the current philosophy is to have the patient active immediately or shortly after arriving in the monitoring area. The intention is early identification of patients with potential pacemaker system malfunctions. The patient with a precariously placed electrode who is kept on strict bed rest may not demonstrate malfunction, giving a false sense of security at discharge. The active patient gives a better indication whether reliable pacemaker sensing and capture are occurring. This approach is important in the patient being managed on an ambulatory basis. The practice of placing the patient’s arm on the side of implantation in a sling should be avoided. This only provides another false sense of security and can result in a “frozen shoulder.” If the pacemaker or defibrillator leads were placed so poorly that simple motion of the extremity on the side of the implant results in dislodgement and pacemaker system failure, the operator needs to be aware of this problem immediately. Hiding this potential problem with a sling is counterproductive. If the patient stays in the hospital postoperatively, noninvasive pacemaker evaluation and programming may be performed, including reevaluation of sensing and pacing thresholds as

481

well as initial activation and setup of the rate-adaptive system. If the patient will be managed as an outpatient, these functions can be carried out at the initial postoperative visit to the pacemaker clinic. The documentation of the pacemaker procedure is crucial from both a clinical and a medicolegal point of view. It is essential to have a surgical report that identifies indications; pacemaker and lead manufacturer, make, and model; details of the implantation procedure; and pacemaker-programmed settings. A clear description of the procedure, including problems encountered as well as electrical testing data, is important. Copies of the surgical report should be sent to the pacemaker clinic as well as to the referring and follow-up physicians. Further documentation includes the manufacturer’s registration forms for all pacemaker, ICD, and biventricular systems. Also, in 2005, the U.S. Centers for Medicare and Medicaid Services mandated a national registration of all primary prevention ICDs in the United States for all covered patients. It is extremely important to have multiple resources for retrieving pacemaker implantation information. Many manufacturers supply convenient stickers containing pulse generator and lead data for the patient’s chart. A postoperative chest radiograph is essential for documentation of the lead position immediately after surgery. It can be used for comparison if subsequent dislodgement is suspected. In the case of a percutaneous procedure, the chest radiograph is crucial to rule out a pneumothorax. Generally, it is useful to obtain both PA and lateral films for documentation of lead position. The postoperative radiograph should be overpenetrated. Similarly, a 12-lead electrocardiogram (ECG) with and without magnet application is essential to document initial appropriate pacemaker sensing and capture. The chest radiograph and ECG also have medicolegal value if a question arises subsequently. The timing of patient discharge is controversial, with considerable variability among institutions. The current trend is toward a more abbreviated hospital stay. For example, at the University of Oklahoma, patients are now discharged routinely the day after implantation unless there is a specific reason for prolonging the hospital stay. During the short stay, the patient ambulates within 2 hours of completion of the procedure; a chest radiography study and ECG are performed; and preliminary interrogation, threshold testing, and programming are accomplished. Even highly pacemaker-dependent patients are approached this way. No complications or morbidity after discharge that would have been averted by longer hospitalization have been observed. Some centers use postoperative days 1 and 2 for more extensive testing of the pacemaker system and the patient-pacemaker system interface. Such testing might include Holter monitoring, extensive reprogramming with particular attention to pacing and sensing thresholds, and exercise testing to adjust rate-adaptive parameters. In some centers, the pacemaker-dependent patient may be hospitalized longer. At the other end of the spectrum is a completely ambulatory approach. Patients are discharged on the same day, immediately after the pacemaker procedure, regardless of whether or not they are pacemaker dependent. This has been the approach at the El Cajon Pacemaker Center. This experience in the United States, in addition to a large series of ambulatory procedures in Europe, has been very encouraging. The El Cajon experience is now longer than 20 years and includes more than 1000 ambulatory pacemaker procedures. There have been no postoperative pacemaker deaths or pacemaker emergencies. The El Cajon experience suggests that between 70% and 75% of pacemaker procedures can be safely conducted on an ambulatory basis. Patients referred for a pacemaker procedure on an ambulatory basis likely are at no greater risk from bradyarrhythmia than before they entered the hospital, in the unlikely event the entire system were to fail postoperatively. If specific concerns exist about the pacemakerdependent patient, the hospital stay can always be extended. As previously noted, it is important that patients who undergo ambulatory procedures are active during the monitored postoperative period so that potential problems can be detected. This philosophy also applies to any patient who is considered to be at higher risk for a problem or complication.

482

SECTION 3  Implantation Techniques

The timing of initial follow-up varies according to the timing of discharge and which physician will perform follow-up of the pacing system. If the implanting physician is to discharge the patient and perform the follow-up, there should be excellent continuity of care. Parenthetically, we have a strong bias that implanting physicians must be involved substantially in both short-term and long-term follow-up of the pacemaker recipient, to enable them to understand and appreciate many important aspects of the process as related to implantation. If the discharging physician did not perform the procedure but is responsible for the follow-up, there again may be good continuity of care. Of concern is the situation in which the implanting physician discharges the patient to someone else for follow-up. In this case, ideal pacemaker follow-up may not occur. This situation is common when a patient is discharged to a nursing home, when the implanting or discharging physician must arrange some form of reliable follow-up. It is important that patients undergoing ambulatory procedures be seen the following day for an initial follow-up visit. At the other extreme are patients who have been hospitalized and evaluated intensively for days postoperatively with Holter monitoring and extensive reprogramming; these patients may not need to be seen for a week or even a month. SPECIAL CONSIDERATIONS AND SITUATIONS Use of the Jugular Vein If initial venous access is unsuccessful, jugular vein placement may be considered.95 This is less desirable than subclavian, axillary, or cephalic vein placement because of the greater risk for lead fracture and the potential for erosion. An acute bend must be created in the lead after it exits the venous structure and is brought down to the pacemaker pocket under or over the clavicle. In addition, some form of tunneling is required to bring the lead to the pacemaker pocket. If one tunnels under the clavicle, there is increased risk of vascular injury. If the lead is tunneled over the clavicle, the tissue is typically thin, with greater risk of erosion. Both the internal and the external jugular vein have been used. Generally, the right jugular approach is preferred (Fig. 21-55). For a jugular venous approach, two separate incisions are required, one above and one below the clavicle. In detailed descriptions of anatomic dissection involving the internal and external jugular veins, particular attention is paid to precise anatomic landmarks. An alternative, simple percutaneous technique is proposed that requires little attention to anatomic landmarks or dissection. Also, an initial supraclavicular

Common carotid artery Internal jugular Lesser supraclavicular fossa

Clavicle Subclavian artery Subclavian vein Clavicular Sternal head head Sternocleidomastoid muscle

Figure 21-55  Venous anatomy for right internal jugular approach.

incision is not required. This approach involves the percutaneous access of the right internal jugular vein. Once the decision is made to place the electrodes through the jugular vein, the neck must be prepared and draped accordingly in sterile fashion. To save time, this step may be performed in the initial preparation. If done in such a manner, the sterile field can be moved directly to the right supraclavicular area. If not, an effective sterile barrier can be created with the use of an iodoform-impregnated, seethrough plastic drape. Access to the internal jugular vein is best obtained with the patient in the normal anatomic position, with the head facing anteriorly. Turning the head to the left should be avoided because doing so may distort the anatomy. The carotid artery is palpated in the lower third of the neck. The internal jugular vein is lateral to the common carotid artery. The two structures are parallel and lie side by side. Standing on the right side of the patient (for a right jugular vein approach), the implanting surgeon places the left middle finger along the course of the common carotid artery. The course of the internal jugular vein is under the implanter’s index finger. In fact, the index and middle fingers are, side by side, generally analogous in size and orientation on the surface of the skin to the internal jugular vein and common carotid artery as they run side by side underneath the skin. A puncture anywhere along this course should enter the internal jugular vein. The higher the puncture is in the neck, the less the risk of pneumothorax. Some prefer to make the needle puncture roughly perpendicular to the plane of the neck rather than angled; this maneuver also helps avoid a pneumothorax. Once the vein is entered, the needle and syringe can be gently angled inferiorly for passage of the guidewire. If the carotid artery is inadvertently punctured, the needle is removed, pressure over the puncture site is maintained briefly, and a second attempt at venipuncture is made slightly lateral to the initial stick. The remainder of the lead placement technique is essentially identical to the previously described percutaneous technique. A small incision is carried laterally down the shaft of the needle to the surface of the muscle (sternocleidomastoid). If more tissue depth is required, the muscle can be split and the incision carried down to the vein. A small, Weitlaner retractor is used for retraction. A figure-of-eight or purse-string suture can be applied for hemostasis. Two leads for dual-chamber pacing can be placed using the retained-guidewire technique. After the leads have been placed, the hemostasis suture is tied, and the leads are anchored to the muscle with the anchoring sleeve. A second incision for pocket formation is made infraclavicularly. A pacemaker pocket is created with conventional techniques. The leads are then tunneled to the pocket with the techniques previously described. The tunneling technique described by Roelke et al.120 for submammary implantation of a pacemaker may also be used for transclavicular tunneling. A long, 18-gauge spinal needle can be passed from the infraclavicular incision to the supraclavicular incision. The guidewire is passed, and the sheath set is applied and tunneled to the supraclavicular incision. The rubber dilator is removed. The lead to be used is inserted in the distal end of the sheath and tied down. Once the lead is secured, the lead and sheath are pulled through the infraclavicular incision (Fig. 21-56). The external jugular vein is used less often for venous access because it is more inferiorly located, with a high risk of pneumothorax and vascular complications. Again, its location is less precise, and successful cannulation may be frustrating. If the electrodes are tunneled under the clavicle, care must be taken to avoid vascular trauma. Conversely, when tunneling over the clavicle, the implanter should make every effort to ensure optimal tissue thickness. Use of the Iliac Vein Ellestad and French121 reported a 90-patient experience using the iliac vein as an alternative source of venous access for both single-chamber and dual-chamber pacemaker implantations (Fig. 21-57). The iliac vein can be used for transvenous lead placement when an abdominal pocket is desired, as in patients with little pectoral tissue, those who have just undergone bilateral radical mastectomy, those with extensive pectoral radiation damage, and for a variety of cosmetic reasons. A



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Supra clavicular

Infra clavicular

Figure 21-56  Lead(s) tunneled over and under the clavicle to the infraclavicular pocket. (From Belott PH: Pacemaker implantation: the old and new. In Singer L, Barold SS, Camm AJ: Nonpharmaceutical therapy of arrhythmias for the 21st century. Armonk, NY, 1998, Futura, p 726.)

small incision is made just above the inguinal ligament over the vein (just medial to the palpable artery) and carried down to the fascia above the vein. The vein is punctured through the use of the sheath set technique with the guidewire retained for dual-chamber implantations. A figure-of-eight or purse-string suture is placed for hemostasis

483

through the fascia around the lead as it enters the vein. Long, 85-cm leads are positioned in a conventional manner and secured to the fascia with a tie around the suture sleeve and lead. A second horizontal incision is made lateral to the umbilicus and is carried to the surface of the rectus abdominis sheath. A pacemaker pocket is created with blunt dissection. Preparations are made to tunnel the leads from the initial incision to the pacemaker pocket through use of one of the previously described techniques.122 Active-fixation leads are recommended for both atrial and ventricular lead placement. Lead dislodgement is the major weakness of this approach, with 9 of 42 (21%) of the atrial and 5 of 67 (7%) of the ventricular leads in the Ellestad and French121 experience requiring repositioning. Lead fracture and venous thrombosis do not appear to be problems, although the published experience with this approach is relatively small, and thrombosis especially could be difficult to discern. The complication of pneumothorax essentially does not exist with this approach. Extraction of these leads can be challenging because many of the conventional tools used for extraction of leads placed in the axillary subclavian and cephalic veins are not long enough to handle these significantly longer systems. Iliac vein implantation is particularly useful when the left and right subclavian approaches are unavailable because of venous occlusion or after extraction of an infected system. This approach has been also used for ICD implantation.123 Alternative (Cosmetic) Locations for Pacemaker Pocket If the patient is greatly concerned about the negative cosmetic effects of standard pacemaker pocket location, at least two alternative techniques may be considered.124 Both can be performed with local anesthesia, but are best performed with general or modified general anesthesia for patient comfort because more extensive surgery is involved. Both procedures lend themselves well to the percutaneous approach for both single-chamber and dual-chamber pacing. In both procedures, after the subclavian vein is accessed, a limited (1.5-cm)

Pacemaker pocket

Penrose drain

Inguinal ligament Pacemaker lead Needle in femoral vein

Figure 21-57  Right iliac vein used for placement of pacemaker lead(s). Percutaneous capture of the iliac vein is performed, and the lead is tunneled up to an upper-quadrant pacemaker pocket with the use of a Penrose drain. (From Ellestad MH, French J: Iliac vein approach to permanent pacemaker implantation. Pacing Clin Electrophysiol 12:1030, 1989.)

484

SECTION 3  Implantation Techniques

Pulse generator

Pectoralis fascia

Figure 21-58  Inframammary placement of pulse generator after percutaneous lead placement for optimal cosmetic effect. A small incision is made near the clavicle, and the pocket incision is made in the hidden fold under the breast. The lead is tunneled deep to the breast, between the incisions. (From Belott PH, Bucko D: Inframammary pulse generator placement for maximizing optimal cosmetic effect. Pacing Clin Electrophysiol 6:1241, 1983.)

initial skin incision is made. The incision is carried to the surface of the pectoral muscle, allowing only enough room to secure the lead or leads. A second incision is then made. For one of the alternative pocket locations, an incision is made under the breast along the breast fold or reflection. A standard pacemaker pocket is created under the breast, with care taken to keep the incision line on the pectoral fascia (Fig. 21-58). The pocket is carefully inspected for hemostasis. Similarly, as another alternative pocket location, a second incision can be made in the axilla with the patient’s arm abducted 60 degrees. This incision can be carried to a depth that exposes the muscle fascia, where a pocket can be formed with appropriate attention to hemostasis. With either of these approaches, tunneling of leads can be carried out with the previously described techniques. As previously noted, Roelke et al.120 describe a submammary pacemaker implantation technique that uses unique tunneling. In this technique, a 1-cm horizontal incision is made over the deltopectoral groove 1 cm inferior to the clavicle. A direct subclavian-axillary puncture or cephalic cutdown for venous access is performed. The electrodes are positioned and anchored. A 2-cm to 3-cm horizontal incision is made in the medial third of the inframammary crease. The incision is carried down to the level of the pectoralis fascia, and blunt dissection is used to create a pocket superficial to the pectoralis fascia behind the breast. A 20-cm, 18-gauge pericardiocentesis needle is directed from the inframammary pocket to the infraclavicular incision. A 145-cm J wire is then passed from the submammary pocket through the needle and to the infraclavicular incision. The needle is removed and, with use of the retained-guidewire technique, two appropriate-sized introducer dilators are passed consecutively over the guidewire. The free ends of the atrial and ventricular electrodes from the infraclavicular incision are placed in the sheaths and secured with a suture (Fig. 21-59). The sheath sets are then withdrawn to the infraclavicular pocket. This innovative tunneling technique has been extremely successful and well tolerated. Shefer et al.125 describe a retropectoral transaxillary percutaneous technique for optimal cosmetic effect. This technique is performed with local anesthesia and IV sedation. Venography is used to confirm the relationship of the axillary vein to the surface anatomy. A marker is then placed in the axillary vein through the antecubital fossa (Fig. 21-60). This marker usually consists of a temporary transvenous pacing wire or a .03-inch guidewire. The skin in the ipsilateral axilla is then prepared and draped. With local anesthesia and under fluoroscopic control, a 16-gauge, thin-walled needle is inserted and guided

Figure 21-59  Subcutaneous tunneling with guidewire and sheath. (Redrawn from Roelke M, Jackson G, Hawthorne JW: Submammary pacemaker implantation: a unique tunneling technique. Pacing Clin Electrophysiol 17:1793, 1994.)

medially in a cranial and anterior direction to meet and cross the temporary pacing wire marker in the axillary vein (Fig. 21-61). The axillary vein is punctured when the tip of the needle touches and moves the marker wire. Venipuncture is confirmed by aspiration of venous blood. A .038-inch guidewire is then introduced and the needle discarded. A longitudinal incision is made along the posterior border of the pectoralis muscle in the axilla (Fig. 21-62). The pectoralis fascia is then exposed with blunt dissection and the retropectoral space opened. One or two pacing electrodes can then be placed using conventional techniques. The electrodes are secured by their suture sleeve to the pectoralis fascia. The leads are then connected to the pacemaker and inserted in the retropectoral pocket. At the completion of the operation, the temporary pacing lead and guidewire marker are

Cephalic

Axillary

Brachial

Long thoracic

Guidewire Basilic Needle Latissimus dorsi muscle

Figure 21-60  Stylized illustration of axillary venipuncture using the guidewire as a landmark.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Guidewire

485

Incision at anterior axillary line

Needle

Figure 21-61  Radiograph of needle accessing the axillary vein using the guidewire as a landmark. (From Shefer A, Lewis BS, Gang ES: The retopectoral transaxillary permanent pacemaker: Description of a technique for percutaneous implantation of an invisible device. Pacing Clin Electrophysiol 16:1646, 1996.)

removed. This technique offers excellent cosmetic results, with no restriction in physical activity or movement of the shoulder joint (Fig. 21-63). With any of these techniques, the pulse generator and leads are connected, and the incisions closed. A polyester (Dacron) Parsonnet pouch can be used to prevent rotation of the pulse generator and leads in the tissue (see Fig. 21-5). To avoid the problems of diaphragmatic stimulation, a bipolar system should be used, especially with the inframammary pocket. Transvenous Lead Placement in Infants and Children Historically, epicardial pacing has persisted substantially longer in children than in adolescents and adults, for many reasons. Much of the need

A

Figure 21-62  Incision in the anterior axillary line for optimal cosmetics. (From Shefer A, Lewis BS, Gang ES: The retropectoral transaxillary permanent pacemaker: Description of a technique for percutaneous implantation of an invisible device. Pacing Clin Electrophysiol 16:1646, 1996.)

for pacemaker implantation during infancy and childhood has occurred as a comorbidity of cardiac surgery for congenital heart disease.126 In this context, epicardial implantation at the time of surgery has been typical. Additionally, certain forms of congenital heart disease (e.g., tricuspid atresia) make transvenous pacing difficult, if not impossible. Expertise in transvenous pacing in children has also been difficult to acquire because of the relatively smaller number of patients in this age group who need pacemaker therapy.127 Also, there has been a perception that the relatively rapid growth in body size that occurs in childhood makes transvenous pacing problematic with respect to the intravascular length of leads. Also, parents and physicians have been reluctant about placement of pacemakers in the traditional prepectoral area in children,

B

Figure 21-63  Frontal (A) and lateral (B) views of patient after transaxillary retropectoral pacemaker implantation. There are no visible scars. (From Shefer A, Lewis BS, Gang ES: The retropectoral transaxillary permanent pacemaker: Description of a technique for percutaneous implantation of an invisible device. Pacing Clin Electrophysiol 16:1646, 1996.)

486

SECTION 3  Implantation Techniques

instead preferring abdominal implantation of pulse generators. Lastly, the lead diameters for transvenous pacemaker system implantation and pulse generator sizes are believed to be too large for conventional techniques of transvenous implantation in children. Conversely, as problems with epicardial pacemaker implantation have been more clearly elucidated, especially epicardial lead fracture and epicardial exit block, transvenous approaches have been appropriately reconsidered.128 An encouraging trend in this regard is the evolution of transvenous pacemaker implantation expertise by pediatric cardiologists, or in concert with pacemaker implantation experts. More sophisticated lead placement techniques, coupled with smallerdiameter leads and smaller pulse generators, have also encouraged this relatively recent trend toward transvenous implantation in the pediatric age group.129 New technologies in electrodes that help prevent exit block have also supported the trend toward transvenous systems. Also, the clear capacity to implant transvenous pacing systems successfully in patients in a variety of pediatric age groups with a range of congenital cardiac problems has been a crucial factor. With all these considerations, especially with anticipated future developments in pacing technology, transvenous pacing will become progressively dominant in children as it has in adolescents and adults. The relative infrequency of pacemaker implantation in children compared with adults makes acquisition of pediatric expertise in implantation difficult. Although consulting experts in pediatric implantation seems ideal, the level of regionalization necessary might be unrealistic. A team approach is a reasonable alternative, pairing an expert in pacemaker implantation (adult cardiologist or cardiac surgeon) with an invasive pediatric cardiologist or pediatric electrophysiologist. Although this type of redundancy in physician services is generally inefficient and is not often well compensated by third-party payers, it may be the most attractive of a variety of options. Pediatric pacemaker implantation can be carried out with local anesthesia and relatively substantial IV sedation and pain control without the services of an anesthesiologist. Conversely, although uncommon in children, excessive sedation must be monitored closely by an experienced clinician. It is appropriate to consider general anesthesia for pediatric pacemaker implantation, which is the safest approach in many patients.130 For transvenous pacemaker implantation in children, the techniques of venous access are precisely those described for adults. Smaller venipuncture needles and guidewires are available, although they typically are not necessary, except perhaps in infants. An important consideration in children is blood loss. Generally, the younger and smaller the patient, the greater is the impact of blood loss. Special attention to this issue is warranted in young patients, unlike in their older counterparts. In choice of pacemaker leads for pediatric implantation, the five most important considerations are bipolar or unipolar leads, the lead diameters, the fixation mechanisms (active vs. passive), the higher incidence of exit block in children, and lead length. Bipolar leads and the resulting bipolar (and optional unipolar) pacing systems have distinct advantages, but in small infants or when maximal lead flexibility is necessary, unipolar leads and pacing systems may be appropriately chosen. Most children beyond infancy tolerate not only the thicker bipolar systems but also dual-chamber bipolar systems. As lead (and pulse generator) technology moves toward smaller diameters, bipolar dual-chamber systems may be more comfortably used in even smaller patients. The fixation mechanism is another important consideration. The advantages of the types of fixation are much the same as those previously discussed. The flexibility for placement of leads in a variety of locations using active-fixation leads is attractive. It is also an unproved hypothesis that active-fixation leads may be less likely to become dislodged than their passive counterparts in a population of patients not able to understand the importance of temporary immobilization of the shoulder and arm after implantation. In contrast, electrode technologies such as that of steroid elution have proved useful in reducing the problem of exit block, which occurs in substantially greater frequency in children. This steroid elution technology has been combined more effectively with passive-fixation leads.

Lead length is a crucial issue in children. Excessive lead that must be coiled in the pacemaker pocket beneath the pulse generator creates formidable bulk in these small patients. Leads of various lengths should be available and the choices for a specific patient carefully made. In this regard, one should remember that these patients will grow significantly, so an adequate extra length of lead to accommodate this growth is desirable. One of the advantages in unipolar lead technology is that leads can be shortened or lengthened with splicing techniques, although this is certainly an imperfect solution to this vexing problem. Once the leads have been positioned, the implanter may secure them (if such a procedure is desired) in the manner previously described using the anchoring sleeve. Alternatively, one may use an absorbable suture material for securing the leads with the anchoring sleeve. This latter approach has the advantage of good security of the lead while the electrode-myocardium interface is unstable and dislodgement is most likely. It also provides for eventual elimination of the fixation to the pectoral fascia and muscle by dissolution of the suture material, facilitating movement of the lead through the anchoring sleeve and into the vein as growth occurs. Another alternative is to use activefixation leads and avoid the anchoring sleeve completely. The formation of the pediatric pacemaker pocket follows the same guidelines outlined previously for adults. There has been greater enthusiasm for subpectoral implantation of pacemakers in children, although as pulse generators decrease in size, this trend may wane. Certain unusual situations, especially those related to congenital anomalies and their surgical correction, are particularly challenging. One example involves the need to pace the left ventricle, left atrium, or both in patients who have undergone a Mustard-type baffle procedure for transposition of the great arteries. Another example is successful transvenous pacing in patients with tricuspid atresia. This can be accomplished with passage of a transvenous lead through the right atrium into the coronary sinus and, respectively, into one of the posterior ventricular veins, such as the middle cardiac vein. A caveat relates to the higher risk of diaphragmatic pacing, especially if a unipolar system is employed. In children with congenital heart disease, intracardiac shunting creates special concern about the risks of systemic embolization related to placement of endocardial pacing systems. Normally, placement of endocardial systems should not be the procedure of choice in these patients before the shunts are surgically corrected. Although a question often arises about the minimum age or size considered acceptable for transvenous pacing, the answer is not easily provided. At the University of Oklahoma and many other medical centers, transvenous implantation is considered appropriate for infants weighing 10 pounds (4.5 kg) or more, although as leads and pulse generators become progressively smaller, this minimum size likely will also decrease. Alternatives to Radiography During Implantation The use of radiography may be problematic in certain situations, such as during pregnancy. The prospect of implanting a pacemaker in a pregnant patient becomes particularly challenging. Guldal et al.130 have described an implantation technique for single-chamber (ventricular) pacemakers using two-dimensional echocardiography and intracardiac ECG. The technique involves subcostal visualization of the structures of the right side of the heart and the lead with two-dimensional echocardiography. The electrode position is verified by recording an intracardiac electrogram (EGM), and adequate capture is ensured by intermittent pacing. More recently, Lau et al.131 used ultrasound to position an electrode in a patient with severe pulmonary tuberculosis. In this patient, collapse of the right side of the chest caused deviation of the heart to the right, making fluoroscopic visualization impossible. A passive-fixation lead was introduced by means of a left cephalic cutdown and was passed with fluoroscopic visualization to a poorly defined cardiopulmonary shadow in the right side of the chest. The lead could then apparently no longer be visualized adequately on fluoroscopy. Two-dimensional echocardiography identified the lead in



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

487

relation to the anatomy and assisted in its final placement. Lead placement was verified by the EGM. Repositioning of Electrodes Repositioning of a malpositioned or dislodged permanent pacemaker electrode traditionally requires a surgical procedure—the pacemaker pocket must be surgically reopened, and the pacemaker and leads freed of adhesions and disconnected. Morris et al.132 describe a nonsurgical approach that uses principles similar to those of lead extraction through the femoral vein. The malpositioned lead is hooked and pulled into the inferior vena cava with the use of a 3-mm J-shaped deflecting wire passed through a catheter placed in the femoral vein. This is accomplished by forming a closed loop in the deflecting wire and “capturing” the lead tip with the loop. The lead tip in the IVC is snared by a loop formed with a 300-cm 0.021-inch exchange wire. The loop is passed through an 8F catheter with a 2-cm radius curve steamed into its tip. The snared lead tip is then repositioned in the RV apex. Iatrogenic repeated dislodgment is avoided by release of the snare, which is accomplished by advancing one end of the .0210-inch guidewire, forming a large loop, while retracting the other end of the wire from the catheter. Alternatives to Transvenous Lead Placement Transvenous endocardial lead placement is occasionally contraindicated, impractical, or impossible. Westerman and Van Devanter133 describe a transthoracic technique requiring general anesthesia and a limited thoracotomy for electrode placement. The electrodes are passed and positioned transatrially through the sixth intercostal space (Fig. 21-64). The right atrium is identified, and the electrode is passed

Figure 21-64  Transatrial endocardial lead placement during thoracotomy allows low-threshold transvenous leads to be implanted at thoracic surgery. (From Barold SS, Mugica J: New perspectives in cardiac pacing. Mt Kisco, NY, 1988, Futura, p 271.)

Figure 21-65  Transatrial endocardial atrial pacing in congenital heart disease. The ventricular leads were epicardial because the patient also needed a prosthetic tricuspid valve. (From Hayes DL, Vliestra RE, Puga FJ, et al: A novel approach to atrial endocardial pacing. Pacing Clin Electrophysiol 12:125, 1989.)

transatrially through an incision or by using a sheath set. Hemostasis is ensured with a purse-string suture around the entry site. Fluoroscopy can be used for the ventricular placement of a tined or screw-in electrode. All the electrodes are secured to the endocardial surface. A tined electrode can be directly secured to the atrial endocardium. Double-ended sutures are tied around the leads under the tines of the electrode. Before introduction of the lead, the needles are driven through the atriotomy into the atrial cavity and then out of the atrial muscle at the point of desired endocardial atrial fixation. The electrode is then pulled through the incision into the atrium and “snugged” to the endocardium by retraction and tying of the double-ended suture. In many situations, this approach may have more merit than the epicardial approach, because better long-term electric thresholds are typically achieved. This technique may be useful for some pediatric implantations. Hayes et al.134 described a similar technique of endocardial atrial electrode placement at corrective cardiac surgery (Fig. 21-65), avoiding atrial epicardial pacing because of poor pacing and sensing thresholds. The patient had severe tricuspid regurgitation and a dual-chamber pacemaker and long-term endocardial electrodes. All four previously implanted endocardial leads and placement of a prosthetic tricuspid valve were required. New epicardial electrodes were placed on the ventricle. Stable atrial pacing and sensing were achieved with a transatrial endocardial placement in the RA appendage. In this case, the lead was secured by purse-string ligatures around the incision. Byrd and Schwartz135 described another epicardial approach based on experience in five patients. The technique also allows conventional transvenous leads to be implanted in patients requiring an epicardial approach, including those with SVC syndrome or anomalous venous drainage, as well as young patients with one innominate vein occluded by thrombosis. The technique uses a limited surgical approach with general anesthesia. The RA appendage is exposed through a 4-cm to 5-cm incision. The third and fourth costal cartilages are excised. A

488

SECTION 3  Implantation Techniques

Left superior vena cava Coronary sinus

Figure 21-66  Endocardial lead placement by means of limited thoracotomy with removal of only the third and fourth costal cartilages. Standard fluoroscopy and peel-away introducer techniques are used with transatrial access. (From Byrd CL, Schwartz SJ, Siviona M, et al: Technique for the surgical extraction of permanent pacing leads and electrodes. J Thorac Cardiovasc Surg 89:142, 1985.)

sheath set is placed inside an atrial purse-string suture and secured in a vertical position. The atrial and ventricular leads are passed down the sheath into the atrium (Fig. 21-66). The electrodes are positioned with the use of standard techniques, including fluoroscopy. Once the electrodes are positioned, the sheath is removed, and the purse-string suture around the atriotomy is secured. The pacemaker is placed in a pocket created at the incision on the anterior chest wall. The advantage of this technique for patients in whom conventional transvenous systems are contraindicated or impossible is that it provides for implantation of a more conventional transvenous pacing system with minimal morbidity compared with a standard epicardial implantation. The chest is not entered (except for the atrium), and the time required is similar to that for transvenous implantation. The disadvantages (although not necessarily in relation to other nonstandard transvenous techniques) include the requirement for general anesthesia, violation of the pericardia and epicardia, and the necessity of a right-sided approach (which may not be possible because of prior infection, mastectomy, and so on). Occasionally, one encounters an anomalous venous structure, such as a persistent left superior vena cava (SVC). Embryologically, the normal left SVC becomes atretic. However, a 0.5% incidence of structural persistence of patency is associated with the coronary sinus (CS). Persistence of the left SVC usually represents failure in the development of the left innominate vein. This vein normally forms from communication of the right and left anterior cardinal veins. In this situation, the left anterior cardinal vein persists and continues to drain to the brachiocephalic veins and sinus venosus. It ultimately develops into a left SVC, which empties directly into the CS (Fig. 21-67). Normally, the left innominate vein develops as an anastomosis between the left and right anterior cardinal veins. Occasionally, with persistent left SVC, there is an associated atresia and incomplete absence of the right SVC system (Fig. 21-68). In 10% to 15% of patients, one encounters total absence of the right SVC. In this situation, venous access for pacing from the right is virtually impossible. Despite reported classic physical and radiographic findings for absence of the right SVC, the diagnosis is typically discovered unexpectedly at pacemaker or ICD implantation.

Figure 21-67  Persistent left superior vena cava.

Placement of electrodes through a persistent left SVC can prove challenging, if not impossible.136-141 A knowledge of anatomy and radiographic orientation is essential. If one proceeds from the left and is confronted with a persistent left SVC, one must realize that the lead or leads actually are passed through the CS and out its ostium into the right atrium. For RV apex lead positions to be achieved, the lead must then be manipulated at an acute angle to cross the tricuspid valve. One can best accomplish this by having the lead form a loop on itself, using

Figure 21-68  Persistent left superior vena cava with absence of the right superior vena cava.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

489

Figure 21-69  Placement of atrial and ventricular electrodes through persistent left superior vena cava in a patient with absence of the right superior vena cava. (From Belott PH: Unusual access sites for permanent cardiac pacing. In Barold SS, Mugica J: Recent advances in cardiac pacing for the 21st century. Armonk, NY, 1998, Futura.)

epicardial approach was also less desirable because of the multiple surgical procedures already performed. The authors selected a retroperitoneal approach through a transvenous right-flank incision. The IVC was infiltrated and cannulated retroperitoneally (Fig. 21-70). Bipolar active-fixation screw-in electrodes were used in both the atrium and the ventricle. The venous insertion site was secured and hemostasis effected by purse-string sutures. The pulse generator was implanted in a subcutaneous pocket formed in the anterior abdominal wall. Similarly, pacemaker leads have been placed through transhepatic cannulation. Fischberger et al.146 describe percutaneous transhepatic cannulation using fluoroscopic guidance (Fig. 21-71). Once venous access has been achieved percutaneously with the guidewire inserted transhepatically, a sheath set is applied, affording the subsequent introduction of a permanent pacemaker electrode. This procedure, which has been reserved for use in complex congenital anomalies that preclude venous access through a superior vein, avoids a thoracotomy. The coronary sinus has been used for pacing both by design and by accident (Fig. 21-72). At present, the evolution of cardiac resynchronization therapy has placed the CS center stage (see Chapter 22). In the past, the CS has been unreliable for ventricular pacing and generally avoided, although posterior and lateral cardiac veins and sometimes the middle cardiac vein are used more often now to achieve LV pacing. The main CS can be an acceptable location for atrial pacing.147,148 The problems with CS atrial pacing have been access and lead stability. Before the development of reliable atrial electrodes, the CS was a popular site of lead placement for atrial pacing. The best place for atrial pacing is the proximal CS, but this is also the least stable location. Special CS leads have been developed to enhance position stability. These leads have a flexible, elongated tip that reaches deep into the CS, wedging in the great cardiac vein for stability. Gaining access to the CS requires experience (unless one is trying to avoid it, in which case it seems to be routinely entered). With more implanting

the lateral RA wall for support (Fig. 21-69). This maneuver can prove extremely challenging. Occasionally, depending on anatomy, such efforts prove unsuccessful, and one must consider changing the site of venous access. At this point, it is prudent to assess the patency of the right venous system with contrast administration and angiographic techniques.142 This can be done by advancing a standard end-hole catheter from the left SVC to the vicinity of the right SVC. Occasionally, such communication does not exist. If the right SVC is absent, the iliac vein approach, as previously described by Ellestad and French,121 or one of the epicardial approaches is recommended. In the case of persistent left SVC in which an atrial electrode is required, a positive-fixation screw-in electrode is recommended.143,144 The use of a preformed atrial J wire will prove difficult if not impossible. Dislodgement of the preformed J is also a concern. When using a positive-fixation electrode, one should take care to avoid pacing of the right phrenic nerve. This can be accomplished by high-output pacing after fixation. As a rule, the anterior RA position is preferred. Discovery of absence of the right SVC during a right-sided approach may also require changing approach sites. In this case, if an attempt is to be made from the right, the expected venous tortuosity of the persistent left SVC should alert one to request longer electrodes. At times, an 85-cm lead is required. Again, it is advisable to use positive-fixation leads in anticipation of dislodgement problems. Permanent pacemakers have also been implanted through the inferior vena cava using a retroperitoneal approach. West et al.145 described a 48-year-old man with congenital heart disease who had undergone multiple procedures (e.g., palliative Blalock shunt, Glenn) to correct transposition of the great vessels, with a functional single ventricle and subvalvular pulmonic stenosis. At age 47, the patient demonstrated a complete atrioventricular block. Given the complex congenital anomalies and subsequent corrective procedures, venous access to the right atrium and ventricle was complicated by loss of continuity between the RA and SVC, precluding a standard transvenous access. An

Figure 21-70  Posteroanterior abdominal radiograph showing the position of the pacemaker and generator lead inserted into the inferior vena cava. (From West JNW, Shearmann CP, Gammange MD: Permanent pacemaker positioning via the inferior vena cava in a case of a single ventricle with loss of right atrial to vena cava continuity. Pacing Clin Electrophysiol 16:1753, 1993.)

490

SECTION 3  Implantation Techniques

Placement of a CS lead is generally easier from the left side. A generous curve is required on the lead stylet. CS placement is confirmed by visualization of a posterior lead position on lateral fluoroscopy. In addition, lead placement is not associated with ventricular ectopy. Although once a popular approach to atrial pacing, use of the CS is uncommon today. This change is largely the result of the development of extremely reliable atrial leads equipped with fixation devices and tips that preclude dislodgement and ensure effective capture. Misplacement of Lead in Left Ventricle A final cautionary note on lead placement involves the risk of inadvertently placing a permanent ventricular pacing lead in the left ventricle rather than the right ventricle (Fig. 21-73, A). This can occur if the lead is passed from the right atrium through a patent foramen ovale into the left atrium and is then advanced into the left ventricle across the mitral valve. The radiographic appearance can be deceptive in an anteroposterior projection. A lateral radiographic projection (Fig. 21-73, B) and an ECG showing a right bundle branch block (RBBB) QRS pattern during ventricular pacing (Fig. 21-73, C) can usually clarify this occurrence. Computed tomography scans can also identify the mislocation of the lead on the left side of the heart (Fig. 21-73, D). If the mislocation is promptly detected, repositioning within 24 hours is the reasonable course of action. If the detection delay is longer, longterm anticoagulation without repositioning of the lead is advisable.

Implantation of Implantable Cardioverter-Defibrillators Figure 21-71  Lateral fluoroscopic view demonstrating transhepatic lead implantation.

electrophysiologists routinely using the CS for diagnostic studies, this experience becomes moot. In addition, as more implantations are performed in the catheterization laboratory, which is equipped with sophisticated radiographic equipment including biplane fluoroscopy, the required beneficial fluoroscopic projections for placement are easily achieved.149

A

A variety of ICD implantation techniques have been developed employing both epicardial and transvenous approaches. Initially, all ICD systems were placed using an epicardial approach for placement of rate-sensing and pacing leads as well as defibrillation patch electrodes. The large size of the ICD pulse generator required an abdominal pocket. With the development of the transvenous pacing and defibrillating electrodes and active can defibrillator systems, there has been a shift to a nonthoracotomy approach. The radical reduction in the size of ICD devices has allowed their placement in pectoral pockets. At present, the overwhelming majority of ICD systems are placed using

B

Figure 21-72  A, Posteroanterior radiograph of a patient with a permanent, coronary sinus pacemaker electrode. The lead tip is superior and to the left side across the midline. B, Lateral film shows that the coronary sinus and the lead curve posteriorly and superiorly, precluding right ventricular placement.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

a nonthoracotomy transvenous approach and in a subcutaneous or subpectoral pocket.150-153 The epicardial approach is reserved for unique and extenuating circumstances. Many more ICD procedures are now performed in the electrophysiology or catheterization laboratory with intravenous sedation.7,154 The various ICD epicardial and nonthoracotomy implantation techniques are reviewed here, along with the equipment, personnel, and preparation for safe and expeditious ICD implantation. PERSONNEL AND EQUIPMENT The personnel required for insertion of an ICD are similar to those needed for pacemaker implantation. The primary surgeon may be an electrophysiologist, a cardiologist, or a cardiothoracic surgeon. If an epicardial approach is employed, the cardiothoracic surgeon is mandatory, but the skills usually obtained during an EP fellowship are needed to evaluate defibrillation efficacy and choose the programmed parameters.155,156 Although the practice is controversial, the ICD manufacturer’s representative can be an important member of the implantation team and can prove to be invaluable for providing leads, defibrillators, and support equipment. The earlier ICD implantations that were limited to epicardial placement required a minimum of two trained physicians, an electrophysiologist and a cardiothoracic surgeon. With the transition to the nonthoracotomy approach, a device specialist (electrophysiologist, cardiologist, or cardiothoracic surgeon) working with the ICD manufacturer’s representative may be all that is required. If general anesthesia is to be used, a nurse-anesthetist or anesthesiologist is also needed.157 Box 21-9 outlines the preferred members of an ICD implantation team.158 Each member of the ICD implantation team should be completely familiar with the unique requirements of an ICD implantation, including a protocol for patient rescue. The circulating nurse should be

A

491

Box 21-9 

PERSONNEL REQUIRED FOR ICD IMPLANTATION AND TESTING Implanting physician (cardiothoracic surgeon, electrophysiologist) Anesthesiologist Electrophysiologist Technical support personnel: Engineer Technician Electrophysiology nurse Device manufacturer’s representative

responsible for operating the external defibrillator for rescue, as directed by an electrophysiologist or implanting physician. Similarly, the manufacturer’s representative should be responsible not only for equipment and supplies but also for threshold testing, programming, arrhythmia induction, and even rescue; this person functions under the guidance of the implanting physician or electrophysiologist. As the ICD implantation procedure becomes less electrophysiologically complex, more nonelectrophysiologists want to implant ICDs. The technique for ICD implantation, now almost exclusively transvenous, has become similar to that for a permanent pacemaker implantation. The Heart Rhythm Society has published formal guidelines for documenting skills and obtaining privileges for the insertion of implantable defibrillators and cardiac resynchronization therapy (CRT) devices.159 These guidelines, published as a clinical competency statement and endorsed by the American College of Cardiology, set forth an alternative pathway for physicians not trained during an EP fellowship to document their ICD and CRT device implantation skills. The stringent curriculum requirements are (1) documentation of

B

Figure 21-73  A, Anteroposterior chest radiograph with the ventricular electrode placed in the lateral wall of the left ventricle. This view can be very deceiving. At first glance, the electrode appears to be appropriately placed in the apex of the right ventricle. The high takeoff across the tricuspid valve is a clue that the lead is in reality crossing a patent foramen ovale. B, Lateral radiographic projection of the same patient clearly demonstrates the posterior placement of the ventricular electrode. Continued

492

SECTION 3  Implantation Techniques

I

aVR

II

aVL

III

aVP

V1

V4

V2

V5

V3

V6

II

C

RV

RA

LV

D Figure 21-73, cont’d  C, Twelve-lead electrocardiogram of the same patient. Note the prominent right bundle branch block pattern in the precordial leads. D, Computed tomography (CT) scan of the same patient; LV, left ventricle; RV, right ventricle; RA, right atrium.

current pacemaker implantation experience, (2) proctored ICD implantation experience, (3) completion of a formal didactic course, and (4) passing a formal examination such as the International Board of Heart Rhythm Examiners (IBHRE) examination. Monitoring of patient outcomes and complications and maintenance of competence are also recommended. The two parts to ICD implantation are (1) the implantation of a lead and device and (2) the intraoperative EP measurements, including not only pace and sense threshold determinations, but also arrhythmia induction, defibrillation threshold (DFT) determination, patient rescue, and defibrillator programming. The second part of ICD implantation

can best be performed by a trained electrophysiologist; in any case, one should be immediately available. Although the initial ICD implantations took place solely in the operating room with the patient under general anesthesia, ICD implantation now may be performed either in the cardiac catheterization laboratory or the OR. The choice of the implantation facility is subject to operator preference, hospital policy, and economics. The safety and efficacy of ICD implantation in the CCL have been well established.160-164 In many institutions, the ICD implantation may take place in either venue and with IV sedation. The concerns about infection appear to be unfounded, even with complex tunneling and



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

493

Box 21-10 

EQUIPMENT AND SUPPLIES FOR ICD IMPLANTATION Alternating current (AC) fibrillator box Lead adapter sleeves and caps External defibrillator Large Parsonnet (Dacron) pouches (1.5 × 6 inches) Guidewires Imaging contrast material Introducers (long and short lengths, 9F-12F and 14F) Jackson-Pratt drainage system Multiple stylets Multiple torque wrenches Tunneling tool with multiple lead adapters Transvenous rate sensing lead Subcutaneous patches Y adapters Subcutaneous array Extra transvenous rate-sensing leads Lead extensions Lead repair kit

abdominal ICD placement. As previously stated, it is well accepted that the OR offers a strict sterile environment and unlimited surgical supplies as well as ease of emergency thoracotomy, but these advantages do not preclude performance of the procedure in the CCL, where imaging and support equipment are optimal. The CCL also seems to offer a less expensive procedure with lower hospital charges.165,166 The basic required equipment for nonthoracotomy ICD insertion is identical to that for permanent pacemaker insertion. Additional considerations are arterial blood pressure monitoring and equipment and supplies unique to the ICD, such as high-voltage cables, programmable stimulator, external defibrillator with sterile external and internal paddles, alternating current (AC) fibrillator, sterile programming wand for ICD communication, an external programmer, and the tunneling tools unique to ICD implantation167,168 (Box 21-10). As for the pacemaker implantation procedure, one cannot have too many supplies and spare parts for ICD implantation. GENERAL CONSIDERATIONS

Figure 21-74  Epicardial cup and helical spring electrodes.

The epicardial approaches that were used for cardiac pacing have been employed for ICD implantation. In addition to those approaches previously mentioned, the median sternotomy166-178 has become the approach of choice for combined open-heart surgery and ICD implantation.179,180 The common approaches for epicardial ICD implantation are the subxiphoid approach, subcostal approach, left lateral thoracotomy, and sternotomy. Historically, the first clinical ICD implants used an epicardial cup electrode on the ventricular apex in conjunction with a helical spring electrode in the superior vena cava181 (Fig. 21-74). High DFTs from this system ultimately led to the preference of two epicardial patch electrodes.182 The epicardial patches were manufactured in a variety of sizes and shapes and vary among manufacturers (Fig. 21-75). Pacing and sensing function was achieved by placing of two sutureless screw-in electrodes side by side (Fig. 21-76). Because epicardial pacing and sensing electrodes have less optimal long-term performance characteristics, the rate-sensing and pacing electrodes may be placed transvenously using standard techniques. These leads are then tunneled to the device pocket using the standard tunneling technique previously outlined. Epicardial lead and patch placement has historically involved an abdominal pocket because of the larger sizes of the devices. Abdominal pockets could be achieved by creation of a subcutaneous pocket or, if optimal comfort and cosmetics were desired, placement under the rectus abdominis muscle.

General considerations for ICD implantation are largely identical to those for permanent pacemaker implantation, although some subtle differences exist. Although not mandatory, many centers require intraarterial blood pressure monitoring for ICD insertion. In addition, appropriate device selection and choice of anesthesia must be determined. Because of the drastically reduced ICD size and required surgery, as well as protocols for more expeditious device testing, the procedures are now even performed on an outpatient basis. The choice of anesthesia is related to operator preference or, in some cases, hospital protocol.169-171 As previously mentioned, the procedure may be performed with either general anesthesia or IV sedation. In a patient in whom multiple DFT determinations as well as subpectoral dissection are required, general anesthesia might be a better selection.172 General anesthesia offers optimal patient comfort and airway control. At many centers where subcutaneous prepectoral muscle ICD implantation is performed, IV sedation with local anesthesia for periods of ventricular fibrillation arrhythmia induction is used, and the patient receives brief periods of deeper sedation with a short-acting medication such as midazolam, methohexital, propofol, or fentanyl.173-175 APPROACHES TO IMPLANTATION Epicardial Approach The epicardial approach was the initial means for implanting an ICD. Currently, it is merely of historical interest and has been abandoned and replaced by transvenous techniques.

Figure 21-75  Electrodes for automatic ICD. Left to right, Endocardial bipolar rate-sensing lead, superior vena cava shocking coil, large epicardial patch lead, small epicardial patch lead, and epicardial screw-in rate-sensing electrodes. (Courtesy Guidant, Boston Scientific, Natick, Mass.)

494

SECTION 3  Implantation Techniques

Figure 21-76  Leads and electrodes for ICD. Left, Epicardial screw-in, rate-sensing electrode. Center, Rectangular epicardial patch electrode. Right, Transvenous rate-sensing electrode. (Courtesy Guidant, Boston Scientific, Natick, Mass.)

Median Sternotomy Approach.  The median sternotomy is preferred by most cardiothoracic surgeons because it provides optimal exposure and access to the entire heart. It is generally used in patients undergoing an open-heart procedure who also require ICD implantation (Fig. 21-77). The median sternotomy results in less pain and optimal exposure.176 Left Anterolateral Thoracotomy Approach.  The left thoracotomy approach, as with the median sternotomy, is attractive because it allows for excellent exposure of the heart and, more specifically, the left ventricle (Fig. 21-78). The left lateral thoracotomy is ideal for epicardial placement of a left ventricular (LV) lead for cardiac CRT. This is

Figure 21-78  Left lateral thoracotomy with epicardial rate-sensing and patch electrodes tunneled to subcutaneous pocket in the left upper quadrant.

generally reserved for cases in which coronary sinus lead placement has failed or is unacceptable. In some centers, it has been used as a primary approach to CRT. The left lateral thoracotomy exposes the posterolateral LV aspect and, as such, is ideal for resynchronization. Subxiphoid Approach.  The subxiphoid approach was used for patients undergoing an isolated ICD implantation. This approach offers decreased morbidity and discomfort compared with the median sternotomy and thoracotomy183-185 (Fig. 21-79). Left Subcostal Approach.  The left subcostal approach was originally developed for placement of epicardial pacing and sensing electrodes186-188

Rectus abdominis muscle

Figure 21-77  Median sternotomy with epicardial rate-sensing and patch electrodes tunneled to an implantable cardioverter-defibrillator pocket in the left upper quadrant.

Figure 21-79  Subxiphoid epicardial approach with rate-sensing and patch electrodes tunneled to a subrectus abdominis muscle pocket in the left upper quadrant.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

495

thoracotomy and sternotomy, it carries the lowest morbidity of all the epicardial approaches.195 This approach is also being used for the placement of LV leads. Robotic techniques are also being developed for epicardial lead placement.196 Endocardial Approach

Figure 21-80  Left subcostal epicardial approach with rate-sensing and patch electrodes tunneled to subcutaneous pocket in the left infracostal space.

(Fig. 21-80). This approach can be used in patients who have had prior cardiac surgery.189,190 In essence, the subcostal approach improves exposure over the subxiphoid approach while minimizing pulmonary complications and problems. A transdiaphragmatic approach has been described that offers the same advantages and disadvantages as the subcostal approach.191,192 Thoracoscopic Approach.  ICD patches can be placed by means of a thoracoscope193,194 (Fig. 21-81). Because this approach avoids

Portal for grasping forceps

The endocardial, or nonthoracotomy, approach was initially described in 1987 when the ENDOTAK (Guidant, Boston Scientific, Natick, Mass.) was introduced197,198 (Fig. 21-82). Unfortunately, the early experience was associated with a high incidence of lead fractures, which slowed its initial acceptance.199 Most manufacturers now offer an endocardial pacing and shocking electrode, and the endocardial approach has become the technique of choice. Initially, the endocardial and transvenous electrode system required a subcutaneous patch to achieve effective acceptable DFTs.200,201 With the development of new electrical defibrillation waveforms and lead configurations, electrically active can systems, and efficient energy delivery systems, the transvenous approach is now the main technique for ICD implantation.202 The transvenous lead systems vary in configuration from manufacturer to manufacturer, but venous access is identical, and lead positioning nearly identical, to the techniques previously described for the ventricular pacing electrode. Because of concerns about the subclavian crush syndrome, cephalic cutdown or percutaneous access to the axillary vein is recommended.203,204 If more than one electrode will be inserted, a simple venous puncture is made using the retainedguidewire technique, or two separate punctures can be used. Left-sided venous access is preferred. As with pacemaker systems, the left-sided venous access offers a more direct and facile approach to the right ventricular (RV) apex. If a two-coil system is used, the proximal coil is more easily and effectively positioned against the lateral right atrial (RA) wall or in the left innominate or subclavian vein from the left subclavian venous approach. Also, DRTs appear to be higher for an active (“hot”) can when a right-sided approach is used.205-207 The techniques for endocardial placement of defibrillator electrodes are identical to those for pacing. An RV apex position is desired, which can frequently be facilitated with a right anterior oblique fluoroscopic projection. Once positioned, the leads are secured to the pectoralis muscle with the suture sleeve. Because the early nonthoracotomy lead systems were frequently tunneled to an abdominal pocket, the tiedown sleeves were often used to reduce strain by being fashioned into an S shape just proximal to the venous entry site. This provided slack to prevent dislodgement during manipulation of the pulse generator. A complete loop should be avoided because this tends to form pressure points that may lead to erosion. The need for a strain-reducing S configuration has been lessened by the use of pectoral pockets and smaller generators.

Portal with thoracoscope Incision for insertion of patches and electrodes Figure 21-81  Thoracoscopic epicardial rate-sensing and patch electrode placement. Electrodes tunneled subcutaneously to ICD pocket in the left upper quadrant.

Figure 21-82  ENDOTAK transvenous endocardial pace and shock electrode. (Courtesy Guidant, Boston Scientific, Natick, Mass.)

496

TABLE

21-6 

SECTION 3  Implantation Techniques

Subcutaneous vs. Submuscular Pocket for ICDs

Site Subcutaneous

Submuscular

Advantages Limited surgery Better control of bleeding Better analgesia Easier pulse generator change Optimal cosmetics

Disadvantages Less cosmetic Greater risk of erosion Higher risk of dislodgement from twiddler’s syndrome Increased problems with hemostasis Greater postoperative pain

Less twiddling and dislodgement Greater patient acceptance

Potential lateral migration to axilla

POCKET CREATION Initially, ICD pockets were created almost exclusively in the left upper quadrant of the abdomen. The reasons were the predominance of the epicardial approach and the rather generous size of the device. With the advent of the nonthoracotomy approach, the ICD pocket is almost exclusively placed in the left pectoral area. Most abdominal pockets are subcutaneous, but if excellent cosmetics and comfort are desired, an intra–rectus abdominis sheath or even a submuscular approach can be used. In the pectoral area, because of device size, many centers initially used a submuscular approach. With the radical reduction in device size, the subcutaneous pocket is becoming much more common. The concern associated with a subcutaneous pocket, whether abdominal or pectoral, is the higher risk of erosion (Table 21-6). Abdominal Pocket If an abdominal pocket is to be created, the implanting surgeon must be completely familiar with the anatomy of the anterior abdominal wall, including the multiple muscular and fascial layers (Fig. 21-83). One must be able to identify the anterior rectus abdominis sheath, rectus muscle, posterior rectus sheath, linea alba, and peritoneum. Failure to understand the anatomy of the abdominal wall may result in inadvertent access of the peritoneal cavity. An abdominal pocket is created with an initial 3- to 4-inch transverse incision high in the left upper quadrant. This incision is carried through the subcutaneous tissue and fat to the surface of the anterior rectus sheath. The incision can be held apart with one or two Weitlaner retractors. A Goulet or Richardson retractor may then be applied to retract the subcutaneous tissue; then, with the electrocautery unit in cutting function, an inferior pocket is created just on top of the anterior rectus sheath. A plane is created directly on top of the anterior rectus sheath, and an attempt

Anterior rectus sheath Posterior rectus sheath Aponeurosis

is made not to violate this structure. The subcutaneous tissue is separated from the anterior rectus sheath, creating a pocket large enough to accommodate the particular pulse generator. The pocket is carefully inspected for hemostasis and lavaged with antibacterial solution. The pocket should be low enough to avoid the costal margin and yet above the belt line. The pocket receives the leads by means of standard tunneling techniques (see later). When epicardial approaches are used, most leads are tunneled with a small chest tube and Kelly clamp for guidance. When transvenous leads are tunneled to an abdominal pocket, a special tunneling tool may be used (Fig. 21-84). Whether a tunneling tool or elongated clamps is used, care should be taken to achieve optimal depth of the tunneling track so as to avoid future lead erosion. A modification of the subcutaneous approach calls for the creation of a submuscular abdominal pocket. This pocket allows placement of the ICD in a space created between the posterior rectus sheath and the rectus muscle. This space may be approached by a vertical incision through the anterior rectus sheath at either its medial or lateral margin. The muscle can then be easily retracted off the posterior rectus sheath. Occasionally, vascular pedicles are encountered; these should be clipped with vascular staples. Once this submuscular compartment has been carefully inspected for hemostasis, the ICD may be inserted. A redundant lead can be placed in a separate subcutaneous space. The aponeuroses and subcutaneous tissue are then reapproximated with standard closure techniques. Once again, the deeper submuscular approach is associated with potential violation of the peritoneal cavity as well as postoperative erosion into the peritoneal cavity (Fig. 21-85). As a general rule, the abdominal pocket should not be located or placed over previous abdominal surgery, including previous abdominal incisions and drain sites. Such scar tissue raises the risk of direct communication between the ICD pocket and the peritoneal cavity. Similarly, one should avoid placing an abdominal pocket in the vicinity of abdominal hernias, which have the propensity to extend into an ICD pocket. Finally, if one is aware of potential future abdominal surgical requirements, an alternate abdominal location or pectoral approach should be considered. Tunneling Techniques The initial epicardial ICD systems required tunneling of leads from the epicardium to an abdominal pocket. This step was usually carried out with a large chest tube. The proximal ends of the electrodes were stuffed into the back end of a chest tube for protection, and the chest tube was guided by a large clamp subcutaneously to the abdominal pocket. The tip of the chest tube was grasped with a large, curved Kelly clamp, and with use of an index finger for palpation, the clamp guided the chest tube through the tissue to the abdominal pocket. The distance

Linea alba Subcutaneous fat Skin

External oblique muscle Internal oblique muscle Transverse abdominis muscle

Falciform ligament Peritoneum Extraperitoneal (subserous) tissue

Rectus abdominis muscle Transversalis fascia

Figure 21-83  Cross-sectional anatomy of the rectus sheath above the arcuate line.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

497

is removed from the sheaths, and the limbs of the array are passed down each sheath. The sheaths are slit and retracted, leaving the array limb in position (Figs. 21-88 and 21-89). The proximal end of the array lead is connected to the ICD, and additional DFTs are obtained. The hub of the array is fixed to the chest wall to prevent dislodgement. Once acceptable DFTs have been achieved, the proximal end of the lead is tunneled to the device pocket. Similarly, Medtronic manufactures a single subcutaneous coil that is implanted through a single slittable sheath. The sheath is first loaded onto a blunt-tipped, malleable rod that is hand-molded to slide subcutaneously from the prepectoral pocket around the lateral chest wall to the middle of the posterior chest wall at the level of the mid–left ventricle and medial, 1 to 2 cm from the spine. The lead is inserted into the sheath after removal of the stylet, and then the sheath is slit for removal. The subcutaneous patch, the array, or the coil can be Linea alba

Skin

Figure 21-84  Subcutaneous tunneling tool with interchangeable handle, tunneling rod, and tunneling bullet. (Courtesy Guidant, Boston Scientific, Natick, Mass.)

from the epicardium to the abdominal pocket was relatively short, and this tunneling technique proved simple and expeditious. This is not the case when one is tunneling from a transvenous insertion site in the upper chest to an abdominal pocket. To assist in long stretches of tunneling, CPI (now CPI/Guidant) developed a tunneling tool to resolve this problem. The tunneling tool had multiple components and basically consisted of a rod with a handle at one end and a distal bullet that could be replaced with a lead adapter (see Fig. 21-84). Tunneling should never be carried out until acceptable lead position and DFTs have been achieved. Even with the tunneling tool, tunneling over large areas can prove to be extremely challenging. It is important to maintain optimal depth of the tunneled track. Care should be taken to avoid intrathoracic entry as well as superficial cutaneous exit. The tunneling device may be introduced through the abdominal pocket or a venous access incision. Care should be taken to avoid an intramuscular track to prevent hematoma formation (see Fig. 21-85). Once the tunneling track has been established, the bullet is exchanged for the lead adapter. With the leads placed in the adapter, a suture is sometimes required to secure them in place. After the leads are secured to the adapter, the tunneling tool is retracted back to the abdominal pocket, and the leads are released from the adapter. If the tunneling tool was initially passed from the venous entry incision, the handle and bullet must be exchanged. The tunneling tool comes with two rod sizes; the shorter, 12-inch rod is used for tunneling over short distances, and the longer, 20-inch rod is used for pectoral-to-abdominal communication. The short rod is reserved for tunneling of subcutaneous array, for pocket-to-pocket communication, and for venous entry site–to–pectoral pocket communication. After tunneling, pacing and defibrillation parameters should be reconfirmed.

Peritoneum

Rectus

A Linea alba

Peritoneum

Rectus

Anterior rectus sheath

Posterior rectus sheath

Device

Skin Device

Posterior rectus sheath

Anterior rectus sheath

B

Subcutaneous Defibrillation Electrodes Occasionally, the endocardial lead system alone fails to provide an adequate DFT. In this case, a small electrode patch may be added through a small, left anterior chest incision208 (Fig. 21-86). This incision is usually placed along the left inframammary skin fold. A subcutaneous pocket is developed in the vicinity of the anterior axillary line. The patch is sutured to the chest wall, and the proximal lead tunneled to the ICD pocket. A variation on this system is the subcutaneous array developed by Guidant (Boston Scientific)209 (Fig. 21-87). The array consists of three flexible defibrillator leads that are joined at a common connector. The leads are designed to be placed subcutaneously along the contour of the left chest wall. The leads fuse as a common electrode that connects to the ICD. The array is placed through a small incision to the left lateral inframammary skin fold. The incision is created down to the muscular fascia. Three subcutaneous tracks are created with blunt-tipped malleable rods preloaded with slittable sheaths. The rod

C Figure 21-85  Cross-sectional anatomy of rectus sheath above arcuate line with ICD placement. A, ICD placed on top of the posterior rectus sheath beneath the rectus muscle. B, ICD placed anterior to the anterior rectus sheath in a subcutaneous pocket above the rectus muscle. C, Smooth retractor exposing the posterior rectus sheath with gentle retraction of the rectus abdominis muscle positioned anteriorly.

498

SECTION 3  Implantation Techniques

Proximal spring

Subcutaneous patch Distal spring Figure 21-87  Subcutaneous array system. Left, sheaths; middle, tunneling tool loaded with sheath; right, subcutaneous array. (Courtesy Guidant, Boston Scientific, Natick, Mass.)

Figure 21-86  Endocardial pacing and shocking electrode positioned in right ventricular apex. The electrode has been tunneled to the ICD in the right upper quadrant; the subcutaneous patch has been placed and similarly tunneled to the ICD.

connected directly into the header or often is Y-connected with the superior vena cava (SVC) coil into the header with an adapter. Azygos Vein Defibrillation Coil As an alternative approach in patients with high DRTs and routine endocardial lead systems, one can place a defibrillation coil (e.g.,

Malleable stylet

Medtronic Model 6937A) into the azygos/hemiazygos vein system.210 The advantages of use of the azygos vein defibrillation coil theoretically relates to the shift in the electrical defibrillation vector that occurs between the RV apex electrode and the azygos vein electrode, shunting the electric current posteriorly and more directly across the left ventricle.211 This coil electrode can then be incorporated into the defibrillation system instead of using an SVC coil, or it can be coupled with an SVC coil by a Y adapter. The azygos vein ascends in the posterior mediastinum to the level of the fourth thoracic vertebra, then arches anteriorly above the right pulmonary hilum to terminate in the superior vena cava before the SVC penetrates the pericardium. The body of the azygos vein lies anterior to the thoracic vertebrae and to the right of the descending aorta, directly behind the heart. The technique for placing the azygos vein defibrillation coil involves cannulation of the ostium of the azygos vein in the posterior portion of the high SVC.212 This can be accomplished from either the right or the left axillary vein. A 6F Judkins Right

Stylet with guide sheath

Removal of guide sheath after insertion of array

A

B

C

Figure 21-88  A, Malleable tunneling stylet passed laterally, creating a tract in the subcutaneous tissue of the intercostal space. B, Malleable tunneling stylet loaded with sheath passed along previously created track in the subcutaneous tissue of the intercostal space. C, Arms of the subcutaneous array passed down previously placed sheaths. Sheaths are then peeled away, and the array is fixed to the chest wall.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

499

Proximal spring Subcutaneous array

Distal spring

A

Figure 21-89  A, Endocardial pacing and shocking electrode tunneled to the pocket in the left upper quadrant. Subcutaneous array similarly positioned and fixed to the left anterior chest wall and tunneled to the device. B, Anteroposterior and lateral radiographic views of the ENDOTAK subcutaneous array system.

B

4 (JR4) diagnostic coronary catheter loaded with a .035-inch-diameter Wholey wire is advanced through a long, 45-cm 9F peel-away sheath with a hemostatic valve into the high SVC. The ostium of the coronary sinus (CS os) lies posteriorly and usually can be easily cannulated by probing with a combination of the JR4 catheter and the Wholey wire. The wire is advanced inferiorly to a position at or below the diaphragm, and the JR4 diagnostic catheter is advanced over the wire to the area of the diaphragm. In turn, the peel-away sheath can then be advanced over the combination of the wire and the inner catheter to approximately the same location at the level of the diaphragm. The wire and inner catheter are then removed from the sheath and replaced with the defibrillation coil lead, which is advanced through the sheath with the tip at approximately the level of the diaphragm (Fig. 21-90).

Anteroposterior view

Lateral view

It can be difficult to advance the lead beyond the sheath, so it is important to try to position the tip of the sheath at the diaphragm. The sheath can then be removed and the azygos vein defibrillation coil used in place of the SVC coil port in the defibrillator. Venography can be used once the azygos vein os is cannulated, but this is not necessary in most cases. Subcutaneous Implantable Cardioverter-Defibrillator An entirely subcutaneous implantable cardioverter-defibrillator (SICD) system was developed by Cameron Health to avoid the need for an endovascular lead system in patients who have no pacing requirement.213 The S-ICD avoids the potential problems associated with transvenous lead systems (venous access, implant complications,

500

SECTION 3  Implantation Techniques

A

B

Figure 21-90  Anatomy of azygos vein. Note posterior retrocardiac mediastinal location and drainage into the superior vena cava. A, Posteroanterior fluoroscopic image of ICD lead in azygos vein. B, Right anterior oblique (RAO) fluoroscopic image of azygos vein.

lead failures). The system consists of a 3-mm, tripolar parasternal electrode connected to an active can ICD pulse generator. The pulse generator is positioned over the sixth rib between the midaxillary line and the anterior axillary line. The subcutaneous lead is positioned parallel to, and 1 to 2 cm to the left of, the midsternal line (Fig. 21-91). The electrode has an 8-cm shocking coil and two sensing electrodes. The distal sensing electrode is surgically positioned at the level of the manubriosternal junction and the proximal sensing electrode at the level of the xiphoid process. The implant technique is guided solely by anatomic landmarks, without fluoroscopy. Standard tunneling techniques are used to position the electrode. It is crucial that the subcutaneous lead is implanted immediately to the left of the sternum and runs vertically from the manubriosternal junction to the xiphoid and then laterally to the anterior axillary– midaxillary line, where the defibrillation can/electrode is implanted.

Failure to use the appropriate anatomic landmarks has caused unacceptable DFTs. Transiliac ICD Implantation As previously described, the iliac vein can also be used for ICD placement when pectoral placement is impossible or contraindicated. Ching et al.123 reported an experience with 23 patients using two 75-cm to 110-cm, single-coil, active-fixation defibrillator leads. This approach alters the defibrillation vector because a separate defibrillation coil and an upper abdominal pocket are required. After accessing the iliac vein above the inguinal ligament, long guidewires are placed and exchanged for a 24-cm sheath, through which the leads are advanced into the heart. One lead is placed in the high right atrium or RA appendage and other in the RV apex. The leads are secured to the abdominal fascia and tunneled to a newly created pocket in the upper right or left abdominal subcostal region (Fig. 21-92). Occasionally, a subcutaneous coil is required, which is tunneled posteriorly from the axilla to capture the left ventricle (Fig. 21-93). The iliac vein approach has proved to be a safe and effective alternative for ICD implantation. Pectoral Pocket

D

Pulse generator

C

P

Figure 21-91  Location of lead and pulse generator of subcutaneous ICD; C, shocking coil; D, distal sensing electrode; P, proximal sensing electrode.

The creation of a pectoral pocket is generally reserved for ICDs inserted using the endocardial approach. The success and acceptance of the pectoral pocket are largely the result of the considerable reduction of the ICD pulse generator. The ICD has now reached the size of the permanent transvenous pacemakers that were routinely placed in pectoral pockets in the early 1970s. Occasionally, because of the smaller ICD pulse generator, epicardial leads have been tunneled to a pectoral pocket. With the ICDs of 40 to 50 cm3 and a thickness of 1.5 cm, pectoral pockets can easily be achieved. The pocket can be created in either the right or the left pectoral area, although the left is preferred because of lower achievable DFTs with an active can device.207 The pocket created can be either subcutaneous or submuscular. If the subcutaneous approach is used, it is identical to that described for a permanent transvenous pacemaker. The benefit of a subcutaneous pocket is its simplicity and avoidance of deep dissection. Creation of the pocket is also the same as that described for the permanent transvenous pacemaker. We cannot overemphasize that maximum subcutaneous depth should be achieved, with the pocket created directly on top of the pectoralis muscle to avoid potential erosion. The disadvantage of the subcutaneous approach is the concern about erosion. If the pocket is not created deep enough, the corners of the ICD can create pressure points and potential erosion. If the pocket is not made large enough and the pocket is under tension, the risk for erosion is great. Also, the subcutaneous pocket with the ICD at its current size has a



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

501

identical to that for a permanent pacemaker pocket. The need for strict adherence to antiseptic technique cannot be overemphasized. Submuscular Pectoral Pocket

Figure 21-92  Abdominal radiograph of transiliac ICD with the leads tunneled to the ICD in left upper quadrant.

cosmetic disadvantage: a visible bulge, which does not occur with a deeper, submuscular approach. The less attractive cosmetic result with an S-ICD has been a concern for some patients. For the patient who may succumb to twiddler’s syndrome, a Parsonnet pouch can be used.214 The Parsonnet pouch is also of benefit in the asthenic patient with minimal subcutaneous tissue, in the hope of precluding potential erosion. During creation of a subcutaneous pocket, appropriate incision length should be considered as well as pocket size, to avoid skin tension along the suture line, which can result in erosion. The management of pocket hematomas is the same in an ICD pocket as in a permanent pacemaker pocket. When recognized, the hematoma should be evacuated early and a Jackson-Pratt drain placed (removed in 24 hours). Antibiotic lavage of the pocket is also

The submuscular pectoral pocket remains a popular practice for ICD implantation because of its optimal cosmetics and virtual freedom from erosion. Vital to the submuscular pectoral approach is a complete understanding of the regional anatomy.215 The superficial landmarks of the clavicle, deltoid muscle, pectoralis muscle, and deltopectoral groove should be clearly identified (Figure 21-94). The pectoralis major muscle is superior to the pectoralis minor. The pectoralis major muscle has two major subdivisions: the clavicular head attaches to the clavicle, and the sternal head attaches to the lateral border of the sternum. Both heads ultimately fuse and attach to the humerus. The fascial plane that separates these two heads represents an attractive plane of dissection for access to the subpectoral space for creation of a pocket. The much smaller pectoralis minor muscle has two connections. Its superior head is attached to the coracoid process. The muscle then fans out inferiorly, attaching to the anterior ribs. The thoracoacromial neurovascular bundle can be easily identified on the outer surface of the pectoralis minor muscle (Fig. 21-95). With creation of a submuscular pectoral pocket, this bundle should always be identified and avoided because it is a potential source of complication. Tearing the artery or vein may result in pocket hematoma, and interruption of the nerve may result in pectoral muscle dysfunction. The deltopectoral groove is defined by the lateral border of the clavicular head of the pectoralis major muscle. The anterior axillary fold is defined by the inferolateral border of the sternal pectoralis major muscle head. Currently, with the active can and the dual-coil lead system, the submuscular pectoral approach may be performed from either the right or the left pectoral area. The left pectoral approach, however, results in lower DFTs.216 Occasionally, if the right submuscular pectoral approach is used, a patch or array system may be required. There are three distinct submuscular pectoral approaches. The anterior subpectoral approach is created between the clavicular and sternal heads of the pectoralis major (Fig. 21-96). The lateral subpectoral approach is through a lateral reflection of the clavicular head of the pectoralis major (Fig. 21-97). The anterior axillary approach is through the inferolateral border of the pectoralis major muscle (Fig. 21-98). Each approach has its benefits and potential complications. The anterior approach is similar to that for a subcutaneous pacemaker pocket creation. It requires the creation of a dissection plane between the sternal and clavicular portions of the pectoralis muscle. The resultant pocket is anterior and does not interfere with the axilla. The lateral

Subcutaneous coil RA coil

RA coil

Subcutaneous coil

RV coil

A

B

RV coil

Figure 21-93  A, Posteroanterior chest radiograph of single-coil active-fixation ICD leads in the high right atrium (RA) and right ventricular (RV) apex. A subcutaneous coil is also seen posterior to the left ventricle. B, Lateral chest radiograph demonstrating the position of the leads and subcutaneous coil. Arrows indicate leads.

502

SECTION 3  Implantation Techniques

To subpectoralis pocket Sternal head of pectoralis major

Clavicular head of pectoralis major

Cephalic vein

Edge of sternal head of pectoralis major muscle

Edge of clavicular head of pectoralis major muscle

Figure 21-96  Anterior subpectoralis muscle approach. The clavicular and sternal heads of the pectoralis major muscle are gently retracted, and a plane of dissection is established postpectorally.

Figure 21-94  Initial incision for subpectoralis muscle placement of ICD. Inset, The deltopectoral groove and the clavicular and sternal heads of the pectoralis major muscle.

approach requires dissection of the pectoralis major muscle along the deltopectoral groove. Because this approach is more lateral, the ICD tends to drift into the axilla. Similarly, the axillary approach requires dissection and establishment of a plane at the anterior axillary fold, and the device tends to drift into the axilla and cause discomfort. Surgical techniques are available to help prevent this device drift. Both the

Axillary vein Cephalic vein

lateral and the axillary approach also carry the risk of interrupting the long thoracic nerve, leading to “wing” scapula. The skin incision for the anterior approach is similar to that used for a permanent pacemaker pocket. One palpates the coracoid process and notes the angle of the deltopectoral groove. The incision is initiated just medial to the coracoid process and is carried from the level of the coracoid process inferomedially and perpendicular to the deltopectoral groove for about 3 inches (7.5 cm). With a Weitlaner retractor for retraction and electrocautery, the incision is carried down to the surface of the pectoralis fascia. With this approach, one may access the cephalic vein, the axillary vein, or the subclavian vein. After venous access is achieved and the leads are positioned, the leads are anchored to the pectoralis muscle with the suture sleeve. One creates the submuscular pectoral pocket by first identifying the border between the clavicular and sternal heads of the pectoralis muscle—usually as a line of fat. Using the smooth end of two Senn retractors, one establishes a plane of dissection between the two heads of muscle, which are gently peeled back until the surface of the chest wall is visualized as a clear plane of fatty tissue (Fig. 21-99, A and B). One can then insert a finger

To subpectoralis pocket Pectoralis major

Thoracoacromial neurovascular bundle Pectoralis minor

Figure 21-95  Superficial and deep anatomy of deltopectoral area. Note relationship of the superficial pectoralis major and deep pectoralis minor muscles, axillary and cephalic veins, and thoracoacromial neurovascular bundle.

Cephalic vein

Edge of clavicular head of pectoralis major muscle Figure 21-97  Deltopectoral groove, subpectoral approach. The lateral border of the pectoralis major muscle’s clavicular head is gently retracted, and a plane of dissection is established medially, behind the pectoralis muscle.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Cephalic vein To subpectoralis pocket Edge of pectoralis major muscle Figure 21-98  Anterior axillary fold, subpectoralis muscle approach. The lateral border of the pectoralis major sternal head at the anterior axillary fold is gently retracted, and a plane of dissection is established retropectorally.

503

access and tunneling to the axillary fold incision. One has the option of cephalic, axillary, or subclavian venous access. Some operators also create a small, subcutaneous pocket for placement of the strain-relief loop and excess lead. The inferolateral margin of the pectoralis major muscle is easily separated from the adjacent subcutaneous tissue to establish a large plane of dissection. The plane of blunt dissection is created on top of the pectoralis minor muscle. After the pocket is created, the electrodes and ICD are united, and thorough device testing is done. The ICD should be placed as medially as possible, with the leads lateral to the generator to avoid the risk of can abrasion. With the ICD in the pocket, a multilayer closure is used. The lateral margin of the anterior axillary soft tissue and pectoralis major muscle are approximated. Care should be taken to avoid suturing the pectoralis major and pectoralis minor muscles together, because this would limit motion of the upper extremity. The leads are anchored to the pectoralis muscle through the separate incision for venous access. As mentioned previously, with this axillary approach as well as the lateral approach, care should be taken to avoid interrupting the long thoracic nerve. All three approaches call for a multilayer closure. The submuscular layer is closed by gentle approximation of the muscular heads. Care is taken to avoid tight ties that may damage the muscular tissue. The subcutaneous tissue and skin are approximated as previously discussed. Cosmetic Approach

and continue the dissection bluntly. Underneath the pectoralis major muscle, one can palpate superiorly the leads entering the axillary vein and identify the fibers of the pectoralis minor as well as the thoracoacromial neurovascular bundle. Occasionally, this bundle may be torn, and electrocautery or vascular clamps may be applied to effect hemostasis. Care should be taken to avoid interrupting the nerve. Once the subpectoral pocket has been established, a Goulet clamp may be inserted and the pocket visually inspected for any unusual bleeding. The leads are connected to the ICD, which is inserted into the submuscular pectoral pocket. It is recommended that longer lead lengths be used for this anterior pocket. Particularly in a dual-chamber ICD system, the atrial electrodes should be a minimum of 52 cm long. After successful, thorough testing, the device may be rendered inactive and removed from the pocket. The pocket is carefully inspected for hemostasis as well as lavaged with antiseptic solution. The device is then reinserted into the pocket, and a multilayer closure is completed. Closure usually involves placement of several interrupted sutures to approximate the clavicular and sternal portions of pectoralis muscle, then standard subcutaneous skin closure. If the lateral submuscular approach through reflection of the lateral clavicular head is used, an initial vertical incision along the deltopectoral groove is recommended. Dissection is carried down to the surface of the pectoralis fascia. After venous access and lead placement are achieved through the cephalic, axillary, or subclavian vein, the lateral border of the clavicular head of the pectoralis major is retracted medially, and a plane of dissection on top of the pectoralis is established. Care should be taken to extend the pocket sufficiently medially to avoid interference with the abductor motion of the lateral humeral head. After thorough device testing and careful pocket inspection for hemostasis, a multilayer closure is performed as described for the anterior approach. The lateral anterior axillary subpectoral approach involves creation of a dissection plane in the anterior axillary fold.217 If this approach is used, careful sterile skin preparation of the entire axilla should be performed. Some operators prefer this approach because it is less traumatic. A dissection plane is easily established in the separation of planes created between the pectoralis major and pectoralis minor muscles. This approach is usually carried out with the patient’s left arm in abduction. A skin incision is created inferiorly along the anterolateral axillary fold. The incision is carried down to the surface of the pectoralis major muscle; the pectoralis major and minor muscles are identified and separated; and a plane of dissection is created between them. This approach usually requires a separate incision for venous

A technique for optimal cosmetic placement of an ICD was developed for young patients concerned with appearance.218 It is performed under general anesthesia and involves two separate incisions. An initial vertical incision is made along the skin fold at the inferior aspect of the deltopectoral groove. Using venography, the axillary vein is located and accessed. Separate punctures and sheath placement are made for each lead to be implanted. The leads are positioned and tied down. A second incision is made along the inferior aspect of the breast. The incision is carried down to the pectoralis major muscle. The muscle fibers are separated to access the subpectoral space. The leads are then tunneled down to the subpectoral pocket using standard tunneling techniques previously described. The leads and the device are connected and inserted into the subpectoral pocket (Fig. 21-99, C and D). The muscle is approximated and both skin incisions closed. Giudici et al.219 reported a 9-year experience with this technique in 51 female patients. Most patients were satisfied with their choice and the cosmetic results, with no mammography issues and few complications (three lead dislodgements, one pneumothorax). SELECTIVE SITE PACING The preceding traditional implantation techniques describe positioning the transvenous leads in the RV apex or RA appendage. Historically, these techniques have been unproved and unscientific, their evolution largely driven by available techniques and technology. A clear example is the transition from the epicardial to the endocardial approach and RV apex. This is because the RV apex is readily available, reliable, and proved to be stable over time. In addition, it is easily achieved. More recently, the conventional sites for placement of RA and ventricular leads have been challenged as inadequate and nonphysiologic.220,221 RV apex pacing has been demonstrated to cause LV dysfunction. The resultant contraction from RV apex pacing has been shown to produce abnormalities in regional systolic fiber shortening, mechanical work, blood flow, and oxygen consumption.222 Right ventricular apex pacing has also resulted in a higher incidence of atrial fibrillation (AF),223 as underscored by the recent experience with CRT. Atrial pacing has a beneficial effect in preventing AF.224-227 The prolonged times of signal conduction from high to low atrium that can occur with pacing from the atrial appendage may play an important role in the induction of AF. Low atrial selective and multisite atrial pacings have been shown to reduce the incidence of AF.228-233 As a result, the conventional approach to cardiac pacing has been challenged. The term “alternative sites” has entered the cardiac pacing

504

SECTION 3  Implantation Techniques

Clavicle Clavicle Axillary artery Axillary artery

Axillary vein

Axillary vein ICD Pectoralis minor muscle

Pectoralis major muscle

Pectoralis major muscle

A

B

C

Pectoralis minor muscle

D

Figure 21-99  A and B, Sagittal sections of shoulder girdle showing superficial and deep anatomy. B, Placement of automatic ICD under pectoralis major muscle. C, Submammary approach showing superior and inferior incisions. D, Posteroanterior radiograph of submammary implant.

literature. In an attempt to optimize cardiac function, RV leads are no longer simply placed in the RV apex but are being positioned along the intraventricular septum and outflow tract.234 The atrial leads are no longer simply placed in the high RA or atrial appendage but are now being positioned in one or more sites in the right atrium and sometimes the left atrium in an attempt to suppress AF.233 These concepts have resulted in the term “selective site pacing” as the preferred means of cardiac stimulation in any given patient. Selective site pacing has resulted in new challenges for implantation, from venous access to final lead position. A thorough knowledge of cardiac anatomy and, more specifically, radiographic cardiac anatomy

is essential. In addition, the tools and techniques for achieving a selective site are evolving. Also, many problems must be solved and questions answered if selective site pacing is to become the standard of care. First, the scientific community must define the best sites to pace in the heart. At present, the suggested selective sites include the interatrial septum, RV septum and outflow tract, the His bundle, and CS os. Precise lead placement requires identification of locations that will have optimal clinical benefit. The following discussion reviews the current state of the art of selective site pacing with respect to lead location, implantation techniques, and tools. LV pacing implantation techniques are reviewed in Chapter 22.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

505

General Considerations General considerations are largely identical to those for permanent pacemaker implantation, with several important issues. The recommended location for the procedure is the cardiac catheterization or electrophysiology laboratory, because selective site pacing requires high-quality imaging equipment and the ability to easily achieve multiple radiographic projections. In addition, a physiologic recorder capable of obtaining high-quality EGMs for mapping is essential. The choice of anesthesia is related to operator preference. Most procedures can be done with IV sedation on an outpatient basis. Venous access for selective site pacing is essentially the same as previously discussed for conventional pacing techniques. The challenges involve the addition of multiple electrodes, which is best achieved with the retained-guidewire technique.108 Simply retaining the guidewire enables introduction of multiple additional pacing leads into the central circulation. This ability becomes important with multisite atrial pacing and biventricular (BiV) pacing, in which three or more leads are introduced into the venous system. If one anticipates the addition of multiple electrodes after venous access is achieved, a 6F sheath set can be placed over the guidewire, and additional guidewires, corresponding to the number of required leads, can be passed down the sheath and retained. The extra guidewires are then pinned to the drape for future use. If multisite atrial pacing is to be performed, lead Y adapters are usually needed to connect the atrial leads to the pacemaker. An assortment of adapters for any given situation should be kept on hand at all times. Selective site pacing requires the use of active-fixation leads, either extendable, retractable, or with a fixed extended helix. Positioning the lead for the selected site can be quite challenging. At times, a selected site is almost inaccessible with conventional leads, particularly in the atrial septum or for direct His bundle pacing. Special J-shaped stylets are often required. Two types of delivery systems are now available for such difficult clinical situations. The first is a steerable stylet (Fig. 21-100). In its current design, the curves achieved by the stylet preclude access to some selective sites. A steerable stylet is connected to a handle with a slide bar. This activates and adjusts the curve. The stylet is Lead retention assembly

Curvable part of stylet

Lead over stylet

Turning clockwise 8-10 times will make the screw appear

Slide bar actuator

Handle

Tip curve control

Figure 21-100  Steerable stylet (locator; St. Jude Medical Model 4036). Top, The slide lies next to the clamp, and the tip of the stylet is straight. Middle, The slide is moved from the clamp toward the handle, resulting in the tip of the stylet being curved. Bottom, The lead retention assembly is rotated to activate the screw active-fixation mechanism. (From De Voogt WG, Van Mechelen R, Van Den Bos A, et al: A technique of lead insertion for low atrial septal pacing. Pacing Clin Electrophysiol 28:639, 2005.)

Figure 21-101  Selectsite steerable catheter (Medtronic Model 1063439). (From Mond HG, Grenz D: Implantable transvenous pacing leads: the shape of things to come. Pacing Clin Electrophysiol 27:892, 2004.)

actually inside a .0016-mm tube attached to the slide bar on the handle. The tube is passed down the pacing lead to be inserted. The lead is slipped over the tube and attached to the handle, and the desired curve is made with the lead in the heart. The handle is also used to turn the lead around its axis, maneuvering the curve clockwise or counterclockwise. The stylet can also be manually curved to achieve desired secondary curves, which can help achieve stability of the lead in the SVC. The stylet curves the distal 4 cm of the pacing lead. This system was used successfully by De Voogt et al.235 in 100 patients to position leads in the low RA septum. The second system builds on the concept of a catheter delivery system. Unlike in the catheter delivery systems for CRT that had fixed curves, a line of steerable catheters (Selectsite, models 10634-39 and 10635-49, Medtronic) has been developed to guide pacing leads to selective sites (Fig. 21-101). In these products, the 4F active-fixation lead is passed down the steerable catheter to the desired position for fixation. This lead is a simple cable and has no guiding stylet, being delivered by a guide catheter. Anatomic Considerations A complete understanding of the gross and radiographic cardiac anatomy is essential for successful selective site pacing. An appreciation of the RA anatomy is necessary for targeting of the low atrial septum and CS cannulation. As previously mentioned, appreciation of the RV spatial orientation is important for direct His bundle, RV septal, and outflow tract pacing. Right Atrium.  In the frontal plane, the RA cavity is located to the right and anteriorly. The left atrium is located to the left and mainly posterior to the interatrial septum; when viewed in the transverse plane, the LA runs obliquely from a left anterior position to a right posterior position. The RA is somewhat larger than the LA, but its walls are thinner. Traditionally, the RA is viewed as having two parts: a posterior smooth-walled part into which the SVC and IVC enter and a very-thinwalled trabeculated part located anterolaterally.236 The two parts are separated by a muscular ridge, the crista terminalis. The ridge consists of muscle that is more prominent superiorly, tapering toward its inferolateral end. Externally, the crista terminalis corresponds to a seam, the sulcus terminalis. The pectinate muscles travel laterally in parallel fashion from the crista terminalis along the RA free wall. The atrial wall between the pectinate muscle bundles is almost paper thin and

506

SECTION 3  Implantation Techniques

Aorta Supravalvar ridge

Left posterior cusp of aortic valve

Orifice of left coronary artery

Right atrium

Subaortic curtain

Right coronary artery

Membranous atrioventricular septum

Anterior papillary muscle of right ventricle

Tendon of Todaro Limbus fossae ovalis Valve of coronary sinus Valve of inferior vena cava Triangle of Koch Right coronary artery

Muscular interventricular septum Anterior cusp of mitral valve

Tendon of Todaro Triangle of Koch

Septal cusp of tricuspid valve Posterior papillary muscle of right ventricle Muscular interventricular septum

Orifice of coronary sinus Septal cusp of tricuspid valve

Figure 21-102  Interior of the heart. Incising the heart along its right and lower surfaces and excising the pulmonary trunk and infundibulum reveal the interior. The rest of the heart has been turned over to the left. (From Johnson D: Heart and great vessels. In Standring S: Gray’s anatomy: the anatomical basis of clinical practice. Philadelphia, 2005, Elsevier, p 1002.)

translucent. The RA appendage is the triangular superior portion of the RA. It is filled with pectinate muscles. The eustachian valve is a fold of tissue that guards the anterior border of the IVC os. In humans, it demonstrates considerable variability and may even be absent. Occasionally, the eustachian valve is perforated and even fenestrated, forming a lacelike network (network of Chiari). Anterior and medial to the eustachian valve, the CS enters the RA. The thebesian valve is a valvelike fold of tissue that guards the CS os. The interatrial septum forms the posterior or medial wall of the RA. The central ovoid portion, which is thin and fibrous, forms a shallow depression, the fossa ovalis. The remainder of the septum is muscular, forming a ridge known as the limbus fossa ovalis (Fig. 21-102). Developments in interventional electrophysiology, CRT, and selective site pacing have mandated a better understanding of atrial anatomy. Contemporary anatomists Ho and Anderson have led the way to a better understanding of the RA anatomy as it relates to the cardiac EP interventions.237 Ho238 considers the RA to consist of three components, the appendage, a venous part, and the vestibule (Fig. 21-103). The interatrial septum, a fourth component, is shared by the RA and LA. When viewed from the epicardium, the atrial appendage is a triangular structure located anteriorly and laterally. The sulcus terminalis corresponding to the crista terminalis can be seen running along the lateral wall as a fat-filled groove. Epicardially, the sinus node is located in this groove adjacent to the SVC-RA junction. The RA musculature extends from the SVC externally and terminates at the entrance of the IVC. When viewed externally, the pectinate muscles, as previously noted, can be seen radiating from the terminal crest. The pectinate muscles spread throughout the entire wall of the atrial appendage, extending to the lateral and inferior walls of the atrium. The pectinate muscles never reach the orifice of the tricuspid valve. The vestibule is a smooth muscular rim that surrounds the tricuspid valve orifice (Fig. 21-104). The posterior smooth wall of the atrium constitutes the venous component. The terminal crest marks the division between the venous smooth and trabeculated parts of the atrium. The terminal crest is a muscular bundle that begins on the superior aspect of the medial wall and passes anteriorly and laterally to the orifice of the SVC. It then descends obliquely along the lateral atrial

wall. Its terminal portion consists of a number of smaller muscle bundles extending to the vestibule and orifice of the IVC. The eustachian valve, a triangle or flap of fibromuscular tissue, guards the entrance of the IVC. This valve inserts medially and forms the eustachian ridge or sinus septum, which is the border between the fossa ovalis and CS. The eustachian valve may be quite large, fenestrated, perforated, or delicate. The free border of the eustachian valve extends as a tendon that runs into the musculature of the sinus septum. Called

Sup caval vein

A

Sinus node

P Terminal e crest c t i n Right a t atrium Oval e Superior fossa m u s Posterior Anterior c l e Inferior s Eustachian valve and ridge

B

Figure 21-103  A, Right anterior view of the right atrium (RA) from outside showing the relationship of the superior vena cava and atrial appendage. The RA is thin walled with a rough texture. The sinus node is shown. B, Interior of the RA as seen from the right anterior oblique view. The RA free wall is retracted posteriorly. The septal aspect and the venous components are visible. The pectinate muscles arise from the terminal arch of the crista terminalis. The eustachian ridge and valve as well as a fenestrated thebesian valve are seen. (From Ho S: Understanding atrial anatomy: implications for atrial fibrillation ablation. In Cardiology International for a global perspective on cardiac care. London, 2002, Greycoat, S17-S20.)



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

are separated in the roof of the RV by a prominent supraventricular crest called the crista supraventricularis. This is a thick muscular structure that extends obliquely forward and to the right from a septal extension on the interventricular septal wall to a mural or parietal extension on the anterolateral RV wall. The inlet and outlet regions extend apically into the ventricle. The inlet component is trabeculated, whereas the outlet is predominantly smooth walled. The many irregular muscular ridges and protrusions are responsible for the trabeculated appearance. The protrusions and grooves result in great variation in wall thickness. The papillary muscles are prominent protrusions from the ventricular wall. The septal marginal trabecula or septal band is a prominent protrusion in the RV chamber. It supports the septal surface at its base and divides into limbs that embrace the supraventricular crest. The apex of the septal band supports the anterior papillary muscle. At this point, it crosses to the parietal wall of the ventricle and is called the moderator band. The infundibulum or outflow tract is smooth walled and extends leftward below the arch of the supraventricular crest to the pulmonary orifice.

Superior

Posterior

Anterior

Inferior SCV

ule

b sti Ve

OF

ICV

507

CS

Figure 21-104  Landmarks of Koch’s triangle superimposed on exposed right atrial cavity. The relationship of the structural landmarks to the coronary sinus (CS) is seen. ICV, inferior caval vein; OF, flap valve: SCV, superior caval vein. (From Ho S: Understanding atrial anatomy: implications for atrial fibrillation ablation. In Cardiology International for a global perspective on cardiac care. London, 2002, Greycoat, S17-S20.)

the tendon of Todaro, it forms the posterolateral border of Koch’s triangle. The anterior border is marked by a hinge of the septal leaflet of the tricuspid valve. The vestibular portion of the RA that surrounds the valvular orifice is the common location for slow-pathway ablations of AV node reentrant tachycardia. The thebesian valve is a small, flat, crescentic flap of fibrous tissue that guards the CS os. It varies considerably in size and thickness and is occasionally fenestrated. The atrial wall inferior to the CS os often forms a pouch known as the subeustachian sinus. The coronary sinus, the terminal portion of the great cardiac vein, is located posteriorly in the left atrioventricular groove. It is frequently covered by muscular fibers of the LA. The CS receives the veins draining the left ventricle, including the great cardiac vein, posterior cardiac vein, left cardiac vein, and anterior cardiac veins. The CS terminates in the inferoposterior aspect of the RA and forms the inferior border of Koch’s triangle. Right Ventricle.  As previously stated, the RV is an anterior mediastinal structure, extending from the RA ventricular orifice to the cardiac apex (Fig. 21-105). It ascends leftward to become the infundibulum or conus arteriosus, reaching the pulmonic valve. The RV consists of an inlet component, which supports the tricuspid valve, and an apical component, a coarsely trabeculated and muscular infundibulum or outlet that attaches to the pulmonic valve. The anterior surface of the RV is convex and constitutes the majority of the heart under the anterior thoracic wall. Its inferior aspect is flat, resting on the diaphragm. The RV left and posterior walls constitute the ventricular septum. This structure is slightly curved and bulges into the ventricular chamber. The RV inlet and outlet components that support the tricuspid and pulmonic valves are separated and covered by the roof of the RV. These

Radiographic Anatomy.  In addition to understanding the gross anatomy of the RA, CS, and RV, one must have a thorough knowledge of the radiologic and angiographic anatomy in order to succeed in selective site pacing and CRT. Previously, few studies were devoted to the angiographic anatomy of the right heart, but with the popularity of CRT, the CS angiographic anatomy has now been extensively described. Farré et al.239 elegantly describe the gross and fluoroscopic cardiac anatomy for interventional electrophysiology. They recommend the use of the visible human slice and surface server developed by Hersch for understanding and correlating the cardiac anatomy to the fluoroscopic projections. It is important to understand the fluoroscopic anatomy in the frontal and oblique projections when one is implanting leads. The frontal view is generally used for introduction and positioning of leads in the RV apex and high RA. For selective site pacing, it is difficult to locate with certainty the position of the lead by means of a single fluoroscopic projection. This is when oblique views are very important to help position the pacemaker lead within the three dimensions of the heart. The right anterior oblique (RAO) and left anterior oblique (LAO) projections define what is anterior, posterior, inferior, and superior in cardiac planes that are parallel to the input of the image intensifier (Fig. 21-106).

Ascending aorta Right auricle Infundibulum

Pulmonary trunk Left auricle

Left anterior cusp of pulmonary valve

Supraventricular crest Anterior cusp of tricuspid valve Anterior papillary muscle of right ventricle Moderator band

Anterolateral papillary muscle of left ventricle

Posteromedial muscle of left ventricle

Figure 21-105  Dissection opening the ventricles, viewed from the front. (From Johnson D: Heart and great vessels. In Standring S: Gray’s anatomy: the anatomical basis of clinical practice. Philadelphia, 2005, Elsevier, p 1002.)

508

SECTION 3  Implantation Techniques

RV OT

Ao

RA

Ao

RAA

LAA

SVC LA

ICV RA

A

B

Figure 21-106  Sections of the male heart. A, Right anterior oblique projection; B, left anterior oblique (LAO) projection. A shows the inferior caval vein (ICV), the supraventricular crest (SVC), the aorta (Ao), and right ventricular outflow tract (RVOT). The white dot identifies the site corresponding to the membranous septum or the area the maximal His bundle potential is usually recorded. In the LAO projection, the right atrial appendage (RAA) and the right and left atria (RA and LA) at the level of the atrioventricular junctions are depicted. As in A, white dot signals the area where the His bundle potential is recorded. The left atrial appendage (LAA) is superior. (From Farré J, Anderson RH, Cabrera JA, et al: Fluoroscopic cardiac anatomy for catheter ablation of tachycardia. Pacing Clin Electrophysiol 25:88, 2002. From Ecole Polytechnique Fédérale de Lausanne: Visible human surface server. visiblehuman.epfl.ch.)

In the frontal plane, the RV occupies most of the cardiac silhouette as an anterior structure. The upper half of the right-sided heart border is formed by the SVC, and the lower portion is formed by the lateral wall of the RA. The plane of the lateral valve is sandwiched between the anterior RV and posterior LV. It can be conceptualized as an oval ring tipped somewhat to the left. The CS is located at the inferior aspect of the cardiac silhouette at the level of the diaphragms, approximately in the midline. The RAO projection rolls the RV to the left. In this view, the SVC, IVC, and RA become an anterior structure. The plane of the tricuspid and mitral valves becomes more vertical and perpendicular to the anteroposterior plane (Fig. 21-107). The RV is pushed to the left.

In the LAO projection, the plane of the tricuspid and mitral valves becomes frontal, with the CS tipped in a horizontal position and crossing over the spine as it courses to the left, crossing over the spine from right to left and turning superiorly along the left heart border (Fig. 21-108). For placement of a pacemaker lead in the RA appendage, the frontal projection is preferred. The tip of the RA appendage is superior and anterior. When the lead tip is placed in the apex of the atrial appendage, it moves from right to left. In the RAO projection, the tip points to the right, and in the LAO projection, it points to the left. The triangle of Koch is in the inferior paraseptal RA region. This region is important LAO

RAO Projection

Coronary sinus

MV

MV

Plane of AV valves

TV Plane of AV groove and valves Figure 21-107  Heart rotated in the right anterior oblique (RAO) view showing the relationship of the atrioventricular (AV) groove and spine; MV, mitral valve; TV, tricuspid valve. (From Belott PH: Implantation techniques for cardiac resynchronization therapy. In Barold SS, Mugica J: The fifth decade of cardiac pacing. Armonk, NY, 2004, Futura, p 6.)

TV

Coronary sinus

Figure 21-108  Heart rotated in the left anterior oblique (LAO) view in which the atrioventricular groove is tipped horizontally; AV, atrioventricular; MV, mitral valve; TV, tricuspid valve. (From Belott PH: Implantation techniques for cardiac resynchronization therapy. In Barold SS, Mugica J: The fifth decade of cardiac pacing. Armonk, NY, 2004, Futura, p 6.)



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

for RA septal and His-bundle selective site pacing. In the RAO projection, the plane of Koch’s triangle is parallel to the image intensifier. The LAO projection helps differentiate paraseptal lead positions. The region of the His bundle is located superiorly, and the CS os inferiorly. In the RAO and LAO projections, the CS os can be found at the inferior aspect of the cardiac silhouette at the level of the diaphragms just to the right of the spine. Rotating from the RAO to the LAO projection and back becomes important in attempts to cannulate the CS os. As a simple example, the frontal projection makes the catheter appear to be in the vicinity of the CS os with the trajectory pointing inferiorly and to the left; when the image is rotated to the LAO projection, however, the catheter is seen to be actually 180 degrees away from the CS os, pointing anteriorly and to the right. After the catheter is adjusted to a posterior and leftward position, the RAO projection may show the catheter pointing laterally to the right, away from the CS os. This simple example points to the importance of multiple views in achieving a selected site. With respect to the CS, the LAO projection is extremely important in distinguishing anterior and posterior tributaries of this sinus (Fig. 21-109). In the frontal and RAO projections, CS tributaries appear to run perpendicular to the CS, obliquely from a superior to inferior direction (Fig. 21-110). The branches appear to be parallel, making differentiation of anteroseptal, lateral, and posterolateral branches almost impossible. Atrial Septal Pacing Atrial fibrillation, the most common sustained tachycardia arrhythmia in clinical practice, is associated with considerable morbidity and mortality. It is believed that atrial pacing might help prevent the onset of AF through a variety of mechanisms. Atrial pacing should prevent relative bradycardia, which is often a trigger for AF. In addition, atrial

45º RAO

AP

LAO

Figure 21-109  Coronary sinus in left anterior oblique (LAO) projection. The plane of the sinus is more horizontal and posterior. The posterior and lateral branches are directed inferiorly and to the left, whereas the anterior branches are directed superiorly to the right. (From Belott PH: Implantation techniques for cardiac resynchronization therapy. In Barold SS, Mugica J: The fifth decade of cardiac pacing. Armonk, NY, 2004, Futura, plate 1.4.)

509

45º RAO

AP

RAO

Figure 21-110  Coronary sinus in right anterior oblique (RAO) projection. The plane of the sinus is vertical with the branch tributaries at a right angle. In this view, all the branches come into coronary sinus at almost a right angle and are directed slightly inferiorly into the left. (From Belott PH: Implantation techniques for cardiac resynchronization therapy. In Barold SS, Mugica J: The fifth decade of cardiac pacing. Armonk, NY, 2004, Futura, plate 1.3.)

pacing should suppress bradycardia-induced dispersion of refractoriness in the atrium as well as escape atrial ectopy, which are potential causes of AF. In 1907, Bachmann240 described a distinct band of muscle tissue extending from the base of the LA appendage, called the anterior interatrial band. Bachmann’s bundle was later defined as a band of fibers traversing the LA, curving posteriorly within the interatrial septum, and reaching the crest of the atrioventricular node.241 RA activation mapping, when the heart is being paced from the LA and CS, has demonstrated preferential sites of the transseptal conduction (Figs. 21-111 and 21-112). The earliest RA activation has been found to be near the insertion of Bachmann’s bundle.242-245 Electroanatomic mapping has confirmed the role of Bachmann’s bundle in intra-atrial propagation. Bachmann’s bundle may therefore be an ideal selective site for prevention of AF.242 The selective sites for RA pacing include the high RA septum and the low RA septum in the vicinity of the CS os. The area of the high RA septum involves the crista terminalis, and Bachmann’s bundle is particularly difficult to pace with conventional tools. The selective site for low RA septum is the mouth or CS os. The usual target for lead attachment is just superior to the CS os. Atrial septal pacing from this position will result in negative P waves in leads II, III, and aVF. For atrial septal pacing, a permanent pacing lead is placed in the posterior RA septal wall. To achieve a selective site, an active-fixation lead is mandatory. Koch’s triangle is situated in the lower aspect of the interatrial septum. It is confined by the borders of the tricuspid valve anulus and the eustachian ridge superiorly. The base of the triangle, as mentioned previously, is formed by the CS. The posterior aspect of the triangle is the muscular part of the interatrial septum. The 45-degree LAO fluoroscopic projection is used to guide the pacing lead at a right angle into the intra-atrial septum. The interatrial septum is oriented at about 45 degrees from right posterior to left anterior. The 45-degree LAO projection helps confirm lead fixation to Koch’s triangle (Fig. 21-113).

510

SECTION 3  Implantation Techniques

LSPV

RSPV

LAA

Figure 21-111  Axial section of the heart. LAA, Left atrial appendage; LSPV, left superior pulmonary vein; RSPV, right superior pulmonary vein. (From Farré J, Anderson RH, Cabrera JA, et al: Fluoroscopic cardiac anatomy for catheter ablation of tachycardia. Pacing Clin Electrophysiol 25:88, 2002. Ecole Polytechnique Fédérale de Lausanne: Visible human surface server. visiblehuman.epfl.ch.)

Selective site atrial septal lead placement is next to impossible with the frontal or RAO projection. These views can be used only for secondary confirmation of appropriate lead position. In the frontal plane, the lead appears in the neutral position or somewhat directed to the left, depending on the contraction phase of the atrium. Unlike the fluoroscopic movement of the lead tip in the RA appendage—that is, to and fro—the RA septal lead tip moves up and down. If the ventricular lead has been implanted before the atrial lead, its undulation over the tricuspid valve marks the position of the structure. The ventricular lead marks the inferior part of the tricuspid ostium. The CS os has also been used to locate the interatrial septum, with active-fixation leads

BB

Figure 21-112  Axial section of heart. Magnification of Figure 21-111, depicting the area of Bachmann’s bundle (BB, arrows). (From Farré J, Anderson RH, Cabrera JA, et al: Fluoroscopic cardiac anatomy for catheter ablation of tachycardia. Pacing Clin Electrophysiol 25:88, 2002. Ecole Polytechnique Fédérale de Lausanne: Visible human surface server. visiblehuman.epfl.ch.)

placed just superior to the ostium. This site is recommended for dualsite RA pacing.246 The second lead is usually placed in the atrial appendage. Achieving the desired location is directly related to stylet management and the skill of the operator. Local EGM and stimulation analysis, which is important for the recognition of far-field R-wave (FFRW) detection, can cause inappropriate mode switching. The height of any FFRW recorded on the atrial channel must be measured. During an implantation, FFRW analysis in sinus rhythm and normal atrioventricular (AV) conduction can be masked by the “current of injury” caused by the active fixation of the atrial septal lead. FFRW signals become superimposed on the current of injury. To avoid this problem, FFRWs can be measured during VVI pacing, in which the wave can be seen to precede the atrial complex, when ventriculoatrial (VA) conduction is present, or can be seen between beats during VA dissociation. FFRW voltages should be less than the P-wave voltage. If high FFRW voltages are found, lead repositioning should be considered. In addition, high FFRWs may also mean that the screw-in mechanism of the atrial lead is protruding into the ventricular myocardium. This possibility can be evaluated with high-output pacing from the atrium, which produces simultaneous atrial and ventricular stimulation if the lead is in the ventricular myocardium. Malpositioning of an atrial septal lead can be deleterious, possibly causing pacemaker syndrome or, if high-rate atrial tachyarrhythmia therapy pacing is used, resulting in inappropriate, dangerously high ventricular rates. Right Ventricular Selective Site Pacing The search for an alternative RV pacing site has gone on for many years. The results of a 2003 quantitative review suggest that the right ventricular outflow tract (RVOT) is the ideal site.247 However, anatomic, ECG, and functional criteria used to describe specific locations of the RV pacing lead are varied and conflicting.248 The heterogeneity of selective site RV pacing studies does not allow the definition of a single beneficial site. Perhaps the single, hemodynamically best site in any given patient must be individually sought. Some studies have suggested that the width of the paced QRS complex could indicate the most favorable site, but this concept has been questioned. At present, the best selected site for RV pacing is in the RVOT. Lieberman et al.249 define the RVOT as a broad area of the RV that is poorly defined and encompasses all areas except the apex. In the frontal projection, the lower border of the RVOT is a line extending from the apex of the tricuspid valve to the border of the RV (Fig. 21-114). The RVOT’s superior limit is the pulmonic valve. Fluoroscopic images and associated ECG patterns are used to define the RVOT. The lower border can be defined by extending an electrophysiologic catheter parallel to the RV inferior border from the tricuspid valve apex to the lateral RV border in the frontal RAO projection (Fig. 21-115). The superior border of the RVOT is determined by positioning the catheter across the pulmonic valve. Monitoring EGMs allows identification of the junction between RVOT and pulmonic valve. Once the RVOT boundaries have been defined, the selective site needs to be identified, by dividing the RVOT into quadrants. The RVOT is divided horizontally by a line midway between the pulmonic valve and the lower border, defining an upper and lower half. These halves are divided vertically by a line that connects the pulmonic valve to the RVOT lower border, dividing the RVOT into a septal wall and a free wall. Thus, the RVOT can be divided into four quadrants: high infundibular and low (outflow) septal RVOT, and high infundibular and low (outflow) free wall RVOT. The RAO fluoroscopic projection is used to determine high and low positions. The 40-degree LAO projection is used to differentiate RVOT, septal, and free wall positions (Fig. 21-116). The ECG is used to confirm pacing from the RV septum. In this position, the QRS in lead I is negative. When the RV free wall is paced, the QRS in lead I is positive. Lead aVF may be used to differentiate high and low positions. Ventricular pacing in the high position results in an upright QRS in lead aVF; lower positions result in a less positive QRS.



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

Frontal

A

511

LAO 45°

B

Frontal

C

LAO 45°

D

Figure 21-113  Fluoroscopic images of RAA and LAS leads. A and B, Position of right atrial appendage (RAA) lead: frontal view (A) and left anterior oblique (LAO) 45-degree angulation (B), where the RAA lead is directed superiorly and anteriorly. C and D, Position of low atrial septum (LAS) lead: Frontal view (C) and LAO 45-degree angulation (D), where the LAS lead is directed at 90-degree angles at the interatrial septum. (From de Voogt WG, van Mechelen R, van den Bos AA, et al: Electrical characteristics of low atrial septum pacing compared with right atrial appendage pacing. Europace 7:62, 2005.)

Direct His Bundle Pacing The normal His-Purkinje activation of the myocardium results in a rapid sequential depolarization of myocardial cells and efficient ventricular contraction. Therefore, the His bundle should be an ideal target for selective site pacing. This site should prevent ventricular dyssynchrony and maintain normal ventricular activation sequence. Human clinical experience with direct His bundle pacing is minimal. In 1992, Karpawich et al.250 described a permanent approach to His bundle pacing in open chests of dogs, using a specifically designed screw-in lead passed through a mapping introducer delivered through a right atriotomy. When an entirely transvenous approach was used, considerable difficulty was encountered directing the lead tip into the desired target. In 2004, Deshmukh et al.251 reported on attempts to perform direct His bundle pacing in 54 patients. All patients had a narrow QRS complex (<120 msec), persistent AF requiring AV node ablation, and a dilated cardiomyopathy. A hexapolar catheter introduced through the femoral vein was used to map and localize the His bundle with RAO projection. Once localized, the His bundle was paced. Criteria for His bundle capture included (1) His-Purkinje–mediated cardiac

activation and repolarization, as evidenced by ECG concordance of the QRS and T-wave complexes, (2) the paced ventricular interval identical to the His ventricular interval, and (3) His bundle capture in an allor-none manner, meaning that the QRS did not widen at a lower pacing output. This last criterion was critical in differentiating paraHisian pacing or indirect capture of the His bundle from direct His bundle pacing. Once the His bundle was localized, an active-fixation pacing lead was advanced into the septum. Conventional lead placement was difficult and required a specially modified, J-shaped stylet with a secondary distal curve orthogonal to the J plane, which allowed the lead to be positioned medially toward the AV septum. An attempt was made to position the lead near the mapping catheter. Once the lead was in position, an EP study was carried out, measuring His ventricular and paced ventricular intervals. Occasionally, because of rapid ventricular rates, radiofrequency ablation was performed. These investigators reported successful direct His bundle pacing in 39 patients. It is clear from their experience that direct His bundle pacing is feasible. Electrophysiologic mapping is critical to the procedure. Precise placement of a permanent pacing lead is extremely difficult, requiring special stylets for lead manipulation. Some form of catheter delivery system needs to be developed for this selective site.

512

SECTION 3  Implantation Techniques

Low septum High septum High free wall Low free wall

RAO

Figure 21-114  Anteroposterior view of right ventricle. The right ventricular outflow tract has been divided into four segments, two on the septum and two on the free wall. (From Lieberman R, Grenz D, Mond HG, et al: Selective site pacing: Defining and reaching the selected site. Pacing Clin Electrophysiol 27:883, 2004.)

The Future of Selective Site Pacing Selective site pacing in the atria and ventricles clearly is evolving. Many studies support this approach in either chamber. Unfortunately, most studies have been small and reflect conflicting and confusing data. The long-term harmful effects of RV apex pacing have been well catalogued and accepted. Unfortunately, there is a paucity of long-term data from carefully designed long-term studies. Patients with compromised LV function are at the greatest risk from RV apex pacing. The incidence of harm from RV apex pacing in patients with normal LV function is unknown, however, because no large, carefully designed studies have been performed. The large landmark trials, such as the Dual Chamber and VVI Implantable Defibrillator (DAVID) study, instruct us to minimize RV apex pacing and use atrium-based modes that promote AV conduction. But what about the patient who requires ventricular pacing? The results of pacing from alternative sites have been disappointing. There is no sound basis to do so from any site other than the RV apex. There

Figure 21-115  Right anterior oblique (RAO) fluoroscopic image of the heart with two catheters in the right ventricle to define the upper and lower limits of the right ventricular outflow tract. (From Lieberman R, Grenz D, Mond HG, et al: Selective site pacing: defining and reaching the selected site. Pacing Clin Electrophysiol 27:883, 2004.)

are problems defining the ideal alternate selective site as well as accurate, reliable, and stable lead placement. The RVOT is a poorly defined, broad area that needs definition of boundaries, both fluoroscopic and electrocardiographic. The scientific community must identify the best site to pace the heart, determine the location that provides optimal hemodynamic benefit, and create the tools to meet the challenge. There are also issues of training necessary for the implanting physician, who must let go of the old techniques and embrace new ones. If selective site pacing proves to be better, then safe, user-friendly, and cost-effective tools requiring minimal advanced training must be developed. Along with these considerations, there is a need for long-term, randomized studies that involve a well-defined patient population and use multiple well-defined pacing sites to evaluate functional hemodynamics, lead stability, extractability, and complication data. Until results of such studies become available, pacing at the RA appendage and RV apex, which has proven reliability, stability, and simplicity, should not be abandoned.

Figure 21-116  Left anterior oblique (LAO) views of the heart. Left, Anatomic diagram showing position of right ventricle (RV) and septum; LV, left ventricle. Right, Fluoroscopic image showing pacing lead in the low septum. (From Lieberman R, Grenz D, Mond HG, et al: Selective site pacing: defining and reaching the selected site. Pacing Clin Electrophysiol 27:883, 2004.)

RV

LV

LAO Septum



21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation

513

REFERENCES 1. Schecter DC: Modern era of artificial cardiac pacemakers. In Schecter DC, editor: Electrical cardiac stimulation, Minneapolis, 1983, Medtronic, pp 110-134. 2. Senning A: Discussion of a paper by Stephenson SE Jr, Edwards WH, Jolly PC, Scott HW: Physiologic P-wave stimulator. J Thorac Cardiovasc Surg 38:639, 1959. 3. Furman S, Schwedel JB: An intracardiac pacemaker for StokesAdams seizures. N Engl J Med 261:948, 1959. 4. Littleford PO, Spector SD: Device for the rapid insertion of permanent endocardial pacing electrode through the subclavian vein: preliminary report. Ann Thorac Surg 27:265, 1979. 5. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implantable automatic defibrillator in human beings. N Engl J Med 303:322, 1980. 6. Parsonnet V, Furman S, Smyth NP, Bilitch M: Optimal resources for implantable cardiac pacemakers. Pacemaker Study Group. Circulation 68:226A, 1983. 7. Parsonnet V, Bernstein AD, Lindsay B: Pacemaker implantation complication rates: an analysis of some contributing factors. J Am Coll Cardiol 13:917, 1989. 8. Tobin K, Stewart J, Westveer D, Frumin H: Acute complications of permanent pacemaker implantation: their financial implications and relation to volume and operator experience. Am J Cardiol 18:774-777, 2000. 9. Harcombe AA, Wood MA, Shepard RK: Late complications following permanent pacemaker implantation or elective unit replacement. Heart 80:240-244, 1998. 10. Harthorne JW, Parsonnet V: Seventeenth Bethesda Conference: Adult cardiac training. Task Force VI: Training in cardiac pacing. J Am Coll Cardiol 7:1213, 1986. 11. Parsonnet V, Bernstein AD: Pacing in perspective: concepts and controversies. Circulation 73:1087, 1986. 12. Parsonnet V, Bernstein AD, Galasso D: Cardiac pacing practices in the United States in 1985. Am J Cardiol 62:71, 1988. 13. Hayes DL, Naccarelli GV, Furman S, et al: Training require­ ments for permanent pacemaker selection, implantation, and follow-up. Pacing Clin Electrophysiol 26:1556-1562, 2003. 14. Bernstein AD, Parsonnet V: Survey of cardiac pacing in the United States in 1989. Am J Cardiol 69:331, 1992. 15. Stamato NJ, O’Toole MF, Enger EL: Permanent pacemaker implantation in the cardiac catheterization laboratory versus the operating room: an analysis of hospital charges and complications. Pacing Clin Electrophysiol 15:2236, 1992. 16. Hess DS, Gertz EW, Morady F, et al: Permanent pacemaker implantation in the cardiac catheterization laboratory: the subclavian approach. Cathet Cardiovasc Diagn 8:453, 1982. 17. Andersen FH, Crossland S, Alexander MB: Use of a threechannel electrocardiographic recorder for limited intracardiac electrocardiography during single- and double-chamber pacemaker implantation. Ann Thorac Surg 39:485, 1985. 18. Sutton R, Bourgeois I: Techniques of implantation. In Sutton R, Bourgeois I, editors: The foundations of cardiac pacing: an illustrated practical guide to basic pacing, vol I, pt 1, Mt Kisco, NY, 1991, Futura. 19. Levine PA, Balady GJ, Lazar HL, et al: Electrocautery and pacemakers: management of the paced patient subject to electrocautery. Ann Thorac Surg 41:313, 1986. 20. Belott PH, Sands S, Warren J: Resetting of DDD pacemakers due to EMI. Pacing Clin Electrophysiol 7:169, 1984. 21. Chauvin M, Crenner F, Brechenmacher C: Interaction between permanent cardiac pacing and electrocautery: the significance of electrode position. Pacing Clin Electrophysiol 15:2028, 1992. 22. Hauser RG, Edwards LM, Guiffe VW: Limitation of pacemaker system analyzers for evaluation of implantable pulse generators. Pacing Clin Electrophysiol 4:650, 1981. 23. Gregoratos G, Abrams J, Epstein AE, et al: ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers in Arrhythmia Devices: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Am Coll Cardiol 40:1703, 2002. 24. Zegelman M, Kreyzer J, Wagner R: Ambulatory pacemaker surgery: medical and economical advantages. Pacing Clin Electrophysiol 9:1299, 1986. 25. Belott PH: Outpatient pacemaker procedures. Int J Cardiol 17:169, 1987. 26. Dalvi B: Insertion of permanent pacemakers as a day case procedure. Br Med J 300:119, 1990. 27. Hayes DL, Vliestra RE, Trusty JM, et al: Can pacemaker implantation be done as an outpatient? J Am Coll Cardiol 7:199, 1986. 28. Hayes DL, Vliestra RE, Trusty JM, et al: A shorter hospital stay after cardiac pacemaker implantation. Mayo Clin Proc 63:236, 1988. 29. Haywood GA, Jones SM, Camm AJ, et al: Day case permanent pacing. Pacing Clin Electrophysiol 14:773, 1991. 30. Belott PH: Ambulatory pacemaker procedures: a 13-year experience. Pacing Clin Electrophysiol 19:69, 1996. 31. Health Care Financing Administration: Hospital manual, pub 10, sect 210A. 32. Douketis JD, Berger BP, et al: The perioperative management of antithrombotic therapy: American College of Chest Physicians’ evidence-based clinical practice guidelines (8th edition). Chest 133:299S-339S, 2008.

33. Belott PH, Finn Hulan KF: Optimal management of anticoagulation: Is interruption of anticoagulation necessary? Denver, Colorado, 2010, Heart Rhythm. 34. Goldstein DJ, Losquadro W, Spotnitz HM: Outpatient pacemaker procedures in orally anticoagulated patients. Pacing Clin Electrophysiol 21:1730, 1998. 35. Giudici MC, Barold SS, Paul DL: Pacemaker and implantable cardioverter defibrillator implantation without reversal of warfarin therapy. Pacing Clin Electrophysiol 27:358, 2004. 36. Ahmed I, Gertner E, Nelson WB, et al: Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation. Heart Rhythm 7:745-749, 2010. 37. Thal S, Moukabary T, et al: The relationship between warfarin, aspirin, and clopidogrel continuation in the peri-procedural period and the incidence of hematoma formation after device implantation. Pacing Clin Electrophysiol 33:385-388, 2010. 38. Dreger H, Grohmann A, et al: Is antiarrhythmia device implantation safe under dual antiplatelet therapy? Pacing Clin Electrophysiol 33:394-399, 2010. 39. Ghanbari H, Feldman D, et al: Cardiac resynchronization therapy device implantation in patients with therapeutic international normalizing ratios. Pacing Clin Electrophysiol 33:406, 2010. 40. Connolly S, Ezekowitz MD, Yusuf S, et al: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139-1151, 2009. 41. ECRI: A clinician’s guide to surgical fires. Health Devices 32:5-24, 2003. 42. Philip BK, Corvino BG: Local and regional anesthesia. In Wetchler BV, editor: Anesthesia for ambulatory surgery, ed 2, Philadelphia, 1991, Lippincott, pp 309-334. 43. Bubien RS, Fisher JD, Gentzel JA, et al: NASPE expert consensus document: use of IV (conscious) sedation/analgesia by nonanesthesia personnel in patients undergoing arrhythmia-specific diagnostic, therapeutic, and surgical procedures. Pacing Clin Electrophysiol 21:375, 1998. 44. Page CP, Bohen JMA, Fletcher R, et al: Antimicrobial prophylaxis for surgical wounds: guidelines for clinical care. Arch Surg 128:79, 1993. 45. Muers MF, Arnold AG, Sleight P: Prophylactic antibiotics for cardiac pacemaker implantation: a prospective trial. Br Heart J 46:539, 1981. 46. Ramsdale DR, Charles RG, Rowlands DB: Antibiotic prophylaxis for pacemaker implantation: a prospective randomized trial. Pacing Clin Electrophysiol 7:844, 1984. 47. Bluhm G, Jacobson B, Ransjo U: Antibiotic prophylaxis in pacemaker surgery: a prospective trial with local and systemic administration of antibiotics at pulse generator replacement. Pacing Clin Electrophysiol 8:661, 1985. 48. DaCosta A, Kirkorian G, et al: Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation 97:1796-1801, 1998. 49. Antimicrobial prophylaxis in surgery. Med Lett Drugs Ther 34:58, 1992. 50. De Olivereira JC, Martinelli M, et al: Efficiency of antibiotic prophylaxis before the implantation of pacemakers and cardioverter-defibrillator: results of a large, prospective, randomized double-blinded placebo-controlled trial. Circ Arrhythm Electrophysiol 2:29-34, 2009. 51. Antibiotic prophylaxis for surgery: treatment guidelines. Med Lett 2:27-32, 2004. 52. ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 56:1839-1887, 1999. 53. Bratzler DW, Houck PM: Antimicrobial prophylaxis for Surgery: an advisory statement from the national infection prevention project. Am J Surg 189:395-404, 2005. 54. Golightly LK, Branigan T: Surgical antibiotic irrigations. Hosp Pharm 24:116, 1989. 55. Agostinho A, James G, et al: Inhibition of Staphylococcus aureus biofilms by a novel antibacterial envelope for use with implantable cardiac devices. Clin Transl Sci 2:193-198, 2009. 56. Bloom LH, Constantin L, Dan D, et al: Implantation success and infection in cardiovascular implantable electronic device procedures utilizing an antibacterial envelope. Pacing Clin Electrophysiol 33:1-10, 2010. 57. Smyth NPD: Techniques of implantation: atrial and ventricular, thoracotomy and transvenous. Prog Cardiovasc Dis 23:435, 1981. 58. Smyth NPD: Pacemaker implantation: surgical techniques. Cardiovasc Clin 14:31, 1983. 59. Netter FH: Atlas of human anatomy, West Caldwell, NJ, 1992, CIBA Geigy. 60. Gray H, Pick TP, Howden RE: Anatomy: descriptive and surgical, 1901 ed, Philadelphia, 1974, Running Press, p 60. 61. Byrd C: Current clinical applications of dual-chamber pacing. In Zipes DP, editor: Proceedings of a symposium, Minneapolis, 1981, Medtronics, p 71. 62. Netter FH: The CIBA collection of medical illustrations, vol 5, Heart Summit, NJ, 1981, CIBA Medical Education Division, pp 22-26. 63. Furman S: Venous cutdown for pacemaker implantation. Ann Thorac Surg 41:438, 1986.

64. Feiesen A, Kelin GJ, Kostuck WJ, et al: Percutaneous insertion of a permanent transvenous pacemaker electrode through the subclavian vein. Can J Surg 10:131, 1977. 65. Littleford PO, Spector SD: Device for the rapid insertion of permanent endocardial pacing electrodes through the subclavian vein: preliminary report. Ann Thorac Surg 27:265, 1979. 66. Littleford PO, Parsonnet V, Spector SD: Method for rapid and atraumatic insertion of permanent endocardial electrodes through the subclavian vein. Am J Cardiol 43:980, 1979. 67. Miller FA, Jr, Homes DR, Jr, Gersh BJ, Maloney JD: Permanent transvenous pacemaker implantation via the subclavian vein. Mayo Clin Proc 55:309, 1980. 68. Belott PH, Byrd CL: Recent developments in pacemaker implantation and lead retrieval. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing 2, Mt Kisco, NY, 1991, Futura, pp 105-131. 69. Stokes K, Staffeson D, Lessar J, et al: A possible new complication of the subclavian stick: conductor fracture. Pacing Clin Electrophysiol 10:748, 1987. 70. Fyke FE, III: Simultaneous insulation deterioration associated with side by side subclavian placement of two polyurethane leads. Pacing Clin Electrophysiol 11:1571, 1988. 71. Fyke FE, III: Infraclavicular lead failure: tarnish on a golden route. Pacing Clin Electrophysiol 16:445, 1993. 72. Jacobs DM, Fink AS, Miller RP, et al: Anatomical and morphological evaluation of pacemaker lead compression. Pacing Clin Electrophysiol 16:373, 1993. 73. Magney JE, Flynn DM, Parsons JA, et al: Anatomical mechanisms explaining damage to pacemaker leads, defibrillator leads, and failure of central venous catheters adjacent to the sternoclavicular joint. Pacing Clin Electrophysiol 16:445, 1993. 74. Subclavian venipuncture reconsidered as a means of implanting endocardial pacing leads. Angleton, Texas, 1987, Issues Intermedics, pp 1-2. 75. Subclavian puncture may result in lead conductor fracture. Medtronic News 16:27, 1986-1987. 76. Byrd CL: Safe introducer technique for pacemaker lead implantation. Pacing Clin Electrophysiol 15:262, 1992. 77. Nichalls RWD: A new percutaneous infraclavicular approach to the axillary vein. Anesthesia 42:151, 1987. 78. Taylor BL, Yellowlees I: Central venous cannulation using the infraclavicular axillary vein. Anesthesiology 72:55, 1990. 79. Byrd CL: Clinical experience with the extrathoracic introducer insertion technique. Pacing Clin Electrophysiol 16:1781, 1993. 80. Magney JE, Staplin DH, Flynn DM, et al: A new approach to percutaneous subclavian needle puncture to avoid lead fracture or central venous catheter occlusion. Pacing Clin Electrophysiol 16:2133, 1993. 81. Belott PH: Blind percutaneous axillary venous access. Pacing Clin Electrophysiol 22:1085, 1999. 82. Belott PH: How to access the axillary vein. Heart Rhythm 3:366369, 2006. 83. Varnagy G, Velasquez R, Navarro D: New technique for cephalic vein approach in pacemaker implants. Pacing Clin Electrophysiol 18:1807a, 1995. 84. Spencer W, III, Kirkpatrick C, Zhu DWX: The value of venogram-guided percutaneous extrathoracic subclavian venipuncture for lead implantation. Pacing Clin Electrophysiol 19:700, 1996. 85. Spencer W, III, Zhu DWX, Kirkpatrick C, et al: Subclavian venogram as a guide to lead implantation. Pacing Clin Electrophysiol 21:499, 1998. 86. Ramza BM, Rosenthal L, Hui R, et al: Safety and effectiveness of placement of pacemaker and defibrillator leads in the axillary vein guided by contrast venography. Am J Cardiol 80:892, 1997. 87. Fyke FE, III: Doppler-guided extrathoracic introducer insertion. Pacing Clin Electrophysiol 18:1017, 1995. 88. Gayle DD, Bailery JR, Haistey WK, et al: A novel ultrasoundguided approach to the puncture of the extrathoracic subclavian vein for surgical lead placement. Pacing Clin Electrophysiol 19:700, 1996. 89. Nash A, Burrell CJ, Ring NJ, Marshall AJ: Evaluation of an ultrasonically guided venipuncture technique for the placement of permanent pacing electrodes. Pacing Clin Electrophysiol 21:452, 1998. 90. Lamas GA, Fish DR, Braunwald NS: Fluoroscopic technique of subclavian venous puncture for permanent pacing: a safer and easier approach. Pacing Clin Electrophysiol 11:1398, 1987. 91. Higano ST, Hayes DL, Spittell PC: Facilitation of the subclavianintroducer technique with contrast venography. Pacing Clin Electrophysiol 15:731, 1992. 92. Belott PH: Implantation techniques: new developments. In Barold SS, Mugica J, editors: New perspectives in cardiac pacing, Mt Kisco, NY, 1988, Futura, pp 258-259. 93. Bognolo DA: Recent advances in permanent pacemaker implantation techniques. In Barold SS, editor: Modern cardiac pacing. Mt Kisco, NY, 1985, Futura, pp 206-207. 94. Parsonnet V, Werres R, Atherly T, et al: Transvenous insertion of double sets of permanent electrodes. JAMA 243:62, 1980. 95. Bognolo PA, Vijayanagar RR, Eckstein PR, et al: Two leads in one introducer technique for A-V sequential implantation. Pacing Clin Electrophysiol 5:217, 1982.

514

SECTION 3  Implantation Techniques

96. Vander Salm TJ, Haffajee CI, Okike ON: Transvenous insertion of double sets of permanent electrodes through a single introducer: clinical application. Ann Thorac Surg 32:307, 1981. 97. Belott PH: A variation on the introducer technique for unlimited access to the subclavian vein. Pacing Clin Electrophysiol 4:43, 1981. 98. Gessman LJ, Gallagher JD, MacMillan RM, et al: Emergency guidewire pacing: new methods for rapid conversion of a cardiac catheter into a pacemaker. Pacing Clin Electrophysiol 7:917, 1984. 99. Ong LS, Barold SS, Lederman M, et al: Cephalic vein guidewire technique for implantation of permanent pacemakers. Am Heart J 114:753, 1987. 100. August DA, Elefteriades JA: Technique to facilitate open placement of permanent pacing leads through the cephalic vein. Ann Thorac Surg 42:112, 1986. 101. Parsonnet V, Bernstein AD: Cardiac pacing in the 1980s: treatment and techniques in transition. J Am Coll Cardiol 1:399, 1983. 102. Furman S: Venous cutdown for pacemaker implantation. Ann Thorac Surg 41:438, 1986. 103. Furman S: Subclavian puncture for pacemaker lead placement. Pacing Clin Electrophysiol 9:467, 1986. 104. Sutton R, Bourgeois I: The foundations of cardiac pacing. I. An illustrated practical uide to basic pacing. Mt Kisco, NY, 1991, Futura, pp 235-243. 105. Barrold SS, Mugica J: Recent advances in cardiac pacing, Vol 19. Goals for the 21st century. Mt Kisco, NY, 1998, Futura, pp 213-231. 106. Rosso R, Teh AW, Medi C, et al: Right ventricular septal pacing: the success of stylet-driven active-fixation leads. Pacing Clin Electrophysiol 33:49-53, 2010. 107. Mond HG, Hiiock RJ, Stevenson IH, et al: The right ventricular rout flow tract: the road to septal pacing. Pacing Clin Electrophysiol 30:482-491, 2007. 108. Belott PH: Retained guidewire introducer technique, for unlimited access to the central circulation: a review. Clin Prog Electrophysiol Pacing 1:59, 1981. 109. Bognolo DA, Vijayanagar R, Ekstein PF, et al: Anatomical suitability of the right atrial appendage for atrial J lead electrodes. In Proceedings of the Second European Pacing Symposium, Padova, Italy, 1982, Piccin Medical, p 639. 110. Bognolo DA, Vigayanagar R, Ekstein PF, et al: Implantation of permanent atrial J lead using lateral fluoroscopy. Ann Thorac Surg 316:574, 1981. 111. Thurer RJ: Technique of insertion of transvenous atrial pacing leads: the value of lateral fluoroscopy. Pacing Clin Electrophysiol 4:525, 1981. 112. Jamidar H, Goli V, Reynolds DW: The right atrial free wall: an alternative pacing site. Pacing Clin Electrophysiol 16:959, 1993. 113. Saxonhouse SJ, Conti JB, Curtis AB: Current of injury predicts adequate active lead fixation in permanent pacemaker/ defibrillation leads. J Am Coll Cardiol 45:412, 2005. 114. Bognolo DA, Vijaranagar RR, Eckstein PF, Janss B: Method for reintroduction of permanent endocardial pacing electrodes. Pacing Clin Electrophysiol 5:546, 1982. 115. Bognolo DA, Vijay R, Eckstein P, Jeffrey D: Technical aspects of pacemaker system upgrading procedures. Clin Prog Pacing Electrophysiol 1:269, 1983. 116. Belott PH: Use of the contralateral subclavian vein for placement of atrial electrodes in chronically VVI paced patients. Pacing Clin Electrophysiol 6:781, 1983. 117. Parsonnet V: A stretch fabric pouch for implanted pacemakers. Arch Surg 105:654, 1972. 118. Sagar PM, Meagher A, Sobczak S, Wolff BG: Chemical composition and potential hazards of electrosurgical smoke. Br J Surg 83:1792, 1996. 119. Baggish M: Presence of human immunodeficiency virus DNA in laser smoke. Laser Surg Med 11:197-203, 1993. 120. Roelke M, Jackson G, Hawthorne JW: Submammary pacemaker implantation: a unique tunneling technique. Pacing Clin Electrophysiol 17:1793, 1994. 121. Ellestad MH, French J: Iliac vein approach to permanent pacemaker implantation. Pacing Clin Electrophysiol 12:1030, 1989. 122. Antonelli D, Freedberg NA, Rosenfeld T: Transiliac vein approach to a rate-responsive permanent pacemaker implantation. Pacing Clin Electrophysiol 16:1637, 1993. 123. Ching CK, Elayi CS, Di Biase L, et al: Transiliac ICD implantation: defibrillation vector flexibility produces consistent success. Heart Rhythm 6:978-983, 2009. 124. Belott PH, Bucko D: Inframammary pulse generator placement for maximizing optimal cosmetic effect. Pacing Clin Electrophysiol 6:1241, 1983. 125. Shefer A, Lewis SB, Gang ES: The retropectoral transaxillary permanent pacemaker: description of a technique for percutaneous implantation of an invisible device. Pacing Clin Electrophysiol 16:1646, 1996. 126. Young D: Permanent pacemaker implantation in children: current status and future considerations. Pacing Clin Electrophysiol 4:61, 1981. 127. Smith RT, Jr: Pacemakers for children. In Gillette PC, Garson A, Jr, editors: Pediatric arrhythmias: electrophysiology and pacing, New York, 1990, Grune & Stratton, pp 532-558. 128. Smith RT, Jr, Armstrong K, Moak JP, et al: Actuarial analysis of pacing system survival in young patients. Circulation 74(Suppl II):120, 1986. 129. Gillette PC, Zeigler VL, Winslow AT, Kratz JM: Cardiac pacing in neonates, infants, and preschool children. Pacing Clin Electrophysiol 15:2046, 1992.

130. Guldal M, Kervancioglu C, Oral D, et al: Permanent pacemaker implantation in a pregnant woman with guidance of ECG and two-dimensional echocardiography. Pacing Clin Electrophysiol 10:543, 1987. 131. Lau CP, Wong CK, Leung WH, et al: Ultrasonic assisted permanent pacing in a patient with severe pulmonary tuberculosis. Pacing Clin Electrophysiol 12:1131, 1989. 132. Morris DC, Scott IR, Jamesson WR: Pacemaker electrode repositioning using the loop snare technique. Pacing Clin Electrophysiol 12:996, 1989. 133. Westerman GR, Van Devanter SH: Transthoracic transatrial endocardial lead placement for permanent pacing. Ann Thorac Surg 43:445, 1987. 134. Hayes DL, Vliestra RE, Puga FJ, et al: A novel approach to atrial endocardial pacing. Pacing Clin Electrophysiol 12:125, 1989. 135. Byrd CL, Schwartz SJ: Transatrial implantation of transvenous pacing leads as an alternative to implantation of epicardial leads. Pacing Clin Electrophysiol 13:1856, 1990. 136. Dosios T, Gorgogiannis D, Sakorafas G, et al: Persistent left superior vena cava: a problem in transvenous pacing of the heart. Pacing Clin Electrophysiol 14:389, 1991. 137. Hussaine SA, Chalcravarty S, Chaikhouni A: Congenital absence of superior vena cava: unusual anomaly of superior systemic veins complicating pacemaker placement. Pacing Clin Electrophysiol 4:328, 1981. 138. Ronnevik PK, Abrahamsen AM, Tollefsen J: Transvenous pacemaker implantation via a unilateral left superior vena cava. Pacing Clin Electrophysiol 5:808, 1982. 139. Cha EM, Khoury GH: Persistent left superior vena cava. Radiology 103:375, 1972. 140. Colman AL: Diagnosis of left superior vena cava by clinical inspection: a new physical sign. Am Heart J 73:115, 1967. 141. Dirix LY, Kersscochot IE, Fiernen SH, et al: Implantation of a dual-chambered pacemaker in a patient with persistent left superior vena cava. Pacing Clin Electrophysiol 11:343, 1988. 142. Giovanni QV, Piepoli N, Pietro Q, et al: Cardiac pacing in unilateral left superior vena cava: evaluation by digital angiography. Pacing Clin Electrophysiol 14:1567, 1991. 143. Robbens EJ, Ruiter JH: Atrial pacing by unilateral persistent left superior vena cava. Pacing Clin Electrophysiol 9:594, 1986. 144. Hellestrand KJ, Ward DE, Bexton RS, et al: The use of active fixation electrodes for permanent endocardial pacing via a persistent left superior vena cava. Pacing Clin Electrophysiol 5:180, 1982. 145. West JNW, Shearmann CP, Gammange MD: Permanent pacemaker positioning via the inferior vena cava in a case of single ventricle with loss of right atrial to vena caval continuity. Pacing Clin Electrophysiol 16:1753, 1993. 146. Fischberger SB, Cammanas J, Rodriguez-Fernandez H, et al: Permanent pacemaker lead implantation via the transhepatic route. Pacing Clin Electrophysiol 19:1124, 1996. 147. Moss AJ, Rivers RJ, Jr: Atrial pacing from the coronary vein: ten-year experience in 50 patients with implanted pervenous pacemakers. Circulation 57:103, 1978. 148. Greenberg P, Castellanet M, Messenger J, Ellestad MH: Coronary sinus pacing. Circulation 57:98, 1978. 149. Hewitt MJ, Chen JTT, Ravin CE, Gallagher JJ: Coronary sinus atrial pacing: Radiographic considerations. Am J Radiol 136:323, 1981. 150. Trappe H, Pfitzner P, Heintze J, et al: Cardioverter-defibrillator implantation in the catheterization laboratory: Initial experiences in 46 patients. Am Heart J 129:259-264, 1995. 151. Koukal C, Hemmer W, Oertel F, et al: ENDOTAK lead alone configuration, a new standard when using biphasic shocks [abstract]? Pacing Clin Electrophysiol 18:1189, 1995. 152. Bardy GH, Johnson G, Poole JE, et al: A simplified, single-lead unipolar transvenous cardioversion-defibrillation system. Circulation 88:543, 1993. 153. Raitt MH, Bardy GH: Advances in implantable cardioverterdefibrillator therapy. Curr Opin Cardiol 9:23, 1994. 154. Bernstein AD, Parsonnet V: Survey of cardiac pacing in the United States in 1989. Am J Cardiol 69:331, 1992. 155. Flowers NC, Abildskov JA, Armstrong WF, et al: ACC Policy Statement: Recommended guidelines for training in adult clinical cardiac electrophysiology. J Am Coll Cardiol 18:637, 1991. 156. Scheinman M, Akhtar M, Brugada P, et al: Teaching objectives for fellowship programs in clinical electrophysiology. Report for the Ad Hoc Committee of the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol 12:255, 1988. 157. Natale A, Kearney MM, Brandon MJ, et al: Safety of nurseadministered deep sedation for defibrillator implantation in the electrophysiology laboratory. J Cardiovasc Electrophysiol 7:301, 1996. 158. Lehmann MH, Saksena S: Implantable cardioverter defibrillators in cardiovascular practice: report of the Policy Conference of the North American Society of Pacing and Electrophysiology. Pacing Clin Electrophysiol 14:969, 1991. 159. Curtis AB, Ellenbogen KA, Hammill SC, et al: Clinical Competency Statement: Training pathways for implantation of cardioverter defibrillators in cardiac resynchronization devices. Heart Rhythm 1:371, 2004. 160. Fitzpatrick AP, Lesh MD, Epstein LM, et al: Electrophysiological laboratory, electrophysiologist-implanted, nonthoracotomyimplantable cardioverter defibrillators. Circulation 89:2503, 1994.

161. Strickberger SA, Hummel JD, Daoud E, et al: Implantation by electrophysiologist of 100 consecutive cardioverter-defibrillators with nonthoracotomy lead systems. Circulation 90:868, 1994. 162. Strickberger SA, Niebauer M, Ching Man K, et al: Comparison of implantation of nonthoracotomy defibrillators in the operating room versus the electrophysiology laboratory. Am Heart J 75:255, 1995. 163. Bardy GH, Hofer B, Johnson G, et al: Implantable cardioverterdefibrillators. Circulation 87:1152, 1993. 164. Brooks R, Garan H, Torchiana D, et al: Determinants of successful nonthoracotomy cardioverter-defibrillator implantation: experience in 101 patients using two different lead systems. J Am Coll Cardiol 22:1835, 1993. 165. Luceri RM, Zilo P, Habal SM, David IB: Cost and length of hospital stay: comparisons between nonthoracotomy and epicardial techniques in patients receiving implantable cardioverter defibrillators. Pacing Clin Electrophysiol 18:168, 1995. 166. Stanton MS, Hayes DL, Munger TM, et al: Consistent subcutaneous prepectoral implantation of a new implantable cardioverter defibrillator. Mayo Clin Proc 69:309, 1994. 167. Mower M, Mirowski M, Pitt B, et al: Ventricular defibrillation with a single intravascular catheter system having distal electrode in left pulmonary artery and proximal electrode in right ventricle or right atrium [abstract]. Clin Res 20:389, 1972. 168. Schuder JC, Stoeckle H, West JA, et al: Ventricular defibrillation with catheter having distal electrode in right ventricle and proximal electrode in superior vena cava [abstract]. Circulation 43/44:99, 1971. 169. Tung RT, Bajaj AK: Safety of implantation of a cardioverterdefibrillator without general anesthesia in an electrophysiology laboratory. Am J Cardiol 75:908, 1995. 170. Lipscomb KJ, Linker NJ, Fitzpatrick AP: Subpectoral implantation of a cardioverter defibrillator under local anesthesia. Heart 79:253, 1998. 171. Pacifico A, Cedillo-Salazar FR, Nasir N, Jr, et al: Conscious sedation with combined hypnotic agents for implantation of implantable cardioverter-defibrillators. J Am Coll Cardiol 30:679, 1997. 172. Moerman A, Herregods L, Foubert L, et al: Awareness during anaesthesia for implantable cardioverter defibrillator implantation: recall of defibrillation shocks. Anaesthesia 50:733, 1995. 173. Hunt GB, Ross DL: Comparison of effects of three anesthetic agents on induction of ventricular tachycardia in a canine model of myocardial infarction. Circulation 78:221, 1988. 174. Natale A, Jones DL, Kim Y-H, et al: Effects of lidocaine on defibrillation threshold in the pig: evidence of anesthesia related increase. Pacing Clin Electrophysiol 14:1239, 1991. 175. Gill RM, Sweeney RJ, Reid PR: The defibrillation threshold: a comparison of anesthetics and measurements methods. Pacing Clin Electrophysiol 16:708, 1993. 176. Shepard RB, Goldin MD, Lawrie GM, et al: Automatic implantable cardioverter defibrillator: surgical approaches for implantation. J Card Surg 7:208, 1992. 177. Watkins L, Jr, Taylor E, Jr: The surgical aspects of automatic implantable cardioverter-defibrillator implantation. Pacing Clin Electrophysiol 14:953, 1991. 178. Watkins L, Jr, Guarnieri T, Griffith LS, et al: Implantation of the automatic implantable cardioverter defibrillator. J Card Surg 3:1, 1998. 179. Daoud EG, Strickberger SA, Man KC, et al: Comparison of early and late complications in patients undergoing coronary artery bypass graft surgery with and without concomitant placement of an implantable cardioverter defibrillator. Am Heart J 130:780, 1995. 180. Trappe HJ, Klein H, Wahlers T, et al: Risk and benefit of additional aortocoronary bypass grafting in patients undergoing cardioverter-defibrillator implantation. Am Heart J 127:75, 1994. 181. Watkins L, Jr, Mirowski M, Mower MM, et al: Automatic defibrillation in man: the initial surgical experience. J Thorac Cardiovasc Surg 82:492, 1981. 182. Troup PJ, Chapman PD, Olinger GN, et al: The implanted defibrillator: relation of defibrillating lead configuration and clinical variable to defibrillation threshold. J Am Coll Cardiol 6:1315, 1985. 183. Watkins L, Jr, Mirowski M, Mower MM, et al: Implantation of the automatic defibrillator: the subxiphoid approach. Ann Thorac Surg 35:515, 1982. 184. Flaker G, Boley T, Walls J, et al: Comparison of subxiphoid and traditional approaches for ICD implantation. Pacing Clin Electrophysiol 15:1531, 1992. 185. Beckman DJ, Crevey BJ, Foster PR, et al: Subxiphoid approach for implantable cardioverter defibrillator in patients with previous coronary bypass surgery. Pacing Clin Electrophysiol 15:1637, 1992. 186. Lawrie GM, Griffin JC, Wyndham CRC: Epicardial implantation of the automatic implantable defibrillator by the left subcostal thoracotomy. Pacing Clin Electrophysiol 7:1370, 1984. 187. Shahian DM, Williamson WA, Streitz JM, Jr, Venditti FJ: Subfascial implantation of implantable cardioverter defibrillator generator. Ann Thorac Surg 54:173, 1992. 188. O’Neill PG, Lawrie GM, Kaushik RR, et al: Late results of the left subcostal approach for automatic implantable cardioverter. Am J Cardiol 67:387, 1991. 189. Lawrie GM, Kaushik RR, Pacifico A: Right mini-thoracotomy: an adjunct to left subcostal automatic implantable cardioverter defibrillator implantation. Ann Thorac Surg 47:780, 1989.



190. Damiano RJ, Jr, Foster AH, Ellenbogen KA, et al: Implantation of cardioverter defibrillators in the post-sternotomy patient. Ann Thorac Surg 53:978, 1992. 191. Obadia JF, Claudel JP, Rescigno G, et al: Subdiaphragmatic implantation of implantable cardioverter defibrillator generator. Ann Thorac Surg 59:239, 1995. 192. Shapira N, Cohen AI, Wish M, et al: Transdiaphragmatic implantation of the automatic implantable cardioverter defibrillator. Ann Thorac Surg 48:371, 1989. 193. Frumin H, Goodman GR, Pleatman M: ICD implantation via thoracoscopy without the need for sternotomy or thoracotomy. Pacing Clin Electrophysiol 16:257, 1993. 194. Krasna MJ, Buser GA, Flowers JL, et al: Thoracoscopic versus laparoscopic placement of defibrillator patches. Surg Laparosc Endosc 6:91, 1996. 195. Tobin M, Ching E, Firstenberg M, et al: Thoracoscopy ICD implantation compared to a subxyphoid approach [abstract]. Eur J Cardiac Pacing Electrophysiol 4:118, 1994. 196. Jansens JL, Jottrand M, Treumont N, et al: Robotic-enhanced biventricular resynchronization: An alternative to endovenous cardiac resynchronization therapy in chronic heart failure. Ann Thorac Surg 76:413, 2003. 197. Saksena S, Parsonnet V: Implantation of a cardioverter/ defibrillator without thoracotomy using a triple electrode system. JAMA 259:69, 1988. 198. Saksena S, Tullo NG, Krol RB, Mauro AM: Initial clinical experience with endocardial defibrillation using an implantable cardioverter/defibrillator with a triple-electrode system. Arch Intern Med 149:2333, 1989. 199. Tullo NG, Saksena S, Krol RB, et al: Management of complications associated with a first-generation endocardial defibrillation lead system for implantable cardioverter-defibrillators. Am J Cardiol 66:411, 1990. 200. McCowan R, Maloney J, Wilkoff B, et al: Automatic implantable cardioverter-defibrillator implantation without thoracotomy using an endocardial and submuscular patch system. J Am Coll Cardiol 17:415, 1991. 201. Trappe H, Klein H, Fieguth H, et al: Initial experience with a new transvenous defibrillation system. Pacing Clin Electrophysiol 16:134, 1993. 202. Bhandari AK, Isber N, Estioko M, et al: Efficacy of low-energy T wave shocks for induction of ventricular fibrillation in patients with implantable cardioverter defibrillators. J Electrocardiol 31:31, 1998. 203. Roelke M, O’Nunain SS, Osswald S, et al: Subclavian crush syndrome complicating transvenous cardioverter defibrillator systems. Pacing Clin Electrophysiol 18:1968, 1995. 204. Lawton JS, Wood MA, Gilligan DM, et al: Implantable transvenous cardioverter-defibrillator leads: the dark side. Pacing Clin Electrophysiol 19:1273, 1996. 205. Kirchhoffer JB, Cook JR, Kabell GG, et al: Right-sided implantation of defibrillators using nonthoracotomy lead system is feasible. The Jewel Investigators. Pacing Clin Electrophysiol 18:874, 1995. 206. Epstein AE, Kay GN, Plumb VJ, et al: Elevated defibrillation threshold when right-sided venous access is used for nonthoracotomy implantable defibrillator lead implantation. The ENDOTAK Investigators. J Cardiovasc Electrophysiol 6:979, 1995. 207. Bardy GH, Yee R, Jung W: Multicenter experience with a pectoral unipolar transvenous cardioversion-defibrillation. Active Can Investigators. J Am Coll Cardiol 28:400, 1996. 208. Saksena S, DeGroot P, Krol RB, et al: Low-energy endocardial defibrillation using an axillary or a pectoral thoracic electrode location. Circulation 88:2655, 1993. 209. Jordaens L, Vertongen P, van Bellegham Y: A subcutaneous lead array for implantable cardioverter defibrillators. Pacing Clin Electrophysiol 16:1429, 1993.

21  Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation 210. Cesario D, Bhargava M, Valderrabano M, et al: Azygos vein lead implantation: a novel adjunctive technique for implantable cardioverter-defibrillator placement. J Cardiovasc Electrophysiol 15:780-783, 2004. 211. Cooper JA, Latacha MP, Soto GE, et al: The azygos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series. Pacing Clin Electrophysiol 31:1405-1410, 2008. 212. Cooper JA, Smith TW: How to implant a defibrillation coil in the azygos vein. Heart Rhythm 7:1, 2009. 213. Bardy GH, Smith WM, Hood MA, et al: An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 363:3644, 2010. 214. Crossley GH, Gayle DD, Bailey JR, et al: Defibrillator twiddler’s syndrome causing device failure in a subpectoral transvenous system. Pacing Clin Electrophysiol 19:376-377, 1996. 215. Eastman DP, Selle JG, Reames MK, Sr: Technique for subpectoral implantation of cardioverter defibrillators. J Am Coll Surg 181:475, 1995. 216. Bardy GH, Yee R: Worldwide experience with the Jewel 7219C unipolar, single-lead active can implantable pacer-cardioverter/ defibrillator. The International Active Can Investigators. Pacing Clin Electrophysiol 18:806, 1995. 217. Foster AH: Technique for implantation of cardioverter defibrillators in the subpectoral position. Ann Thorac Surg 59:764, 1995. 218. Giudici MC: Experience with a cosmetic approach to device implantation. Pacing Clin Electrophysiol 24:1679-1680, 2001. 219. Giudici MC, Carlson JI, Krupa RK, et al: Submammary pacemakers and ICDs in women: long-term follow-up and patient satisfaction. Pacing Clin Electrophysiol 33:1373-1375, 2010. 220. Wilkoff BL, Cook JR, Epstein AE, et al: Dual chamber pacing or ventricular backup pacing in patients with an implantable defibrillator. The Dual Chamber and VVI Implantable Defibrillator (DAVID) trial. JAMA 288:3115, 2002. 221. Nielson JC, Kristensen L, Anderson HR, et al: A randomized comparison of atrial and dual-chambered pacing in 177 consecutive patients with sick sinus syndrome. J Am Coll Cardiol 42:614, 2003. 222. Prinzen FW, Peschar M: Relationship between the pacinginduced sequence of activation and left ventricular pump function in animals. Pacing Clin Electrophysiol 25:484, 2002. 223. Rosenqvist M, Isaaz K, Botvinick EH, et al: Relative importance of activation sequence compared to atrial ventricular synchrony in left ventricular function. Am J Cardiol 67:148, 1991. 224. Rosenqvist M, Brandt J, Schuller H: Long-term pacing in sinus node disease: effects of stimulation mode on cardiovascular morbidity and mortality. Am Heart J 116:16, 1988. 225. Stangl K, Seitz K, Wirtzfeld A, et al: Differences between atrial single-chamber pacing (AAI) and ventricular single-chamber pacing (VVI) with respect to prognosis and antiarrhythmic effect in patients with sick sinus syndrome. Pacing Clin Electrophysiol 13:2080, 1990. 226. Brandt J, Anderson H, Fahraeus T, et al: Natural history of sinus node disease treated with atrial pacing in 213 patients: Implications for selection of stimulation mode. J Am Coll Cardiol 20:633, 1992. 227. Anderson HR, Thuesen L, Bagger JP, et al: Prospective randomized trial of atrial versus ventricular pacing in sick sinus syndrome. Lancet 344:1523, 1994. 228. Daubert C, Gras D, Berder V et al: [Permanent atrial resynchronization by synchronous bi-atrial pacing in the preventive treatment of atrial flutter associated with high degree interatrial block]. Arch Mal Coeur Vaiss 87:1535, 1994. 229. Saksena S, Prakash A, Hill M, et al: Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing. J Am Coll Cardiol 28:687, 1996.

515

230. Levy T, Walker S, Rochelle J, Ball V: Evaluation of biatrial pacing, right atrial pacing, and no pacing in patients with drugrefractory atrial fibrillation. Am J Cardiol 84:426, 1999. 231. Levy T, Walker S, Rex S, et al: No incremental benefit of multisite atrial pacing compared to right atrial pacing in patients with drug-refractory atrial fibrillation. Heart 85:48, 2001. 232. Leclercq JF, DeSisti A, Fiorello P, et al: Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? Pacing Clin Electrophysiol 23:2101, 2000. 233. Padeletti L, Porciani MC, Michelucci A, et al: Intraatrial septum pacing: a new approach to prevent recurrent atrial fibrillation. J Interv Card Electrophysiol 3:35, 1999. 234. Frohlig G, Schwaab B, Kindermann M: Selective site pacing: the right ventricular approach. Pacing Clin Electrophysiol 27:855, 2004. 235. De Voogt WG, Van Mechelen R, Van Den Bos A, et al: A technique of lead insertion for low atrial septal pacing. Pacing Clin Electrophysiol 28:639, 2005. 236. Netter FH: Atria and ventricles, right atrium. In Yonkman FF, editor: CIBA collection of medical illustrations, vol 5. Heart. Newark, NJ, 1969, CIBA-Geigy, p A. 237. Ho S, Anderson RH, Sanchez-Quintana D: Gross structure of the atriums: more than an anatomical curiosity. Pacing Clin Electrophysiol 25:842, 2002. 238. Ho S: Understanding atrial anatomy: implications for atrial fibrillation ablation. In Cardiology International for a global perspective on cardiac care, London, 2002, Greycoat, pp S17-S20. 239. Farré J, Anderson RH, Cabrera JA, et al: Fluoroscopic cardiac anatomy for catheter ablation of tachycardia. Pacing Clin Electrophysiol 25:76, 2002. 240. Bachmann G: The interauricular time interval. Am J Physiol 1:1, 1907. 241. James TN, Sherf L: Specialized tissues and preferential conduction in the atria of the heart. Am J Cardiol 28:414, 1971. 242. Roithinger FX, Cheng J, Sippens A, et al: Use of electroanatomical mapping to delineate transseptal atrial conduction in humans. Circulation 100:1791, 1999. 243. Anderson RH, Ho SY: The architecture of the sinus node, the atrioventricular conduction axis in the intranodal atrial myocardium. J Cardiovasc Electrophysiol 9:1233, 1998. 244. Chauvin M, Shah DC, Hauissaguerre M, et al: The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation 101:647, 2000. 245. DePonti R, Ho SY, Salerno-Uriarte JA, et al: Electroanatomical analysis of sinus impulse propagation in normal human atria. J Cardiovasc Electrophysiol 13:1, 2002. 246. Saksena S, Prakash A, Hill M, et al: Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing. J Am Coll Cardiol 28:687, 1996. 247. De Cock CC, Giudici MC, Twisk JW: Comparison of the hemodynamic effects of right ventricular outflow tract pacing with right ventricular apex pacing: a quantitative review. Europace 5:275, 2003. 248. Stambler BS, Ellenbogen KA, Zhang X, et al: Right ventricular outflow versus apical pacing in pacemaker patients with congestive heart failure and atrial fibrillation. J Cardiovasc Electrophysiol 14:1180, 2003. 249. Lieberman R, Grenz D, Mond HG, et al: Selective site pacing: defining and reaching the selected site. Pacing Clin Electrophysiol 27:883, 2004. 250. Karpawich P, Gates J, Stokes K: Septal His-Purkinje ventricular pacing in canines: a new endocardial electrode approach. Pacing Clin Electrophysiol 15:2011, 1992. 251. Deshmukh PM, Romanyshyn M: Direct His-bundle pacing, present and future. Pacing Clin Electrophysiol 27:862, 2004.

516

SECTION 3  Implantation Techniques

22  22

Left Ventricular Lead Implantation SETH J. WORLEY

C

ardiac resynchronization therapy (CRT) reduces the chance of hospitalization, improves quality of life, and lowers mortality from congestive heart failure.1-4 CRT requires left ventricular (LV) pacing, usually by a lead placed transvenously through a coronary vein on the epicardium.5-7 Transvenous pacing of the LV epicardium through the coronary venous system can be technically difficult,2,8 but it is safe, and thresholds remain stable.7,9

Although catheters from interventional radiology and cardiology can be used as vein selectors, they are the wrong length, the tips are too stiff, and the shapes are not ideal (Fig. 22-2). Fortunately, additional vein selectors are now available in multiple shapes (Fig. 22-3).

Transvenous LV lead implantation was new in 1998 and, as with most new therapeutic procedures, required the development of tools and techniques for its safe and cost-effective implementation into clinical practice.10 Because CRT devices were implanted predominantly by electrophysiologist (EP) physicians, their skill set and experience determined the initial tool set. Unfortunately, the EP-suited tools did not overlap well with those useful for LV lead implantation, resulting in a steep learning curve, long case times, and failed implants. Using the EP skill set, pioneering physicians and early adopters eventually developed their own technique, employing a combination of the limited tools designed for the procedure and existing tools that proved useful through improvisation;11-20 however, some patients experienced adverse results.21-25 Having endured the painful and at times humiliating process of learning to implant LV leads with the EP skill set and suboptimal tools available, there was resistance to learning a new, interventional skill set to use tools better adapted to LV lead implantation. In the end, however, it is better to learn an unfamiliar skill set to use new tools than to continue with a familiar skill set and tools not as well suited to the procedure.

Because the terms, tools, and techniques used in the interventional approach to device implantation may be unfamiliar, this section describes key devices for the reader’s reference.

Overview Several notable developments have occurred since the last edition of this textbook. Electronic repositioning in conjunction with bipolar leads (soon to be multipolar leads) has greatly improved success.26 The most important development involves delivery systems.27,28 Telescoping guide support–based delivery systems employ sliceable, preshaped guides for insertion through a separate coronary sinus (CS) access catheter that delivers leads directly to the target vein, allowing for interventional techniques.29,30 Optimal use requires the physician to learn and apply such principles as safe use of contrast, manipulation of open-lumen catheters, effective and efficient injection of contrast, and importance of table position.31 Although an important advance, the new guide support–based delivery systems have two limitations: (1) most do not offer a delivery guide for leads with diameter of 6 to 7 French, and thus only leads 5 Fr (5F) or less usually are deliverable, and (2) most lack a vein selector. A vein selector serves two functions. First, it locates and cannulates the target vein. The design parameters required for a delivery guide, however, limit the ability to locate and cannulate the target vein. It is easier and safer to use a small catheter with a flexible tip to locate the target vein than a catheter designed to provide support for lead delivery. Second, the vein selector provides a rail for the delivery guide. Once the delivery guide locates the vein, it may not be possible to advance into the vein. If a small, flexible-tip catheter is telescoped into the vein through the delivery guide, it can be used as a rail to ensure the tip of the guide engages the vein. The small catheter with a flexible, tapered tip that telescopes through the delivery guide to locate the vein, then act as a rail over which to advance the guide, is a “vein selector” (Fig. 22-1).

516

DEFINITIONS

Coronary Sinus Access Catheter The CS access catheter is defined as a catheter designed to cannulate the coronary sinus and provide access and support for delivery of a left ventricular lead to the target vein. Delivery guides are intended to be advanced through a CS access catheter. The lumen size of the CS access catheter determines subsequent implant options. Device company CS access catheters are 7F or less, which restricts the ability to add a CS support wire while working close to the CS os, use a snare, or employ other advanced techniques. The device companies do not offer delivery guides for 6F leads because they require at least an 8F lumen in the CS. The SafeSheath CSG Worley provides a 9F lumen in the CS, expanding options that include a delivery guide for leads as large as 7F. Delivery Guide The delivery guide is defined as a sliceable catheter designed to fit into the target vein and provide direction and support for advancing the LV lead. Delivery guides are not intended for CS cannulation. I believe that device company delivery guides have two important limitations. First, they are too small to deliver the many 6F leads currently available. Second, by providing several shapes to try and match the venous anatomy, commercial delivery guides are intended to locate and cannulate the target vein and deliver the lead. In my experience, it can be difficult, if not impossible, to locate, insert a wire, and cannulate the target vein without the assistance of a vein selector. Vein Selector The vein selector is defined as a small (5F), soft-tip catheter that tel­ escopes inside a delivery guide to extend beyond the delivery guide and locate the target vein using puffs of contrast, provide direction and support for advancing wires into the vein, then serve as a rail over which to advance the delivery guide. None of the device companies offers vein selectors, relying on their delivery guides to act as both vein selector and delivery guide. In my experience, there are many situations where the delivery guide alone is not sufficient, and the only way to insert the delivery guide into the vein is to use a vein selector inside the guide. Extra Support Wires When attempting to advance a balloon catheter or sheath over a wire, it may be necessary for the wire to be stiffer to prevent buckling. The 0.035-inch Amplatz Extra Stiff (Cook) is suitable in most cases, but on occasion the .035-inch Amplatz Ultra Stiff (Cook) is required. Currently, the Ultra Stiff is available only in the cumbersome length of 260 cm. The Amplatz wires are also available in .032-inch size, which may be required for some sheaths. These stiff wires do not advance easily through areas of venous narrowing and thus are inserted using an exchange procedure with a small catheter.



22  Left Ventricular Lead Implantation

517

VEIN SELECTOR REQUIRED TO ENSURE PLACEMENT OF DELIVERY GUIDE Vein selector

Delivery guide

Delivery guide will not advance

Figure 22-1  Delivery guide advanced using vein selector and wire as rail. A, Delivery guide is inserted into the coronary sinus (CS) through the CS access catheter, but will not advance into the vein over the wire. B, Vein selector is telescoped through the delivery guide and used to locate and cannulate the target vein. A wire is advanced into the vein, and the vein selector/wire is used as a rail over which to advance the delivery guide. The design of each component can be optimized for its specific purpose.

A

Exchanging of Wires to Augment Support When a more supportive wire (e.g., Amplatz) is required to advance the delivery guide or sheath, a small catheter (4F-5F) is advanced over the existing wire into the pulmonary artery (PA) or inferior vena cava (IVC), the wire removed, the Amplatz wire inserted, and the exchange catheter removed. In this situation, a hydrophilic 4F to 5F catheter will advance where a catheter with a standard surface will not; thus it is important to have hydrophilic catheters on hand for exchange. To avoid the need for exchange-length wires, the catheter should be 60 to 70 cm in length, although this length may not be readily available. Thus, we often cut the hub and 30 to 40 cm from a 100- to 130-cm catheter, once the less supportive wire is removed.

CS access catheter

CS access catheter

B

disadvantage of hydrophilic wires/catheters is that they can be difficult to handle. A torque device (steering handle) is required to effectively direct the tip of the wire . PHILOSOPHICAL APPROACH This chapter employs the mindset that left ventricular lead implantation should use the most effective tools and techniques to succeed with

Hook

Vert

Standard

Hydrophilic Wires/Catheters and Balloons Materials that are intrinsically hydrophilic (strong affinity for water) or that have a hydrophilic coating are slippery to the touch when wet and offer much less resistance to passage through vascular structures than standard materials of the same size and configuration. The

Figure 22-2  Variety of shapes used to locate and cannulate target veins over last decade. (Courtesy Boston Scientific and AngioDynamics.)

Figure 22-3  Vein selectors. Left to right, Impress Standard p/n 1628Y8, Impress CS Vert p/n 1628-017, and Impress CS Hook p/n 1628-019. Vein selectors are used to locate, cannulate, and advance wires into the target vein, then provide a rail over which to advance the delivery guide. More than 90% of cases can be done with the Standard, which is included with all the Pressure Products delivery guides (SafeSheath Worley Series, Telescopic Series lateral vein introducers). The catheters are 5 French (5F) outer diameter (OD) and 75 cm long with soft, tapered tips. The CS Hook can be useful near the CS os and with other veins that have a very acute takeoff. The CS Vert is helpful when the takeoff is less acute but tortuous. The black distal section of the catheter is soft and can be easily straightened as the selectors are advanced over wires into the target vein. Thus, once the os of the vein is identified by a puff of contrast, the wire can be advanced, followed by the vein selector to add a second wire. The ability of the vein selector to be advanced deep into the vein over the wires allows creation of a stable rail over which to advance the delivery guide. The Merit Medical vein selectors can be used with the delivery guides provided by the device companies.

518

SECTION 3  Implantation Techniques

function and even worsened it in some cases.”38 If surgical placement is attempted, the surgeon needs the same dedication as the implanting physician to place the LV lead in the appropriate location with good thresholds. Although data are limited, without a prospective randomized comparison, complications and mortality appear to be much higher than the transvenous approach.39-41 In the series by Ailawadi et al.,39 the mortality was double, and postprocedural complications of acute renal injury (26.2% vs. 4.9%; P < .001) and infection (11.9% vs. 2.4%; P < .03) were more common in the surgical group. Based on analysis of the Replace Registry, surgical LV lead mortality may be greater than 8%; 48 patients (11% of 434 attempted LV lead placements) had a failed EP lab attempt. There were four deaths in the patients sent for surgical epicardial LV placement. Assuming every patient with a failed attempt went to surgery for an epicardial lead, the mortality is 8%.40 However, we do not know how many of the 48 were actually sent for an epicardial lead, or if the patients who required surgical intervention were similar to those who did not. Figure 22-4 is from a patient who underwent lead placement through an epicardial approach, showed no response, and then experienced improvement with a transvenously placed lead. Figure 22-5 contains the lateral chest radiographs of three patients who had failed

a transvenous approach. Often this requires tools supplied by more than one vendor and multiple techniques. This approach puts the welfare of our patients first and increases the responsibility of the implanter. If the traditional transvenous approach fails, one option is transseptal, an approach that can be technically difficult and associated with the risk of thromboembolism.32 However, recent studies found a superior hemodynamic performance associated with endocardial compared with epicardial stimulation,33 possibly by allowing access to previously inaccessible pacing sites.34 Our experience in four patients who declined a surgical lead is favorable. Chapter 23 provides a more detailed discussion of transseptal LV lead placement. Surgical epicardial LV lead placement is covered in the final section of this chapter. Although the surgical approach is an easy way for the implanting physician to complete the procedure,35 “the importance of maximizing the use and safety of transvenous approaches is stressed because while the electrical and functional limitations of trans-CS LV epicardial coronary vein leads are well publicized, the limitations of available transthoracic, transepicardial, and true epicardial electrodes may be less appreciated,”36 with 15% LV lead failure at 5 years.37 In addition to lead failure, lead position, morbidity, and mortality must be considered. Utilizing pressure-volume loops, Dekker et al.38 found epicardial sites that “did not significantly change left ventricular

EPICARDIAL LEAD FOR CRT POOR POSITION NOT USED

Mid-lateral wall target vein

B

A

Epicardial screw

Attain 4194

C

D

Figure 22-4  Epicardial versus transvenous lead placement for biventricular pacing. A, The IS-1 connector end of the epicardial lead is shown in relation to the axillary vein. B, The epicardial screw-in lead and the occlusive coronary sinus (CS) venogram are shown. C, Anteroposterior view of the Attain 4194 lead (Medtronic) and the epicardial lead. D, Left anterior oblique view of the Attain 4194 and epicardial lead. The transvenous lead is in an ideal anatomic position on the midlateral wall according to the CS venogram. The epicardial lead is not in the ideal anatomic position.



22  Left Ventricular Lead Implantation

519

EPICARDIAL NONRESPONDERS CONVERTED TO RESPONDERS WITH TRANSVENOUS LEAD

Transvenous Epicardial

Epicardial

RV

Epicardial

RV

RV

Transvenous

Transvenous

C

B

A

Figure 22-5  Initial transvenous implant (CRT) “nonresponders.” Three patients with initially failed implants who were epicardial LV nonresponders, but then had a successful transvenous implant and improved clinically. RV, Right ventricle.

trans­venous implants, then did not respond to an epicardial lead, but improved when a lead was placed transvenously using guide-based delivery system and interventional techniques. If the patient is to be exposed to surgical risk, it is important to insist that the surgically placed leads are located on the midlateral free wall.

Left Ventricular Lead Position and Response As mentioned earlier, not only does cardiac resynchronization therapy require pacing of the left ventricle, but the location of the lead can be

important as well.38,42 The midlateral wall of the left ventricle usually is the best location for an LV lead. When considering whether a patient is not responding to CRT, lead position can be important. The left anterior oblique (LAO) view on fluoroscopy at implantation should define the LV lead position. However, if the fluoroscopy is not performed in a standard manner, it can be deceptive. Kistler et al.43 describe a case in which electrocardiographic analysis showed that a lead fluoroscopically thought to be in the left ventricle at implantation was actually in the right ventricle. Another example of fluoroscopic error is shown in Figures 22-6 and 22-7. The LAO fluoroscopic image in Figure 22-6, A, appeared

COMPARISON OF FLUOROSCOPY TO LATERAL CHEST X-RAY

Nonresponder LV lead position

LV lead

RV-LV lead separation

LA fluoroscopy Lateral chest X-ray

A

B

Figure 22-6  Fluoroscopy and chest radiography at initial implantation of left ventricular (LV) lead. A, Left anterior oblique (LAO) fluoroscopic view shows the LV lead in what appears to be a lateral position, next to the epicardial screw-in leads from a prior implantable cardioverter-defibrillator (ICD). B, Lateral chest radiograph shows that the nonresponder LV lead position is actually anterior; black arrow indicates the separation between right ventricular (RV) and LV leads.

520

SECTION 3  Implantation Techniques

COMPARISON OF FLUOROSCOPY TO LATERAL CHEST X-RAY

Nonresponder LV lead position

Nonresponder LV lead position

Responder LV lead position Responder LV lead position

LAO view during second implant

A

RV-LV lead separation

Lateral chest X-ray after second implant

B

Figure 22-7  Fluoroscopy and chest radiography at second implantation. A, Steep left anterior oblique (LAO) fluoroscopic view reveals the original Nonresponder left ventricular (LV) lead position (labeled LV lead position) to be anterior. The new responder LV lead position (labeled LV lead position) is midlateral. B, Lateral chest radiograph taken after the second LV lead was implanted confirms the posterior lateral lead position.

to document a lateral position. However, the lateral chest radiograph demonstrated the anterior location (Fig. 22-6, B). In Figure 22-7, A, the steeper LAO projection reveals the anterior nature of the first (“nonresponder”) LV lead position. It is important for the implanting physician to take personal responsibility for reviewing the final location of the LV lead, to ensure that the patient has received the best possible lead position. In follow-up of patients after implantation, we demonstrated that the left ventricular (LV)– right ventricular (RV) lead separation on the lateral chest radiograph is essential in evaluating “nonresponders” in whom LV lead

placement has been “successful.”44 Heist et  al.45 demonstrated that the acute hemodynamic effect of CRT is predicted by the LV-RV interlead distance, as measured on the lateral chest radiograph after the procedure. Placement of the LV lead on the anterior surface of the left ventricle is at best subo­ptimal, resulting in deteriorating LV function in some patients rega­rdless of the method of impla­ntation.38 Unless convincing, specific information to the contrary is available, the midlateral free wall of \the left ventricle appears to be the optimal position for the LV lead. When the LV lead is on the midlateral wall, its position on a lateral chest

AP AND LATERAL CHEST X RAY OF AN LV LEAD IN “GOOD” POSITION

A

B

Figure 22-8  Chest radiographs of patient showing response to cardiac resynchronization therapy (CRT). A, Anteroposterior (AP) view; B, lateral view. Arrow indicates the tip of the Attain 2187 left ventricular (LV) pacing lead (Medtronic, Minneapolis). The LV lead in B is located directly posterior the maximal distance from the right ventricular lead. This is the lateral chest radiograph of an LV lead on the midlateral wall.



22  Left Ventricular Lead Implantation

Nonresponder position

521

Responder position

LV lead in anterior vein

LV

LV

RV RV

A

B

Nonresponder position

Responder position

LV lead in lateral vein RV

RV

LV LV

C

D

Figure 22-9  Chest radiographs of CRT nonresponders versus responders. A, Anterior left ventricular (LV) lead is in the anterior vein. B, New lead is placed in a lateral vein, converting a CRT nonresponder to a responder. C, The lead starts in the lateral wall target vein but is advanced distally, which places the tip anterior (not apical) well beyond the ideal location. In both A and C, the physical separation between the right ventricular (RV) and LV leads (white arrows) is small. In both patients, new leads were placed (B and D) in positions similar to those shown in Figure 22-8, with marked improvement in symptoms. In the patient in C and D the new LV lead was placed more proximal in the same vein.

radiograph is directly posterior. Figure 22-8 shows the typical postimplantation chest radiographs of a “responder” in whom the LV lead is located on the midlateral wall of the left ventricle. Note that the LV and RV leads are maximally separated on the lateral chest radiograph. Figure 22-9 includes the lateral chest radiographs of two patients who showed no response to CRT with their original lead position but did respond when a lead was positioned on the midlateral free wall. Figure 22-9, A, is the lateral chest radiograph of a nonresponder in whom the lead was placed in the anterior interventricular vein; patients with a lead in this location are not expected to show response. Figure 22-9, C, however, is the lateral chest radiograph of a patient who showed no response even though the LV lead had been placed in the vein to the midlateral free wall. What happened? The LV lead is advanced distally in the midlateral vein, which wraps around anteriorly toward the septum. Although the lead started in the vein to the midlateral free wall, it ended up anterior, close to the RV lead. Note that in Figure 22-9, A and C, the tip of the LV pacing lead is closer to the RV pacing lead than the ideal position seen in Figure 22-8, B. When a second LV lead was placed, this time on the lateral

wall (Fig. 22-9, B and D), the patients improved clinically and were regarded as “responders.” The clinical question raised is whether repositioning the LV lead of the patient in Figure 22-9, C, to a more proximal position in the same vein, thus increasing the RV-LV separation, would change a nonresponder to a responder. Figure 22-10 illustrates the original and new, more proximal positions in the same vein of a patient in whom such repositioning was performed. The RV-LV lead separation was increased, and the patient demonstrated a marked symptomatic improvement, objectified by reductions in both serum creatinine level and dose of diuretics. Figure 22-11, A, is the lateral chest radiograph of a patient in whom the original implanting physician was not prepared to perform coronary vein venoplasty. The vein to the midlateral wall was distal to a stenosis in the main body of the CS. Although the implantation was regarded as “successful,” the pacing lead was not placed on the midlateral wall of the left ventricle. The patient did not improve after the procedure, was regarded as a CRT “nonresponder,” and listed for heart transplantation. He was evaluated at our facility, where the lead position on the lateral chest radiograph was discovered. He subsequently

522

SECTION 3  Implantation Techniques

CONVERSION OF NONRESPONDER TO RESPONDER WITH CHANGE IN LEAD POSITION

RV-LV lead separation

Nonresponder LV lead position

Responder LV lead position RV-LV lead separation

A

B

Figure 22-10  Lateral chest radiographs before and after repositioning. A, Left ventricular (LV) lead is anterior near the right ventricular (RV) lead. There is minimal RV-LV lead separation (black arrow). B, The LV lead is lateral; RV-LV lead separation (black arrow) is larger. Although the LV lead was placed in a midlateral wall vein, it was advanced distally, resulting in a more anterior position and lack of symptom response. When the lead was withdrawn more proximally in the same vein, the RV-LV lead separation increased, and the patient’s symptoms improved.

underwent venoplasty of the main body of the CS, and the lead was placed on the lateral wall of the left ventricle (Fig. 22-11, B); dramatic resolution of symptoms eliminated the need for a heart transplant. Both the acute hemodynamic effect and the subsequent clinical response to CRT are predicted by the RV-LV lead separation on the lateral chest radiograph. On the basis of the work of Heist et al.,45 the RV-LV separation in the horizontal plane is more important than the total RV-LV separation, and the RV-LV separation in the vertical plane was not predictive.

Guide Support–Based Delivery System Since 1997, LV pacing leads have evolved from unipolar 6F styletdriven to quadripolar 5F over-the-wire leads. Despite improvements in LV pacing leads, their placement continues to be limited by the coronary venous anatomy. Frequently, guide support is required because the angioplasty wire does not provide adequate support to advance the LV lead into the vein (Fig. 22-12). Guide support is present

CRT nonresponder

CRT responder

New LV position

A

RV LV

Original LV lead position

RV

B

Figure 22-11  Chest radiographs of nonresponder before and after coronary sinus (CS) venoplasty and lead repositioning. A, Lateral chest radiograph shows that left ventricular (LV) lead is anterior, near the right ventricular (RV) lead. Because of a stenosis in the main CS, the LV lead was placed in a posterolateral vein. To ensure stability and low pacing thresholds, it is advanced distally. There is minimal RV-LV lead separation.  B, Venoplasty of the main CS was performed to provide access to the vein to the LV midlateral wall. The LV lead is directly posterior on the lateral chest radiograph. The RV-LV lead separation is greatly increased. With venoplasty of main CS and placement of LV lead on lateral wall, the clinical response was dramatic, and the patient’s name was removed from the heart transplant list.



Figure 22-12  Despite wire placement, pacing lead does not track into target vein. A, Wire is advanced into the target vein. B, Angioplasty wire does not provide adequate support for the acute angle; wire and lead pull out of the vein.

22  Left Ventricular Lead Implantation

523

B

A

when the tip of the guide rests securely within the target vein and the back of the guide is supported by the coronary sinus, as occurs with a catheter where the tip is preshaped specifically to cannulate the target vein, not the CS. The magnitude of support provided by the preshaped guide depends on its shape, as shown in Figure 22-13; the compound shape in B offers greater support than the single curve in A because the secondary curve is supported by the CS back wall. For the purposes of this chapter, a delivery guide is defined as a braided, slittable catheter preshaped for LV lead delivery (not for CS access) that is inserted through a separate catheter in the CS. A CS access catheter is defined as a removable catheter designed specifically for CS cannulation and to provide a platform for LV lead delivery. CS access catheters can occasionally provide guide support when it inadvertently cannulates the target vein or is forced into the vein. Forcing a CS access catheter requires an angle of less than 30 degrees, a situation where guide support is usually not required. Furthermore, the potential exists for dissection as the straight tip of the CS access catheter is forced around the curve (Fig. 22-14). A delivery guide is the most reliable way to deliver a lead to the target vein, particularly when the anatomy is difficult (Fig. 22-15), but also even when the anatomy seems favorable (Fig. 22-16). In addition, the delivery guide makes it easier to deal effectively with lead instability, high thresholds, and phrenic pacing; inject contrast to identify

branches; provide support to reposition the lead; or change to a lead of different size or shape and to a different method of fixation. Lastly, because the delivery guide allows the stylet to be safely advanced to the tip (Fig. 22-17), the final step of removing catheters from the CS is less likely to displace the lead. Accordingly, the approach to LV lead implantation described in this chapter is based on using a guide support– based delivery system. The guide support–based delivery system comprises four separate components, allowing optimized design of each component for its particular function. Although an LV lead can be delivered with a singleor two-component system, use of the following four components provides the best opportunity for success in the least amount of time with the shortest learning curve: 1. Coronary sinus access catheter. The role of the CS access catheter is to provide rapid, reliable CS cannulation, a stable platform once in place, and adequate diameter to accommodate insertion of a delivery guide for 6F leads and to be removable without lead displacement. 2. Cannulation telescoping assist catheter. This catheter assists in catheter insertion and CS cannulation (Fig. 22-18). Further details are provided in the CS cannulation section. 3. Vein selector. This braided catheter with a soft, tapered tip is designed to locate the target vein with contrast injection, deliver the wire(s)

Figure 22-13  Shape of delivery guide determines magnitude of support. A, The back of the delivery guide has a single curve and is not supported by the coronary sinus (CS). B, Delivery guide has a compound shape, such that the back of the guide is supported by the CS, and is expected to provide more support for the lead than that in A.

A

B

524

SECTION 3  Implantation Techniques

FORCING THE CS ACCESS CATHETER INTO THE VEIN CAN CAUSE DISSECTION

A

Figure 22-14  Perforation of vein by coronary sinus (CS) access catheter. A, Limitations of attempting to advance the CS access catheter into the target vein. The wire and vein selector are in the target vein. Attempts to bend the straight tip of the CS access catheter into the target vein are not successful; the tip digs into the vein, causing a perforation. B, Radiographic example of the diagram. A contrast stain can be seen at the tip of the CS access catheter where it would not “turn the corner” into the target vein.

B

into the vein, and serve as a rail (with the wires) over which to advance the delivery guide into the target vein. Over the last 10 years we have used a variety of shapes to locate and cannulate target veins (see Fig. 22-2). Through the process of elimination, we have arrived at the three shapes shown in Figure 22-3. These vein selectors can be used with the device companies’ delivery guides. The “standard” is included with Pressure Products delivery guides. 4. Delivery guide. A braided catheter designed to provide support for inserting the LV lead into the target vein (not for CS access). Boston Scientific, Medtronic, and St. Jude Medical now offer sliceable delivery guides for 5F and smaller leads. Pressure Products offers two

sizes of sliceable delivery guides, a 9F outer diameter (OD) for 7F and smaller leads and a 7F OD for 5F and smaller leads (see later section on commercially available delivery systems). SHAPE AND USE OF DELIVERY GUIDES Previous Approach In the third edition of this book, I emphasized matching delivery guide shape to the target vein anatomy for two reasons. First, at that time we used either interventional guides from radiology or the first-generation Pressure Products delivery guide (Fig. 22-19, A). Both had very firm

Attain 4194

Stenotic acute angle vein

A

Delivery guide

B

Figure 22-15  Use of delivery guide. Renal-shaped lateral vein introducer (LVI) for lead placement in a stenotic, acutely angled vein (SafeSheath Worley, Telescopic Series, Pressure Products). A, Occlusive coronary sinus (CS) venogram identifies the midlateral wall target vein with an acute angle and a stenosis near the os. B, Delivery guide is advanced without venoplasty into the target vein. The lumen of the guide and vein are coaxial. The pacing lead (Attain 4194, Medtronic) advances into the vein.



22  Left Ventricular Lead Implantation GUIDE SUPPORT REQUIRED FOR LEAD TO ADVANCE

6F lead will not advance Target vein CS access catheter

A

B

5F lead will not advance Figure 22-16  Delivery guide required for lead placement. A, Target vein is large, and it appears that LV lead placement will be easily accomplished.  B, Attempts to advance the 6-French (6F) LV lead (Attain 4194, Medtronic) from the straight 7F ID coronary sinus (CS) access catheter (Attain Access 6218) is unsuccessful. C, Attempts to advance the 5F lead (Attain 4193, medtronic is also unsuccessful. D, CS access catheter is upsized to 9F ID (Worley-STD, Pressure Products) and the 7F ID delivery guide (Worley Renal LVI) is advanced into the target vein. With the delivery guide in place the 6F LV lead is advanced.

6F lead advanced

CS access catheter

C

Figure 22-17  Reducing risk of lead dislodgment as catheters removed. A, Delivery guide is in place, and the stylet is advanced to the tip of the lead.  B, Delivery guide is removed without displacing the lead.

Delivery guide

D

With delivery guide in place the stylet is advanced to tip without displacing lead

With stylet at tip, lead is less likely to dislodge as catheters are removed

Delivery guide

A

B

525

526

SECTION 3  Implantation Techniques

Telescoping catheters provided to assist cannulation of the CS

CS access catheter

tip sections, which could not be advanced into the target vein or did not remain stable once advanced (Fig 22-20). However, with the new soft-tip design (Fig. 22-19, B), the Pressure Products delivery guide can be advanced deep into the target vein and remains stable. Second, it initially appeared that the delivery guide could be used reliably to locate the vein, advance the wire, and then be advanced over the wire into the vein. Although effective in some cases, we found that the delivery guides were not optimal for small or off-axis target veins, necessitating the addition of a small, diagnostic catheter telescoped through the delivery guide (see Fig. 22-1). It thus became clear that a small diagnostic catheter (vein selector) was an essential component of a guide support–based delivery system and needed to be included with the delivery guide (see Fig. 22-3). New Approach Recognizing that a vein selector will be needed to locate and cannulate the target vein in at least some cases, and that the soft tip of the new Pressure Products delivery guide can be advanced to a stable position deep in the vein if needed, we now rely on the shape of the vein selector for off-axis and difficult veins and use a single shape of delivery guide. Using the included vein selector and wire(s) as a rail the “renal” delivery guides can be inserted into the vast majority of target veins, regardless of takeoff (Fig. 22-21). We rarely if ever use one of the other shapes of Pressure Products delivery guides (hook, hockey stick, or multipurpose). The vein selectors also work in the same manner with the device company delivery guides.

Telescoping assist catheter

Figure 22-18  Telescoping cannulation assist for coronary sinus (CS) access catheters. The CPS AIM cannulator is telescoped within the CPS Direct outer guide (St. Jude Medical). The braided core is telescoped within the SafeSheath CSG Worley (Pressure Products). The CPS Direct and CSG Worley are CS access catheters. The CPS Aim and Braided Core are telescoping cannulation assist catheters. Manipulation of the telescoping assist catheter within the CS access catheter facilitates location and cannulation of the CS. The SafeSheath CSG Worley (CSG/ Worley/BCore-1-09) includes the Braided Core, which also serves as a temporary metal braid to provide torque control for the peel-away sheath (CS access catheter).

Left Ventricular Lead Implantation with Interventional Techniques STEP-BY-STEP SUMMARY Start a free-flowing intravenous line in a proximal vein on the side of the implant, or on both sides if there is a previously implanted system. Prepare the patient for contrast. • ­­Start normal saline, 3 mL/kg/hr for 1 hour, starting 1 hour before the procedure, then 1 mL/kg/hr during and continuing for 6 hours after the procedure. Prepare the room. In addition to the guides and sheaths that will be used for every case, the following must be readily available in the room:

Soft tip section Uniform tip and shaft

A

Firm shaft

B

Figure 22-19  Comparison of tip section of original and current delivery guides. A, Tip of the original Pressure Products delivery guides was the same stiffness as the shaft, similar to the interventional guides that were used initially. The stiff tip section is difficult to advance deep into a vein and is not stable if advanced. B, In the current version of the delivery guide (Telescopic Braided Renal LVI/75-5-66-55-RE) the tip section is much softer than the shaft. Using the included vein selector, it can be advanced deep into a vein and remains stable; thus multiple shapes are no longer necessary. (Courtesy Pressure Products, San Pedro, Calif.)



22  Left Ventricular Lead Implantation

AP

527

LAO 5F vein selector

Old model delivery guide with stiff tip

A

B

C

Old model delivery guide with stiff tip Old model delivery guide with stiff tip

D

E

Figure 22-20  Stiff tip prevents secure advancement of interventional and delivery guides into target vein. The tortuous vein segment is shown in anteroposterior (A) and left anterior oblique (B) views. C, The older-model Pressure Products 7-French (7F) ID renal delivery guide is advanced through the 9F ID CS access catheter to the ostium of the target vein over a 5F vein selector (Williams Right Diagnostic, Boston Scientific, Miami) and an angioplasty wire. D, Renal delivery guide is advanced over the 5F vein selector beyond the tortuous segment. E, When the vein selector is removed, the stiff tip of the older-model delivery guide retracts proximal to the tortuous vein segment. The soft tip of the current-model renal delivery guide (Telescopic Braided Renal LVI/75-5-66-55-RE, Pressure Products) can be advanced deep into the vein over a vein selector and remains stable once in place.

• ­­Glide wires: 0.035-inch and .018-inch angled tip • ­­Torque devices for .014 to .025–inch wires and .025 to .038–inch wires • Extra-stiff wire: 0.035-inch extra-support guidewire • “Vert”: 5F hydrophilic left vertebral–shaped angiographic catheter • Subclavian balloon: 6 mm × 4 cm, 30 to 60 cm • Vein selectors (3 shapes, Merit Medical)

• Coronary balloon rapid exchange: 2.5 × 14 to 16 mm and a 3 × 14 to 16 mm • Balloon inflation device Prepare the implant table. In addition to the usual implant equipment: • Assembled contrast injection system • 50 mL of undiluted contrast

528

SECTION 3  Implantation Techniques

Soft tip

A

7F OD/5F ID “renal” delivery guide and CS std vein selector

Soft tip

B

9F OD/7F ID “renal” delivery guide and CS std vein selector

Figure 22-21  Renal-shaped delivery guides with vein selector. A, The 7-French (7F) “renal” delivery guide is shown with the included 5F standard vein selector (Telescopic Braided Renal LVI 75-5-66-55-RE, Pressure Products). It has a 7F outer diameter (OD), 5.5F inner diameter (ID), and a working length of 66 cm. B, The 9F OD renal delivery guide is shown with the included 5F standard (std) vein selector (Telescopic Braided Renal LVI 75-5-62-07-RE). It has a 9F OD, 7F ID, and working length of 63 cm. The soft tip section of the delivery guide can be advanced deep into a target vein over the vein selector, if needed. As a result, we now rely on the shape of the vein selector, not the shape of the delivery guide, to accommodate the takeoffs of various veins. When used with a vein selector, the renal-shaped delivery guide is suitable for the vast majority of cases. In approximately 10% of cases, one of the other two vein selectors (Impress CS Vert p/n 1628-017 or Impress CS Hook p/n 1628-019, Merit Medical; see Fig. 22-3) may be required to locate and cannulate the target vein.

Elevate the legs to increase central pressure. Obtain venous access using contrast. • Position the implanting physician scrubbed and ready to stick. • Inject 10 to 30 mL of contrast, and flush with 30 to 50 mL of saline. • Stick the vein with the contrast flowing. Obtain three separate axillary vein access lines. • Two short wires • One long wire • Coil the long wire and clip it to the drapes. Insert the right ventricular (RV) and right atrial (RA) leads. Turn the implant table perpendicular to patient. Position fluoroscopy in a close and comfortable position. Unclip the long wire and insert the long peel-away sheath. Attach the braided core to the injection system and insert into the sheath. Torque the catheter with both hands and have the assistant inject. Locate the coronary sinus and cannulate the CS with the braided core and sheath. Perform the occlusive CS venogram. Select the vein and choose lead shape and size. Choose the appropriate shape of vein selector (3 choices). Choose the appropriate size of “renal” lateral vein introducer (LVI) delivery guide. • 7F inner diameter (ID) for leads 5F or less. • 9F for leads 7F or less. Load the vein selector into the delivery guide. Attach the injection system to the vein selector. Insert the guide/vein selector into the CS access catheter. Advance until the delivery guide reaches the tip of the catheter. Advance the vein selector out of the delivery guide into the CS. Put both hands on the vein selector.

Rotate the vein selector laterally just above the target (based on CS venogram). Slide the vein selector up and down the lateral wall of the CS. Have the assistant inject contrast when either of the following events occurs: • The tip drops outside the curve of the CS. • The tip stops moving freely. Insert a floppy .014-inch hydrophilic angioplasty wire into the vein. Advance the vein selector slightly into the vein. Insert an extra-support .014-inch hydrophilic angioplasty wire into the vein. Advance the vein selector further over the two wires to a stable position in the vein. Hold the wires and vein selector stable, and advance the delivery guide. Rotate the vein selector gently as it approaches the ostium of the vein. With the delivery guide at the os, advance/withdraw the vein selector as needed. Make certain the equipment table is perpendicular to the patient (T-bone). Remove the vein selector retaining the wires. Advance the lead into the vein, remove the wires, and test. Advance a soft, curved stylet to the tip of the lead. Position the tip of the access catheter in the proximal CS. Position the patient under anteroposterior (AP) fluoroscopy such that: • The tip of the lead is at the right edge of the screen (not in the middle). • The CS os is in the middle of the screen. Slice the delivery guide. Remove the peel-away CS access catheter from the CS, not displacing the lead. • Do not crack the hub.



• While watching the lead tip under fluoroscopy, withdraw the sheath. • Add slack to the lead as needed. When the hemostatic hub of the sheath reaches the IS-1 connector: • Have the assistant compress the walls of the sheath against the lead. • Crack the hub and peel down to the assistant’s fingers. Slide the remaining sheath back until it clears the lead. • Have the assistant secure the lead. • Finish peeling the sheath. Adjust the lead slack in the LAO projection. Remove the stylet quickly. Secure the lead. DETAILS AND RATIONALE This section describes my recommendations for implanting LV leads and the tools used. Chapter 23 describes more advanced interventional technique, including crossing total occlusions, subclavian and coronary vein venoplasty, using balloons as anchors, and use of snares. With these techniques, we have successfully implanted all 27 patients with failed implants referred from other centers, including five who had epicardial leads but did not respond. When a biventricular (BiV) implantation is begun, there is no way to predict what lies ahead. For example, it may be difficult to find the vein; the subclavian vein may be stenotic or occluded; the CS os may be difficult to locate; and the main CS may be tortuous. The CS venogram may reveal a range of target veins, from easy to extremely difficult. Once the lead is in the target vein, the implanter must be prepared to deal with phrenic pacing or high pacing thresholds. Once the lead is in a satisfactory location, the implanter must anticipate and prevent the lead from being displaced either spontaneously or as the final catheter or stylet is removed. A CRT implantation ultimately fails as a result of patient anatomy for which the implanter is not prepared. In effect, the implanting physician and the patient are “victimized” by the patient’s anatomy. To succeed, the implanter must be prepared to deal with whatever anatomy is encountered, starting with venous access and ending with the final removal of the stylet. Prepare Patient for Iodinated Contrast Material The safe use of contrast is discussed in detail in Chapter 23. In summary, contrast improves safety, reduces implant time, and is essential to the use of a guide support–based delivery system. Rather than only trying to limit contrast, it is better to take steps to prevent nephropathy. Use of contrast can then be individualized; many patients will be at relatively low risk, whereas others (e.g., diabetics with increased creatinine) remain at high risk. Because the serum creatinine can vary substantially in CRT patients depending on volume status, we recommend hydration for all patients as follows: Normal saline or sodium bicarbonate, 3 mL/kg/hr for 1 hour starting 1 hour before the procedure and continuing 6 hours after the procedure. This hydration protocol is as effective as giving 1 mL/kg/hr of normal saline 12 hours before, during, and for 12 hours after the procedure, and the patient receives less volume. Although volume overload is possible, it is rare and offset by the advantage of preventing nephropathy. Equipment and Room Setup Four of the most important and most easily overlooked parts of LV lead implantation are mechanical issues that can be easily resolved before the procedure starts. Careful attention to these issues and actions to avoid them can make the difference between an agonizing unsuccessful attempt and a 15-minute LV lead placement. Collect Available LV Lead Implantation Equipment and Review Its Use.  The worst mistake may be to assume that the equipment required for a successful efficient LV lead implantation either is in the room

22  Left Ventricular Lead Implantation

529

or has been provided by the manufacturer. Some of the equipment is readily available in the hospital but is not part of the usual repertoire of many implanting physicians. Knowledge of the equipment used in interventional radiology and interventional cardiology can be extremely useful during an LV lead implantation (see Interventional Implant Equipment List at end of chapter). The technical staff and physicians from interventional cardiology and radiology often have helpful suggestions for solving the mechanical problems posed by an LV lead implantation, and equipment specifically tailored to LV lead placement is slowly making its way into the world of electrophysiology. Access to these new tools can make the difference between an easy success and a painful, demoralizing failure. Organize Equipment to be Readily Available in Room.  It is important to remember that the interventional implant equipment needed is not usually available in a room used for either pacer implantation or an EP study. To avoid spending more time surveying the interventional cardiology and radiology laboratories than actually working on the patient, the physician should make certain of having the most basic equipment in the room. These tools are additional to the device company equipment and sheaths used for pacemaker implantation. To be certain we have the proper tools regardless of the room, our staff created a “BiV Cart.” This cart also contains equipment for performing subclavian and coronary vein venoplasty (Fig. 22-22). Assemble “Always Used” Equipment on Table before Starting.  Having a routine and setting the table with equipment needed for the procedure give the operator the freedom to concentrate on the procedure and help avoid “rethinking” the tools for each implantation (Fig. 22-23). Pay Careful Attention to Orientation of Instrument Table During Procedural Stages It is remarkable how important the position of the instrument table can be to a successful implantation. It is even more remarkable how frequently even an experienced implanter forgets to change to a table position appropriate to the stage of the procedure until either the support staff provides a gentle reminder or something that should be easy feels difficult. Figure 22-24, A, demonstrates the usual “backfield” position of the instrument table. We keep the table in this position until we start CS access, at which point the table is turned perpendicular to the patient (Fig. 22-24, B). Once the LV lead is in place and it is time to start removing the guide and sheath, the table is returned to the backfield position so the assistant can support the sheath and lead during sheath and guide removal. The perpendicular position of the table from the start of CS cannulation until removal of the guide or sheath can be cumbersome with standard tables, for the following reasons: • The legs of the table closer to the patient interfere with the position of the operator’s feet and the fluoroscopy pedals. • The legs of the table interfere with rotation of the fluoroscopy unit, particularly in the right anterior oblique (RAO) position. • The height of the standard instrument table is lower than the height of the patient. As a result, wires and catheters do not make a smooth transition from the patient to the table. The custom-built table shown in Figure 22-25 addresses all three issues. The legs are recessed to provide room for the fluoroscopy unit, the operator’s feet, and fluoroscopy pedals. The height is adjustable so that the top of the table can be raised to reduce the vertical stepoff between the patient and the table. Interventional principles teach that when working with catheter, it is important that the implant table be turned perpendicular to the patient table (T-bone position) so that the wires and catheters exit the body falling naturally onto the table (see Fig. 22-24, B). Further, the assistant is in the optimal position to assist with the catheter manipulation, contrast injection, and wire exchanges required for LV lead implantation and the use of balloons. Application of torque to the catheters is not lost in a right angle, and the openlumen catheters are not prone to kink. Testing the left and right

530

SECTION 3  Implantation Techniques

A

B

Figure 22-22  Biventricular (BiV) cart. A, Front view; B, back view. Cart keeps equipment readily available in any implantation room when needed.

ventricles simultaneously for pacing thresholds can be difficult with standard testing cables. Simply attaching an additional alligator clip eliminates this problem (Fig. 22-26). APPROACH TO CONTRAST An important point frequently overlooked is the approach to contrast injection. EP physicians accustomed to working alone with solid catheters naturally try to inject contrast and control the

Contrast reservoir 30-mL syringe

3-way stopcock

12–18 inch tubing with male and female ends

10–12 mL control syringe

Y adapter with hemostatic valve and rotating hub Figure 22-23  Simplified system to allow assistant to inject contrast while operator manipulates catheter with both hands. For righthanded operator, the right hand is on the rotating hub on the Y adapter, and the left hand is on the catheter. The system is used to inject contrast for location of the coronary sinus os, for the occlusive venogram, and for locating the target vein with the vein selector. The system can be constructed from equipment readily available in most laboratories and is available as a kit (Pressure Products or Merit Medical; see equipment list at end of chapter for details). The scrub technician should have the pieces on the table and assembled before notifying the implanting physician to scrub for surgery.

catheter. However, interventional principles clearly show that catheter control is degraded when one hand is removed from the catheter and attention is turned to contrast injection. Suboptimal catheter control will result in increased use of contrast and a greater chance of misadventure. For optimal catheter control, the operator keeps both hands on the catheter and attention focused on tip position (Fig. 22-27). VENOUS ACCESS At first, venous access may seem like a minor issue, but keep in mind the cascade of events that follows a difficult venous access. If compression between the clavicle and first rib, friction between the leads, or subclavian stenosis restricts manipulation of the leads or sheath, the operator is handicapped for every subsequent step. The operator will not be prepared for difficult anatomy in sub­ sequent steps if the result of the first step limits options. A poorly considered initial venous access will be problematic throughout the procedure. Preventing Restricted Catheter/Lead Movement Separate Access for Each Lead.  Having separate access sites for each lead reduces the interaction among the three leads. If only two access sites can be obtained, the RV and RA leads should be placed through the same access site to minimize the potential for movement of either lead to displace the LV lead. When leads share the same access, friction between the two may result in the stable lead being withdrawn by manipulation of the other lead. To help prevent lead withdrawal, keep the stylet of the stable lead at the junction between the inferior vena cava (IVC) and superior vena cava (SVC) until manipulation of both leads is complete, even after the stable lead is tied down. Without a stylet, the stable lead can withdraw, even when tied to the muscle, by forming an S configuration within the subclavian vein distal to the tie-down (Fig. 22-28). Axillary versus Subclavian Access.  With subclavian vein access, compression between the first rib and clavicle can restrict lead manipulation. In a non-BiV or an easy BiV implantation, restricted manipulation of the leads may be only a minor difficulty. However, precise mani­pulation is required, and the friction may make it impossible to



22  Left Ventricular Lead Implantation

531

Monitor Catheters don’t kink; fall naturally onto the table Monitor Catheters prone to fall off table Patient Equipment table Patient Catheters kink

Operator

Assistant

Operator

Assistant

Equipment table

A

B

Figure 22-24  Instrument table position during LV lead implantation. A, Instrument table in traditional “backfield” position; the acute angle of the catheters results in loss of torque control, tendency for catheters to kink, and catheters prone to fall off the table. The table position is ideal for working with the right ventricular (RV) and right atrial (RA) leads, retraction for pocket formation, and trimming suture. B, Instrument table is perpendicular to patient. As soon as the operator begins to obtain venous access for the left ventricular (LV) pacing lead, the instrument table is moved into a position perpendicular to the patient. The long wires, sheaths, and guides may thus be kept straight as they exit the body. The assistant works at the table beside the operator to assist with contrast injection; control the long guidewires, sheaths, and torque devices; and insert the pacing lead onto the wire as the procedure progresses. Ideally, the table would be at the same height as the patient’s chest. Some centers use a Mayo stand for this purpose, but my colleagues and I value the additional table length over the ideal height. However, the perpendicular table position blocks the assistant’s access to the field. The table must be returned to the standard backfield position to slice the guide and to peel the sheath.

A

B

Figure 22-25  Custom-made table to facilitate LV lead implantation. A, Side view of custom-designed biventricular (BiV) implantation table. The importance my colleagues and I place on the perpendicular position of the table is exemplified by the time and energy we devoted to optimizing the table for the LV lead implantation phase of the procedure; we (1) moved the supporting legs of the table back 18 inches (45 cm) from one end and (2) added height adjustment to the table. When placed perpendicular to the patient, the legs of a standard table interfere with the position of the foot pedal for fluoroscopy as well as the operator’s feet. In addition, the legs interfere with the table position when the radiograph tube is rotated for a right anterior oblique projection. Moving the supporting legs of the table back 18 inches from one end allows the table edge to approximate the patient without interfering with either radiography or the operator’s feet. The height of the table is adjustable to ensure a smooth transition of catheters and wires from the patient to the table while the operator is working perpendicular to the patient (BiV position). B, Skew view of the same table (Oscor, Palm Harbor, Fla).

532

SECTION 3  Implantation Techniques

Suboptimal catheter control

A Operator can focus on catheter manipulation = better control

Assistant injects

B Figure 22-26  Biventricular pacing cables. When determining LV and right ventricular (RV) pacing thresholds to a single cathode, it is timeconsuming and tedious to attach both anodes of the pacing leads to a single alligator clip. Simply having a second anode alligator clip greatly facilitates this phase of the procedure.

place the LV lead. Axillary vein access ensures that lead manipulation will be unrestricted by compression between the clavicle and first rib. Axillary vein access also minimizes the risk of lead fractures and pneumothorax. Response to Subclavian Obstruction in Patient with Preexisting Leads In about 20% to 30% of patients with previously implanted leads, one or more stenotic areas will develop between the site of venous insertion and the right atrium (Figs. 22-29 to 22-32). Before the advent of LV

A

Figure 22-27  Contrast injection by operator and assistant. A, Operator attempts to inject contrast and manipulate the catheter simultaneously. Interventional principles teach that both hands need to be on the catheter for good control, one on the hub and the other on the shaft where it enters the sheath. In addition, when contrast is injected, focus is diverted from the position of the catheter tip to the injection syringe. B, Simplified injection system is connected to the catheter by a rotating-hub Y adapter. Extension tubing is connected to the Y adapter and a three-way stopcock with reservoir syringe and injection syringe. The assistant has room to stand next to the operator and inject contrast when requested. The operator can keep both hands on the body of the catheter and keep attention focused on the tip of the catheter.

lead placement, the response of the implanting physician to a subclavian stenosis was to go to the other side or to advance progressively larger dilators until the sheath could be advanced. Dilator opening of a stenotic area, if possible, is always incomplete. The stenotic area continues to restrict wire and catheter manipulation, making LV lead

B

Figure 22-28  Friction between lead and guide pulls back lead, even though sewn down. A, Atrial lead is in place and secured to the muscle. B, Atrial lead is pulled back, creating a loop in the subclavian vein created by friction during manipulation of the other pacing leads, sheaths, and guides that share the same vein. After a lead is positioned and sewn down, it is prudent to reinsert a stylet into the superior vena cava–right atrium junction until manipulation of other sheaths, guides, and leads is complete.



22  Left Ventricular Lead Implantation

placement much more difficult if not impossible; also, distal stenotic areas are not addressed. Venoplasty safely creates much less restricted access than progressively larger dilators and can address a central stenosis (see Figs. 22-31 and 22-32). Details of how to deal with a subclavian occlusion is discussed in detail in Chapter 23. PLATFORM FOR LEAD PLACEMENT The lumen size, catheter shape, and method of removal (cutting vs. peeling) influence the suitability of a CS access catheter to function as a platform for LV lead placement. Lumen Size The platform available for LV lead placements starts with the choice of venous access for the LV lead. Typically, short peel-away sheaths are used to access the venous circulation for insertion of leads in the right atrium and right ventricle (Fig. 22-33, A). When the CS access catheter is an 8F to 9F OD guide provided by the device company, venous access is obtained with a short, 9F sheath. This results in a 7F ID access to the coronary sinus. The small-caliber CS access limits the use of a guide to one that only delivers 5F or smaller leads. By comparison, when the sheath in Figure 22-33, B, is used for venous access, it is also the CS access catheter; thus a 9F ID lumen is available in the CS. The largercaliber CS access alloys the use of guides that can deliver up to 7F leads. Long, peel-away sheaths are used for both venous and CS access (Fig. 22-34, A). Catheter Shape An anatomically shaped CS access catheter is easier to place in the CS than other shapes. Shape also determines whether the access catheter is prone to kinking. Catheters tend to kink when bent; thus, if the manufactured shape of the catheter matches the anatomy, it is less likely to be bent and thus less likely to kink. The shape of the CS access catheter determines the support provided. If not anatomically shaped, the catheter must be deformed

533

from its original shapes to fit the cardiac anatomy. The deformed catheter is under tension and prone to dislodge from the CS. The anatomically curved catheter not only is stable in the CS but provides support during LV lead placement from contact with the lateral wall and floor of the right atrium and eustachian ridge (Fig. 22-34, B). The shape of the CS access catheter determines whether it is likely to displace the lead as it is removed from the CS. A deformed CS access catheter under tension while in the CS loses its support as it is withdrawn and suddenly resumes the original shape, directing its tip to the floor of the right atrium, a movement that may pull the lead out of the target vein (Fig. 22-35). By comparison, an anatomically shaped catheter is not under tension as it rests in the CS. When removed, the tip of such a guide rises above the CS (Fig. 22-36). Cutting versus Peeling to Remove Peeling is a familiar, simple procedure that can be performed in a stable, controlled manner. When both venous and CS access is the same peel-away sheath, the last step of lead placement is to peel the sheath away once the lead is positioned. If the CS access catheter is braided and placed through a short sheath, the last step of lead placement is to slice the steel mesh in the wall of the guide. Cutting is unfamiliar to many implanting physicians, who find it clumsy and difficult. Many physicians have displaced leads while cutting. If the procedure does not start with a long, peel-away sheath for both venous and CS access, the risk of lead displacement at the end is increased. This issue is covered in detail in the section on removing the guide sheath. Why Peel-away Sheaths Are Not Provided for CS Access.  When CRT first began, the device companies offered long, peel-away sheaths but quickly switched to braided, sliceable catheters because (1) peel-away sheaths did not have the torque control required for reliable CS cannulation, and (2) the peel-away sheaths used initially (Fig. 22-37) were not anatomically shaped and thus had to be bent to reach the CS, resulting in kinks with lumen collapse (Fig. 22-38). To maintain the

Cephalic

Internal jugular

External jugular

J wire Axillary

Needle enters near cephalic

A

B

Figure 22-29  Axillary vein venogram before and after insertion of retention wire. A, Anatomy of the venous system proximal to the brachiocephalic vein is well outlined with contrast material. B, Needle enters the axillary vein near the junction of the cephalic and axillary veins. The 0.035-inch J-shaped retention wire is advanced from the axillary vein into the subclavian vein.

534

SECTION 3  Implantation Techniques

Arm venogram

A

Local venogram

B

Figure 22-30  Contrast injection demonstrates typical high-grade stenosis. A, Contrast material (15-20 mL) is injected into a vein in the distal left arm and reveals extensive collaterals at the junction of the axillary and subclavian veins. It is difficult to be certain of the severity of the obstruction. B, Contrast material injected through the dilator from a 5F sheath inserted in the axillary vein distal (peripheral) to the stenosis better defines the degree of obstruction. To create a flexible, stable platform from which to approach the occlusion, based on the peripheral venogram, venous access is obtained in the axillary vein as far peripheral to the occlusion as possible. A standard 0.035-inch J wire is advanced to the occlusion, and the dilator from a 5F sheath is inserted. If venous access is too close to the occlusion, it will also be difficult to direct the wire to different potential routes through the stenosis.

A

B

Figure 22-31  Dilation of peripheral subclavian vein occlusion. A, Collateral vessels are seen (arrows) around the subclavian vein occlusion that developed in association with the leads of a previous implantable cardioverter-defibrillator (ICD). B, Despite what appeared to be a total occlusion, contrast injection at the site of occlusion revealed an opening, and a 0.035-inch angled Glidewire (Terumo Medical) crossed the occlusion and advanced through the heart into the pulmonary artery. A 6-mm-diameter, 4-cm-long balloon with a 0.038-inch wire lumen is across the occlusion and inflated to 15 atm, where two residual waists are seen. With inflation to 20 atm, both waists were eliminated.



22  Left Ventricular Lead Implantation

Proximal dilation

535

Distal dilation

Waist

A

B

Figure 22-32  Dilation of proximal and distal subtotal venous occlusions in same patient. A, Balloon is inflated at site of proximal occlusion to 15 atm, with elimination of the waist and proximal stenosis. B, After the CS access catheter failed to advance, a central stenosis was identified, and the balloon was reinserted to the junction of the superior vena cava and the brachiocephalic vein and inflated, demonstrating a waist in the balloon at the second stenotic location. Approximately 30% of patients who have a peripheral stenosis also have a central stenosis.

Sheath provides venous access and coronary sinus access

advantages of a peel-away CS access catheter, Pressure Products solved the problem as follows: 1. Torque control was provided through a temporary metal braid inside a long, peel-away sheath (braided core). Once the sheath is in the CS, the braided catheter is removed, leaving the peel-away sheath in place. 2. Kinking was eliminated by bending the sheath to an anatomic shape at manufacture in anticipation of the anatomy. CORONARY SINUS ACCESS

B Venous access sheath A

The first step in CRT is to create a stable platform in the CS with the access catheter. Al-Khadra46 notes that failure to cannulate the CS continues to contribute significantly to failure of LV lead implantation. In addition to experience and patient anatomy, factors that help ensure successful CS cannulation include the use of contrast, catheter shape, and telescoping cannulation assist catheters. Use of Contrast

Figure 22-33  Venous access sheaths for LV lead placement. A, Straight, short, 9F sheath is the one usually used for access to the venous circulation to place leads in the right side of the heart. When in place, the tip of the sheath is in the proximal brachiocephalic vein, severely limiting the options to the operator when used for left ventricular (LV) lead venous access. B, Anatomically shaped, long, 9F peel-away sheath is designed for venous access for the LV lead, coronary sinus cannulation (when used with the braided core), a conduit for preshaped guides (lateral vein introducers) designed for target vein cannulation, and delivery of the LV pacing lead to the target vein.

With early CRT, EP physicians typically did not use contrast for CS cannulation and were often uncomfortable or unfamiliar with its use. As a result, despite the inherent superiority of contrast for CS cannulation, many physicians continue to struggle without contrast, sometimes failing as a result. Limitations of Noncontrast Method.  In many cases the problem is not finding the CS os but advancing the catheter into the CS. Without contrast, the operator cannot determine if the tip is in the os until the catheter advances into the CS (Fig. 22-39). In addition, CS cannulation requires working with the fluoroscopy in the LAO projection, which is uncomfortable for the patient and increases radiation exposure. Limitation of Contrast Method.  Transient renal insufficiency may result from administration of contrast agents, but this risk can be

536

SECTION 3  Implantation Techniques

A

B

Figure 22-34  Properly curved coronary sinus sheath. A, The 9F sheath designed for left ventricular (LV) lead venous access. B, The properly curved sheath in the coronary sinus provides support by resting on the eustachian ridge, floor of the right atrium, and superior vena cava (arrows).

CS support lost Tension released Tip uncoils into RA

Guide under tension

CS support

A

B

Figure 22-35  Removal of nonanatomic catheter. A, The nonanatomic shape of a catheter without a proximal curve is deformed to fit into the coronary sinus (CS). The shape of the catheter is the result of the bending forces exerted on the catheter as it was inserted. The shape is maintained by pressure on the distal section of the catheter (arrows) and thus is not stable in the CS. B, Tip of the catheter is withdrawn from the CS. The distorted shape is no longer supported by the CS. The catheter resumes its native shape and falls to the floor of the right atrium (RA, arrow), an event that can dislodge the left ventricular lead.



22  Left Ventricular Lead Implantation

537

B

A

Figure 22-36  Removal of anatomically shaped catheter. A, Catheter is withdrawn to the coronary sinus (CS) os. Because the proximal curve is preformed, the tip is not under tension. B, Sheath is withdrawn from the CS. Because it is not under tension, the sheath does not uncoil and fall to the floor of the right atrium (RA) as the tip clears the os. Tip of the sheath lifts upward (arrow) into the RA as it is withdrawn.

To fit into the CS this section must bend

Figure 22-37  Original long, peel-away sheath designed for both venous access and CS cannulation/access. The catheter is not anatomically shaped because it lacks a proximal curve and thus is prone to kink when bent to fit into the coronary sinus (CS).

minimized (see Chapter 27). Physicians who do not plan to use contrast create a self-fulfilling prophecy by not understanding who is at risk and taking steps to prevent contrast nephropathy. Success with and Failure Without Contrast.  Figure 22-39 demonstrates two cases where CS cannulation failed without contrast because the operator did not recognize that the tip of the catheter was in the CS os. With contrast, it was easy to find the os but difficult to advance the catheter beyond it. CS cannulation with contrast allows for a two-step process: (1) locating the CS os and (2) advancing the sheath or guide into the CS. The combination of contrast, an injection system, the appropriately shaped catheter, table position, and proper catheter manipulation effectively eliminates failed CS access.

No kink

Kink

A

B

Figure 22-38  Peel-away sheaths kink at sharp bends unless curved at manufacture. A, Long, straight, peel-away sheath was advanced into the CS over braided guide but kinked when the guide was removed. B, Peel-away sheath was manufactured with a curve in anticipation of the anatomy and did not kink.

538

SECTION 3  Implantation Techniques

A

B

Figure 22-39  Difficulty advancing guide beyond CS os, sigmoid CS, and large proximal vein. A, Hook shape of the proximal coronary sinus (CS) makes it difficult to advance the guide (arrow). B, Large posterior vein catches the tip of the guide (arrow), preventing it from advancing into the vertically oriented CS. In both cases, without use of contrast material, the operator would be unaware that the tip of the guide was at or beyond the CS os. Contrast material not only confirms location but also defines why it is difficult to advance the catheter.

Shape of Cannulation Catheter As mentioned, the shape of the CS access catheter has an important impact on the ease of CS access. How catheter shape influences cannulation success is described later. Anatomy Surrounding Coronary Sinus Os.  Successfully locating the CS os is facilitated by a complete understanding of the anatomy. Figure 22-40 shows the structures that affect locating the os. A catheter approaching the CS os along the posterior wall of the right atrium (RA) clearly will be deflected away from the os by the eustachian ridge (Fig. 22-41, A). When approaching the CS from below (Fig. 22-41, B), catheter entrance is blocked by the thebesian valve. The key to easy, rapid location of the CS os is for the catheter tip to approach the os from the posterior superior tricuspid annulus (Fig. 22-42, B), thus using the eustachian ridge and thebesian valve to direct the catheter toward (not away from) the os, as seen with the femoral approach, in which the catheter reaches over the eustachian ridge, approaching the os from above (Fig. 22-42, A). Using counterclockwise torque and the correct technique, a properly shaped catheter can be directed into the CS os from the posterosuperior tricuspid annulus inferiorly toward the RA, thus using the eustachian ridge and thebesian valve to guide the tip of the catheter toward the os. Figure 22-43 demonstrates the effect of counterclockwise torque. The tip is directed posteriorly where it contacts the heart. With additional torque, the tip moves inferiorly and toward the RA. To approach the CS from above, the catheter tip must be superior to and on the RV side of the os. If the guide starts at or below the CS os, counterclockwise torque directs the tip posteriorly and inferiorly away from the os into the RA (Fig. 22-44). Changing the shape of traditional catheter by adding a “proximal curve” places the tip above the CS on the tricuspid annulus or in the right ventricle so that torque will direct the tip into the CS (Fig 22-45; see also Fig. 22-48, A). Currently all the device companies provide a braided catheter with an anatomic shape with the proximal curve (Fig. 22-46). To provide the torque control required for CS cannulation and still retain a peel-away sheath, the Pressure Products CSG-Worley Braided Core Series uses a temporary metal braid, the braided core (Fig. 22-47, A). The extra length of the braided core also serves as a telescoping cannulation assist catheter (see Fig. 22-18). By extending the braided core, the implanter can change trajectory and shape of the CS access catheter (Figs. 22-47, B and C, and 22-48, B). St. Jude Medical offers cannulation assist catheters in their new delivery system (CPS AIM SL, CSL/SL AL2).

Locating CS Os with Contrast Injection System.  Pressure Products CS cannulation includes the injection system attached to the braided core, which is telescoped into the SafeSheath CSG Worley (Fig. 22-49). The injection syringe is attached to a three-way stopcock. The reservoir syringe is also connected to the stopcock. A short piece (8-12 inches) of extension tubing is connected from the stopcock to a Y-shaped adapter with a Touhy-Borst valve. The extension tubing allows the operator to manipulate the guide while the assistant injects contrast material. The reservoir syringe is filled from a small bowl of contrast

Tricuspid annulus

Eustachian ridge

Coronary sinus os

Thebesian valve

Figure 22-40  Anatomic structures surrounding coronary sinus (CS) os. The eustachian ridge protrudes into the right atrium (RA) from its posterior wall. The ridge is most prominent inferiorly near the inferior vena cava. As the CS is approached from the RA, the CS os is located behind the eustachian ridge. The thebesian valve protrudes from the posterior wall of the RA and forms the inferior boundary of the CS os. The posterior inferior tricuspid annulus forms the boundary of the CS os on the right.



22  Left Ventricular Lead Implantation

A

539

B

Figure 22-41  Eustachian ridge and thebesian valve inhibit CS cannulation. A, Eustachian ridge (small arrows) blocks entrance to the coronary sinus (CS) os as it is approached from the atrium along the posterior wall (large arrow). B, Thebesian valve (small arrows) blocks the entrance to the CS os as it is approached from below (large arrow).

A

B

Figure 22-42  Thebesian valve and eustachian ridge assist CS cannulation. A, Femoral approach to the coronary sinus (CS) uses the eustachian ridge and thebesian valve to advantage by approaching the CS from above as the catheter is deflected. B, Both eustachian ridge and thebesian valve direct the tip of the guide into the CS os as it is approached from the posterior superior tricuspid annulus.

540

SECTION 3  Implantation Techniques

1 2

1

3

2 3

A

B

Figure 22-43  Effect of counterclockwise torque when catheter tip starts above coronary sinus. A, Three positions of a catheter with progressive application of torque are superimposed. 1, Initial counterclockwise torque at the hub of the guide directs the tip of the guide back. 2, With additional counterclockwise torque, the guide tip can no longer move back. Torque directs the tip of the guide down and to the left. 3, As more counterclockwise torque is added, the tip of the guide continues to move down and to the left. At positions 2 and 3, the proximal section of the catheter lifts off the surface (out of the plane of the illustration). B, Position 1 is the initial position on the posterior superior tricuspid annulus; additional counterclockwise torque moves the tip to positions 2 and 3.

1

1 2

2

3

A

3

B

Figure 22-44  Effect of counterclockwise torque when catheter tip starts below coronary sinus. A, Three positions of a catheter with progressive application of torque superimposed. 1, Initial counterclockwise torque at the hub of the guide directs the tip of the guide back. 2, With additional counterclockwise torque, the guide tip can no longer move back. Torque directs the tip of the guide down and to the left. 3, As more counterclockwise torque is added, the tip of the guide continues to move down and to the left. At positions 2 and 3, the proximal section of the catheter lifts off the surface (out of the plane of the illustration). B, Position 1 is the initial position on the eustachian ridge below the CS. Additional counterclockwise torque moves the tip to positions 2 and 3, down and away from the CS os.



22  Left Ventricular Lead Implantation

541

Proximal curve

Proximal curve

A

B

Figure 22-45  Starting position of catheter with “proximal curve.” A, Guide shape with proximal curve. B, Position of the guide (black dotted lines) in the heart. Note that the proximal curve carries the tip of the catheter across the right atrium and lifts the tip above the coronary sinus os. When counterclockwise torque is applied, the tip will be directed posterior and inferior toward the CS os. The eustachian ridge and thebesian valve direct the tip into the os.

agent (not shown). One can fill the injection syringe several times from the reservoir syringe by rotating the stopcock open to the reservoir syringe. A Terumo Glidewire can be inserted through the Touhy-Borst valve on the Y-adapter if needed. Note that the entire system is contained on the table to help preserve sterility. Extended hook Medtronic

Coronary Sinus Cannulation: Two-Step Process with Contrast Injection STEP 1: LOCATING CORONARY SINUS OS

Wide St. Jude Medical

Worley-STD Pressure Products

Figure 22-46  Three coronary sinus access catheters. Anatomic shape of catheters is produced by the proximal curve. Not shown are the Extended Hook (Biotroniks) and CS Wide (Boston Scientific), which are also similar.

The variable location of the CS os in patients with congestive heart failure explains why it can be difficult to find even with contrast injection. The location of the os varies because of cardiac rotation, cardiac dilatation, and distortion from previous open-heart surgery. When viewed on the fluoroscopy screen in the AP view, the CS os can be to the right or left of the spine (Fig. 22-50). Note that in both cases shown, the os of the CS is at the proximal end of the distal coil. In addition, the os may be high or low relative to the floor of the tricuspid annulus (Fig. 22-51). Systematic use of contrast injection with an understanding of the anatomy allows the operator to recognize quickly where the catheter tip is in relation to the CS os (Fig. 22-52). The direction of the catheter can then be adjusted. Anatomy Surrounding CS Os as Defined by Contrast Injection The right ventricle (RV), tricuspid annulus, eustachian ridge (valve of IVC), thebesian valve (valve of CS), os of the CS, and subeustachian space are all important structures in the search for the coronary sinus os. These landmarks are readily identified with full-strength contrast

542

SECTION 3  Implantation Techniques

EXTENDING THE BRAIDED CORE PROVIDES TELESCOPING CS CANNULATION ASSISTANCE

Core advanced Registration marker

Registration marker

Core extended

Core

C

B

A

Figure 22-47  Braided guide for torque control and shape modification. A, Braided guide (core) has torque control. A black band (registration marker) identifies the length to be inserted into the sheath. B, Braided guide (core) is inserted into the peel-away sheath, giving it torque control. The braided core is 5 cm longer than the peel-away sheath. When the registration marker is at the hemostatic hub, the tip of the core extends 3 mm out of the sheath. C, Core is advanced beyond registration marker, extending the core out the tip of the sheath and creating a new shape. In addition to creating new shapes, advancing the core while holding the sheath stable creates tip trajectories not possible with a single catheter.

3 2 1

A

B

Figure 22-48  Demonstration of torque control and change in shape and trajectory. A, Effect of applying counterclockwise torque to the braided core. The core gives the peel-away sheath torque control to facilitate finding the coronary sinus. As more and more torque is applied, the tip of the sheath/core combination moves posteroinferior to and toward the right atrium (1, 2, and 3). B, Effect of advancing the core while holding the sheath constant creates a variety of tip trajectories and catheter shapes not possible with a single catheter.



22  Left Ventricular Lead Implantation

Injection system Steering handle

SafeSheath CSG Worley

Touhy-Borst Y-adapter Glide wire

Braided core

Figure 22-49  Device combination used for CS cannulation. The Touhy-Borst Y-adapter of the injection system is attached to the braided core of the Safe Sheath CSG-Worley STD (Pressure Products). Glidewire (Terumo Medical) with attached steering handle is advanced through the hemostatic valve to the tip of the braided core. The glide wire and steering handle is used if the braided core will not advance easily.

A

543

injection. In Figure 22-53, A, the tip of the CS access catheter is across the tricuspid annulus and directed posteriorly with 20 to 30 degrees of counterclockwise torque. A 2-mL puff of contrast agent outlines the trabeculae and confirms the location of the CS access catheter in the RV. In Figure 22-53, B, additional counterclockwise torque directs the tip inferiorly and toward the right atrium (RA). Trabeculae confirm that the CS access catheter is still in the RV. In Figure 22-54, contrast agent is trapped between the tricuspid valve and posterior wall of the RV, outlining the tricuspid annulus. In Figure 22-55 the tip of the CS access catheter is in the RA near the fossa ovalis. In Figure 22-56 the tip of the CS access catheter enters the CS os. The subeustachian space is another important landmark defined by contrast injection (Figs. 22-57 and 22-58). It must be recognized that when the tip of the CS access catheter is in the subeustachian space, it is below and on the atrial side of the CS os. Counterclockwise torque will direct the tip from the subeustachian inferiorly and toward the RA away from the CS os. Before starting to search for the CS, the tip of the CS access catheter must be advanced across the tricuspid valve into the RV. This can be accomplished by withdrawing the CS access catheter 1 cm, applying 20 degrees of clockwise torque to orient the tip toward the tricuspid valve, and then advancing the CS access catheter into the RV. If the tip of the CS access

B

Figure 22-50  Variability of coronary sinus os on anteroposterior projection. A, The CS os (arrow) is on the left border of the spine. B, The CS os (arrow) is to the right of the spine; “right” and “left” are as viewed on the fluoroscopy screen in the AP view. Note that in both cases, the CS os is at the proximal end of the distal coil.

A

B

Figure 22-51  High-to-low variability of coronary sinus os. A, The CS os is high relative to the floor of the tricuspid valve. B, The CS os is low. In both views, the floor of the tricuspid valve is defined by the pacing lead.

544

SECTION 3  Implantation Techniques

G

A

B

Figure 22-52  Composite illustration with guide high in right ventricle. A, Anteroposterior projection with the guide (G) rotated 20 to 30 degrees counterclockwise, placing the tip of the guide posterior and superior to the pacing lead. A 2-mL puff of contrast material outlines the trabeculae (short arrows), confirming that the tip of the guide is in the right ventricle. B, Drawing of the heart corresponding to A, showing location of the guide tip (long arrow).

G

A

B

Figure 22-53  Composite illustration with guide in right ventricle. A, Anteroposterior projection with the guide (G) rotated 20 to 30 degrees further counterclockwise than in Figure 22-52. The additional counterclockwise torque directs the tip down toward the coronary sinus os. A 2-mL puff of contrast material outlines the trabeculae (short arrows), confirming that the tip of the guide is in the right ventricle. The guide is inferior to the position of the guide in Figure 22-52. B, Drawing of the heart corresponding to A, showing location of the guide tip (long arrow).



22  Left Ventricular Lead Implantation

545

G

B

A

Figure 22-54  Composite illustration with guide at tricuspid annulus. A, Anteroposterior projection of the guide (G) in the right ventricle just under the tricuspid valve. Contrast material fills the space between the right ventricle and the tricuspid valve, outlining the tricuspid annulus (short arrows) from the ventricular side. B, Drawing of the heart corresponding to A, showing location of the guide tip (long arrow).

G

A

B

Figure 22-55  Composite illustration of guide in right atrium. A, Anteroposterior projection with a linear stream of contrast material, without trabeculae (short arrows) formed, using 2-mL injection. The position of the pacing lead and the lack of trabeculae confirm the position of the guide (G) in the right atrium. B, Drawing of the heart corresponding to A, showing location of the guide tip (long arrow).

546

SECTION 3  Implantation Techniques

G

A

B

Figure 22-56  Composite illustration with guide in coronary sinus. A, Anteroposterior projection with the guide (G) in the CS. B, Drawing of the heart corresponding to A, showing location of the guide tip (long arrow).

A

B

Figure 22-57  Composite illustration of catheter in subeustachian space. A, Anteroposterior projection of the guide tip (G) is in the subeustachian space (short arrows) below and on the atrial side of the coronary sinus os. Contrast material outlines the subeustachian space. B, Drawing of the heart corresponding to A, showing the subeustachian valve, as well as the guide tip (long arrow).



22  Left Ventricular Lead Implantation

547

G

B

A

Figure 22-58  Composite illustration of catheter in coronary sinus. A, Anteroposterior projection of the guide tip (G) in the CS os. Residual contrast pooling can be seen in the subeustachian space (short arrows). B, Drawing of the heart corresponding to A, showing the eustachian valve, as well as location of the guide tip (long arrow).

catheter remains in the RA, a wire may be advanced through the Touhy-Borst valve and through the tip of the CS access catheter into the RV (Fig. 22-59). Once the wire is in the RV, the CS access catheter is advanced over the wire into the RV (Fig. 22-60). Procedural Steps Quickly finding the CS os involves the following steps: 1. Turn the equipment table perpendicular to the patient table. 2. Attach the loaded contrast injection system to the hub of the CS access catheter. 3. Start with the tip of the CS access catheter across the tricuspid valve. 4. Position the tip on the tricuspid annulus above the CS. 5. Apply 20 degrees of counterclockwise torque to the hub of the CS access catheter, directing the tip to the posterior superior tricuspid annulus. 6. Hold the location, and have the assistant inject 2 mL of contrast to confirm the location. 7. Apply an additional 20 to 40 degrees of counterclockwise torque, watching the tip of the CS access catheter for inferior deflection. 8. As the tip of the CS access catheter “walks” inferiorly and toward the right atrium in response to the torque, have the assistant inject 2-mL puffs of contrast agent to visualize the structures demonstrated in Figures 22-52 through 22-58.

Wire

9. On the basis of the anatomy demonstrated by the contrast agent, the CS access catheter can be either advanced or withdrawn, and more torque or less torque can be applied to direct the tip into the CS os. CORONARY VENOUS ANATOMY Compared with the coronary arterial system, the coronary venous system receives little attention. With CRT for heart failure, the coronary venous system is used to access target areas and implant the LV pacing lead.47,48 In the early days of CRT, implanters were forced to use a “take what’s available” approach to LV lead implantation. With experience and new implantation tools, physicians are increasingly inclined to place the lead in a specific location. As a result, the implanting physician will need to study the patient’s coronary venous circulation to determine the best way to direct the LV lead to the desired location. Under these circumstances, a complete set of well-performed cinevenograms is important. In the absence of information to the contrary, such as with tissue Doppler ultrasonography, the midlateral wall of the LV should be the location of choice. When tissue Doppler ultrasound (or another method) defines a specific area for LV lead placement, the operator studies the coronary veins to decide how to use the available anatomy to reach the chosen destination.

Y adapter with Touhy-Borst

Braided core Figure 22-59  Insert a wire into Touhy-Borst valve.

Peelaway sheath

548

SECTION 3  Implantation Techniques

Sheath and braided core

Wire

A

B

Figure 22-60  Advance catheter over wire into right ventricle. A, Wire inserted through the Touhy-Borst valve extends out the catheter into the right ventricle. B, Wire is held taut and used as a rail to advance catheter across the tricuspid valve into the right ventricle.

Half-Strength versus Full-Strength Contrast Physicians who do not take steps to prevent contrast nephropathy may favor the use of half-strength contrast agent for occlusive CS venography to reduce the load. However, half-strength contrast does not fully define the coronary venous anatomy; collateral vessels are not well seen, retrograde filling of proximal veins is difficult to appreciate, and a potential venous approach to the target area may be missed. Even when any lateral vein is acceptable, subsequent contrast injections are often required because of difficult anatomy (stenotic areas, phrenic pacing, or high pacing thresholds). Because of incomplete visualization on the initial half-strength venogram, the total contrast load may be ultimately greater than if full-strength contrast had been used initially. It is better to understand and take steps to prevent contrast nephropathy.

Limited visualization is obtained with occlusive CS venography using half-strength contrast agent (Fig. 22-61). Full-strength contrast provides much better visualization of the venous system, both antegrade filling and retrograde filling (Fig. 22-62). Full-strength contrast agent also visualizes venous collateral vessels that may be used for retrograde placement of the LV lead if the antegrade approach is problematic (Fig. 22-63). Venous anomalies that may be important to lead placement also are better visualized (Fig. 22-64). Occlusive Coronary Sinus Venography The occlusive CS venogram is the best way to establish the coronary venous anatomy for LV lead placement. Full-strength contrast should be used; otherwise, vessels are not well seen, retrograde filling of proximal veins is difficult to appreciate, and a potential approach to

Coronary veins

A

Coronary veins

B

Figure 22-61  Occlusive coronary sinus venograms with half-strength contrast material. A, On right anterior oblique projection, the venous anatomy is difficult to define. B, Left anterior oblique projection of the CS venogram with half-strength contrast material. As in A, it is difficult to appreciate the lateral wall target veins.



22  Left Ventricular Lead Implantation

A

549

B

Figure 22-62  Occlusive coronary sinus venograms with full-strength contrast material. A and B, The veins can be well seen beyond the balloon occlusion. Retrograde filling clearly identifies the middle cardiac vein (white arrows) and the posterior lateral cardiac vein (black arrows).

A

B

Figure 22-63  Occlusive CS venograms with full-strength contrast, showing collateral vessels. A and B, Large collateral vessels that can be used to place the left ventricular lead retrograde are well shown. Patient in A had prior open-heart surgery; patient in B did not. The arrows indicate venous collaterals.

A

B

Figure 22-64  Occlusive CS venograms with full-strength contrast, showing anomalous venous return. A and B, The veins that drain the anterior wall of the left ventricle (arrows) form a second CS that empties into the left atrium with a separate CS os.

550

SECTION 3  Implantation Techniques

B

A

Figure 22-65  Proximal origin of lateral wall vein, seen only on RAO view. A, In left anterior oblique (LAO) projection, the origin of the lateral wall target vein appears to be in the mid-CS (arrow), as also seen in anteroposterior projection (not shown). B, Right anterior oblique (RAO) view shows that the origin of the vein is close to the CS os (arrow). Hours were lost trying to advance the left ventricular pacing lead into the vein from the mid-CS in this patient, until the RAO venogram (originally omitted) revealed the proximal origin of the vein.

the target area may be missed. Because of incomplete visualization, the total contrast load may be ultimately greater with half-strength injections. If the balloon does not occlude the mid-CS, it can be advanced further into a narrow portion of the CS and inflated. The vessels proximal to the occlusion can usually be seen as they fill retrograde. Alternatively, the balloon may be double-inflated. When imaging the coronary venous system, it is tempting to “jump ahead” after the first injection; for efficient, effective lead placement in every case, however, it is essential to obtain all three views to fully visualize the anatomy. In many cases, the critical anatomic information required is apparent in only one view. Without all views the implanter may work for hours on the basis of a false assumption about the venous anatomy. For example, as illustrated in Figure 22-65, both the AP (not shown) and LAO venogram views make it appear that the patient’s venous anatomy is straightforward, with no further contrast agent required. After more than one hour of unsuccessful lead manipulation, the RAO CS venogram showed the proximal takeoff and parallel course of the target vein. With the venous anatomy understood, the lead was quickly placed. The time wasted because of

the lack of knowledge about the venous anatomy in one case easily justifies multiple additional occlusive venogram projections. Figures 22-66 to 22-70 provide examples of the importance of multiple views. Measures to Overcome Failure to Visualize Anatomy Selective Injection of Anterior or Middle Cardiac Vein.  In some cases, despite adequate occlusive CS venograms, no lateral veins are identified but the anterior and middle cardiac vein are seen. Injection of the anterior or middle cardiac with the vein selector usually fills a lateral wall vein via collaterals. If more contrast is needed, the delivery guide is used (Fig. 22-71). In some cases, contrast injection through a delivery guide into the body of the vein may not be helpful (Fig. 22-72); in this case, the vein selector (Impress CS Standard) can be advanced into a small-branch vein. Contrast injection into the small branch will usually reveal a target vein to the lateral wall through collateral filling (Fig. 22-72, C), with subsequent lead placement (Fig. 22-73).

Double density

A

B

Figure 22-66  Stenotic coronary sinus proximal to lateral wall vein, seen only on RAO view. A, Initial coronary sinus venogram indicates simple venous anatomy. Closer inspection, once additional projections are obtained, shows a double density (arrows) near the ostium of the lateral wall vein. B, Right anterior oblique (RAO) venogram reveals the stenotic segment of the main CS proximal to the target vein. Without knowledge of the CS stenosis, the operator could have spent hours trying to advance a lead into the vein.



22  Left Ventricular Lead Implantation

551

Stenotic

Stenotic

A

B

Figure 22-67  Stenotic coronary sinus and lateral wall vein, seen only on RAO view. A, On anteroposterior (AP) occlusive CS venogram, the lateral wall vein (arrow) appears easily accessible. B, Right anterior oblique (RAO) view, however, shows that the main CS and target vein are stenotic. What initially appeared to be an easy case on the basis of appearance on the AP and left anterior oblique (not shown) projections is revealed to be difficult only in the RAO projection. Recognition of the stenotic areas affects the approach to the midlateral wall, the choice of left ventricular lead, and the choice of delivery system.

A

AP

B

RAO

C

LAO

D

Steep LAO

Figure 22-68  Complex origin of lateral wall vein, only seen in steep LAO projection. A, Anteroposterior (AP) view; B, right anterior oblique (RAO) projection; C, left anterior oblique (LAO) view. The density along the medial wall of the coronary sinus (STE T) raises the possibility of a complex takeoff. D, Steep LAO projection taken to clarify the origin of the target vein. The origin of the vein from the CS is medial, rather than lateral as suggested by the initial images. If such a situation is unrecognized, the implanter will waste time in a fruitless attempt to direct the wire/ lead laterally.

552

SECTION 3  Implantation Techniques

Branch

Branch

Valve

A

B

Figure 22-69  Apparent CS dissection on LAO clarified on AP view. A, In left anterior oblique (LAO) projection, the coronary sinus appears to be dissected, with contrast material apparently in the pericardial space. B, Venous branches of the coronary sinus (CS) are evident in the anteroposterior (AP) CS venogram. Without the AP images, it is difficult to be certain that image in A is not a dissection.

A

B

C

D

Figure 22-70  Defibrillator lead in large posterior lateral vein. A, No lateral wall target vein is identified in anteroposterior projection. The defibrillation lead appears to be placed in the mid–right ventricular (RV) septum. B, No lateral wall target veins are identified on left anterior oblique (LAO) projection. However, location of the defibrillator lead is unusual for the midseptum. C, Right anterior oblique projection reveals that the defibrillator lead is in the large posterior lateral wall vein, not the RV septum as originally thought. Arrows mark subtle retrograde filling of the vein. D, Defibrillator lead is removed from the posterior lateral wall vein. The LAO projection now shows the vein previously obscured by the lead. In B, C, and D the arrows indicate the location of the posterior lateral wall vein.



22  Left Ventricular Lead Implantation

553

9F renal LVI

C

B

A

Figure 22-71  Lateral wall veins identified with selective injection of contrast. A, No lateral wall vein is identified despite double inflation of the balloon and injection of full-strength contrast material. B, No lateral wall veins are identified. C, The 9F delivery guide [renal telescopic lateral vein introducer (LVI)] is advanced in the coronary sinus selectively to engage a target vein. Injection of contrast material in the anterior lateral vein also fills the posterior lateral vein retrograde by collaterals.

Middle cardiac vein

A

9F delivery guide

B

Target vein

Vein selector Vein selector

Delivery guide

Target vein

Delivery guide

CS access catheter

C

D

Figure 22-72  Subselective injection of middle cardiac vein is required to identify and cannulate a lateral vein. A, Multiple occlusive venograms failed to reveal a lateral vein but did demonstrate the middle cardiac vein. B, Injection of contrast through a 9F delivery guide in the middle cardiac vein does not reveal a lateral vein. C, The 5F vein selector is in a superior branch of the middle cardiac vein that drains the lateral wall of the left ventricle. Contrast injection fills the lateral vein, which is seen to drain into the coronary sinus. D, Lateral vein is engaged with tip of the 5F vein selector, and contrast is injected. Venoplasty was required for LV lead placement (see Fig. 22-73).

554

SECTION 3  Implantation Techniques

LAO Delivery guide

Balloon

LV lead

A

B

Figure 22-73  Vein requiring venoplasty for lead to advance. A, The 9F delivery guide is at the ostium of the lateral vein shown in Figure 22-72. The balloon is inflated just inside the ostium. As the balloon is deflated, the delivery guide is advanced into the vein. B, Left anterior oblique (LAO) projection of the left ventricular (LV) lead is in place in the lateral vein after venoplasty,

In patients with a persistent left SVC where an occlusive venogram is not possible, our initial approach was to place a 5F pigtail catheter in the mid CS and use a power injector (Fig. 22-74). However, this is not always successful (Fig. 22-75). The soft, tapered-tip vein selector (Impress CS Standard) can be advanced into the CS, turned laterally, and manipulated carefully along the lateral wall in the LAO projection. When the tip is seen or felt to engage a structure, careful contrast injection will locate a coronary vein. Figure 22-75 shows a patient with a persistent left SVC where three 40-mL power injections of contrast failed to reveal veins to the lateral wall. Vein dissection is possible with forceful injections, but the tip of the Impress CS vein selector is softer than most catheters available from the cardiac catheterization laboratory and thus less likely to dissect. Coronary Artery Injection with Venous-Phase Images.  If no veins draining the lateral LV wall can be visualized with the first three

approaches, injection of the coronary artery with delayed images for venous return can be effective49 (Figs. 22-76 and 22-77). Basic Patterns of Coronary Venous Anatomy The variability of the venous anatomy may at first seem infinite, but there are basic patterns. Recognition of the venous pattern is important in selecting an approach to the target area and the type of lead. The venous anatomy can be classified according to the size of the vein that drains a particular area and characterized by the takeoff angle of the vein from the CS. The four patterns in the proximal-to-distal caliber of veins draining into the CS are as follows: 1. Midlateral dominant (Fig. 22-78, A). 2. Posterior lateral dominant (Fig. 22-78, B). 3. Balanced (Fig. 22-79, A). 4. Anterior lateral dominant (Fig. 22-79, B).

40 mL injection of contrast using power injector through pigtail

Lateral vein

A

B

Figure 22-74  Patient with a persistent left superior vena cava. A, Power injector used to inject 40 mL of contrast (20 mL/sec) through a 5F pigtail catheter placed in the mid–coronary sinus. A lateral wall vein is identified. B, Lateral vein is selectively cannulated with a 9F delivery guide (Renal Telescopic Lateral Vein Introducer), and contrast is injected to better define the anatomy.



22  Left Ventricular Lead Implantation

Anterior vein

40 mL injection of contrast using power injector through pigtail

A

Vein selector

CS access catheter

B

Contrast stain

555

Lateral vein

Lateral vein

Vein selector

C

D

Figure 22-75  Patient with persistent left superior vena cava. A, Power contrast injection in the coronary sinus (CS) did not reveal coronary veins. B, The vein selector (Impress Standard) has engaged the anterior cardiac vein. C, Contrast is injected through the vein selector that has engaged the lateral vein. Note the contrast stain from injecting in the CS to locate the vein. D, Contrast is injected through 9F delivery guide (Renal Telescopic Lateral Vein Introducer) to better define the vein.

CANNULATION OF THE DIFFICULT CORONARY SINUS As discussed previously, it is much easier to cannulate the CS with a telescoping, anatomically shaped CS access catheter and contrast than with other approaches. Contrast with the appropriate tools eliminates the need for the more complex approaches described by Bashir et al.50 Finding the Difficult CS Os Catheter Shape Not Suited to Anatomy.  The most common cause of difficulty finding the CS os is when the shape of the CS access catheter does not place the tip across the tricuspid valve and above the CS os when counterclockwise torque is first applied. This situation is common with nonanatomic-shaped CS access catheters. It can also occur with a massive right atrium where the proximal curve of an anatomicshaped catheter is too short to carry the tip across the RA to the tricuspid annulus (Biotronik ACS Extended Hook, Boston Scientific Acuity CS Extended Hook, Medtronic Attain Command Extended Hook, Pressure Products CSG-Worley STD, St. Jude Medical CPS Direct Wide). Catheters designed to solve this problem by extending the proximal curve include the Boston Scientific Acuity CS-W, Medtronic Attain Command Extended Hook XL, Pressure Products CSG-Worley Jumbo with braided core, and St. Jude Medical CPS Direct Extra Wide (Fig. 22-80). In addition, the reach of the catheter can be extended with a telescoping cannulation assist catheter, such as the included braided core of the Pressure Products Jumbo or the

addition of the optional St. Jude CPS AIM SL. Diagnostic catheters such as an AL2 can also be tried. Anatomic Variants.  The anatomic variants that make it difficult to locate the CS os include the high CS, tricuspid ring, huge right atrium, and a CS that empties into the left atrium. High Coronary Sinus Os.  If the CS is high (superior), as in Figure 22-81, the tip of the catheter must start above or else counterclockwise torque will direct the tip of the catheter posteriorly and inferiorly, away from the CS os. Tricuspid Valve Ring.  The tricuspid repair/ring placed in patients with severe congestive heart failure and tricuspid regurgitation may distort the anatomy. As illustrated in Figure 22-82, the CS os is easily found in one case (A) and difficult to find in another case (B). Giant Right Atrium.  When the RA is greatly dilated, as in permanent atrial fibrillation and tricuspid regurgitation, the tip of even a properly shaped guide/sheath may end up in the RA below the tricuspid valve where torque will direct the tip away from the CS. A sheath/ guide with an extended proximal curve specifically designed for the massive RA may be selected (Fig. 22-83). Coronary Sinus Empties into Left Atrium.  In rare cases, the CS empties into the left atrium (Fig. 22-84). Injection of contrast material into a coronary artery with imaging of the venous phase demonstrates the location of the CS os. In addition, a small vein leading to the CS is cannulated. The only way to reach the CS is via the transseptal approach.

556

SECTION 3  Implantation Techniques

RCA

A

Coronary veins

Coronary veins

C

5F catheter

B

D

Figure 22-76  Coronary veins identified only on delayed images after contrast injection into coronary artery. A, The coronary sinus (CS) is identified. Despite multiple attempts, including double-balloon inflation and injection of full-strength contrast material, the veins draining the lateral wall are not visualized. B, Attempts are made selectively to cannulate and inject veins to the lateral wall with a 5F catheter. After the veins have not been identified by occlusive venography or selective retrograde injection, arterial access is obtained, and selective injection of the right coronary artery (RCA) is performed. The RCA is shown with imaging during the initial contrast injection. C, Left anterior oblique projection of delayed imaging after RCA injection shows the coronary veins draining into the CS. D, Right anterior oblique projection of delayed imaging after RCA injection reveals the coronary veins draining into the CS. Currently, coronary injection can usually be avoided by the use of the soft tip vein selectors as described for patients with a persistent left superior vena cava (see Figure 22-75).



22  Left Ventricular Lead Implantation

557

9F renal LVI

9F renal LVI

Veins

A

B

5F Williams right catheter 9F renal LVI

5F catheter

Vein

C

D

Glide wire

Figure 22-77  Selective cannulation of coronary veins identified on delayed images after arterial injection. A, Manipulation of a 9F OD/7F ID renal-shaped guide (renal lateral vein introducer [LVI]) in the coronary sinus (CS) is unable to locate and cannulate the target vein identified in the venous phase after injection of the right coronary artery. B, After selective injection of the anterior coronary vein, the lateral coronary veins are seen to fill retrograde. C, A 5F Williams right catheter is inserted into the 9F renal LVI. The combination is used successfully to cannulate the lateral wall vein. D, The renal LVI is advanced into the vein using the combined support of a glide wire (Terumo Medical) and the 5F Williams catheter.

A

B

Figure 22-78  Midlateral and posterolateral dominant patterns of coronary veins. A, The largest coronary vein drains into the midportion of the coronary sinus (CS) and is thus midlateral dominant. B, The largest coronary vein drains into the posterior CS and is thus posterolateral dominant.

558

SECTION 3  Implantation Techniques

MCV

A

B

Figure 22-79  Balanced and anterior lateral dominant patterns of coronary veins. A, The lateral wall target veins are of approximately equal size. B, The midlateral wall veins are small (two arrows center right). The anterior lateral vein is large and thus dominant. MCV, Middle cardiac vein.

STEP 2: ADVANCING A SHEATH OR GUIDE INTO THE CORONARY SINUS Sheath/Guide Difficult to Advance When it is difficult to advance, maintain control of the catheter with both hands, and have the assistant inject 1 to 2 mL of contrast to determine the problem; once identified, a solution can be devised. For example, if the tip is caught in a large, proximal venous branch, withdrawing the guide a few millimeters and applying additional torque may free the tip and allow the guide to advance. The following issues may be the cause when it is difficult to advance: • Proximal branch that catches and misdirects the guide tip (Fig. 22-85)

CS access catheters with extended proximal curve

“Jumbo” SafeSheath CSG Worley Braided Core

CSP Direct Extra Wide

Attain Command EHXL

• Tortuous CS (Fig. 22-86) • Sigmoid CS (Fig. 22-87) • Initial angle of approach from the RA to the CS os • Vertical CS (Fig. 22-88) • CS stenosis from previous surgery • Valve at the CS os (Figs. 22-89 and 22-90) • Downward sigmoid CS (Figs. 22-91 and 22-92) • Mid-CS valve • Double-os CS • Thebesian valve When the CS is tortuous, sigmoid, vertical, or the initial angle of approach is problematic, creating a progressively supportive rail is often effective. Starting with the most supportive wire that will fully advance into the CS, the operator adds progressively more support by advancing a catheter over the wire. Thin floppy wires are easier to advance, but a stiff wire provides more support once in place. If only an angioplasty wire will advance, a small, flexible catheter should be next. Once in place, the wire and first catheter are held taut, and the next-larger catheter is advanced over the wire and first catheter. Usually, a .035-inch Terumo Glidewire will advance. This can be followed by a 5F or 6F multipurpose guide, then an 8F guide, followed by the 9F sheath. Anchor Balloon Technique In some cases, a .014-inch angioplasty wire is all that will advance, and attempts to advance a catheter result in wire displacement. In this situation the venogram balloon or a coronary balloon can be inflated in the CS or a branch vein and used as an anchor (see Fig. 22-88 and Chapter 23). When there is a downward sigmoid CS valve near the os, the telescoping approach can be used to redirect the angle of approach. If the sheath is placed on the lip of the CS and held in position, and the braided core is advanced out the sheath, the sheath will help support the guide and resist the downward trajectory, allowing the braided core to advance into the CS rather than dropping down into the right atrium. Figure 22-93 illustrates this concept diagrammatically, and Figure 22-94 provides a patient example. Selecting Target Vein

Figure 22-80  Coronary sinus (CS) access catheters. The extended proximal curve allows for the massive right atrium: Pressure Products CSG Worley “Jumbo” with braided core, St. Jude Medical CPS Direct Extra Wide, and Medtronic Attain Command Extended Hook XL (Boston Scientific Acuity CS-W not shown).

Selection of the target vein determines the shape of vein selector and the size of delivery guide. Recent speculation (wishful thinking) suggests that one LV pacing site is as good as the next for CRT, in which case the target vein becomes the easiest vein in which to place the lead. Our experience with CRT nonresponders does not support this position. We have seen too many CRT nonresponders improve dramatically when the pacing



22  Left Ventricular Lead Implantation

A

559

B

Figure 22-81  High coronary sinus (CS) os is difficult to locate. A, The only vein found on the initial attempt by a previous operator is low. B, The high CS os is easily cannulated with use of the approach described in Figure 22-60. Retrograde filling of the previously injected vein can be seen (arrows).

Tricuspid ring Tricuspid ring

Mitral valve

Mitral valve

A

B

Figure 22-82  Variable location of coronary sinus (CS) os. In two patients with tricuspid rings, CS os is located A, just below the tricuspid ring, and B, well below the tricuspid ring.

Worley Jumbo

Worley-STD

Figure 22-83  Standard (STD) and “Jumbo” versions of proximal curve. The larger version (Worley Jumbo) was specifically designed for massively dilated hearts with huge right atria. The reach of the curve is sufficient for the tip to reach across the tricuspid valve.

560

SECTION 3  Implantation Techniques

LA

LA CS

Catheter in left main

RAO

A

Catheter in left main

CS

LAO

B

CS

LA

LA

CS RA catheter in collateral to CS

C

RAO

RA catheter in collateral to CS

D

LAO

Figure 22-84  Coronary sinus (CS) drains into left atrium (LA). A, Contrast material is injected into the left main artery in the right anterior oblique (RAO) projection with delayed imaging to demonstrate the venous return. The CS drains into the LA. B, The venous return of the left main artery injection draining into the LA is shown in the left anterior oblique (LAO) projection. The contrast material stays to the right. C, RAO projection of the CS filling from an injection of a collateral vessel found in right atrium; RA, right atrial. D, LAO projection of the CS filling from an injection of a collateral vessel in right atrium. The course of the collateral vessel helps define the limits of right and left atria.

site is moved from an anterior or apical position to the lateral free wall (see Figs. 22-5 to 22-7 and 22-9 to 22-11). For now, we make every effort to place the LV lead on the midlateral LV free wall by whatever means possible. Placing Lead in Target Vein Once insertion of the CS access catheter has established a stable platform with adequate lumen size, it is time to place the LV lead. Multiple factors determine how difficult it is to place a lead in a specific vein, including the angle a vein forms as it empties into the CS (Fig. 22-95), its tortuosity (Fig. 22-96), small size (Fig. 22-97), and presence or absence of stenosis (Fig. 22-98). In many cases the takeoff looks easy but is deceptive and difficult (Fig. 22-99). The size, method of delivery, method of fixation, and lubricity of the LV lead not only affect lead placement but also whether a vein is suitable for LV pacing; the physical characteristics affect stability, pacing thresholds, and phrenic pacing. Replacement with a lead that is larger or that has a different shape or method of fixation can resolve stability and pacing issues in the target vein. Matching Left Ventricular Lead to Venous Anatomy Variables that affect how an LV lead behaves in a given vein include lead size, location of the pacing electrode (tip vs. ring), method of fixation (tines cannot spiral), and bipolar or unipolar design. Lead Size.  Remember that a delivery guide is designed to be placed in the coronary sinus through a CS access catheter; thus the internal diameter (ID) of the CS access catheter ultimately determines the size of the lead that can be delivered through a delivery guide. For example, the ID of the Boston Scientific Acuity Outer CS access catheter is 6.7 French, and thus the outside diameter (OD) of the Acuity Inner delivery guide must be 6.7F or less, which results in ID of 4.8F; thus the lead must be 4.8F or less. By comparison, ID of the Pressure Products

SafeSheath is 9F; thus the OD of the lateral vein introducer delivery guide can be 9F or less, which results in an ID of 7F; thus the lead can be up to 7F. Matching the size of the lead to the target vein is the most important first step. If the LV lead is too large for the target vein, it will not advance into the vein. However, a lead that is too small placed in a large target vein is more likely to be unstable and have high pacing thresholds. Electrode Location.  An LV lead with the pacing electrode at the tip will behave differently than a lead with a ring set back from the tip. The Boston Scientific EasyTrak and Acuity Spiral are the only pacing leads with the distal electrode is a ring set back from the tip. To make contact with the myocardium, the lead must be wedged into the target vein. By comparison, when the pacing electrode is at the tip, the electrode may contact the myocardium without being wedged. Method of Fixation.  Fixation can be either active or passive. Approaches to passive fixation include tines (straight), single curve, double curve (S shape),51,52 and double cant. In the right atrium and right ventricle, tines catch in the trabeculae, but in a venous branch of the CS, tines are intended to wedge in the vein as it is advanced distally. Nof et al.53 found no significant differences in success or complication rates among passive-fixation leads. However, high pacing thresholds, phrenic pacing, and an unstable lead position can be resolved by changing to an alternative form of passive fixation;54 that is, change the lead. If lead selection is limited to one company’s products, a less desirable target vein or even implantation failure may result. Left ventricular leads can be actively fixed via screw (Select Secure, Medtronic)55 or deployed lobes (Attain 4195 StarFix, Medtronic).56,57 Although fewer dislocations occur and thresholds are more stable with deployed lobes than passive fixation, fibrotic tissue growth into the Text continued on page 568



22  Left Ventricular Lead Implantation

Br

561

Br

A

B

C

D

Figure 22-85  Counterclockwise torque to redirect guide into coronary sinus (CS). A, Tip of the guide (arrow) is in a venous branch (Br) of the posterior lateral vein. B, Guide tip (arrow) is withdrawn back into the posterior lateral vein with counterclockwise torque; branch is still visible. C, Guide tip (arrow) is back in the CS. Additional counterclockwise torque is added. D, Guide tip (arrow) is advanced beyond the ostium of the posterior lateral vein into the CS. With limited experience, the entire procedure is accomplished in a single motion with 3 to 5 mL of contrast material.

A

B

Figure 22-86  Coronary sinus (CS) difficult to cannulate because of tortuous initial segment. A, Anteroposterior projection shows result of attempts to advance the guide into the CS. The guide is laid out on the floor of the right atrium. B, Right anterior oblique projection demonstrates that the forces are directed from left to right initially, rather than up into the CS. Application of torque to the catheter to provide a straight approach can resolve the problem. Reviewing the line of the guiding catheter into the CS in various projections is important to understanding how to adjust the torque to keep the catheter as straight as possible as it is advanced.

562

SECTION 3  Implantation Techniques

A

B

C

D

Figure 22-87  Sigmoid coronary sinus (CS) in patient with previous mitral valve repair. A, The tip of the guide rests at the CS os but will not advance into the CS. B, After injection of contrast material, right anterior oblique projection reveals the sigmoid shape of the proximal CS. C, A J-tip guidewire is advanced out the tip of the guide deep into the CS. D, The guidewire is held taut, and the guide is advanced over the guidewire deep into the CS. Several important points are demonstrated in sequence. First, without the use of contrast material, the operator would not be aware that advancing into the CS rather than finding the CS was the problem. Contrast material also demonstrated the nature of the anatomic variant, which provided a potential solution (use of a guidewire). Advancing the guidewire through the sigmoid section of the CS is possible because the guide provides support for the wire as it is advanced. The wire, once in place deep in the CS, provides a rail over which to advance the wire. It is important to hold the wire taut to create a rail as the guide is advanced over the wire.



22  Left Ventricular Lead Implantation

Venogram balloon

563

Venogram balloon

Sheath tip Sheath tip

A

B

Venogram balloon

Sheath tip

Sheath tip

C

D

Figure 22-88  Balloon catheter used as anchor to “pull” sheath into vertical coronary sinus (CS). A, Tip of sheath is at os of backward sigmoid CS. The compliant trackable balloon is advanced into the distal CS over the 0.014-inch guidewire and inflated with 2 mL of air. With the additional support provided by the anchoring balloon, an Amplatz stiff wire (J-tip wire) is advanced into the CS to add support. B and C, Sheath is “pulled” over balloon catheter and Amplatz wire deep into the CS. D, Balloon catheter is removed.

A

B

Figure 22-89  Valve near the coronary sinus (CS) os prevents guide from advancing. A, Anteroposterior projection shows the valve (arrow). B, Left anteroposterior projection with the Terumo Glidewire beyond the valve (arrow). The guide would not advance despite normal takeoff of the CS. Manipulation of the catheter did not succeed in advancing the guide beyond the valve. A 0.035-inch angled Terumo Glidewire was advanced through the hemostatic valve in the Y-adapter and out the tip of the guide. With manipulation, Terumo Glidewire advanced beyond the valve. The wire was held taut, and the catheter is advanced over the wire beyond the valve.

564

SECTION 3  Implantation Techniques

A

B

Figure 22-90  Coronary sinus stenosis preventing guide advancement. A, Anteroposterior projection reveals the proximal stenosis (arrows). B, Right anterior oblique projection shows the proximal stenosis as well as the distal stenosis (arrows) in the body of the coronary sinus. Without venoplasty, this case would require surgical implantation of epicardial leads. DOWNWARD SIGMOID CS

CS os Fulcrum

A

B

Figure 22-91  Downward sigmoid coronary sinus (CS). A, The CS os is not difficult to find, but it is difficult to advance the guide beyond the os. B, The effect of trying to advance the guide is a downward trajectory. The majority of the force is directed inferiorly, with little force to advance the catheter into the CS. DOWNWARD SIGMOID CS

Fulcrum

A

Fulcrum

B

Figure 22-92  Downward sigmoid coronary sinus (CS). A, Tip of the guide is in the CS, and a wire is advanced into CS. B, During attempts to advance the guide, lip of CS acts as a fulcrum. The forces are directed down toward the inferior vena cava.



22  Left Ventricular Lead Implantation

565

Sheath advanced over core and wire

Wire

Sheath

Braided core

A

B

Figure 22-93  Braided core advanced into coronary sinus (CS) over wire, followed by sheath. A, Wire is advanced into the CS and held taut. The sheath is held fixed at the CS os while the braided core is advanced into the CS. The trajectory cannot be achieved by advance of a catheter alone. B, Wire and braided core are held taut to form a rail over which the sheath is advanced.

BC

BC

S S

A

B

Figure 22-94  Using telescopic features of braided core–sheath combination to cannulate coronary sinus. A, Sheath (S) is held at the CS os while the braided core (BC) is advanced into the CS. B, Braided core is held in place as the sheath is advanced over the core into the CS. The core is then removed.

566

SECTION 3  Implantation Techniques

T

A

B

Figure 22-95  Placement of left ventricular (LV) pacing lead on lateral wall through ideal venous anatomy. A, Anteroposterior (AP) projection of the coronary sinus venogram; T, target vein. B, AP projection of Medtronic Attain 2187 LV pacing lead in place. The stylet-driven lead easily advances into the lateral wall target vein. The takeoff of the target vein lines up with the sheath. The forward vector of the lead is not degraded by the need to change direction to enter the target vein. In addition, no twists, turns, or stenotic segments limit access to the vein.

PROXIMAL CORONARY VEINS ARE FREQUENTLY TORTUOUS AFTER MITRAL VALVE SURGERY

Mitral valve Mitral valve ring

A

B

Figure 22-96  Two patients with highly tortuous, proximal coronary veins after mitral valve replacement or repair. A, Patient has St. Jude Medical mitral valve (arrowheads). Note the tortuous lateral wall vein (black arrow). B, Second patient underwent placement of a mitral ring (arrowheads). The lateral wall vein is highly tortuous (black arrow). In both cases, initial attempts at left ventricular (LV) lead placement were unsuccessful. With the use of delivery guides, LV lead placement on the lateral wall was successful. Highly tortuous, proximal coronary veins are often seen after mitral valve replacement or repair, presumably because of distortion of the mitral annulus.



22  Left Ventricular Lead Implantation

Figure 22-97  Small target veins. A, Target vein is small with a tortuous segment indicated by the double density (arrow). B, Vein takeoff is not difficult, but the small vein is extremely tortuous. In both cases, the combination of vein selector and delivery guide was essential to successful lead placement.

Small target vein

567

Small and tortuous target vein

B

A

Acute and tortuous

A

Acute and stenotic

B

Figure 22-98  Target veins with acute tortuous and acute stenotic takeoff. A, Takeoff from the coronary sinus is acute and tortuous. B, Takeoff from CS is acute and stenotic. DECEPTIVE TARGET VEIN ANATOMY

Anterior takeoff

Target vein

A

B

Figure 22-99  Target vein with deceptively difficult takeoff. A, Target vein appears relatively easy for cannulation and lead placement. B, Close inspection reveals the double density over the coronary sinus, reflecting the anterior takeoff from the CS. A vein selector was required to advance the lead and provide a rail over which to advance the delivery guide.

568

SECTION 3  Implantation Techniques

extendable lobes will seriously complicate extraction.57-60 Although limited data support screw fixation, the leads are expected to remain extractable.55 With the current selection of leads with different forms of passive fixation, a patient in whom implantation previously failed or resulted in a compromised lead position can undergo successful lead implantation through selection of the appropriate lead for the vein, without the need for active fixation.54 Preformed Lead Shape.  Medtronic, Guidant, St. Jude, Biotronik, and ELA have unique, preformed distal shapes intended to promote stability and orient the tip electrodes toward the myocardium. On occasion, the physical characteristics of the CS vein and the preformed lead shape result in “walking back” of the lead to a very proximal location or out of the vein entirely. It is important that the fixation shape match the vein. Over-the-Wire or Stylet-Driven Design.  The only company that continues to offer leads that are only stylet driven is ELA. “Personality” of LV Pacing Lead.  Each lead has a size, shape, and electrode configuration that produces a “personality” that will have advantages and disadvantages when the lead is used in anatomically different veins. Changing the method of lead fixation can solve problems of lead instability, high thresholds, and phrenic pacing (see later discussion). Selecting Shape of Vein Selector As mentioned, the current approach relies on the shape of the vein selector, not the delivery guide, for target vein cannulation, which is now possible because of the soft tip on selectors and guides. One of the three shapes of vein selector (see Fig. 22-3) will be suitable to locate, cannulate, and wire “all” target veins encountered. The CS Standard is suitable for the majority of veins, although the CS Hook and CS Vert are occasionally needed. In some cases it is clear from the venogram that the CS Standard is not ideal (Fig. 22-100), but in other cases it is a matter of trial and error (Fig. 22-101). The CS Hook can be useful near the CS os and with other veins that have an acute takeoff. The CS Vert is helpful when the takeoff is less acute but tortuous. The black distal section of the catheter is soft and can be easily straightened as it is advanced over wires into the target vein. Thus, once the ostium of the vein is identified by a puff of contrast, the wire can be advanced, followed by the vein selector to add a second wire. The vein selector is advanced deep into the vein over the wires and allows creation of a stable rail over which to advance the delivery guide.

Selecting Lumen Size of Delivery Guide The size of the lead suitable for the target vein determines the lumen size of the delivery guide to be used. For 6F to 7F leads, use the 9F OD/7F ID renal shape delivery guide (SafeSheath, Worley Telescopic Renal Shape Lateral Vein Introducer: LVI/75-5-62-07-RE) (see Fig. 22-21, B). For the 4F to 5F leads, use the 7F OD/5F ID renal-shaped delivery guide (LVI/75-5-66-5.5-RE) (see Fig. 22-21, A) or the device company delivery guides. The soft-tip section of the delivery guide can be advanced deep into a target vein over the vein selector if needed. As a result, we now rely on the shape of the vein selector, not the shape of the delivery guide, to accommodate the takeoff of various veins. Selecting Shape of Delivery Guide In the previous edition of this book, there was emphasis on matching the shape of the delivery guide to the anatomy because of the stiff-tip section of the guides in use at the time (guides obtained from radiology and first-model LVI). The soft tip of the current Pressure Products delivery guide used with the new soft-tip vein selector allows for one shape (the Renal, with the longest soft-tip section) to accommodate almost all venous anatomy (Fig. 22-102). Deploying Vein Selector and Guide Through Access Catheter Figure 22-103 demonstrates how to use the combination of the vein selector and delivery guide with the CS access catheter. When looking for the target vein with the vein selector, proper interventional technique must be used. Do not attempt to manipulate the catheter with one hand and inject contrast with the other (Fig. 22-104). Locate, “Wire,” and Create Rail in Target Vein for Guide.  To locate the target, the vein selector ID is rotated laterally and directed along the CS to where the vein was seen on the occlusive venogram. When the tip of the catheter falls outside the body of the CS or the tip fails to advance with gentle pressure, this suggests the vein selector is in the target. Ideally, puffs of contrast are only used to verify position, but may be necessary to reveal the target vein location. With the vein selector in or near the target vein, a .014-inch floppy wire is advanced, followed by the vein selector, then another wire (Figs. 22-105 and 22-106). Advance Guide over Selector/Wire Rail into Target Vein for Lead Delivery.  Figure 22-106 describes this process in detail.

Hook vein selector in proximal target vein

Proximal vein acute takeoff

A

B

Figure 22-100  Hook vein selector is best for the proximal vein with acute takeoff. A, Left anterior oblique occlusive venogram demonstrates a proximal target vein with acute takeoff. B, Hook vein selector engaged the vein as soon as it was extended from the delivery guide and turned laterally.



22  Left Ventricular Lead Implantation

569

Standard vein selector

Target vein

Target vein

A

B

Standard vein selector

Standard vein selector

Target vein

Target vein

C

D

Figure 22-101  Failure of vein selector to cannulate target vein. A, Target vein is seen in anteroposterior (AP) coronary sinus (CS) venogram. B, Standard-shape 5F vein selector tip does not fit into the target vein (Impress CS Standard p/n 1628-Y8, Meritt Medical) in the AP view. C, Standard-shape 5F vein selector tip does not fit into the target vein in the right anterior oblique (RAO) view. D, Standard-shape 5F vein selector tip does not fit into the target vein in left anterior oblique (LAO) view.

570

SECTION 3  Implantation Techniques

Wire

Delivery guide

Vein selector

Tortuous segment CS access catheter

A

B

Delivery guide Delivery guide

C

LV lead Vein selector

2 wires

CS access catheter

D

Figure 22-102  Coronary sinus (CS) standard vein selector and delivery guide in tortuous vein. A, Target vein has extremely tortuous proximal segment. B, With the support of the vein selector (Impress CS Standard), the angioplasty wire is advanced through the tortuous vein segment. The CS access catheter and the renal-shaped delivery guide are seen in the mid-CS. C, Vein selector is advanced over two wires (0.14-inch floppy and 0.014-inch extra support) deep into the target beyond the tortuosity. Using the rail created by the delivery guide and wires the soft flexible tip of the renal delivery guide is advanced deep into the vein. D, After vein selector removed, delivery guide remains deep in the vein, and the left ventricular (LV) lead is delivered. The delivery guide acts as a temporary stent to keep the vein straight. Previously delivery guides with stiff-tip sections would retract proximal to the tortuous segment, and the lead would not advance.



22  Left Ventricular Lead Implantation

571

Vein selector

Introducer

Hub

Delivery guide

B

A Vein selector

Delivery guide

Vein selector Tip of CS access catheter

Hub of CS access catheter

C

Tip of delivery guide

D

Figure 22-103  Load vein selector and delivery guide into CS access catheter. A, The 9 French (9F) OD delivery guide (renal LVI) is for a 6F lead in a medium to large vein, and the standard 5F OD vein selector (CS Standard) works to locate and cannulate most target veins. B, Vein selector is inserted into the black, peel-away introducer through the integrated hemostatic hub of the delivery guide. C, With tip of vein selector at tip of delivery guide, the combination is inserted through hemostatic hub of CS access catheter. Placing the tip of the vein selector at the tip of the delivery guide makes it easier to advance through the hemostatic hub. D, Tip of delivery guide is positioned at tip of the CS access catheter while the vein selector is advanced into the CS and turned laterally to locate and cannulate the target vein.

572

SECTION 3  Implantation Techniques

the mid-CS level. As the delivery guide is sliced away, the CS access catheter supports the lead. Slicing a delivery guide for removal is less problematic because the lead is still supported by the CS access catheter. Once the delivery guide is sliced away, the CS access catheter must be removed. Removing CS Access Catheter

A

The delivery system chosen at the start of the case has a major impact on the risk of lead dislodgment as the CS access catheter is removed. Interactions of delivery systems and factors in the risk of lead dislodgment include the following: 1. Use of a delivery guide impacts lead dislodgment through the size and final position of the lead. 2. Use of a delivery guide impacts lead dislodgment through the final position of the stylet. 3. Shape of the CS access catheter impacts lead dislodgment through rebound and lead length. 4. Method of CS access catheter removal (peeling vs. slicing) impacts lead dislodgment. 5. Hub design of the CS access catheter impacts lead dislodgment. Final Lead Size and Position.  A delivery guide helps insert a lead that is appropriately sized and positioned in the vein and is less likely to be displaced. When used, a delivery guide provides better support than a wire alone to advance the LV lead more securely into the vein. With large veins, a 9F delivery guide allows larger (6F-7F), more stable leads to be placed, versus the smaller, 6F to 7F delivery guides (4F-5F leads).

B Figure 22-104  Attach injection system to hub of vein selector, not to injection syringe. A, Injection syringe is attached to the vein selector; catheter control is poor. B, Injection system is attached to the vein selector through a rotating Y adapter. With this configuration, both hands are used for optimal catheter control, and attention is not diverted to inject contrast. Again, to use the vein selector in a safe and effective manner and to reduce contrast use, both hands must be on the catheter.

Techniques for Cannulation of Target Veins Close to CS os Delivering a lead to a target vein where the takeoff is just inside the CS os can be difficult because CS access is lost as the catheters are withdrawn in an attempt to engage the vein. Figure 22-107 illustrates a method that we have found helpful. Removing Vein Selector (Retain Wires and Deliver Lead) It is particularly important that the instrument table be perpendicular to the patient table as the vein selector is withdrawn. To prevent the delivery guide from being displaced during the process of removal, it is important not to advance the wires as the vein selector is removed. To maintain wire access in the vein, it is important not to pull the wires out as the vein selector is removed. Keeping the wires in a stable position during the process is best accomplished with the catheters in a straight line resting on the table. Once the lead is in place, it is time to discuss removing the delivery system without displacing the leads. Figures 22-108 to 22-112 provide step-by-step illustrations of how to use the vein selector with the delivery guide. Removing Delivery Guide Once the LV pacing lead is in place with satisfactory pacing thresholds and no phrenic or diaphragmatic pacing, the delivery guide (if used), CS access catheter, and stylet must be removed without dislodging the lead. All the delivery guides available (BSC, St. Jude, Medtronic, Pressure Products) must be sliced to be removed. Before the delivery guide is removed, the operator must ensure that the CS access catheter is at

Final Stylet Position.  Delivery guides also allow the stylet to be advanced to the tip of the lead without displacing the lead. When overthe-wire pacing leads are used, it is critical to remove the angioplasty wire and replace it with a soft stylet or fixing wire to stabilize the lead before delivery guide and CS access catheter removal. If either is removed with the angioplasty wire in place, friction between the guide/ sheath and the pacing lead slides the lead back over the wire (Fig. 22-113). Figure 22-114 illustrates one of the advantages of using a delivery guide for the LV lead. The telescoping delivery guide supports the lead in the target vein while the angioplasty wire is removed and the stylet advanced. Before the stabilizing stylet is inserted, the distal 8 to 10 cm of the stylet should be gently curved (Fig. 22-115). The importance of using a soft, curved stylet becomes apparent once guides and sheaths are removed. The stylet should always be advanced to the tip of the pacing lead. When the stylet is not at the tip of the lead, friction between the CS access catheter and the pacing lead will slide the lead back over the stylet (Fig. 22-116). If the stylet is at the tip, the lead position will remain constant as long as the position of the stylet is fixed (Fig. 22-117). The stylet should never be left at the mid-CS level, but should be advanced all the way to the tip of the lead. The telescoping delivery guide supports the lead so that the stylet can be advanced to the tip of the lead without fear of displacing the lead out of the target vein (Fig. 22-118). Once the soft, curved stabilizing stylet is in place, the delivery guide and CS access catheter can be removed. Nonanatomic Catheter Shape.  An anatomically shaped CS access catheter fits into the CS without being bent or forced. If the CS access catheter is not anatomically shaped, two interrelated issues tend to result in lead displacement: catheter rebound and lead length. Catheter Rebound.  When the catheter is forced into the CS, its shape is maintained by pressure against the CS. When the tip clears the CS os, the catheter resumes its intrinsic shape, falling into the right atrium and potentially displacing the lead (Fig. 22-119). If the CS access catheter is anatomically shaped, it does not require CS support to maintain its shape thus when it clears the CS, it does not fall into the right atrium. Figure 22-120 illustrates withdrawal of an anatomically shaped sheath from the CS. Lead Length.  With the CS access catheter in place, the length of lead in the body is determined by the length of the catheter between CS Text continued on page 578



22  Left Ventricular Lead Implantation

Hook vein selector advanced over wire

Target cannulated with vein selector

Vein selector

Wire

Vein selector

573

Delivery guide

Delivery guide

Target vein

CS access CS access

B

A Wire advanced into target vein

Second wire and vein selector advanced

Vein selector Delivery guide Delivery guide

Vein selector

Wire Wires CS access

CS access

C

D

Figure 22-105  Locate, cannulate, and wire target vein with CS hook. A, Coronary sinus (CS) hook vein selector is advanced over a wire until it reaches a position above the target vein, where the wire is removed. The CS access catheter and delivery guide are positioned in the proximal CS. Unlike the CS standard and CS vert, the acute bend on the CS hook makes it necessary to advance it over a wire in most cases. The CS standard and CS vert were not effective in locating the target vein in this patient. B, CS hook is turned laterally, withdrawn slightly, and a puff of contrast indicates the tip is in or near the target vein. The CS access catheter and delivery guide are positioned in the proximal CS. C, With support and direction from the vein selector, a floppy .014-inch hydrophilic wire is advanced into the target vein. The CS access catheter and delivery guide are positioned in the proximal CS. D, An extra-support .014-inch hydrophilic wire has been added and the vein selector advanced deep into the vein. Soft tip of the vein selector allows the acute bend to be straightened as it is advanced into the vein. Using the support provided by the vein selector and wires, the delivery guide is advanced toward the ostium of the target vein. CS access catheter remains in the proximal CS near the os.

574

SECTION 3  Implantation Techniques

Guide advanced over vein selector and wires

Torque guide coaxial with vein selector

Delivery guide

Vein selector Vein selector

Delivery guide

Wires

Wires

CS access CS access

A

B Guide in vein selector out

Lead resistance push CS access and guide back Delivery guide

Delivery guide

Lead Wires

Wire

CS access CS access

C

D

Figure 22-106  Delivery guide advanced into target vein and lead delivered. A, With vein selector and wires held in position, the delivery guide is advanced toward the target vein over the rail created by the vein selector and wires. The coronary sinus (CS) access catheter remains in the proximal CS near the os. B, As the delivery guide reaches the ostium of the vein, it is rotated slightly as it is advanced to ensure it is coaxial with the vein selector and target vein. The vein selector may be gently advanced and withdrawn over the wires to assist entry of the delivery guide into the target vein. C, Tip of delivery guide is secure in the vein, and the vein selector is removed. CS access catheter remains near the CS os. D, CS access catheter and delivery guide are pushed back by the resistance encountered as the 6F lead was advanced into the target vein. Without the support of the delivery guide and a stable CS platform, it would no longer be possible to advance the lead.



22  Left Ventricular Lead Implantation

575

HOW TO CANNULATE A VERY PROXIMAL VEIN USING A VEIN SELECTOR AND EXTRA-STIFF WIRE

Insert extrastiff wire Advance vein selector CS access catheter

B

A

Rotate vein selector laterally to engage vein Vein selector assumes shape

Withdraw CS access catheter

C

D

Figure 22-107  Cannulation of proximal target vein using guidewire to maintain CS access and vein selector to cannulate vein. A, With 9F ID coronary sinus (CS) access catheter in place, a .035-inch extra-stiff J-tip guidewire is advanced deep into the CS. B, The 5F vein selector (Impress CS Standard) is advanced into the CS. The CS access catheter prevents the vein selector from taking shape. C, CS access catheter is withdrawn out of CS os, and the vein selector takes shape. CS access catheter is maintained in position by the extra-stiff wire. D, Vein selector is rotated laterally, and puffs of contrast are used to locate the target vein. The ability to control the catheter with both hands and inject contrast without diverting attention from the location of the catheter tip is important for success; thus, contrast must be injected as shown in Figure 22-104, B, not A. If the vein selector falls out of the CS while attempting to engage the target vein, it is withdrawn into the CS access catheter, which is advanced back into the CS and the process repeated.

576

SECTION 3  Implantation Techniques

CS access catheter and delivery guide

A

Target vein?

“Hook” vein selector

A

CS access catheter and delivery guide

Vein selector Wire

B

Target vein

B

Figure 22-108  Small target vein identified on occlusive CS venography. A, Small, midlateral target vein is suspected on the anteroposterior (AP) occlusive coronary sinus venogram. B, Small target vein is confirmed on the left anterior oblique (LAO) occlusive coronary sinus (CS) venogram.

Figure 22-110  Hook vein selector used to identify, cannulate, and deliver wire to target vein. A, The 9F ID coronary sinus (CS) access catheter is at the os, and renal-shaped 5F ID delivery guide is at the tip of the CS access catheter (SafeSheath, Pressure Products). Contrast injection through the hook vein selector reveals the tip is in a smaller branch just below the target vein. B, Hook vein selector is positioned in lateral wall target vein, and a .014-inch floppy hydrophilic wire is advanced (Choice PT Floppy, Boston Scientific). Contrast injection confirms the wire is in the target vein.

Use support of vein selector/wires to advance the delivery guide

CS access catheter and delivery guide

Delivery guide

Target vein

A

“Standard” vein selector is not a good fit

Wires

Vein selector

A

Delivery guide

CS access catheter and delivery guide

“Hook” vein selector fits better

B Figure 22-109  Standard versus hook vein selector to identify target vein. A, The 9F ID coronary sinus (CS) access catheter is positioned at the os (SafeSheath CSG-Worley STD Braided Core Series, Pressure Products). Renal-shaped 5F ID delivery guide is advanced to the tip of the CS access catheter (Telescopic Series, Renal Lateral Vein Introducer, LVI/75-5-62-07-RE). The standard vein selector is telescoped into the CS, turned laterally, and puffs of contrast are used to locate the vein. B, Hook vein selector is a better fit for the acute angle of venous anatomy.

Wires

Vein selector

B Figure 22-111  Delivery guide advanced into target vein over rail created by vein selector/wires. A, The 9F ID coronary sinus (CS) access catheter is at the CS os (SafeSheath, Pressure Products). The hook vein selector is well seated in the target vein (Impress CS Hook, Merit Medical). A .014-inch extra-support hydrophilic wire (Choice PT, Boston Scientific) is added to stabilize the vein selector. With the vein selector/ wires held in position, the “renal” 5F ID delivery guide is advanced toward the target vein (SafeSheath). B, Delivery guide reaches the ostium of the target vein. To ensure the system is coaxial with the vein, the delivery guide is rotated slightly clockwise and counterclockwise as it approaches the target vein os.



22  Left Ventricular Lead Implantation

577

Lead advanced using support from delivery guide CS access catheter

Lead Delivery guide

A

CS access catheter

Delivery guide

Lead

A B Figure 22-112  Lead placement. A, The 9F ID coronary sinus (CS) access catheter is at the os (SafeSheath, Pressure Products). The hook vein selector has been removed, retaining the two wires (Impress CS Hook, p/n 1628-019, Merit Medical). “Renal” 5F ID delivery guide is at or just inside the target vein stabilized by the two wires (SafeSheath, LVI/75-5-62-07-RE). The bipolar LV lead (QuickSite Micro, St. Jude Medical) is advanced to the target vein over the floppy wire. B, Support provided by the extra-support wire and the delivery guide allows the lead to be advanced deep into the small vein.

B

Figure 22-114  Delivery guide supports lead as stylet is advanced. A, Angioplasty wire is removed; telescoping guide holds the lead in place. B, Stylet is advanced to the tip of the left ventricular (LV) pacing lead. The telescoping delivery guide ensures that the stylet can be advanced to the tip without displacing the lead. With the stylet at the tip, the lead is less likely to become dislodged during the removal process.

Curve on stylet

A

Figure 22- 115  Gently curved, soft stabilization stylet. A stabilization stylet is formed by curving the distal 10 cm of a soft stylet to the shape of a peel-away sheath with a proximal curve.

B Figure 22-113  Pacing lead slides back on angioplasty wire. A, The pacing lead is free to slide on the angioplasty guidewire. B, As the sheath is withdrawn, friction between the guide/sheath and the pacing lead slides the pacing lead back along the angioplasty wire.

578

SECTION 3  Implantation Techniques

A

Stylet not at tip of lead

B Figure 22-116  When stylet not at tip, pacing lead can slide back. A, Stylet is not at the tip of the pacing lead. The pacing lead can slide back on the stylet until the tip of the stylet is at the tip of the lead.  B, Even when the position of the stylet is fixed, friction between the guide/sheath and pacing lead can slide the lead back until the tip of the stylet reaches the tip of the lead.

and the body surface. There is more catheter (thus more lead) in the heart with the long, sweeping curve of an anatomic catheter than a straighter catheter that takes a direct course to the CS as it is bent to fit into the CS. Once the nonanatomic CS access catheter is removed, additional lead length is required (Fig. 22-121). When the cutting hand is fixed as the CS access catheter is removed, no additional lead is advanced into the body. The lead length will be inadequate and may be displaced between the time the CS access catheter is removed and the time the operator can advance an additional lead. Slicing versus Peeling for Removal.  Slicing requires the operator to fix the lead to the slicer, fix the position of the slicer and lead, and then pull the catheter straight back over slicer without moving the cutting

A

Stylet at tip of lead

B Figure 22-117  When stylet advanced to tip, pacing lead cannot slide back further on stylet. A, Stylet is at the tip of the pacing lead. The pacing lead cannot be moved more proximally B, Guide/sheath is withdrawn. Despite friction between the guide/sheath and lead, the lead will not slide back over the stylet as the sheath is withdrawn, as long as the position of the stylet is fixed.

A

B

Figure 22-118  Advancing lead/stylet to mid-CS level before guide/ sheath removal. A, Stabilization stylet is not advanced to the tip of the left ventricular (LV) pacing lead before the delivery guide is removed. B, The lead/stylet is inadvertently advanced in the process of removing the guide/sheath. The tip of the lead is displaced from the target vein. If the stylet is advanced to the tip of the lead before removal of the guide/sheath, unintentionally advancing the lead/stylet forces the lead further into the vein. The use of a delivery guide makes it possible to advance the tip of the stylet to the tip of the lead without fear of displacing the lead.

hand or allowing the lead to lead to buckle or detach from the slicer. A natural tendency is to pull the catheter off to one side, disengaging the blade from the catheter. If the lead is not dislodged as the blade disengages, the motion of trying to reengage the blade into the catheter frequently does. If additional lead slack is required to prevent lead dislodgment, it cannot be added (fixed slicing-hand position) until after the slicing operation is completed. For many physicians, it can be difficult to remove the CS access catheter by slicing without displacing the lead. Peeling the CS access catheter is much simpler and more secure for many physicians. Before cracking the hemostatic hub and while watching the lead length under fluoroscopy, the catheter is withdrawn over the lead until the hub reaches the I-S1 connector. At this point, the tip of the sheath has cleared the CS and is in the high right atrium. Additional lead can be advanced if needed as the sheath is withdrawn. Before peeling, the assistant stabilizes the lead distally by pinching the walls of the sheath against the lead where the sheath exits the body. With the lead secure, the hub is cracked and the sheath peeled down to the fingers of the assistant. The cycle of withdraw, pinch, and peel is repeated until the sheath clears the body and the assistant secures the lead. Hub Design.  Cutting a braided CS access catheter and/or delivery guide requires a hemostatic hub designed to be either sliced (Figs. 22-122 and 22-123) or removed (Fig. 22-124) after the lead is placed. The Biotronik and Medtronic systems use a removable hemostatic valve and a sliceable hub (see Fig. 22-124). The sliceable plastic hub is joined to the braided catheter by overlapping the plastic and braid. The resistance to cutting increases significantly as the blade reaches the plastic hub to guide overlap, then decreases abruptly as the blade reaches the guide. The sudden change in resistance can cause the cutting hand to jump at the same time as the tip of the guide is prone to disengage from the CS. Acting synergistically, these factors tend to displace the lead. The Boston Scientific and ELA braided CS access



22  Left Ventricular Lead Implantation

579

Tension

A

B

Figure 22-119  Removal of guide/sheath without proximal curve from coronary sinus (CS). A, Native shape of a guide/sheath without a proximal curve is deformed to fit into the CS. The shape of the guide/sheath is the result of the bending forces exerted on the guide as it was inserted. The shape is maintained by pressure on the distal section of the sheath (arrows) as it rests in the CS. B, Tip of the guide is withdrawn from the CS. The distorted shape is no longer supported by the CS. The guide resumes its native resting shape and falls to the floor of the right atrium (arrow), an event that can dislodge the left ventricular (LV) lead.

catheters use the Pressure Products type of breakaway hub, which exposes one-half the circumference of the proximal end of the guide (Fig. 22-125; see also Fig. 22-122). There is no guide-hub overlap, so resistance to slicing is uniform. The Boston Scientific integrated hemostatic valve is similar to the Pressure Products breakaway hub, but hub-guide overlap changes resistance to cutting (see Fig. 22-143). The sliceable hub of the St. Jude braided CS access catheters and delivery guide is a new, asymmetrical design in which the guide extends the full length of the hub, forming part of the outer wall (see Figs. 22-122 and 22-151). Thus, Boston Scientific, ELA, Pressure Products, and St. Jude designs have integrated, slittable hemostatic hubs, which avoids the troublesome hub to guide transition. Splitting Hub/Guide without Grabbing and Displacing Lead.  After it is cut, the thick plastic of the hub of the guide can close around the lead. Unless carefully removed from the grip of the cut hub, the lead will be jerked abruptly when the hub reaches the IS-1 connector (Fig. 22-126). A technique to avoid the issues with slicing that occur as the catheter clears the CS is to withdraw the braided guide over the lead as far as the lead length will permit, often moving the tip above the right atrium before cutting. However, cutting a braided catheter that has been withdrawn to the IS-1 connector can be problematic. There is no way to stabilize the lead and no place to support the cutting hand. The slicer for the Pressure Products delivery guide is designed to mate to the hub of the CS access catheter, providing a defined, stable position to support the cutting hand (Fig. 22-127). Long Peel-away Catheter Removal.  Anatomically shaped, peel-away CS access catheters are less prone to dislodge the lead as they are removed. Before cracking or peeling occurs, the operator withdraws the catheter, watching the tip under fluoroscopy until the hub reaches the IS-1 connector. This permits easier adjustment of the lead length in the right atrium as the tip clears the CS os. Separating the step of removing the sheath/guide from the CS from the step of peeling permits advancement of the lead if its location is demonstrably unstable. Figure 22-128 shows that lead stability and hemostasis are

facilitated if the operator does not remove the hemostatic valve and withdraws the sheath over the pacing lead to the IS-1 connector. As the sheath is withdrawn, both the portion in the atrium and the tip of the LV lead should be in the fluoroscopic field so that the operator can judge the length of lead required as the supporting sheath is removed. This approach minimizes blood loss and the risk of air embolization, because the hemostatic valve is not removed until it is withdrawn to the IS-1 connector. Because there is no braid, the walls of the sheath can be pinching against the lead, reducing blood loss and risk of air embolization once the valve is removed. It is much more difficult, if not impossible, to pinch a catheter effectively with wire braid incorporated in the wall. After the assistant releases the sheath/lead, the rest of the sheath is drawn back over the lead under fluoroscopy. As the tip of the sheath exits the body and the pacing lead becomes visible, the assistant secures the lead position with fingers in the pocket. Stylet Removal The final step is to remove the stylet. Special care is needed; many successful implantations have been lost during this step. The two key issues are the physical characteristics of the stylet and the method of stylet withdrawal. Stylet Characteristics.  When the stylet is in the lead within the CS, the shape of the lead/stylet combination is determined by the course of the CS. Once outside the CS, the stylet is no longer supported. When the shape of the stylet and course of the LV pacing lead do not match, the stylet determines the ultimate shape of the lead/stylet combination, often by withdrawing the tip from the target vein. The stiffer the stylet, the greater is the displacing force applied to the lead. Placing a gentle curve on the stylet that approximates the final course of the lead through the right atrium reduces the tendency for the stylet to displace the lead because of a shape mismatch. A softer stylet exerts less displacing force when the shape of the stylet and course of the lead do not Text continued on page 585

580

SECTION 3  Implantation Techniques

ANATOMICALLY SHAPED CS ACCESS CATHETER WITHDRAWN FROM THE CS

B

A Tip follows the line of the catheter to the SVC

C

D

Figure 22-120  Removing anatomically shaped sheath from coronary sinus (CS). A, Sheath is in the CS with the tip (arrowhead) just inside the os. B, Tip of the sheath (arrowhead) is withdrawn to just beyond the CS os. Note that the tip of the sheath is at the level of the CS os. C, Sheath is withdrawn further. Note that tip of the sheath (arrowhead) is now well above the CS; SVC, superior vena cava. D, Sheath is withdrawn still further. The tip of the sheath (arrowhead) distorts the shape of the lead slightly. Note that the left ventricular (LV) lead remains in place in the target vein. Because of the proximal curve, it is not under tension and does not drop to the floor of the right atrium as it clears the CS.



22  Left Ventricular Lead Implantation

LV pacing lead

Insufficient “slack”

581

Slack added

Guide

A

B

C

Figure 22-121  More lead length is required when the final guide/sheath is removed. A, Left ventricular (LV) pacing lead is in place in the target vein. The lead is supported within the guide/sheath between the skin and the proximal coronary sinus. The sheath determines the length of the lead in the body, particularly in the right atrium. B, Guide/sheath is removed without advance of additional lead. Without the support of the guide/sheath, the length of the lead in the right atrium is insufficient. Because the lead is on stretch, it may displace the tip of the lead from the target vein. C, Additional slack is added to ensure that the tip of the lead is not dislodged when the patient breathes or stands up. After guide/ sheath removal, the length of additional lead required is determined from the shape of the guide/sheath. There is more pacing lead in the heart when an anatomically shaped sheath is removed because of the lead in the long curved section in the right atrium. With a straight or nonanatomic shape, the course of the guide/sheath through the right atrium is more direct, resulting in less lead in the body when the guide/sheath is removed.

St. Jude

ELA

Figure 22-122  Comparison of integrated sliceable hemostatic hub technology for removal of braided CS access catheter. St. Jude has developed a sliceable hemostatic hub in which the braided guide is exposed (arrows) along the length of the intact hub. Pressure Products, ELA, and Boston Scientific have used the breakaway hemostatic hub developed by Pressure Products. In either case, there is no difficulty in slicing hub to guide overlap; thus, resistance to slicing is uniform. In addition, no plastic hub is prone to gripping the lead and resulting in lead dislodgment. Pressure Products achieves this by exposing the catheter when the valve is broken in two pieces. St. Jude Medical incorporates the guide in the side wall of the hub. St. Jude uses the hub on both its coronary sinus (CS) access catheter and its delivery guide. Pressure Products uses the hemostatic hub on its delivery guide and has a peel-away CS access catheter.

582

SECTION 3  Implantation Techniques

Figure 22-123  Integrated sliceable hemostatic hub technology. For removal of a braided coronary sinus (CS) access catheter (St. Jude Medical).

Figure 22-124  Universal Slitter and guide hub (Medtronic). A, Universal Slitter is used with all lead sizes. The operator’s thumb secures the lead to the bottom of the slitter, preventing the cut hub from grabbing and dislodging the lead. B, The plastic hub of the guide with hub-guide transition is shown. At the hub-guide transition, resistance to cutting changes abruptly, which can cause the cutting hand to leap forward and displace the lead.

Hub No hub guide transition

Blade Guide

A

B

Figure 22-125  Cutter and telescoping hub guide (Pressure Products). Also used by ELA. A, Cutter is used with leads of all sizes. The operator’s thumb secures the lead to the back of the slitter, preventing the cut hub from grabbing and dislodging the lead. B, After the hemostatic hub is cracked, one half of the hub detaches from the guide. The blade of the cutter engages the guide directly (not the hub). There is no transition in resistance to cutting to cause the cutting hand to leap forward.



22  Left Ventricular Lead Implantation

583

IF THE LEAD IS NOT SECURED TO THE CUTTER WITH THE THUMB IT WILL GET CAUGHT IN THE HUB AND PULLED BACK WITH THE GUIDE

Lead under thumb

Lead not under thumb caught in hub

A

B

Figure 22-126  Pacing lead caught in cut plastic hub as guide is sliced. A, Universal Slitter (Medtronic) cuts the plastic hub of the guide. The lead is fixed to the back of the cutter with the thumb. As the hub is split, the lead pulls clear of the plastic. B, The lead is not fixed to the cutter with the thumb. The split hub closes around the lead. As the guide is pulled back, it pulls the lead back.

THE CUTTER MATES TO HUB OF SHEATH PROVIDING A DEFINED AND STABLE POSITION FOR THE HAND AS THE GUIDE IS WITHDRAWN OVER THE BLADE

CS access sheath

Stable hand position defined by sheath

Cutter mated to the hub of the sheath

A

Lead secured to cutter by thumb

Sheath

B

Figure 22-127  Hand holding cutter is stabilized on hub of sheath. A, The lead is not attached to the cutter (Pressure Products). B, Without moving the lead, the operator cuts the third-generation guide down to the SafeSheath hub. The curved front of the cutter is mated to the hub. The operator removes the lead from the cut guide and secures it to the cutter by placing the lead in the notch of the cutter under the thumb.

584

SECTION 3  Implantation Techniques

Before peeling, the long sheath is withdrawn from the CS to the high RA by sliding the sheath ---

A

--- over the lead. As the sheath is withdrawn, the pacing lead is watched under fluoroscopy.

B

The tip of the sheath will clear the os of the CS while the operator is under complete ---

C

--- control. The slack in the lead is adjusted as the sheath is withdrawn to the high RA.

D

Pinching the lead between the walls of the sheath stabilizes the lead and sheath distally.

E

The sheath is peeled without moving the lead or sheath within the body.

F

Figure 22-128  Removing long, peel-away sheath from coronary sinus without displacing left ventricular lead. A, Left hand holds lead (with stylet advanced to tip) fixed in place 5 cm from hemostatic valve. Right hand holds peel-away sheath and is ready to withdraw sheath back to left hand. B, Right hand withdraws sheath to left hand holding the lead. Operator performs this step in a careful and controlled manner, watching the lead with fluoroscopy as the tip of the sheath transitions from the coronary sinus (CS) CS to the right atrium (RA). Frequently, additional slack is required as the sheath is withdrawn. Adding slack is easily accomplished by advancing the lead with the right hand as the left hand withdraws the sheath. C, Lead is again fixed 5 cm from hemostatic valve with left hand. Right hand grasps hub of sheath and is ready to withdraw sheath toward left hand. D, Sheath is withdrawn to IS-1 connector. Tip of sheath is now in superior vena cava (SVC), where inadvertent motion is not likely to cause displacement of LV lead. E, Assistant pinches the pacing lead firmly between the walls of the sheath where it exits the body in the pacemaker pocket. With assistant stabilizing LV lead and sheath, operator prepares to remove hemostatic valve. F, With lead and sheath both stabilized by assistant, the operator removes hemostatic valve and rapidly peels sheath down to fingers of assistant, who continues to pinch lead between walls of sheath. Pinching the lead between the walls of the sheath not only stabilizes the sheath and LV lead, but also reduces bleeding and the risk of air embolization (long SafeSheath [Pressure Products] shown). The technique applies for any long, peel-away sheath. As the sheath is withdrawn, the slack on the lead can be adjusted.



22  Left Ventricular Lead Implantation

Stylet at the CS os

585

Stylet straightens when not supported by the CS

LV

LV lead pulled back

A

B

Figure 22-129  Stylet dislodges LV pacing lead as it is slowly withdrawn from coronary sinus (CS). A, Straight, stiff stylet is withdrawn from the tip of the pacing lead to the CS os. The curve on the stylet is maintained through contact of the lead with the wall of the CS. B, Stylet is withdrawn from the CS. The stylet springs back to its original straight shape, pulling the left ventricular (LV) lead out of the vein. The stiffer the stylet, the more displacement force is exerted as it springs back to its straight shape. To avoid loss of lead position at stylet removal, use a soft, anatomically shaped stylet. In addition, rapid removal of the stylet reduces the duration of the displacement force acting to withdraw the lead from the vein.

match despite the curve. I advise use of a soft, gently curved stylet advanced to the tip of the lead (see Fig. 22-115). Figure 22-129 illustrates what can happen if a stiff straight stylet is used. Method of Stylet Withdrawal.  As discussed, when the shape of the stylet and course of the LV pacing lead do not match, the stiffer stylet will prevail, often by displacing the lead. The longer the stylet remains in a position prone to displacing the lead, the more likely the lead will be displaced. To prevent the stylet from displacing the pacing lead when the course of the lead and the shape of the stylet do not match, the stylet is removed quickly (like pulling the cord on a lawn mower). This maneuver gives the stylet less time to displace the lead. Before insertion into the LV pacing lead, the stylet should be curved, as shown in Figure 22-115. Final Slack on Lead The final step in LV lead placement is to be certain that the lead has adequate slack. Appearance on AP and RAO projections can be deceptive about this issue. The LAO projection is best for judging the amount of slack in the lead. In the LAO projection, the RV and LV leads should appear to touch low in the right atrium (RA) and continue parallel in close proximity as they leave the RA into the SVC. Figure 22-130 is an example of dislodgment of the lead caused by insufficient slack; note the trajectory in the LAO projection with insufficient slack in B compared with adequate slack in D. To ensure adequate slack on the LV pacing lead, the operator should inspect the steep LAO projection to confirm that the LV and RV leads appear to touch in the low RA.

Complications of Cardiac Resynchronization Therapy When CRT began, there was overwhelming concern that a misadventure in the CS would be catastrophic. However, experience has not substantiated this view. ARTERIAL VERSUS VENOUS SYSTEM Dissection An intimal disruption affects a coronary artery differently than a coronary vein. In an artery the blood is under high pressure and will squeeze under the flap and extend the dissection. In a vein the blood is flowing in the opposite direction from the flap and is under low pressure, so the dissection is not extended (Fig. 22-131). Perforation When “catheter”-induced trauma results in coronary artery perforation, the situation is difficult because the pressure gradient forces blood into the pericardial space, rapidly leading to cardiac tamponade. With perforation of a coronary vein, however, the pressure gradient is in the opposite direction. After a venous perforation, blood within the vein follows the pressure gradient into the CS and to the right atrium. Unlike the right ventricle, the low pressure and pressure gradient in the coronary veins favor blood flow into the CS and right atrium, not into the pericardial space. The exception is if occlusive CS venography is performed after the perforation (Fig. 22-132).

586

SECTION 3  Implantation Techniques

Not enough slack on the lead

A

AP

B

LAO

Adequate slack on the lead

C

AP

D

LAO

Figure 22-130  Insufficient slack in LV pacing lead results in displacement. A, On anteroposterior (AP) projection of the final left ventricular (LV) pacing lead position, the amount of slack seems adequate. B, On left anterior oblique (LAO) projection, there is not enough slack. Note distance from right ventricular (RV) lead in the atrium. C, AP projection after advancing the lead. D, LAO projection with appropriate slack. Note the course of the LV lead next to the RV lead on the right atrium.

A

B Figure 22-131  Effect of intimal flap in artery versus vein. A, Catheter trauma created an intimal flap in an artery. High pressure and the direction of blood flow in the artery (arrows) will lift the flap and extend the dissection. B, Catheter trauma created an intimal flap in a vein. The direction of blood flow in the vein (arrows) will close and seal the flap.



22  Left Ventricular Lead Implantation

587

Initial trauma from balloon tip

Initial trauma from balloon tip

B

A

Occlusive venogram repeated after 30 minutes

C

Occlusive venogram repeated after 30 minutes

D

Figure 22-132  Coronary sinus (CS) aneurysm formation and rupture with second occlusive CS venogram. A and B, Tip of the balloon produces trauma and staining of the CS. C, Aneurysmal dilatation of the CS expands as the balloon is inflated, and contrast material is injected 30 minutes after the initial CS trauma. D, With balloon occlusion and contrast injection, the aneurysmal area bursts, forcing blood and contrast material into the pericardial space.

Occlusion If catheter trauma results in coronary artery closure, the consequences are abrupt and profound, leading to an acute myocardial infarction. However, the effect of catheter-induced trauma resulting in closure of a venous structure is of no acute or long-term significance other than the lack of venous access. Figure 22-133 demonstrates occlusion of a lateral wall target vein. Despite this, tamponade may develop, related specifically to the placement of the LV lead. It appears to occur with the same frequency as during dual-chamber pacemaker or implantable cardioverter-defibrillator (ICD) implantation. Tamponade during CRT is usually attributed to the LV lead, but also potentially related to the right-sided heart leads. Longer procedure times can increase problems with sedation and infection. ELECTROPHYSIOLOGY VERSUS OPEN-LUMEN CATHETER WITH CONTRAST FOR IMPLANTATION Although many EP physicians are more comfortable manipulating an EP catheter in and around the CS, objectively an EP catheter is stiffer and more prone to inflict vascular trauma than a soft-tip, open-lumen catheter designed to work safely in the arterial system. Despite this, there is residual concern that somehow manipulation of open-lumen

catheters in the coronary venous structures is intrinsically more “dangerous” than in arteries because veins are “thin-walled structures.” Factoring out nephropathy, an open-lumen catheter with contrast is superior to the EP catheter approach for several reasons. Use of contrast material is essential to understand the individual patient’s CS and coronary venous anatomy, to facilitate localization of and advancement into the CS, and to reach the target area of the left ventricle. Contrast stains that develop with the use of open-lumen catheters initially caused great concern, frequently with termination of the procedure. However, we now recognize that contrast stains rarely have clinical consequence. In fact, contrast stains are clues and, when identified, quickly indicate a misstep that can be corrected before significant damage occurs. Use of contrast material identifies the “catheter” location at all times, limiting unintentional trauma. The same misstep with an EP catheter often goes unrecognized until occlusive CS venography is performed or pain or hypotension announces its presence. Thus, the potential for staining with a contrast agent is what makes it safe. It is important to distinguish a contrast stain from a dissection. A dissection occurs when a catheter is advanced after an intimal flap is raised. A dissection is more likely with an EP catheter because the perforation is not recognized and the catheter continues to advance. The trauma from an EP catheter only becomes apparent if contrast is injected or hemodynamic collapse occurs (Fig. 22-134).

588

SECTION 3  Implantation Techniques

B

A

Figure 22-133  Occlusion of lateral wall target vein. A, Small, lateral wall target vein (arrow) can be seen during the initial occlusive coronary sinus venography. B, The target vein is no longer visible on a second venogram performed after an unsuccessful venoplasty; patient had no adverse effects. An alternative lateral wall target vein was used for placement of a left ventricular lead.

OCCLUSIVE CORONARY SINUS VENOGRAPHY Contrast Stains Contrast staining can occur at CS venography but is not of hemodynamic significance. Staining can result from unmasking of CS trauma, local extravasation of contrast, or balloon-induced trauma. Unmasking of Trauma.  When an EP catheter is used to locate and cannulate the CS, an unrecognized dissection may have occurred. The EP catheter is not designed to prevent vascular trauma. It does not have a soft tip as does an open-lumen catheter, and it does not have a J-shaped tip as does a guidewire, to prevent vascular trauma. Thus, unrecognized trauma to the CS is likely with an EP catheter, but becomes apparent only when contrast material is injected into the CS under pressure, reversing the natural pressure gradient. In this case,

occlusive CS venography does not cause the staining, but rather unmasks the unrecognized trauma inflicted by the sharp, stiff EP catheter (see Fig. 22-134). Local Extravasation of Contrast Material.  If the tip of the balloon becomes lodged in a small venous branch during injection of contrast material, the vein is disrupted, and contrast material is extravasated into the interstitial space, causing a stain (Fig. 22-135). Balloon-Induced Trauma.  Balloon trauma is limited by careful inflation of the balloon in the CS under fluoroscopic guidance while contrast material is being injected. Inflation is stopped when the balloon occludes the CS, preventing reflux of contrast material. When overinflation occurs, a noncompliant (nondeformable) balloon is more likely to inflict CS trauma than a compliant balloon. When a compliant

EP CATHETER–INDUCED TRAUMA REVEALED BY PRESSURE REVERSAL WITH OCCLUSIVE CORONARY SINUS VENOGRAM

Contrast extravasation with first injection EP catheter in CS from leg

A

B

Figure 22-134  Extravasation of contrast from EP catheter–induced coronary sinus (CS) trauma. A, Electrophysiology catheter is used to find the CS from the leg. B, During the occlusive CS venogram, contrast material extravasates freely into the pericardial space through the perforation caused by the EP catheter.



22  Left Ventricular Lead Implantation

589

B

A

Figure 22-135  Contrast staining at occlusive coronary sinus (CS) venography. A, Balloon is inflated, and contrast material fills the CS in retrograde fashion. B, Tip of the balloon catheter engages a small venous branch, and contrast material extravasates into the interstitial tissue. Despite their ominous appearance, contrast stains rarely result in hemodynamic complications. At the worst, stains obscure the venous anatomy for 10 to 15 minutes.

balloon is overinflated for the size of the CS, it becomes distorted and conforms to the CS (Fig. 22-136, A). When a noncompliant balloon is overinflated, it enlarges without conforming to the CS, possibly resulting in local trauma (Fig. 22-136, B). Potential Risks If a compliant occlusive balloon is used and the tip of the balloon is watched during injection, CS venography rarely produces a stain, much less a hemodynamic consequence. The following two exceptions to this rule both arise when occlusive venography is performed after initial CS trauma is inflicted: 1. When the EP catheter used to identify the CS from the leg and deliver the sheath/guide to the CS inflicts unrecognized trauma. 2. When the occlusive CS venogram is repeated during the same procedure after venous trauma is recognized. The balloon occlusion increases venous pressure distally, forcing blood into the traumatized area. When contrast is injected with the balloon inflated, the distal pressure increases, further forcing blood and contrast into and through the venous disruption. Enough blood and contrast material can be forced into the pericardial space to result in hemodynamic compromise (see Fig. 22-132).

LEAD PERFORATION It appears much more likely that stylet-driven pacing leads will perforate the coronary veins than catheters, guides, or sheaths. Styletdriven pacing leads, as with EP catheters, have solid, metal tips with wire-reinforced shafts. A considerable amount of tip force can be delivered, as evidenced by the ability of such catheters to perforate the right ventricle. However, unlike RV perforation, coronary venous perforation rarely causes tamponade, because the pressure in the right ventricle is much higher than that in the pericardial space, causing a pressure gradient favoring tamponade. The pressure in a vein is much lower than that in the right ventricle, and a pressure gradient exists from distal to proximal in the vein. Thus, the pressure gradient favors the flow of blood into the more proximal vein, rather than out into the pericardial space (Figs. 22-137 and 22-138). RADIATION EXPOSURE The risk of radiation exposure, including skin burns, increases with prolonged procedure time.61

Shape of compliant balloon deformed by anatomy

A

Shape of less compliant balloon not deformed by anatomy

B

Figure 22-136  Compliant versus noncompliant balloons for occlusive CS venography. A, Compliant balloon deforms to fit in the coronary sinus (CS). B, Noncompliant balloon maintains its shape independent of patient anatomy.

590

SECTION 3  Implantation Techniques

A

B

Figure 22-137  Contrast staining from delivery guide. A, Medtronic Attain 6218 guide is advanced over a wire and small catheter (secondgeneration telescoping system) into the lateral wall target vein. B, Contrast (2 mL) is injected to confirm that the guide is coaxial in the target vein before Attain 2187 LV pacing lead is advanced. The tip of the guide is not coaxial with the lumen of the vein, and 1 mL of contrast material is extravasated into the tissues around the vein. On the basis of this appearance, the position of the guide was adjusted, and the lead was advanced without incident. Vein perforation rather than staining is likely if the pacing lead is advanced without injection of contrast material. This demonstrates the problem with forcing the straight tip of the CS access catheter into the target vein rather than using a preshaped delivery guide.

A

B

C

D

Figure 22-138  Pacing lead–induced vein perforation with free flow of contrast into pericardial space. A, The posterior lateral target vein is demonstrated with occlusive coronary sinus (CS) venography. B, Medtronic Attain 2187 LV pacing lead (arrow) is advanced into the vein. C, Tip of the lead (arrow) advances beyond the limits of the vein. D, Lead is removed, and contrast material is injected into the posterior lateral vein. Contrast under pressure from the injection (3 mL) exits the vein freely (tip of arrow) into the pericardial space. Despite this ominous appearance, no pericardial effusion was found on echocardiography, and there were no hemodynamic consequences. The lead was successfully placed in an anterior lateral vein during the same procedure.



22  Left Ventricular Lead Implantation

Left Ventricular Lead Delivery Systems There has been substantial development of the LV lead delivery systems over the last 5 years. Boston Scientific, Medtronic, and St. Jude Medical as well as Pressure Products have developed guide support–based delivery systems according to interventional principles. This evolution reflects the recognition that the “use what you know” approach is no longer the standard. To make best use of the new delivery systems, physicians need to develop interventional skills that leverage these tools. Experience and changes in catheter design have increased our understanding of how best to use delivery guides. When the tips were stiff, it was necessary for the shape of the delivery guide to match the vein takeoff. With use, we found that despite specific shapes, a small catheter was frequently required to locate the vein and serve as a rail to advance the guide into the vein (i.e., vein selector). Recognizing its essential role, a vein selector with a soft, tapered tip and length specific

7F Multipurpose EP (MPEP)

591

to CRT (see Fig. 22-3) was developed (5F Impress CS series). Compared to borrowed diagnostic catheters, the CRT-specific vein selector is easier to use (proper length), more effective at locating veins (tip shapes), and less prone to cause staining (soft tapered tip). The size, shape, and flexibility of the new vein selector are better suited to deal with difficult vein takeoffs than the delivery guide. It became apparent that the long, soft-tip section on the new Pressure Products delivery guides could be advanced deep into the target vein with the CRTspecific vein selector and remain stable. With the vein selector responsible for locating and providing a rail, only one shape of delivery guide is necessary. Details of each generally available delivery system described in the figure legends for Biotronik (Fig. 22-139), Boston Scientific (Figs. 22-140 to 22-142), ELA/Sorin (Fig. 22-143), Medtronic (Figs. 22-144 to 22-146), Pressure Products (Figs. 22-147 and 22-148; see also 2221), St. Jude Medical (Figs. 22-149 to 22-151). Figure 22-152 (as well as 22-122) shows a comparison of the delivery system hubs. Text continued on page 598

ACS right

SafeSheath sealing adapter ACS extended hook (EH) ACS BIO2 ACS multipurpose hook (MPH)

ScoutPro hemostatic hub

7F hook Slittable hub ACS Amplatz 6.0

A

B

Figure 22-139  Coronary sinus lead delivery system. A, Seven of the eight ScoutPro ACS Introducer System shapes are shown; a straight catheter is also available (Biotronik). The catheters (8.7F OD, 7.1F ID) are available in 45-cm and 50-cm working lengths. B, Slittable hub and hemostatic valve are options. ScoutPro hemostatic valve is locked onto the hub and removed over the IS-1 connector. SafeSheath sealing adapter is presssealed into the hub and removed by cracking the hub into two pieces (Pressure Products).

Delivery guide Delivery guide CS access catheter CS access catheter

A

B

Figure 22-140  Hub and tip of Boston Scientific Delivery System. A, Delivery guide (Acuity Break-Away Inner Catheter) is inserted through the breakaway hub of the coronary sinus (CS) access catheter. B, Delivery guide extends beyond the tip of the CS access catheter (Acuity Break-Away Outer Catheter). A long delivery guide (IC-90 7063 or IC-130 7065) must be used if the CS is cannulated with one of the long (54-cm working length, 61-cm total length) CS access catheters. If a short delivery guide is used (63-cm working length) only 2 cm will extend beyond the tip of the CS access catheter (61-cm overall length).

592

SECTION 3  Implantation Techniques

Figure 22-141  Boston Scientific Acuity Break-Away Inner Catheters and integrated breakaway hubs. A, Two shapes of Acuity delivery guide are shown: the IC-90 and IC-130 (4.8F ID, 6F OD). Two working lengths are available: 63 cm (7064 and 7066) and 68 cm (7063 and 7065). B, Integrated hemostatic hub used on both the Acuity Break-Away Outer Catheters and Inner Catheters, through which the lead is advanced. C, With the lead in place, the breakaway hub is split to expose the guide for slicing. The only currently available left ventricular (LV) pacing lead that can be delivered by the Boston Scientific delivery guide is the 4F Acuity Spiral.

Slittable hemostatic valve Hub breaks into two pieces exposing the guide

Compress to open valve

Spring loaded

Guide Plastic overlap on guide

Figure 22-142  Slittable integrated hemostatic valve (Boston Scientific). The hemostatic hub breaks into two pieces, exposing the guide for slicing. The plastic from the hub that overlaps the guide will result in increased resistance to slicing, decreasing only when the guide is being sliced. The hemostatic valve is spring-loaded. To open the valve to admit a lead or another catheter, the valve is compressed (black arrow).



22  Left Ventricular Lead Implantation

593

MPA (RL066) Slicer

90 degree (RL065) AL3 (RL068)

CS (RL067)

Breakaway hemostatic hub

A

B

Figure 22-143  Delivery system for left ventricular pacing leads. A, Four curves of the Situs LDS-2 lead delivery system with integrated breakaway hemostatic hub with side port (ELA Medical/Sorin Group). B, Integrated breakaway hemostatic hub and slicer. The slicer is designed to mate with the venous access sheath to provide a stable platform for slitting.

Attain Command 6250 series EHXL EH

MP and MPX MB2 and MB2X Amplatz MPR

S45, S50, and S57 Figure 22-144  Medtronic Attain Command 6250 series CS access catheters. The coronary sinus (CS) access catheters (9F OD, 7.2F ID, 50-cm working length) are available in seven shapes; the straight series is available in three lengths (45, 50, and 57 cm). The distal half of the catheters has a hydrophilic coating. The hemostatic valve is not integral to the catheter. The MPX and the MB2X are tapered-shaft versions of the MP and MB2 shapes designed for deep seating.

594

SECTION 3  Implantation Techniques

Attain Select II 6248DEL 6230UNI Universal II Slitter

130D-L 130D 90D-L 90D

6232ADJ Adjustable Slitter

B

A

Figure 22-145  Medtronic delivery guides and slicing tools. A, Four shapes of the Attain Select II 6248DEL delivery guides (7F OD, 5.2F ID). The catheters are designed for delivering the Attain Ability Lead with a 4F lead body but a maximum diameter 5.1F at the ring electrode. The hemostatic valve is not integral to the catheter. B, Two Medtronic slitters. Adjustable Slitter is designed to clamp the lead to the slitter, whereas the lead is secured to the slitter by the thumb with the Universal II Slitter. Once the lead is secured to the slitter, the catheter is pulled over the slitter, keeping the slitter hand fixed. If the lead is not secured to the slitter, it can become trapped in the slit hub and pulled out of place as the catheter is drawn over the slitter.

Attain hybrid guide wires GWR419688 GWR419588 GWR419488 GWR419388

Figure 22-146  Medtronic Attain hybrid guidewires. The stylet-guidewire hybrid is created by attaching an angioplasty guidewire (left of arrow) to the distal end of a stylet. The support provided by the hybrid guidewire is determined by the length and stiffness of the distal guidewire and the stiffness of the stylet proximal to the guidewire. For example, the longer stylet (85 cm) and shorter guidewire (23 cm) of the GWR419688 will provide more support than the GWR419388 (71.5-cm stylet; 36.5-cm guidewire). The hybrid guidewire may allow the stylet to be advanced further without displacing the lead, which is not a concern when a delivery guide (e.g., Attain Select II) is used for lead placement.



22  Left Ventricular Lead Implantation

595

Braided core Worley Jumbo Worley-STD Braided core Worley-STD

Worley Jumbo

B

A

Figure 22-147  Pressure Products coronary sinus (CS) access catheters. A, Worley-STD (SafeSheath CSG-Worley Braided Core, 40 cm long, 9F ID; CSG/Worley/BCore-1-09) and Worley Jumbo (SafeSheath CSG Worley Braided Core, 50 cm long, 9F ID; CSG/Worley/BCor-2-09). B, Braided cores for Worley-STD and Worley Jumbo serve as (1) a temporary metal braid to provide torque control, similar to braided CS cannulation catheters, and (2) a telescoping cannulation assist catheter, to change the shape of the distal portion of the CS access catheter.

9F Hockey stick

9F Hook 9F Multipurpose

9F Renal

7F Renal

Figure 22-148  Pressure Products delivery guide. The 9-French shapes are 9F OD, 7F ID, 63-cm working length, and for leads of 7F or less (Renal LVI/75-5-62-07-RE; Hook LVI/75-5-62-07HO; Hockey Stick LVI/75-5-62-07HS, Multipurpose LVI/75-5-62-07MP). The 7F Renal is 7F OD, 5F ID, 65-cm working length, and for leads 5F or less (Renal LVI/75l5/66/55/RE). Although Pressure Products offers four shapes of the 9F delivery guide, I only use the Renal now that the tip of the delivery guide is soft and the new vein selectors are available. In about 30% of cases, design limitations (imposed by need to deliver a lead) mandate that a delivery guide be assisted by a vein selector in locating and advancing into the target vein. The design of the new vein selector makes it safer and easier to use, and we need only three shapes to cover all vein takeoffs. Also, the soft tips of the new delivery guides can be advanced into a stable position, unlike the stiff-tipped older delivery guides.

596

SECTION 3  Implantation Techniques

Straight

115° Right side

135°

Wide CPS Direct outer guide catheters

Extra wide

A

CPS Aim cannulators

Cannulation assist (CPS Aim cannulator)

CS access catheter (CPS Direct)

CSL

ALII

B

C

Figure 22-149  St. Jude coronary sinus (CS) access catheters and cannulation assist catheters. A, CS access catheters (CPS Direct outer guide) are provided in six shapes (9F OD, 7F ID) and include a slittable, integrated hemostatic valve. B, Cannulation assist catheters (CPS AIM cannulators) are available in two shapes, CSL (CN-CSL model DS2N024) and ALII (CN-ALII model DS2N025), with ID of 5F (1.83 mm), OD of 7F (2.29 mm), and working length of 65 cm. C, As with braided core of Pressure Products CS access catheter, the cannulation assist catheter is introduced into the CS access catheter and used to augment its shape. In addition, CPS AIM cannulators can be advanced into the CS and used as a rail over which to advance CPS Direct outer guide.



22  Left Ventricular Lead Implantation

CPS Aim SL inner catheters

Figure 22-150  St. Jude Medical delivery guides. CPS AIM SL inner catheters with integrated slittable hemostatic valve. A, Three shapes are shown: Acute (SUBACU model DS2N021), the 90 (SUB-90 model DS2N022), and Obtuse (SUB-OBT model DS2N023). These catheters are available in working lengths of 59 and 65 cm, ID of 5F (1.83 mm) and OD of 7F (2.29 mm). B, Delivery guide is introduced into the target vein through the CS access catheter. The LV lead is then delivered directly to the target vein through the delivery guide. The delivery guide and CS access catheter are then sliced away.

CPS Universal Slitter

ACU

90

597

Delivery guide (CPS Aim)

OBT

LV lead (QuickFlex µ)

CS access catheter (CPS Direct)

B

A

CPS Aim SL inner

LV lead

Bypass tool

CPS Universal Slitter

CPS Direct outer SL valve

CPS SL valve CPS Direct outer

A

B

Figure 22-151  Integrated sliceable hemostatic valve and slicer. A, Integrated sliceable hemostatic valve of the CPS Aim SL inner catheter and CPS Direct outer guide catheters, the CPS Universal Slitter (DS2A003), and CPS Aim SL Valve Bypass Tool CPS (DS2A003). The bypass tool allows the pacing lead to pass through the valve. B, Slicer is engaged in the sliceable hub of the CPS Outer CS access catheter.

Delivery guides

Figure 22-152  Comparison of four slittable delivery guide hubs. All four delivery guides available have slittable hubs. St. Jude, Pressure Products, and Boston Scientific have integrated hemostatic valves. The Boston Scientific valve is opened by compressing the spring-loaded top section. Resistance to slicing is uniform with the St. Jude and Pressure Products systems. Both Medtronic and Boston Scientific have plastic overlap from the hub on the guide, resulting in a drop in slicing resistance as the blade transitions from plastic and guide to guide alone. If the drop in resistance is not anticipated and compensated for, the blade can lurch forward and displace the lead.

Pressure Products

St. Jude

Boston Scientific

Medtronic

Comparison of slittable hubs

598

SECTION 3  Implantation Techniques

Left Ventricular Leads BIOTRONIK Biotronik offers a bipolar (Corox OTW BP) and unipolar LV lead that employs passive helical fixation and a bipolar (Corox OTW-S BP) LV lead that employs thread fixation (Figs. 22-153 and 22-154). Biotronik also manufactures a unipolar LV lead that employs passive helical fixation but the maximum diameter (5.85F).

Silicone thread

Corox OTW-S BP

BOSTON SCIENTIFIC Figure 22-155 shows the Boston Scientific family of pacing leads. Boston Scientific leads with isodiametric LV-1 connectors are no longer manufactured but may be encountered at change-out. Oscor (Palm Harbor, Fla) manufactures adapters to convert an LV-1 connector to IS-1 connector, and vice versa, if needed. Acuity Steerable  The Acuity Steerable is the only Boston Scientific lead with an electrode at the tip. It utilizes J fixation. The J can be partially straightened with a style to help direct or steer the lead. In Figure 22-156, A, the Acuity Steerable lead was advanced over a stylet until the tip was just above the takeoff of the vein. When the stylet was partially withdrawn, the shape of the tip approximated the angle of the vein, and it was advanced into the vein (Fig. 22-156, B). Acuity Spiral, EasyTrak 2 and 3  The distal pacing electrode is a ring that is located 2 mm from the tip on the EasyTrak-1, EasyTrak-2, and Acuity Spiral leads and 5 mm from the EasyTrak-3 tip. The Acuity Spiral is unipolar. The proximal

Corox OTW BP

Figure 22-153  Biotronik over-the-wire (OTW) left ventricular (LV) pacing leads. Unipolar versions of the above leads (not shown) are available but rarely used. Both leads are bipolar OTW 5.85F (1.95  mm), recommended introducer 7F, with lead body 5.4F, steroid eluting; have platinum iridium electrodes, 18-mm tip-to-ring distance with fractal surface structure, silicone rubber insulation with an outer sleeve of polyurethane; and accept a guidewire of .014 inch or less. The Corox OTW BP has a fixation bend at the distal end and a threedimensional helix, with the Corox-S BP fixation silicone thread attached to the lead body between the tip and ring electrodes, designed to the fixation bend at distal end and by wedging in smaller vessels. Both leads are available in two lengths: 75-BP/77  cm, 85 BP/87  cm (model/length).

Target vein

ACUITY Spiral

EASYTRAK 3 ACUITY Steerable

A EASYTRAK 2

Corox OTW BP

B Figure 22-154  Left ventricular (LV) pacing lead in suitable target vein. A, Occlusive coronary sinus (CS) venogram demonstrates a large, lateral wall target vein. B, Corox (Biotronik) LV pacing lead in position.

Figure 22-155  Boston Scientific over-the-wire (OTW) left ventricular pacing leads. All the leads are OTW and steroid eluting; have platinum-iridium electrodes with IROX coating, silicone rubber and polyurethane 55D insulation, and polyurethane 55D outer sleeve; and accept a guidewire of .014 inch or less. Acuity Spiral: unipolar 4.5F (1.49 mm) insertion diameter ≥1.93 mm, 4.1F lead body, 3D spiral fixation, 4.1F molded silicone tip tapers to 2.6F; model/length 4591/80 cm, 4592/90 cm, 4593/100 cm. EasyTrak 3; bipolar 6F (1.98 mm), insertion diameter ≥2.16 mm, 3.4F lead body, 3D spiral fixation, 3.4F molded silicone tip expands to 5.3F at distal electrode. Acuity Steerable: bipolar 6.0F (1.98 mm), insertion diameter ≥2.16 mm, 5.3F lead body, J fixation; model/length 4554/80 cm, 4555/90 cm. EasyTrak 2: bipolar 5.3F (1.75 mm), insertion diameter = 1.98 mm, 5.2F lead body, tined fixation.



22  Left Ventricular Lead Implantation

electrode on the EasyTrak-2 and EasyTrak-3 leads is a ring similar to the distal electrode, separated by 11 mm. A steroid collar is contiguous with the ring electrode (white band). The Acuity Spiral and EasyTrak family of leads are designed to be delivered over a .014-inch angioplasty wire, not a stylet.

599

Acuity Spiral.  The Acuity Spiral is a 4.5F unipolar lead designed to be delivered by the Boston Scientific sliceable delivery guide. The small French size and tapered distal tip make it useful for small veins and retrograde placement through collaterals (Fig. 22-157).

RAO Unable to advance antegrade

Target vein

MCV

A

Figure 22-156  Acuity Spiral left ventricular (LV) lead placed in target vein retrograde. A, In right anterior oblique (RAO) view, despite the use of a vein selector and delivery guide, the LV lead could not be advanced into the target vein antegrade. Collaterals between the middle cardiac vein (MCV) and target vein are well seen but are tortuous. B, Anteroposterior (AP) view shows MCV cannulated with a 7F OD delivery guide (Renal LVI, Pressure Products) and advanced into the collaterals using 2.5-mm coronary sinus (CS) balloon as dilator and anchor to advance the lead. The 4.5F size and tapered distal tip were an advantage in the small vein. In situation such as this, venoplasty can be avoided by the use of the snare techniques described in Chapter 23.

AP

Collaterals

Acuity spiral

Target vein Collaterals

B

CS access catheter

MCV

Delivery guide

A

B Figure 22-157  Acuity Steerable left ventricular (LV) pacing lead and target vein. A, Target vein is seen. B, Acuity Steerable LV lead in place.

600

SECTION 3  Implantation Techniques

A

B

C

D

Figure 22-158  Failure of left ventricular (LV) pacing lead in large target vein. A and B, Distal location of EasyTrak 1 (Guidant, Boston Scientific) LV lead resulted in phrenic pacing. C, Proximal location of the lead resulted in pacing thresholds over 5 V. D, Medtronic Attain 2187 lead paced at 0.7 V. Although Attain 2187 is no longer available, this figure demonstrates that without the option of an alternative lead, the target vein would have to be abandoned. Given current lead selection from Boston Scientific, starting with an EasyTrak 3 would have been preferable.

EasyTrak 1.  The EasyTrak 1 is a tined-tip unipolar lead (Fig 22-158), with implant characteristics similar to the EasyTrak 2. EasyTrak 2.  The EasyTrak 2 is bipolar with tines at the tip and tends to migrate either proximally or distally unless wedged in a small branch of the target vein. Also, because the pacing electrodes of the EasyTrak-2 lead are not at the tip, the leads must be wedged in a small branch to achieve optimal thresholds. With these leads it is often difficult or even impossible to find a suitable location in a large target vein because of diaphragmatic/phrenic stimulation distally with high pacing thresholds and lead instability proximally. On the other hand, the EasyTrak lead wedges well in much smaller veins without dislodgment. The EasyTrak-3 lead has solved the problem of lead position in large as well as medium veins. EasyTrak 3.  The EasyTrak-3 lead is an important addition to our “quiver” of LV pacing leads (Fig 22-159). The helical shape is straightened with an angioplasty wire for delivery into the target vein (Fig. 22-160). Once at the desired location, the wire is removed, and the lead resumes a helical shape, securing it in place. Because of the helical design, a larger surface area of lead is in contact with the vessel wall. My experience is that with the EasyTrak 3 in a large vein, the pacing thresholds are not as low as those with a large lead with the electrode at the tip. However, the EasyTrak-3 lead may be more stable. Most important, the location of the lead can be controlled more precisely than the EasyTrak 2. If high pacing thresholds or phrenic pacing is

encountered at a specific site, the EasyTrak-3 lead can be straightened out and moved proximally or distally. When the wire is removed, the lead will remain at that location. Straight leads and preformed leads may move back to the original site (Fig. 22-161). It is usually important that the proximal marker to be in the target vein for the EasyTrak-3 lead to be stable. However, we still have had good results even when the marker was in the CS (see Figs. 22-160 and 22-161). ELA MEDICAL/SORIN GROUP ELA Medical manufactures two transvenous over the wire LV leads; the unipolar Situs (UW28D OTW) and the bipolar Situs (BW28D OTW) (Fig. 22-162). ELA also continues to offer two unipolar stylet-driven leads, the UC28D for smaller veins and the UL28D for larger veins (Fig. 22-163). Both leads have a dual-curve design for fixation. MEDTRONIC Figure 22-164 shows the Medtronic family of leads. There are two bipolar leads (Attain 4194 and the Attain Ability 4196) and one unipolar lead (Attain StarFix). Both the Attain 4194 and the Attain Ability LV use a double-canted shape to stabilize the lead in the vein and direct the tip toward the myocardium. The distance between the distal and proximal bend influences the final position of the lead in the vein. If the lead is advanced or withdrawn slightly (2-4 mm) to avoid phrenic



22  Left Ventricular Lead Implantation

601

Tip marker

Electrodes

Proximal marker outside target vein

B

A

Figure 22-159  Target vein before and after placement of EasyTrak-3 lead. A, Lateral wall target vein shown. Initially, EasyTrak-2 left ventricular (LV) pacing lead was placed, but satisfactory pacing thresholds were achieved only when it was advanced distally. B, EasyTrak 3 (Guidant, Boston Scientific) LV pacing lead is placed in the same vessel. The angioplasty wire is withdrawn when the tip electrode is in the desired location. Even though the proximal marker is not within the target vein, the lead is stable, and the pacing threshold is 1.5 V.

No phrenic pacing

Attain 4194

Phrenic pacing

A

B

Figure 22-160  Phrenic pacing with Attain 4194, but not with EasyTrak 3 lead. A, Shape of Attain 4194 left ventricular (LV) pacing lead (Medtronic) directs the tip inferiorly. Phrenic pacing is found along the inferior portion of the vein. B, Shape of EasyTrak-3 lead (Guidant, Boston Scientific) in the same vein directs the electrodes superiorly, where phrenic pacing is not encountered.

602

SECTION 3  Implantation Techniques

Tip of renal LVI

Proximal marker of the EasyTrak 3 Proximal and distal electrodes of the EasyTrak 3 lead

Midlateral free wall LV

A

B

Attain 4194 lead

Proximal marker of the EasyTrak 3 lead

C

D

Figure 22-161  EasyTrak-3 lead unstable with proximal marker in CS; Attain 4194 is a better choice. A, Anteroposterior projection of coronary sinus (CS) venous anatomy. Arrow indicates the ideal location of the tip of the left ventricular (LV) pacing lead. B, EasyTrak-3 LV pacing lead is placed in the vessel with a renal lateral vein introducer (LVI). To place the distal electrode on the midlateral wall, the proximal marker is not in the target vein. C, EasyTrak-3 lead has withdrawn into the CS. D, Attain-4194 pacing lead (Medtronic) is in a stable position, with the proximal bend in the target vessel and the tip on the midlateral wall of the left ventricle.



22  Left Ventricular Lead Implantation

603

Silicon screw

Silicon screw

Situs UW28D OTW

A

B

Situs BW28D OTW

Figure 22-162  ELA/Sorin over-the-wire (OTW) left ventricular pacing leads. A, The unipolar Situs UW28D OTW LV pacing lead is 2.0 mm (6F), has silicone insulation with a polyurethane coating and a vitreous carbon electrode without steroid, and employs silicon-screw passive fixation.  B, The bipolar Situs BW28D OTW LV lead is 2.0 mm (6F) with the distal 8 cm 4.8F recommended introducer 7F, is steroid eluting, has silicone insulation with a polyurethane coating that stops 8 cm before the tip, and employs silicon-screw passive fixation. The distal electrode is vitreous carbon, the proximal electrode is platinum-iridium with interelectrode spacing of 16.5 mm.

U L 2 8 D

A

U C 2 8 D

B

Figure 22-163  ELA/Sorin stylet-driven left ventricular pacing leads. ELA offers unipolar stylet-driven LV leads for large and small veins. A, Dual-curve LV lead designed for proximal stability is 2.2 mm in diameter and has a vitreous carbon electrode and silicone insulation with lubricant hydrogel coating. The lead is isodiametric for guiding catheter removal along the line of the lead. An IS-1 sleeve transforms the single-diameter connector into a standard IS-1 connector. B, The UL28D LV pacing lead is for large veins and the UC28D for small veins, shown in implantation sheaths.

604

SECTION 3  Implantation Techniques

Attain Ability 4196 Attain 4194 Attain StarFix

Attain StarFix lobes deployed

Figure 22-164  Medtronic Attain left-sided heart leads. The leads include the Attain 4194, bipolar, 6F lead; Attain Ability, bipolar, 4F lead body, 5.1F ring electrode, 4.6F tip electrode, 21-mm tip-to-ring spacing, 3.4F flexible tapered and tip seal; and Attain StarFix, unipolar, 6F lead body with deployable lobes for fixation within the vein. The outer blue covering is fixed to the lead near the tip at the distal marker but free to slide over the lead proximally. The three sections are each 9 mm long, separated by radiodense markers, where the covering is sliced on the long axis every 90 degrees (4 slices) around the circumference. When the covering is advanced, the sliced segments of insulation bunch up, creating the four lobes in each section that serve to anchor the lead in place. With deployment, the radiodense markers move closer together (from 9.5 to 2 mm), which is used to confirm radiographically that the lobes have been created. To prevent the covering from sliding back (collapsing the lobes), it must be secured in the advanced position to the lead near the IS-1 connector.

pacing or high thresholds, the lead tends to return to its original position. The double-cant method of fixation is also prone to migrate proximally if the target vein is large or the proximal bend is not within the target vein. The more acute angles of the Attain Ability were designed to reduce the propensity for proximal migration. The Attain StarFix is designed to eliminate migration with lobes that, when deployed, wedge into the vein. The Attain OTW 4194 LV pacing lead is a steroid-eluting, transvenous, bipolar, LV over-the-wire (or stylet-driven) cardiac vein pacing lead with the distal electrode at the tip (Fig. 22-165). The tip-to-anode spacing is 11 mm. The 5.4-mm-diameter tip electrode is platinum alloy that contains 1.0 mg of dexamethasone. The anode is a platinum/ iridium coil 5.4 mm in diameter with a surface area of 38 mm.2 The lead body is 2 mm with outer polyurethane insulation and inner silicone insulation. The lead’s preformed shape is straightened with either the .018-inch stylet or an angioplasty wire (.014 or .018 inch). Again, the double-cant shape directs the tip toward the myocardium and stabilizes the lead in the target vein. It is delivered over a .014-inch or .018-inch angioplasty wire or with a stylet. The recommended ID of the sheath/guide for delivery of the 4194 is 2.3 mm

(7F sheath/9F guide) (Figs. 22-166 and 22-167). In many cases the larger 4194 produced lower pacing thresholds than the Attain 4193 (Fig. 22-168). Even with favorable venous anatomy, it may be difficult to advance the Attain 4194 sufficiently to achieve stability. The proximal curve of the lead must be within the target vein to be stable. If the tip or anode coil meets resistance, the lead may not advance far enough to be stable. In Figure 22-167, the venous anatomy appears well suited to the Attain 4194. After several attempts with different wires, however, the lead retracted after the wire was removed. An attempt to advance the lead with a stylet was also unsuccessful. Only with the support of a delivery guide was the lead advanced to a stable position. This is another example where starting with a vein selector and delivery guide, even when it appears that lead placement will be easy, would have saved time. After insertion of the lead and removal of the stylet (or angioplasty wire), the proximal and distal bends of the Attain Ability and 4194 tend to migrate to their most stable position (Figs. 22-169 and 22-170). Migration of the bends may cause the lead to move either proximally or distally in the vein. The early migration caused by the bends is usually complete within 1 to 2 minutes but may

Attain 4194

Figure 22-165  Attain 4194 over-thewire lead and suitable coronary vein. A, Anode of the Attain Bipolar OTW 4194 (Medtronic) pacing lead is a coil rather than a typical ring. The greater surface area reduces bipolar pacing thresholds, but the coil section of the lead is less flexible, reducing ease of implantation. B, Large, anterior lateral vein suitable for the 4194.

Coil anode

A

B



22  Left Ventricular Lead Implantation

A

605

B

Coil

Renal delivery guide in target vein Renal delivery guide pushed back as coil passes stenotic segment

C

D

Figure 22-166  Coil anode of Attain OTW 4194 pacing lead reduces lead flexibility, necessitating guide support to advance through narrow, tortuous area. A, Target vein can be seen in anteroposterior view. The origin of the vein is narrowed (arrow). B, Left anterior oblique view reveals the complex origin of the vein from the coronary sinus (CS). Rather than having a direct lateral takeoff, the vein loops under the CS and proceeds medially and then laterally. C, Tip of a third-generation renal telescoping guide is advanced over a wire into the proximal segment of the vein. The narrow area is apparent on the selective venogram. D, The lead is advanced into the vein. The distal portion of the lead advances easily. When the coil anode reaches the narrow area, attempts to advance the lead push the guide out of the vein. The guide abuts the back wall of the CS, providing additional support for advancing the lead. Without the support of the guide, the lead would not advance into the vein.

606

SECTION 3  Implantation Techniques

Lead will not advance further into target vein and is unstable

A

B

Renal delivery guide in target vein

C

With guide support lead is advanced

D

Figure 22-167  Attain 4194 pacing lead requires delivery guide despite favorable anatomy. A, Target vein appears readily accessible without the need for a delivery guide. B, Attain 4194 (Medtronic) is placed in the vein directly through the 9F ID. Coronary sinus (CS) access catheter in the main CS would not advance further, even when the angioplasty wire was replaced with a stylet. The proximal curve remains in the main CS, and the lead is not stable. C, Pressure Products 7F ID delivery guide (Renal Lateral Vein Introducer) was advanced through the CS access sheath (SafeSheath CSG Worley) into the target vein. Because we started with the 9F ID CS access catheter, a delivery guide large enough to deliver the lead could be used without changing CS access. D, With the support provided by the CS access catheter and the delivery guide, the 4194 lead is advanced into the vein until its proximal curve is within the vein. The lead is now stable.

Capture 0.5 V tip to coil

Capture 2.0 V tip to coil

A

B

Figure 22-168  Pacing thresholds. In many cases, the pacing threshold of the larger Attain 4194 lead is lower than that of the smaller Attain 4193 pacing lead (Medtronic). A, Pacing threshold of the 4193 is 2.0 volts. B, Threshold of the 4194 is 0.5 volts. The two leads are in the same patient at the same location.



22  Left Ventricular Lead Implantation

To avoid phrenic pacing lead withdrawn to this position

607

Lead retracts; proximal curve did not match anatomy

Proximal curve Proximal curve

A

B

Figure 22-169  Proximal lead alignment and phrenic pacing. When the proximal curve on the Attain 4194 pacing lead (Medtronic) aligns with the venous anatomy, it advances distally to pace the phrenic nerve. A, The lead is withdrawn to prevent phrenic pacing. The proximal curve of the lead is just inside the ostium of the vein. In this position, the lead does not pace the phrenic nerve. However, the curve of the vein and the curve of the lead are not aligned. The lead is not stable in this position. B, The lead advances spontaneously so that its proximal curve aligns with the venous anatomy. In this position, the proximal curve of the lead and vein match. The lead is stable, but phrenic pacing occurs with the tip in this position. The only way to prevent the lead from advancing in this vein is to change the location of its proximal curve.

Proximal curve Proximal curve

A

B

Figure 22-170  Lead alignment with venous anatomy and withdrawal. When the proximal curve on the Attain 4194 pacing lead (Medtronic) is in a stable position, it aligns with the curve in the vein, withdrawing the lead out of the target vein. A, The proximal curve of the lead is positioned at the ostium of the target vein. In this position, phrenic pacing is not present at 10 V. With the proximal curve slightly deeper in the vein, the lead spontaneously advances, with resumption of phrenic pacing. B, The 4194 lead spontaneously withdraws from the target vein as the proximal curve aligns with the venous anatomy.

608

SECTION 3  Implantation Techniques

Attain 4194 is unstable

Attain 2187 is stable

B

A

Figure 22-171  Replacing unstable pacing lead with another lead. A, Proximal bend of Attain 4194 pacing lead (Medtronic) is too proximal for the target vein. As the proximal bend stabilizes, the lead retracts into the coronary sinus, pulling the tip back. B, Curve on Attain 2187 pacing lead is stable in the vein. Although the 2187 is no longer available, the concept of changing the lead shape or method of fixation to resolve issues of lead stability, high thresholds, and phrenic pacing, rather than moving to a less desirable vein, still applies.

on rare occasions extend to 5 minutes immediately after the lead is placed. The distance from the tip of the lead to the proximal bend is occasionally too long for the target vein. As a result, the proximal bend develops in the CS, pulling the tip of the lead back out of the vein (Fig. 22-171, A). With the shorter tip-to–proximal bend distance of the Attain 2187, the proximal curve fits within the target vein, producing stability (Fig. 22-171, B). Attain Ability 4196 Lead  The Attain Ability 4196 is shown in a large vein (Fig. 22-172) and a small vein (Fig. 22-173). The aggressive distal cant of the 4196

is intended to improve stability, which seems to be the case in Figure 22-172. The attain ability is 5.1F maximum diameter, designed to be delivered through Medtronic delivery guide (Attain II Select). StarFix Lead  The StarFix lead is designed with a fixation mechanism. It can be used when other leads are unstable or when high thresholds or phrenic pacing make it important to fix the tip at a specific location (Fig. 22-174). This lead is designed to allow tissue ingrowth and, unlike all other currently available LV leads, is much more difficult and potentially dangerous to extract with percutaneous techniques.

Target vein branch

A

Attain Ability 4196

B Figure 22-172  Venous anatomy suitable for Attain Ability lead. A, Branch of the lateral wall target vein comes off at an angle suitable for the Attain Ability left ventricular (LV) lead. B, Attain Ability 4196 in place. The angle of the proximal curve matches the takeoff of the vein from the coronary sinus. The angle of the distal cant matches the angle of the inferior branch off the target vein. Because the angles of the lead and venous anatomy match, the smaller LV lead is stable in a relatively large vessel.



22  Left Ventricular Lead Implantation

609

Target vein

A

Attain Ability 4196

B Figure 22-173  Venous anatomy suitable for Attain Ability lead. A, Occlusive coronary sinus (CS) venogram demonstrates a small target vein. B, Attain Ability 4196 positioned in the target vein, which is small enough to prevent distal curve from inching backward.

The distal curve of both Attain leads (4194 and 4196) was unstable when flattened in this straight segment and leads migrated back out of vein

A

Attain StarFix lobes deployed

1

2

3

4

B Figure 22-174  Attain StarFix lead placed in target vein. Angles of target vein were not suitable for either Attain 4194 or Attain 4196. A, Target vein does not have a second bend or branch after the first bend (Y1); thus, when the tip of the lead is advanced to position X and proximal bend is at the takeoff of the target vein (Y1), the distal bend is flattened in the straight section of the lead (X1). Over time, as the distal bend regains its curvature, the lead slides back until the distal bend reaches the takeoff of the vein from the CS (Y1) and the tip moves from position X to Y, placing the proximal bend in the body of the CS. B, StarFix lead in place. Note the long, straight section after the initial bend. The sections of lobes are deployed by advancing the outer covering, as shown in Figure 22-164; the four radiodense markers (1 to 4) move closer together. Note the separation between 2 and 3 is larger than between 1 and 2 or 3 and 4, suggesting that the middle segment is not fully deployed.

610

SECTION 3  Implantation Techniques

LAO QuickFlex XL

Target vein

QuickFlex

QuickFlex µ

A

LAO Figure 22-175  St. Jude Medical over-the-wire (OTW) left ventricular (LV) pacing leads. QuickFlex 1156T (center) LV lead is suggested for medium or tortuous veins, QuickFlex XL 1158T (top) for large veins, and QuickFlex µ (Micro) 1258 for small to medium or acutely angled veins.

QuickFlex XL

B ST. JUDE MEDICAL Figure 22-175 shows the St Jude family of LV pacing leads. All leads are bipolar with distal tip electrodes and double-curve fixation. QuickFlex XL 1158T  The large curves in the QuickFlex XL 1158T are designed for stability in large veins (Fig. 22-176). QuickFlex 1156T  The curves in the QuickFlex 1156T are designed for medium to small veins. The difference in the size of the curves between the QuickFlex 1156T and the QuickFlex XL 1158T place the electrodes at different positions within the vein, which can be used to deal with high thresholds or phrenic pacing (Fig. 22-177). QuickFlex Micro 1258  The QuickFlex Micro (µ) is designed to be delivered with St. Jude’s delivery guide (CPS AIM SL Subselector) to small or medium-sized

Figure 22-176  QuickFlex XL in large vein. A, Occlusive coronary sinus (CS) venogram demonstrates a large, posterior lateral target vein. The large curves of the QuickFlex XL seem to match the vein. B, QuickFlex XL (1158T, St. Jude Medical) is stable with a pacing threshold of 1 volt at 0.5 msec. LAO, Left anterior oblique projection.

veins (Fig. 22-178). It can also be made stable in a large vein when inserted deep into a subbranch, using the delivery guide for support (Fig. 22-179). Quartet  The Quartet is an investigational lead with four poles (Fig. 22-180). Additional poles increase the options for electronic repositioning. In addition, preliminary data suggest that pacing from multiple sites in one vein may provide added benefit. Several device companies are developing multipolar leads.

QuickFlex XL

Target vein

A

B

Figure 22-177  Left ventricular (LV) pacing lead replaced by another lead to eliminate phrenic pacing. A, Occlusive CS venogram demonstrates a lateral wall target vein. B, QuickFlex XL 1158T is stable in the lateral wall target vein without phrenic pacing at 10 V. Previously phrenic pacing was present on both the proximal and the distal pole of the QuickFlex 1156T despite attempts to reposition the lead in the vein. The curvature of the QuickFlex XL placed the electrodes at different locations than the QuickFlex.



22  Left Ventricular Lead Implantation

Surgical Epicardial Left Ventricular Pacing

611

Patients with reduced LV function and conduction abnormalities at open-heart surgery may have surgical epicardial leads placed in anticipation of the need for CRT, with minimal if any additional risk. Temporary dual-site pacing postoperatively may be beneficial in patients with reduced LV function.65 Whether temporary or permanent, attention to lead position is important.38

or robotic assistance.72-77 Although a longer procedure than minithoracotomy,78 VATS is associated with less postoperative pain,79 better pulmonary function, and lower serum cytokine levels,80 although it is less suitable for patients with previous open-heart surgery. Ailawadi et al.39 compared 28 patients who underwent minithoracotomy to 17 VATS patients. Although there was no statistically significant difference in the two approaches, mortality was 7.1% in the thoracotomy group versus 0% in the VATS group. Only one patient with prior cardiac surgery underwent the VATS approach, whereas 50% of patients who underwent thoracotomy had previous heart surgery. Three minithoracotomy patients initially had attempted VATS. The acute success of robotic epicardial LV lead placement for CRT has improved and is feasible in patients with previous open-heart surgery. However, long-term lead survival remains unknown. Robotic lead placement is also limited by expense and availability of the expertise and equipment. Comparison of minithoracotomy, VATS, and robotics is limited.66

UNSUCCESSFUL PERCUTANEOUS INSERTION

COMPARISON WITH TRANSVENOUS APPROACH

For patients in whom percutaneous LV lead insertion is unsuccessful, an epicardial LV lead may be placed using minithoracotomy,66 subxiphoid videopericardioscopy,67 video-assisted thoracoscopy (VATS),68-71

As mentioned earlier, although data are limited with no prospective randomized comparison, complications and mortality appear to be much higher with epicardial lead placement than with the transvenous

Although the initial CRT experience was based on surgical epicardial LV leads,62-64 the majority are now placed transvenously. Surgical LV lead placement is currently performed either at the time of open-heart surgery for another indication or when percutaneous LV lead insertion is unsuccessful. OPEN-HEART SURGERY

Figure 22-178  QuickFlex Micro (µ 1258) placed in tiny vein with delivery guide. A, Lateral wall target vein appears tiny but may  be larger and incompletely filled.  B, Vein is cannulated with 5F vein selector. Contrast injection confirms the vein is very small. Two wires are advanced into the vein to stabilize the vein selector. Delivery guide (7F OD Renal LVI) was advanced over the rail created by the vein selector and wires to the ostium of the vein. The vein selector is withdrawn, retaining the wires, and the lead advanced into the vein. C, Lead is stable in the vein, with pacing thresholds of 0.5 V.

Target vein appears too small for any lead

LAO

Target vein

Target vein

A

B With support from a delivery guide the lead advanced to a stable position

QuickFlex µ

C

612

SECTION 3  Implantation Techniques

Target subbranch Superior branch

Phrenic pacing in target vein

A

B Tip pushed into subbranch with guide support Target subbranch W

Superior branch

Delivery guide W

C

QuickFlex µ stable

D

Figure 22-179  QuickFlex Micro (µ 1258) lead placed in subbranch to avoid phrenic pacing. A, The only lateral wall branch visible is a large low posterior lateral. B, Selective venogram reveals a subbranch that drains the lateral wall superior and medial to the target vein. C, Using a vein selector, a floppy hydrophilic wire (black arrowheads) is directed into the more medial (superomedial) subbranch, then into small collaterals for additional support. The delivery guide advanced over the vein selector and wire into the superior branch. D, Using the support provided by the wire and delivery guide, the QuickFlex µ is advanced deep into the subbranch.

Vein selector

With delivery guide support all 4 poles were advanced into the target vein

Target vein

Quartet

CS access catheter and delivery guide

A

B

Figure 22-180  Delivery guide support to place Quartet. A, Small, lateral wall target vein is selectively cannulated and opacified with the vein selector. The coronary sinus (CS) access catheter and delivery guide are near the CS os. B, All four poles of the Quartet lead are within the target vein. All four poles of the lead could not be advanced into the vein without additional support from the delivery guide.



22  Left Ventricular Lead Implantation

approach.39-41 In a randomized prospective study of epicardial versus transvenous LV lead placement in 80 patients, the transvenous group had a shorter ICU stay (0.66 vs. 3.8 days) and shorter ventilation times (0.34 vs. 3.2 hours).81 The epicardial group had less exposure to radiation (7.4 vs. 23 minutes) and required less contrast material (3.24 vs. 61 mL). At 6-month follow-up, no major differences in LV lead parameters (threshold, sensing, impedance) were observed; however, mortality was not reported. EQUIPMENT The tools designed for epicardial lead placement have only recently advanced from the technology of the 1970s, when epicardial lead placement was more frequently performed. Tools are available (Medtronic) for placement of leads on the posterior and lateral walls, usually in the segment of the myocardium near the base just lateral

613

to the circumflex artery (Fig. 22-181). The same tools can be used through minithoracotomies or through small ports during thoracoscopic implantation (Fig. 22-182). Although sew-on steroid electrodes often have better long-term electrical performance, their placement is reasonable only during a sternotomy or thoracotomy because of otherwise limited access. Consequently, the devices from Boston Scientific are screw-in electrodes that are now available as bipolar leads (Fig. 22-183). The implantation tool from Enpath Medical (Plymouth, Minn) demonstrates the value of using tools from multiple sources during lead implantation (Fig. 22-184). Biotronik offers unipolar and bipolar leads for epicardial pacing. The bipolar lead has a sewing patch, whereas the unipolar lead is a screw-in lead (Fig. 22-185). Box 22-1 shows equipment for interventional implant. Regardless of the approach taken, the 15% 5-year failure of epicardial leads must be considered.37,63

Inferior lateral view of the heart

Left atrial appendage Circumflex artery Obtuse marginal artery Lead placement area Posterior descending artery

A

B

Electrode

Figure 22-181  Surgical placement of epicardial leads. A, Target zone for epicardial left ventricular lead placement. B, Epicardial electrode and placement device (Medtronic).

A

B

Figure 22-182  Minithoracotomy and thorascopic approach to left ventricular lead placement. A, Mini-thoracotomy approach with LV lead placement device. B, Thorascopic approach using Medtronic placement device.

614

SECTION 3  Implantation Techniques

Bipolar leads

Unipolar leads

A

B

Figure 22-183  Pacing leads. Unipolar (A) and bipolar (B) epicardial leads. (Courtesy Boston Scientific, Natick, Mass.)

Figure 22-184  Lead with electrode and tool. Top, MyoPore sutureless bipolar epicardial pacing lead. Middle, Close-up of the electrode portion of the lead. Bottom, FasTac Flex epicardial lead implant tool with a pacing lead attached. (Courtesy Enpath Medical, Plymouth, Minn; marketed by St. Jude Medical, St. Paul.)

A

B

Figure 22-185  Pacing leads. Screw-in (A) and sew-on (B) epicardial leads. (Courtesy Biotronik, Berlin.)



22  Left Ventricular Lead Implantation

615

Box 22-1  

INTERVENTIONAL IMPLANT EQUIPMENT LIST∗ 1. The 9-French (9-Fr, 9F) inside diameter (ID) coronary sinus (CS) access catheters a. Standard SafeSheath CSG-Worley Braided Core Series (not Extruded Core), 40 cm long, 9F ID, standard curve; Order # CSG/Worley/BCore-1-09, Pressure Products. Note: This is the sheath I use 95% of the time. b. “Jumbo” SafeSheath CSG-Worley Braided Core Series for massive hearts; CSG/Worley/BCor-2-09, Pressure Products 2. The 6F and 7F ID CS access catheters (multiple shapes) a. CPS Direct SL II (7F); DS2 series, St. Jude Medical b. Attain Command (7F); Command series, Medtronic c. Acuity Break-Away Outer (6F); CS series, Boston Scientific 3. Delivery guide + vein selector; leads ≤7F diameter (9F outside diameter [OD], 7F ID). a. SafeSheath Worley Series, Telescopic, Renal Shape Lateral Vein Introducer (LVI; 9F OD, 7F ID; 65 cm long) + Impress CS Vein Selector (5F OD; 75 cm long) and slicer; Order # LVI/75-5-62-07-RE3, Pressure Products. Note: This is the shape I use 97% of the time. 4. Delivery guide + vein selectors; leads ≤5F diameter (7F OD, 5F ID) a. SafeSheath Worley Series, Telescopic, Renal Shape LVI (7F OD, 5F ID; 65 cm long) + Impress CS Vein Selector (5F OD; 75cm long) and slicer; Order # LVI/75-5-66-5.5-RE 5. Delivery guide, no vein selector; leads ≤5F diameter (7F OD, 5F ID) a. Attain Select II (4 shapes), Medtronic b. CPS Aim SL Subselector (3 shapes), St. Jude Medical 6. Delivery guide, no vein selectors; leads ≤4.8F (6F OD, 4.8F ID) Acuity Break-Away Inner Catheter (2 shapes), Boston Scientific 7. Vein selectors (to locate, cannulate, and advance wires into vein; 5F × 75 cm), Merit Medical a. Impress CS Standard Order # 1628-Y8 b. Impress CS Vert Order # 1628-017 c. Impress CS Hook Order # 1628-019 Note: The Impress CS Standard is sufficient for 90% of cases and is also included with SafeSheath Worley delivery guides. 8. Contrast injection system (5 pieces) a. Assemble your own injection system: 10-mL contrast injection control syringe, three-way stopcock, 12-inch extension, 30-mL syringe (to serve as contrast reservoir), and Y adapter with Luer lock. b. Contrast Injection Kit; Order # ARM T001, Pressure Products c. Custom Contrast Kit (K12-02489), Merit Medical 9. Extra-support wires a. Amplatz Extra Stiff Wire Guide, .035 inch, 145 cm, 3-mm tip curve; Order # THSCF-35-145-3-AES, Cook b. Amplatz Ultra Stiff Wire Guide, .035 inch, 260 cm, TFE coated, 3-mm tip curve; Order THSCF-35-260-3-AUS2, Cook Note: Amplatz Ultra is substantially more supportive than the Extra, but available only in 260 cm. 10.  Hydrophilic coated angioplasty wires (.018 inch × 182 cm) a. ChoICE PT; Order # 12161-01, Boston Scientific b. ChoICE PT Extra Support; Order # 12161-01, Boston Scientific 11. Hydrophilic coated guidewire (.018 inch × 180 cm) a. Angled Zipwire; Order # 46-232B, Boston Scientific 12. Hydrophilic coated guidewire (.035 × 150 cm) a. Angled Glidewire; Order # GR3506, Terumo Medical b. Angled Zipwire; Order # 46-151B, Boston Scientific 13. Steering handle for glide wire a. Torque device: .025- to .038-inch wires; Order # 50000, Mallinckrodt 14. 5F hydrophilic catheter with 10- to 12-mm angled tip to direct wire across subclavian occlusion and upgrade wire support (e.g., Glidewire to Amplatz; angioplasty wire to Amplatz) a. Vert Slip-Cath Beacon Tip; Order # SCBR5.0-38-100-P-NSVERT, Cook

b. Angled Taper Terumo Glidecath, 5F, 100 cm; Order # CG508, Terumo 15. 4F hydrophilic catheter with 10- to 12-mm angled tip a. Vert Slip-Cath Beacon Tip: 4F, 100 cm; Order # SCBR4.0-38100-P-NS-VERT, Cook b. Angled Taper Terumo Glidecath: 4F, 100 cm; Order # CG508, Terumo Medical 16. Catheters to cannulate azygos vein for high defibrillation thresholds (DFTs) a. Azygos left: Impress 5F Azygous Lt Angiographic Catheter; Order #1628-044, Merit Medical b. Azygos right: Impress 5F Azygous Rt Angiographic Catheter; Order #1628-043, Merit Note: These are softer, shorter versions of cath lab diagnostic JL 3.5 (left) and AL 1 (right) and are easier to advance into the azygos vein. 17. Access catheter to cannulate CS from right side a. Mach 1 MP2 6F: 100 cm, no side holes (MP2); Order # 34356-39, Boston Scientific Steps to cannulate CS from the right: •  Insert Worley sheath 10 to 12 cm, until tip is in right atrium pointing laterally. • Hand-shape distal 40 cm of MP2 into a curve similar to Worley sheath. • Cannulate CS with curved MP2. • Insert .035-inch Amplatz (or Ultra) into MP2. • Slide Worley sheath into CS over the rail created by combination of MP2 and Amplatz wire. 18. Vein occlusion device a. Vascular tourniquet kit; Order # 8888, Sherwood Medical 19. Putting new hub on back of cut guide a. Plastic Luer lock adapter for 3F to 7F catheters; Order # PFLLA-UCC-S, Cook 20. Anchor balloons: wire lumen .014 inch, rapid exchange, compliant (rated burst 14 atm), 3-mm diameter, 20 or 30 mm long a. Apex Monorail, Boston Scientific b. Voyager RX, Abbott Vascular 21. Coronary venoplasty balloon: wire lumen .014 inch, rapid exchange, noncompliant (rated burst 18-20 atm), 6F leads 3 mm, 5F leads 2.5 mm, 15 mm long a. Voyager NC, Abbott Vascular b. NC Sprinter, Medtronic c. NC Quantum Apex Monorail, Boston Scientific 22. Subclavian venoplasty balloon: wire lumen .035 inch, over the wire, “noncompliant” (rated burst 14 atm), 6-mm diameter, 4 cm long a. Cordis PowerFlex-P3; Order # 420-6040S, Cordis 23. Subclavian venoplasty balloon: wire lumen .018 inch, over the wire, “noncompliant” (rated burst pressure 14 atm, 6-mm diameter, 4 cm long a. Sterling; Order # 39032-60404, Boston Scientific 24. Subclavian venoplasty balloon, ultra-noncompliant: wire lumen .035 inch, over the wire, “noncompliant” (rated burst pressure 30 atm), 6-mm diameter, 4 cm long a. Conquest (Kevlar); Order #CQ-7564, Bard Peripheral Vascular 25. CRT implant tables; Models EPLT60 (Standard = 60 inch) and EPLT45 (Short), Oscor 26. Micro-snares for CS left ventricular (LV) lead placement a. Triple-loop EN Snare: Part 1, 8-mm diameter snare, 175 cm long; Part 2, 3.2F snare delivery catheter, 150 cm long; Order #EN1003008, Merit Medical b. Amplatz Goose Neck Snare: Part 1, 10-mm diameter snare, 120 cm long; Part 2, 4F snare delivery catheter, 102 cm long; Order # GN1000, eV3 27. Equipment for Transeptal LV lead placement a. 25-mm loop snare: Amplatz Goose Neck Snare: Part 1, 25-mm diameter snare, 120 cm long; Part 2, 6F snare delivery catheter, 102 cm long; Order # GN2500, eV3

*Disclosure: The author (SW) receives compensation from Pressure Products for the sale of the Worley catheters.

Continued

616

SECTION 3  Implantation Techniques

Box 22-1

INTERVENTIONAL IMPLANT EQUIPMENT LIST—cont’d b. Deflectable sliceable catheter: Selectsite 304-XL74, Medtronic c. 69-cm 4.1F active fixation lead: SelectSecure 3830, Medtronic d. 85-cm 6F active fixation lead: CapSureFix Novus 5076, Medtronic e. Transeptal needle: Brockenbrough curved needle, Medtronic f. 8F transeptal sheath: Preface 8F; Order # 307803M, Biosense Webster g. 12F Transeptal Sheath Check-Flo Performer Introducer, Mullins Design, G09171 RCFW-12.0-38-75-RB-MTS, Cook h. 4F sheath (fixing ring): Avanti +; Order# 504-604X, Cordis i. 11F-long hemostatic sheath: SafeSheath Long HLS2511, Pressure Products j. 0 suture, 30-inch-long braided polyester: Ethibond Excel CT-1; Order # X424, Ethicon k. 6F multipurpose guide: Mach 1 MP2, 100 cm, no side holes; Order # 34356-39, Boston Scientific

l. Slicing tool: Universal II slitter; Order # 6230UNI, Medtronic Ordering Information Abbott Vascular, Santa Clara, CA 95054; 800-227-9902 Bard Peripheral Vascular, Tempe, AZ; 800-321-4254 Biosense Webster, Diamond Bar, CA; 909-839-8500 Boston Scientific, Natick, MA 01760; 800-227-3422 Cook, Bloomington, IN; 800-457-4500 Cordis, Bridgewater, NJ; 800-997-1122 Ethicon, Somerville, NJ; 908-218-0707 eV3, Plymouth, MN; 800-716-6700 Mallinckrodt, St. Louis, MO; 888-744-1414 Medtronic, Minneapolis, MN 55432; 763-574-4000 Merit Medical, South Jordan, UT; 800-626-3748 Oscor, Palm Harbor, FL; 800-726-7267 Pressure Products, San Pedro, CA; 800-600-4973 Sherwood Medical, Deland, FL; 386-734-3685 St. Jude Medical, Sylmar, CA; 818-362-6822. Terumo Medical; 732-302-4900 or 800-283-7866

REFERENCES 1. Abraham WT, Fisher WG, Smith AL, et al: MIRACLE Study Group. Cardiac resynchronization in chronic heart failure: Multicenter Insync Randomized Clinical Evaluation. N Engl J Med 346:1845, 2002. 2. Abraham WT, Young JB, Leon AR, et al: Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation 110:2864, 2004. 3. Bristow MR, Saxon LA, Boehmer J, et al: Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350:2140, 2004. 4. Cleland JGF, Daubert J-C, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539, 2005. 5. Auricchio A, Stellbrink C, Block M, et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 99:2993, 1999. 6. Cazeau S, Leclercq C, Lavergne T, et al: Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873, 2001. 7. Albertsen AE, Nielsen JC, Pedersen AK, et al: Left ventricular lead performance in cardiac resynchronization therapy: impact of lead localization and complications. Pacing Clin Electrophysiol 28:483, 2005. 8. Kautzner J, Riedlbauchova L, Cihak R, et al: Technical aspects of implantation of LV lead for cardiac resynchronization therapy in chronic heart failure. Pacing Clin Electrophysiol 27:783, 2004. 9. Daoud EG, Kalbfleisch SJ, Hummel JD, et al: Implantation techniques and chronic lead parameters of biventricular pacing dual-chamber defibrillators. J Cardiovasc Electrophysiol 13:964, 2002. 10. Auricchio A, Abraham WT: Cardiac resynchronization therapy: current state of the art—cost versus benefit, Circulation 109:300, 2004. 11. De Cock CC, Jessurun ER, Allaart CA, Visser CA: Repetitive intraoperative dislocation during transvenous left ventricular lead implantation: usefulness of the retained guidewire technique. Pacing Clin Electrophysiol 27:1598, 2004. 12. Perzanowski C, Gilliam FR: The buddy wire technique: accessing lateral coronary veins while maintaining coronary sinus position. J Interv Card Electrophysiol 13:231, 2005. 13. Chierchia GB, Geelen P, Rivero-Ayerza M, Brugada P: Double wire technique to catheterize sharply angulated coronary sinus branches in cardiac resynchronization therapy. Pacing Clin Electrophysiol 28:168, 2005. 14. Kranig W, Grove R, Lüdorff G, Thale J: Successful implantion of a left ventricular lead for cardiac resynchronization therapy (CRT) in extremely unfavourable coronary venous anatomy: “over the wire” technique. Herzschr Elektrophys 15:211, 2004. 15. Liu YH, Lai LP, Lin JL: Using multiple buddy wires to facilitate left ventricular lead advancement in cardiac resynchronization therapy. J Interv Card Electrophysiol 18:239, 2007. 16. Meade TH, Lopez JA: Balloon occlusion technique to cannulate angulated and tortuous coronary sinus branches in cardiac resynchronization therapy. Pacing Clin Electrophysiol 28:1243, 2005.

17. Sharifkazemi MB, Aslani A: Stabilization of the coronary sinus lead position with permanent stylet to prevent and treat dislocation. Europace 9:875, 2007. 18. Szilagyi S, Merkely B, Roka A: Stabilization of the coronary sinus electrode position with coronary stent implantation to prevent and treat dislocation: results of a long-term follow-up. J Cardiovasc Electrophysiol 18:303, 2007. 19. Worley SJ, Gohn DC, Pulliam RW: Goose neck snare for LV lead placement in difficult venous anatomy. PACE 32:1577, 2009. 20. Worley SJ: How to use balloons as anchors to facilitate cannulation of the coronary sinus left ventricular lead placement and to regain lost coronary sinus or target vein access. Heart Rhythm 6:1242, 2009. 21. Furman S: Repetitive left ventricular lead dislocation. Pacing Clin Electrophysiol 27:1588, 2004. 22. Love CC: Retention wire: deja vu all over again? Pacing Clin Electrophysiol 27:1587, 2004. 23. Nagele H, Hashagen S, Ergin M, et al: Coronary sinus lead fragmentation: 2 years after implantation with a retained guidewire. Pacing Clin Electrophysiol 30:438, 2007. 24. Vlay SC: The continued saga of the retained guidewire. Pacing Clin Electrophysiol 30:1284, 2007. 25. Ermis C, Benditt DG: Stent-stabilization of left ventricular pacing leads for cardiac resynchronization therapy: a promising concept? J Cardiovasc Electrophysiol 18:308, 2007. 26. Gurevitz O, Nof E, Carasso S, et al: Programmable multiple pacing configurations help to overcome high left ventricular pacing thresholds and avoid phrenic nerve stimulation. Pacing Clin Electrophysiol 28:1255, 2005. 27. Leon AR: New tools for the effective delivery of cardiac resynchronization therapy. J Cardiovasc Electrophysiol 16:S42, 2005. 28. Vogt J, Schwarz T, Gras D, et al: The use of telescoping guide catheters for coronary sinus cannulation and sub-selecting tributaries in left ventricular lead placement. J Interv Card Electrophysiol 19:61, 2007. 29. Worley SJ, Gohn D, Smith TL: Telescoping delivery system for unsuccessful biventricular implants, France, 2002, Presented at Cardiostim, Nice. 30. Worley SJ: CRT delivery systems based on guide support for LV lead placement. Heart Rhythm 6:1837, 2009. 31. Worley SJ, Ellenbogen KA: Application of interventional procedures adapted for device implantation: new opportunities for device implanters. Pacing Clin Electrophysiol 30:938, 2007. 32. Bordachar P, Nicolas Derval N, Ploux S, et al: Left ventricular endocardial stimulation for severe heart failure. J Am Coll Cardiol 56:747, 2010. 33. Derval N, Steendijk P, Gula LJ, et al: Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. J, Am Coll Cardiol 55:566, 2010. 34. Spragg DD, Dong J, Barry J, et al: Optimal left ventricular endocardial pacing sites for cardiac resynchronization therapy in patients with ischemic cardiomyopathy. J Am Coll Cardiol 56:774, 2010. 35. Fisher JD, Garcia J, Kim SG, et al: Easy surgical approach for completion of biventricular pacing. J Cardiovasc Electrophysiol 15:1462, 2004. 36. Tyers GFO: Robotic implantation of resynchronization and defibrillator rhythm management systems. Pacing Clin Electrophysiol 29:807, 2006.

37. Tomaske M, Gerritse B, Kretzers L, et al: A 12-year experience of bipolar steroid-eluting epicardial pacing leads in children. Ann Thorac Surg 85:1704, 2008. 38. Dekker AL, Phelps B, Dijkman B, et al: Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops. J Thorac Cardiovasc Surg 127:1641, 2004. 39. Ailawadi G, LaPar D, Swenson B, et al: Surgically placed left ventricular leads provide similar outcomes to percutaneous leads in patients with failed coronary sinus lead placement. Heart Rhythm 7:619, 2010. 40. Poole JE, Gleva MJ, Mela T, et al: Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE Registry. Circulation 122:1553, 2010. 41. Koos R, Sinha AM, Markus K, et al: Comparison of left ventricular lead placement via the coronary venous approach versus lateral thoracotomy in patients receiving cardiac resynchronization therapy. Am J Cardiol 94:59, 2004. 42. Butter C, Auricchio A, Stellbrink C, et al: Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation 104:3026, 2001. 43. Kistler PM, Mond HG, Corcoran SJM: Biventricular pacing: it isn’t always as it seems. Pacing Clin Electrophysiol 26:2185, 2003. 44. Worley SJ: Cardiac resynchronization failures: the lateral chest radiograph identifies patients who benefit from a new LV lead position, Toronto, 2004, Presented at 8th Annual Scientific Meeting of Heart Failure Society of America. 45. Heist EK, Fan D, Mela T, et al: Radiographic left ventricular-right ventricular interlead distance predicts the acute hemodynamic response to cardiac resynchronization therapy. Am J Cardiol 96:685, 2005. 46. Al-Khadra A: Use of preshaped sheath to plan and facilitate cannulation of the coronary sinus for the implantation of cardiac resynchronization therapy devices: preshaped sheath for implantation of biventricular devices. Pacing Clin Electrophysiol 28:489, 2005. 47. Gilard M, Mansourati J, Etienne Y, et al: Angiographic anatomy of the coronary sinus and its tributaries. Pacing Clin Electrophysiol 21:2280-2284, 1998. 48. Meisel E, Pfeiffer D, Engelmann L, et al: Investigation of coronary venous anatomy by retrograde venography in patients with malignant ventricular tachycardia. Circulation 104:442, 2001. 49. Delarche N, Bader H, Lasserre R, et al: Importance of anterograde visualization of the coronary venous network by selective left coronary angiography prior to resynchronization. Pacing Clin Electrophysiol 30:70-76, 2007. 50. Bashir JG, Frank G, Tyers O, et al: Combined use of transesophageal echo and fluoroscopy for the placement of left ventricular pacing leads via the coronary sinus. Pacing Clin Electrophysiol 26:1951, 2003. 51. Schuchert A, Seidl K, Pfeiffer D, et al: Two-year performance of a preshaped lead for left ventricular stimulation. Pacing Clin Electrophysiol 27:1610, 2004. 52. Tse HF, Yu C, Lee KL, et al: Initial clinical experience with a new self-retaining left ventricular lead for permanent left ventricular pacing. Pacing Clin Electrophysiol 23(11 pt 2):1738, 2000. 53. Nof E, Gurevitz O, Carraso S, et al: Comparison of results with different left ventricular pacing leads. Europace 10:35, 2008.



54. Worley SJ, Gohn DC, Pulliam RW, Coles J: Don’t give up on the optimum LV pacing site! Change the lead, not the vein, Hong Kong, 2009, Presented at CardioRhythm. 55. Hansky B, Vogt J, Gueldner H, et al: Implantation of active fixation leads in coronary veins for left ventricular stimulation: report of five cases. Pacing Clin Electrophysiol 30:44-49, 2007. 56. Nagele H, Azizi M, Hashagen S, et al: First experience with a new active fixation coronary sinus lead. Europace 9:437, 2007. 57. Crossley GH, Exner D, Mead RH, et al: Medtronic 4195 Study Investigators: Chronic performance of an active fixation coronary sinus lead. Heart Rhythm 7:472-478, 2010. 58. Baranowski B, Yerkey M, Dresing T, Wilkoff BL: Fibrotic tissue growth into the extendable lobes of an (lobed) active fixation coronary sinus lead can complicate extraction. PACE 33:3, 2010. 59. Kalahasty G, Ellenbogen KA: The story of an (lobed) active fixation coronary sinus lead: promise and peril. Heart Rhythm 7:479, 2010. 60. Bongiorni MG, DI Cori A, Zucchelli G, et al: A Modified transvenous single mechanical dilatation technique to remove a chronically implanted coronary sinus pacing lead. PACE 33:4, 2010. 61. Perisinakis K, Theocharopoulos N, Damilakis J, et al: Fluoroscopically guided implantation of modern cardiac resynchronization devices: radiation burden to the patient and associated risks. J Am Coll Cardiol 46:2335, 2005. 62. Tyers GFO: Comparison of the effect on cardiac function of single-site and simultaneous multiple-site ventricular stimulation after AV block. J Thorac Cardiovasc Surg 59:211, 1970. 63. Bakker PF, Meijburg H, de Jong N, et al: Beneficial effects of biventricular pacing in congestive heart failure. Pacing Clin Electrophysiol 17:820, 1994.

22  Left Ventricular Lead Implantation 64. Cazeau S, Ritter P, Lazarus A, et al: Four-chamber pacing in dilated cardiomyopathy. Pacing Clin Electrophysiol 17:1974, 1994. 65. Janousek J, Vojtovic P, Chaloupecky V, et al: Hemodynamically optimized temporary cardiac pacing after surgery for congenital heart defects. Pacing Clin Electrophysiol 23:1250, 2000. 66. Mair H, Jansens JL, Lattouf OM, et al: Epicardial lead implantation techniques for biventricular pacing via left lateral minithoracotomy, video-assisted thoracoscopy, and robotic approach. Heart Surg Forum 6:412, 2003. 67. Zenati MA, Bonanomi G, Chin AK, Schwartzman D: Left heart pacing lead implantation using subxiphoid videopericardioscopy. J Cardiovasc Electrophysiol 14:949, 2003. 68. Antonic J, Crnjac A, Kamenik B: Epicardial electrode insertion by means of video-assisted thoracic surgery technique. Wien Klin Wochenschr 113(Suppl 3):65, 2001. 69. Gabor S, Prenner G, Wasler A, et al: A simplified technique for implantation of left ventricular epicardial leads for biventricular re-synchronization using video-assisted thoracoscopy (VATS). Eur J Cardiothorac Surg 28:797, 2005. 70. Jutley RS, Waller DA, Loke I, et al: Video-assisted thoracoscopic implantation of the left ventricular pacing lead for cardiac resynchronization therapy. Pacing Clin Electrophysiol 31:812, 2008. 71. Fernandez AL, Garcia-Bengochea JB, Ledo R, et al: Minimally invasive surgical implantation of left ventricular epicardial leads for ventricular resynchronization using video-assisted thoracoscopy. Rev Esp Cardiol 57:313, 2004. 72. Kleine P, Gronefeld G, Dogan S, et al: Robotically enhanced placement of left ventricular epicardial electrodes during implantation of a biventricular implantable cardioverter-defibrillator system. Pacing Clin Electrophysiol 25:989, 2002.

617

73. DeRose JJ, Ashton RC, Belsley S, et al: Robotically assisted left ventricular epicardial lead implantation for biventricular pacing. J Am Coll Cardiol 41:1414, 2003. 74. Joshi S, Steinberg JS, Ashton RC, Jr, et al: Follow-up of robotically assisted left ventricular epicardial leads for cardiac resynchronization therapy. J Am Coll Cardiol 46:2358, 2005. 75. DeRose JJ, Kypson AP: Robotic arrhythmia surgery and resynchronization. Am J Surg 188:104S, 2004. 76. Shalaby A, Sharma MS, Zenati MA: Robotic implantation of a multi-chamber cardiac resynchronization therapy-defibrillator. Pacing Clin Electrophysiol 29:906, 2006. 77. Kamath GS, Balaram S, Choi A, et al: Long-term outcome of leads and patients following robotic epicardial left ventricular lead placement for cardiac resynchronization therapy. PACE 33:6, 2010. 78. Navia JL, Atik FA, Grimm RA, et al: Minimally invasive left ventricular epicardial lead placement: surgical techniques for heart failure resynchronization therapy. Ann Thorac Surg 79:1536, 2005. 79. Landreneau RJ, Hazelrigg SR, Mack MJ, et al: Postoperative painrelated morbidity: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg 56:1285, 1993. 80. Nagahiro I, Andou A, Aoe M, et al: Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure. Ann Thorac Surg 72:362, 2001. 81. Doll N, Piorkowski C, Czesla M, et al: Epicardial versus transvenous left ventricular lead placement in patients receiving cardiac resynchronization therapy: results from a randomized prospective study. Thorac Cardiovasc Surg 56:256, 2008.

618

SECTION 3  Implantation Techniques

23  23

Interventional Techniques for Device Implantation SETH J. WORLEY  |  KENNETH A. ELLENBOGEN

Initially, device implantation was the province of surgeons, and thus

implant problems were solved with surgical techniques, such as tunneling of a new lead for a patient with an occluded subclavian vein. As devices became smaller and almost exclusively transvenous, implantation moved to the province of the cardiologist and then subsequently to the electrophysiologist (EP). Until recently, the mechanics of transvenous device implantation were generally straightforward, adopting surgical solutions and applying an electrophysiology skill set and tools. Over the last several years, however, with the marked increase in device upgrades and cardiac resynchronization therapy (CRT), the complexity of device implantation has increased greatly, becoming similar to an interventional procedure rather than the traditional device implant. Lacking interventional training, EP physicians have struggled to solve difficult implant problems with their electrophysiology skill set and tools. As a result, even now, the CRT implant failure rate remains at least 7.5% in experienced hands.1

Interventional versus Electrophysiologic Approach It is preferable to learn a new skill set better suited to the procedure than to continue with familiar methods. How would the current implant procedure change if device implantation was assumed by an interventional cardiology skill set rather than electrophysiology? Consider the occluded subclavian vein. With expanded indications for implantable cardioverter-defibrillators (ICDs),2 CRT,3,4 and increased survival of patients with cardiovascular disease,5 the implanting physician encounters a higher percentage of patients who have preexisting leads in whom subclavian vein obstruction or occlusion can be as high as 45%.6 Application of an interventional approach to the occluded vessel offers the implanting physician less invasive solutions, such as venoplasty versus lead extraction or tunneling.7-10 Left ventricular (LV) lead placement for CRT requires the successful completion of multiple steps, many originating in the interventional

GLOSSARY AND DEFINITION OF TERMS LV lead delivery system is defined as the set of catheters used to place an LV lead in a coronary vein. The most effective delivery system consists of three telecopying components: 1, the coronary sinus (CS) access catheter; 2, the delivery guide; and 3, the vein selector. Coronary sinus (CS) access catheter is defined as a removable catheter designed to cannulate the CS and provide access and support for delivery of a left ventricular (LV) lead to the target vein. Delivery guides are intended to be advanced through a CS access catheter. The lumen size of the CS access catheter determines subsequent implant options. The lumen of a device company CS access catheters is 7 French (7F) or smaller, which restricts the ability to add a CS support wire while working close the CS os, and other advanced techniques. There are no device company delivery guides for 6F leads because they require at least an 8F lumen in the CS. The SafeSheath CSG Worley provides a 9F lumen in the CS, expanding options, including a delivery guide for leads a large as 7F. Delivery guide is defined as a sliceable catheter designed to fit into the target vein and provide direction and support for advancing the LV lead. Delivery guides are not intended for CS cannulation. In the opinion of the authors, the device company delivery guides have two important limitations: (1) they are too small to deliver the many 6F leads currently available, and (2) by providing several shapes to try and match the venous anatomy, device company delivery guides are intended to locate and cannulate the target vein and deliver the lead. In the authors’ experience, it can be difficult if not impossible to locate, insert a wire, and/or cannulate the target vein without the assistance of a vein selector. Vein selector is defined as a small (5 French, 5F), soft-tip catheter that telescopes inside a delivery guide to extend beyond the delivery guide and locate the target vein using puffs of contrast, provide direction and support for advancing wires into the vein, then serve as a rail over which to advance the delivery guide. None of the device companies offers vein selectors, relying on their delivery guides to act as both vein selector and delivery guides. In the authors’ experience, there are many situations where the delivery guide alone is not sufficient, and

618

the only way to insert the delivery guide into the vein is to use a vein selector inside the guide. Extra-support wires. Advancing a balloon, catheter, or sheath over a stiffer wire may be necessary to prevent buckling. We find the .035-inch Amplatz Extra Stiff (Cook) suitable in many cases, but on occasion the .035-inch Amplatz Ultra Stiff (Cook) is required. Currently, the Ultra is only available in the cumbersome length of 260 cm. The Amplatz wires are also available in .032-inch size, which may be required for some sheaths. The Amplatz wires are stiff and do not advance easily through tortuous or narrow venous structures; thus they are inserted via an exchange procedure using a small catheter. Exchanging of wires to augment support. When a more supportive wire (e.g., Amplatz) is required to advance the guide/sheath, a small catheter (4F-5F) is advanced over the existing wire into the pulmonary artery or inferior vena cava, the existing wire removed, the Amplatz inserted, and the exchange catheter removed. A hydrophilic 4F to 5F catheter will advance where a catheter with a standard surface will not, so it is important to have hydrophilic catheters on hand for exchange. To avoid the need for exchange-length wires, the catheter should be 60 to 70 cm in length, but this length may not be readily available. Thus, we often cut the hub and 30 to 40 cm off a 100- to 130-cm catheter once the less supportive wire is removed. Focused-force venoplasty. The addition of a stiff wire beside the inflated balloon focuses the force of the balloon against the occlusion. Focused force is used for both focal and diffuse occlusions. Hydrophilic wires/catheters and balloons. Materials that are intrinsically hydrophilic or have a hydrophilic coating are slippery to the touch when wet and offer much less resistance to passage through vascular structures than standard materials of the same size and configuration. Their disadvantage is that hydrophilic wires/catheters can be difficult to handle and direct. “Push-pull” technique is used to advance the tip of a delivery guide into the ostium of the target vein. With the tail of the balloon at the tip of the guide, advance the guide (push), holding traction on the balloon as it is deflated (pull).



arena. Learning to implant an LV lead by application of an existing electrophysiology (EP) skill set and tools can be a long, painful, and humiliating process. Once learned, the EP approach has limited success, even in experienced hands. Because an interventional approach is better suited to the procedure, learning to implant an LV lead is usually faster, less painful, and more satisfying despite the requirement to first learn a new skill set and tools. Subsequently, application of the interventional approach can increase implant success from 88% to 92% with the EP approach to 98% with the interventional approach.11 This chapter takes the position that it is better to learn a new, unfamiliar skill set than to continue with the familiar that may not be best suited to the procedure (Box 23-1). MORBIDITY AND MORTALITY Does the application of an interventional skill set specific to device implantation really reduce morbidity and mortality? Many examples show this may be the case, but the best example is sending a patient for an epicardial lead because the implanting physician does not use guide support or perform venoplasty. Even in the most experienced hands, mortality is doubled (4.8% surgical vs. 2.5% transvenous; P = 0.46), and acute renal injury and infection are quintupled (26.2% vs. 4.9%: P = .0004; and11.9% vs. 2.4%; P = .03, respectively).12 In practice, results may be worse. Surgical LV lead mortality from the REPLACE registry13 was greater than 8%. There were four deaths from among the 48 patients (11% of 434 attempted LV lead placements) who went for an epicardial lead following a failed transvenous approach. The 8% mortality assumes all 48 patients went to surgery, although it is not unusual for patients either to decline a surgical lead or to be rejected as too risky; thus the mortality may be even higher. Interventional techniques safely increase implant success, reducing the need for surgical epicardial leads. DEVICE IMPLANTATION–SPECIFIC INTERVENTIONAL SKILL SET Application of an interventional skill set specific to device implantation can improve patient satisfaction (one incision not two), reduce complications (avoid extraction or surgery), reduce implant time, and reduce overall mortality. With the assumption that the above is true, physicians implanting devices need to have or develop these skills to provide the best possible patient care. EP training programs should include opportunities to observe and learn device-specific interventional techniques as part of the curriculum. Opportunities for education in interventional device implantation techniques can be developed by attending educational programs or working with interventional cardiologists or interventional radiologists. Once it becomes clear that the application of an interventional skill set specific to device implantation really does reduce morbidity, professional societies will promote the importance of the “interventional skills specific to device implantation” (knowledge base and technical skills) and support education and training in the area. We define a skill set as the combination of knowledge base and technical skills. Part of the interventional device implantation skill set involves basic interventional knowledge and technical skills unique to device implantation. A physician with formal interventional training in interventional cardiology or radiology may help provide the knowledge and technical skills necessary for device implantation. Because the terms, tools, and techniques used in the interventional approach to device implantation may be unfamiliar, a glossary box is provided for reference. See also the Interventional Implant Equipment List and manufacturers at the end of Chapter 22 and online. Knowledge Base The knowledge base of an implantation-specific interventional skill set includes equipment required for the procedure, the importance of contrast, patients at risk for contrast nephropathy, use of preprocedure hydration for safe use of IV contrast, and the importance of table

23  Interventional Techniques for Device Implantation

619

Box 23-1 

INTERVENTIONAL MIND-SET APPROACH TO PROBLEMS ENCOUNTERED DURING DEVICE IMPLANTATION 1. Good work cannot be done if you are in an uncomfortable position; you owe it to your patients to insist that the room be set up properly. 2. It is important to be alert to new tools that can make difficult cases easier. 3. Contrast is essential to success. 4. Risk of contrast nephropathy is patient specific. 5. Contrast can be used safely in most patients if pretreated for contrast nephropathy. 6. There is (or should be) a preshaped catheter to locate every vascular structure. 7. If the first catheter does not work, try another shape or create a shape. 8. Catheter manipulation requires both hands on the catheter. 9. The assistant should inject contrast so the operator can focus on catheter control. 10. Catheters must not be bent before they enter the patient because every bend in a catheter reduces control. 11. Almost “all” vascular occlusions can be crossed one way or another. 12. Almost “all” vascular occlusions can be dilated with a balloon. 13. All surgical procedures can be done better with wires, catheters, and balloons. 14. Extra-support wires are essential for advancing catheters through difficult anatomy; the stiffer the better. 15. Guide support is essential for successful balloon dilation.

position for maintaining focus on the procedure. Other areas include open-lumen catheter manipulation (keeping both hands on catheter) and wire exchange, preshaped guiding catheters used to cannulate specific venous structures, and the importance of having the assistant inject contrast while the operator keeps both hands on the catheter. Interventional implanters should know type and size of balloons to use for which veins, how to prevent hemothorax during subclavian venoplasty, which tools to use for crossing a venous obstruction, which implant problems respond to the balloon anchoring technique and which to the snare technique, and how sacrificing a lead, using a wire under the insulation, and snaring can be used to regain venous access. Technical Skills Technical skills in an interventional skill set include torque control using both hands on the catheter, catheter manipulation while contrast is injected by the assistant, vein-specific catheter techniques (specific preshaped catheter used a specific way for a specific vein), and techniques to gain and optimize and maintain guide support. Along with deploying balloons to serve as anchors, implanters must know techniques for crossing venous obstruction associated with device leads (wire manipulation veins and venoplasty of stenotic veins) as well as venoplasty of stenotic or occluded cardiac vein structures in patients with and without prior open-heart surgery. Training Aggarwal and Darzi14 discuss how traditional EP and implanting physicians can become trained in the device implantation–specific interventional skill set. Their editorial “Technical skills training in the 21st century” addresses this issue as it relates to such areas as laparoscopic surgery, bronchoscopy, and colonoscopy. They describe proficiencybased training in which the environment can be modeled to simulate the experiences encountered and to generate feedback about both technical skills and knowledge base. Together, physicians who have adopted the interventional approach, device manufacturers, and professional socie­ ties can create a program to help the traditional EP physician develop the knowledge base and skill set specific to device implantation.

620

SECTION 3  Implantation Techniques

Prevention of Contrast Nephropathy USE OF CONTRAST MATERIAL The interventional mind-set approaches implant problems with the following attitude about contrast: 1. Contrast is essential. 2. Safety of contrast is patient specific. 3. Safe use of contrast requires advanced patient preparation. 4. Most patients with a history of heart failure can be hydrated safely. 5. Renal failure is more difficult to treat than volume overload. When considering the use of contrast for LV lead placement, keep in mind that a successful implant not only improves symptoms, but also reduces morbidity and mortality.15 Although uncommon in most situations,16,17 contrast nephropathy can be an important complication of CRT associated with increased morbidity and mortality and extended hospital stay.18 Patients with congestive heart failure and preexisting renal insufficiency are at increased risk for contrast nephropathy,19 but ultimately, CRT improves renal function by improving cardiac function.20 In fact, patients with moderate renal insufficiency may derive the greatest benefit from successful CRT.21 Recognizing the importance of contrast to a successful procedure, the interventional mind is proactive, always looking for ways to reduce risk,22 whereas the EP mind-set focuses on reducing the use of contrast. Despite every effort to limit its use, the volume of contrast frequently exceeds expectation. Further, the nephrotoxicity of even a small volume of contrast (10-30 mL) in the unprepared patient can be significant, whereas nephropathy can be reduced or eliminated if preventive steps are taken before the implant. Thus, it is important for implanting physicians to adopt the interventional mind-set and take a proactive approach to contrast nephropathy rather than simply trying to limit its use. After exposure to contrast, the kidneys concentrate contrast in the urinary space within the renal tubules, releasing nitric oxide from endothelial cells, triggering a transient vasodilation, followed by more prolonged vasoconstriction, and causing tubular cell damage, extravasation into the peritubular space, and constriction of the lattice-like peritubular blood vessels in the outer medulla. Sustained vasoconstriction can last for hours to days, resulting in ischemic injury to the outer medulla, particularly in those with chronic kidney disease and diabetes mellitus23 (Box 23-2). Contrast-induced nephropathy (CIN) is typically defined as a 25% or greater increase in baseline serum creatinine, or a 0.5-mg/dL increase without another identifiable cause. CIN occurs 24 to 48 hours after exposure, with serum creatinine peaking at 3 to 5 days, returning to normal within 2 weeks, although usually by 7 to 10 days. The approach to the prevention includes (1) hydration to dilute and flush contrast

Box 23-2 

RISK FACTORS FOR CONTRAST-INDUCED NEPHROPATHY Patient Related Chronic kidney disease Diabetes mellitus Age Urgent/elective procedure Anemia Hypotension Hypertension Congestive heart failure LVEF* <40% Intra-aortic balloon pump Non–Patient Related Contrast with high osmolality Contrast volume With or without ionic contrast *Left ventricular ejection fraction.

from the kidney, (2) selection of less nephrotoxic contrast agent, (3) drugs to protect the kidney and prevent vasoconstriction, and (4) hemofiltration or hemodialysis. A bedside risk score stratifies patients into low (0-7 points), medium (8-14), and high-risk (≥15). The score is calculated as follows: age 80 or older (2 points), female (1.5), diabetes (3), urgent (PCI) (2.5), emergent PCI (3.5), congestive heart failure (4.5), serum creatinine of 1.3 to 1.9 mg/dL (5) or 2 mg/dL or greater (10), and pre-PCI use of intra-aortic balloon pump (13). Based on the score, high-risk patients can be identified for early administration of more aggressive and intensive prophylaxis.24,25 Withdrawal of Nephrotoxic Drugs Common nephrotoxic drugs include nonsteroidal anti-inflammatory drugs (NSAIDs), metformin, diuretics (e.g., furosemide), angiotensinconverting enzyme (ACE) inhibitors, aminoglycosides, sulfonamides and penicillin, amphotericin, cyclosporin A, vancomycin, and cisplatin. These agents should be withdrawn before contrast media administration in all patients at risk. Metformin is the most important because it can produce intramedullar metabolic acidosis, which promotes nephropathy. Almost all patients can tolerate suspension of diuretics on the day of the implant procedure. PERIPROCEDURAL HYDRATION Hydration to dilute and flush contrast from the kidney is the most important step in the prevention of CIN. Hydration has two parts: (1) the fluid used: half-normal saline, normal saline, or bicarbonate, and (2) the protocol: (a) “overnight” (12 hours before and 12 hours after) or (b) “bolus” (3 mL/kg 1 hour before and 1-1.5 mL/kg 4-6 hours after procedure). Hydration Fluids Hypotonic Saline.  A 0.45 normal saline (NS) solution (in 5% glucose) should not be used; it is less effective than isotonic saline. In a study of 1383 patients, CIN was 2.0% with 0.45 NS versus 0.7% with isotonic saline.26 Isotonic Saline.  Multiple clinical trials confirm that NS definitively reduces CIN. For example, Solomon et al.27 reported that with saline hydration, “There is little risk of clinically important nephrotoxicity attributable to contrast material (122 ± 90 mL) for patients (220) with diabetes and normal renal function or for nondiabetic patients with preexisting renal insufficiency. The risk for those with both diabetes and preexisting renal insufficiency is about 9%, which is lower than previously reported.” None of their patients required dialysis. Sodium Bicarbonate.  A 2004 study suggested that sodium bicarbonate was superior to saline hydration,28 although the hydration protocols were not the same. Subsequently, five published randomized clinical trials and three meta-analyses have provided conflicting results.29-31 Interpreting the data requires recognizing that in three of the six published studies (and several abstracts), the hydration protocol for saline and bicarbonate were not the same; thus the difference seen may reflect the effect of the infusion protocol rather than the infused solution. Only three published studies used the same infusion protocol.32-34 The smaller studies found bicarbonate superior to saline,33,34 whereas the larger study found no difference.32 Hydration Protocol There is no direct comparison of overnight versus bolus infusion. However, analysis of the bicarbonate versus saline trials suggests bolus hydration is superior to overnight hydration, particularly in patients with congestive heart failure (CHF). When overnight saline was compared to bolus bicarbonate, saline was reduced for CHF patients in two studies35,36 (not defined by Merten et al.28). In the bicarbonate arm, the loading dose (3 mL/kg/hr for 1 hour) was not adjusted, but the infusion (1 mL/kg/hr during and 6 hours after procedure) was reduced to



0.5 mL/kg in one trial.32 Bicarbonate was superior to saline in the two studies where bicarbonate was not reduced, but equal to saline when the bicarbonate infusion was reduced for CHF. These results suggest that reducing the dose of overnight saline results in less effective hydration than bolus hydration, provided it is not adjusted for CHF. For a 70-kg person, the volume of the unadjusted bolus infusion protocol is 620 mL, whereas the overnight infusion protocol (reduced for CHF) is 840 mL; thus the bolus protocol is superior to overnight hydration, particularly in patients with CHF. Our recommendation therefore is to avoid overnight hydration and use acute hydration (3 mL/kg) starting 1 hour before the procedure, then either 1 mL/kg during and 6 hours after the procedure or 1.5 mL/kg for 4 hours. Another advantage of bolus hydration is that it can be started shortly before the procedure. Volume of Contrast Media Although studies show that the risk of CIN is dose dependent, there does not appear to be a threshold value below which CIN does not occur. Patients with preexisting renal dysfunction and diabetes appear to be at highest risk for CIN. Retrospective studies of cardiac catheterization suggest a lower risk of CIN for contrast loads less than 100 mL for interventional procedures. CHOICE OF CONTRAST AGENT Types of Iodinated Contrast Agents All contrast agents consist of a benzoic acid molecule with three atoms of iodine replacing hydrogen atoms on the benzene ring. Classification is based on (1) the charge on the iodinate molecule (ionic vs. nonionic), (2) osmolarity, and (3) molecular structure (monomer vs. dimer). The osmolality of the contrast agents is a measure of the number of particles in solution. The original contrast agents were ionic monomers and very hypertonic (osmolality of metrizoate = 2100), whereas newer contrast agents were nonionic and less hypertonic (osmolality of iopamidol = 796). Thus, ionic metrizoate was called “high osmolar,” referring to its osmolality; the terms high osmolar and ionic were used interchangeably. Currently, the term “high osmolar,” referring to the high osmolality of ionic agents, has no meaning because the osmolality of ionic agents such as ioxaglate (580) are the same or lower than for nonionic agents. More important (and confusing), the term “low osmolar” now refers to an agent with osmolality higher than 290. At present, the higher the osmolality, the more “low osmolar” is the agent, which is the opposite of the original description. By modern convention, iodixanol (osmolality of 290) is “iso-osmolar” and all agents greater than 290 are “low osmolar,” regardless of whether they are ionic or nonionic. The higher the osmolality, the more “low osmolar” it becomes. For example, ionic ioxaglate (osmolality of 580) is “low osmolar” compared to nonionic iodixanol (290). If one used the previous nomenclature, ioxaglate would be both “high osmolar” (because it is ionic) and “low osmolar” because it has a higher osmolality than iodixanol. Do not use the term “high osmolar” in relation to contrast. The osmolality of nonionic agents follows: iodixanol 290, ioxilan 695, iopromide 774, iopamidol 796, and iohexol 884 mOsm/kg. Iodixanol is iso-osmotic, and all the rest are “low osmolar.” Comparison of Contrast Agent Nephrotoxicity Ionic vs. Nonionic.  One randomized prospective evaluation of ionic diatrizoate (measured osmolality = 1500) vs. nonionic iopamidol (osmolality 796) found no difference in the incidence of nephrotoxicity.37 However the subsequent RECOVER study compared ionic, “lowosmolar” ioxaglate (osmolality 580) to nonionic, iso-osmolar iodixanol (osmolality 290) in patients with renal insufficiency undergoing coronary angiography with or without PCI.38 In addition to ionic versus nonionic, a second variable was “low osmolar” (580) versus isoosmolar (291). The incidence of nephropathy was significantly lower with iso-osmolar nonionic iodixanol (7.9%) than with “low osmolar” ionic ioxaglate (17.0%) (P = .021). Unfortunately, some patients received hydration with 0.45 NS (ineffective; see earlier), and thus the

23  Interventional Techniques for Device Implantation

621

difference may be caused by inadequate hydration. Further, the findings may also reflect the difference in osmolality. Low-Osmolar Nonionic vs. Iso-Osmolar Nonionic.  The NEPHRIC Study compared low-osmolar iohexol (osmolality = 884) with an isoosmolar iodixanol (osmolality 290) and found nephropathy less likely to develop in high-risk patients with iso-osmolar iodixanol.39 Because NEPHRIC was small and hydration not uniform, and because several subsequent studies were flawed and produced conflicting results, the CARE trial was conducted to settle the issue. The Cardiac Angiography in Renally Impaired Patients study was a prospective, multicenter, randomized, double-blind comparison of the “low osmolar” nonionic iopamidol (osmolality 796) to the iso-osmolar nonionic iodixanol (osmolality 290) in high-risk patients.40 CIN, defined by multiple endpoints, was not statistically different in high-risk patients, with or without diabetes mellitus. All patients received prophylactic volume expansion with isotonic sodium bicarbonate solution, administered at 3 mL/kg/hr for 1 hour before angiography, and at 1 mL/kg/hr during and for 6 hours after angiography. Prophylactic N-acetylcysteine regimen of 1200 mg twice daily administered on the day before and on the day of the study procedure was used in some centers. The authors concluded that any true difference between the agents was small and unlikely to be clinically significant. Thus, if bolus hydration is used, either nonionic iso-osmolar iodixanol or nonionic lowosmolar iopamidol can be used. The conflicting results of NEPHRIC and CARE may reflect the approach to hydration. In summary, adequate hydration with saline or bicarbonate (3 mL/ kg load, then 1 mL/kg for 6 hours) apparently reduces the difference (if any) among the different agents. When hydration is suboptimal, the nonionic agents, particularly those with an osmolality close to isotonic (iodixanol osmolality = 290) may be superior. Gadolinium.  Although they may be less nephrotoxic than iodinated contrast agents, gadolinium-based contrast agents should never be used because of their association with nephrogenic systemic fibrosis, a relatively recently recognized,41 rapidly progressive fibrosing disorder of skin and internal organs. Nephrogenic systemic fibrosis is seen in patients with kidney disease (estimated glomerular filtration rate <30) who receive gadolinium-containing contrast agents.42 Carbon Dioxide.  For more than five decades, gaseous CO2 has been recognized by interventionalists as an alternative to iodinated contrast for diagnostic as well as interventional procedures.43,44 Winters et al.45 recently described their favorable experience with gaseous CO2 venography rather than iodinated dye in patients undergoing pacemaker or ICD lead revisions. DRUGS TO PREVENT RENAL FAILURE Sodium Bicarbonate Alkalinizing the tubular urine with sodium bicarbonate infusion may attenuate free-radical formation, leading to less oxidant injury and lower CIN rates. As previously outlined, in the initial studies of bicarbonate the hydration protocol was also different. Subsequent studies using the same hydration protocol suggest that bicarbonate and saline may be equally effective. N-Acetylcysteine A potent antioxidant with vasodilator properties, N-acetylcysteine may prevent acute renal dysfunction by scavenging a variety of oxygen-derived free radicals and improving endothelium-dependent vasodilation. Several well-performed randomized clinical trials have demonstrated that the administration of acetylcysteine (Mucomyst) along with either saline or bicarbonate hydration prevented CIN in patients with chronic renal insufficiency.19,46,47 However, some still questioned the value of N-acetylcysteine, and two recent trials using high dose (1.2 grams twice a day for 48 hours) found no advantage over saline hydration alone in randomized trials of 250 STEMI

622

SECTION 3  Implantation Techniques

patients48 and 2308 high-risk patients.48a Acetylcysteine should never be used as a substitute for hydration in CHF patients. Ascorbic Acid In a double-blind, randomized, placebo-controlled trial, the antioxidant ascorbic acid—administered as 3 g 2 or more hours before, 2 g the night after, and 2 g the morning after angiography or intervention— was demonstrated to reduce the risk of contrast-mediated renal dysfunction.49 However, a subsequent well-performed randomized study found no benefit.31 Iloprost A prostacyclin analogue, iloprost works “presumably as a renal vasodilator and cellular protective agent downstream in the prostaglandin cascade to prevent contrast-induced acute kidney injury.”50 In a randomized, double-blind, placebo-controlled study of 208 patients with a serum creatinine of 1.4 mg/dL or greater, Spargias et al.51 reported CIN in 22% of controls and 8% of the iloprost group (1 ng/kg/min). All patients were hydrated with saline. Although dose-dependent hypotension and platelet inhibition are the principal side effects of iloprost, the incidence of hypotension and bleeding was not significantly different between groups. Hemofiltration and Hemodialysis In patients with a creatinine greater than 2 mg/dL, hemofiltration (4 hours before and continued for 24 hours after the procedure) compared to isotonic saline prevented the deterioration of renal function, decreased the need for renal replacement therapy, and improved in-hospital and long-term outcomes.52 Similarly, in patients with a creatinine more than 3.5 mg/dL, hemodialysis (a single, 4-hour treatment initiated immediately after procedure) reduced length of stay and the need for renal replacement therapy at hospital discharge.53 TREATMENTS TO AVOID Fenoldopam (systemic IV administration), dopamine, calcium channel blockers, atrial natriuretic peptide, and l-arginine are not effective, whereas furosemide, mannitol, and endothelin receptor antagonists are potentially detrimental.54 We have successfully adopted the following reasonable approach. Because patients with CHF are at increased risk and the serum creatinine levels of patients with New York Heart Association (NYHA) Class III or IV CHF can vary from day to day, we pretreat all patients undergoing a CRT implant, as follows: 1. Withdraw nephrotoxic drugs. 2. Bolus hydration with either isotonic saline or bicarbonate, 3 mL/ kg/hr for 1 hour before, then 1 mL/kg/hr (consider 0.5 mL/kg/hr for recent CHF decompensation) during, and for 6 hours (or 1.5 mg/kg/hr for 4 hours) after the procedure. Because the total volume of intravenous (IV) hydration is lower with bolus hydration and the results possibly better, we no longer recommend overnight hydration, particularly for those with CHF. 3. Consider iloprost (±) 4. Use either iso-osmolar iodixanol or iopamidol. 5. Consider hemofiltration and hemodialysis in extremely high-risk patients (see Brown risk score earlier). Additional Concerns No data suggest that shellfish allergies predict increased risk of adverse reactions to contrast. It is currently thought that shellfish allergy is related to tropomyosin, and patients with seafood allergies do not have an increased risk of iodine allergy. A variety of regimens are used to prevent allergic reactions to iodine. Specific regimens will vary from center to center. Preprocedure medications include diphenhydramine (Benadryl), a histamine receptor blocker, and steroids beginning 12 hours before the procedure. Typically, prednisone or methylprednisolone is administered 12 hours and immediately before the procedure.

Box 23-3 

STEPS TO PREVENT CONTRAST NEPHROPATHY 1. Hold diuretics on the day of the procedure. 2. Preimplant hydration to prevent contrast nephropathy: NaCl vs. NaHCO3 (probably no advantage of one over the other) Recommendations: a. 3 mg/kg for 1 hour before procedure b. 1 mg/kg during and for 6 hours after procedure, 0.5 mL/kg if recent CHF exacerbation 3. Contrast agents: in general, contrast agents with osmolality closer to isotonic (≈290) seem to be superior to agents with high osmolality (>500) in patients with diabetes mellitus and chronic renal failure. However, isotonic iodixanol and iopamidol (osmolality = 796), seem to be equivalent.

PREIMPLANT HYDRATION Preimplant hydration is discussed earlier. CONCLUSION Implanting physicians who are not accustomed to preimplant hydration are extremely concerned that CRT patients will suffer CHF decompensation. Thus they avoid hydration, increasing the risk of nephrotoxicity that can occur even when small volumes of contrast are used. Our experience with routine hydration for device implantation does not support the level of concern frequently expressed. Further, many CRT patients are hydrated for their interventional procedures (e.g., cardiac catheterization and PCI) without acute decompensation. Finally, there is the risk/benefit ratio of hydration to prevent CIN versus the possibility of exacerbating CHF. Contrast nephropathy results in an increased length of stay, higher morbidity, and both shortterm and long-term mortality. Contrast nephrotoxicity is reduced if not eliminated by hydration. With the new, acute bolus approach to hydration, the total volume of IV hydration is lower, and the patient is under observation during the daytime hours. CHF may or may not develop as a result of hydration and can be treated if it does; thus hydration should be employed (Box 23-3).

Preparations for Implantation ROOM SETUP AND TABLE POSITION The equipment required for the procedure needs to be on hand in the room, including the appropriate implant table (Fig. 23-1). The table and the assistant need to be in the appropriate position (Fig. 23-2). If the monitor is not in a comfortable position, mount a flat-screen monitor on an IV setup pole. CATHETER MANIPULATION AND CONTRAST INJECTION Electrophysiology physicians are used to working with electrode catheters that have almost infinite torque control and do not kink or twist as do open-lumen catheters. As a result, keeping the catheter straight before it enters the body and applying torque with both hands to distribute the force are not as essential as with open-lumen catheters. In addition, we become accustomed to working alone with our EP catheter, so when contrast needs to be injected, it is not the EP mindset to do it alone. To work effectively with open-lumen catheters and inject contrast, the approach needs to change from an EP to interventional simply because the interventional approach to catheter manipulation and contrast injection is the way the tools were designed to be used (Fig. 23-3)



23  Interventional Techniques for Device Implantation

Figure 23-1  Implant table designed for cardiac resynchronization therapy. A, Skewed view; B, side view. The table is designed to be in the T-bone position for dealing with subclavian obstructions and during left ventricular lead implantation. The legs are set back to allow the image intensifier rotate under the table when imaging in the right anterior oblique projection. In addition, there is space between the legs of the implant table and the base of the patient table for the fluoroscopy pedals. (Courtesy Oscor, Palm Harbor, Fla.)

BALLOON BASICS Type of Catheter for Balloon Mounting Balloon catheters are either “over the wire” (OTW) or rapid exchange (Fig. 23-4). The terms rapid exchange and monorail are synonymous. OTW coronary balloons are about 150 cm and thus require a 300-cm wire, which is very difficult to handle. We always use a rapid-exchange coronary balloon that requires a standard-length wire. Peripheral balloons are 40 to 60 cm; thus an OTW peripheral balloon uses a standardlength wire, which makes rapid-exchange models unnecessary. When balloons are made specifically for coronary venoplasty, they will be short enough to be OTW and still use standard-length wires. Choice of Angioplasty Balloon and Inflation Pressure for Venoplasty Compliance of Balloon.  The term compliance refers to how a material deforms, or stretches, under pressure. This is an important consideration when selecting a balloon angioplasty catheter. Balloons of the same dimension will produce considerably greater force at the same

A

623

B pressure if the balloon material does not stretch. When a material stretches or deforms under pressure, it prevents the concentration of force from being focused at the stenosis. The balloon material stretches around the lesion rather than exerting force on it (Fig. 23-5, A) The more noncompliant the balloon material, the more dilating force it transmits, the more uniformly it expands, and the less risk it may pose of dilating healthy tissue (Fig. 23-5, B) A more compliant balloon material exerts less dilation force at the lesion and increases the risk of “dog boning” and potential vessel dissections. Balloon dilation force is potentially applied outside the point of resistance or lesion. A less compliant balloon provides more dilation force within a vessel or metal stent, potentially reducing the risk of trauma outside the edges of the lesion. Figure 23-6 illustrates the impact of compliance on nominal pressure, rated burst pressure, and balloon size between nominal and rated burst pressure. More Compliant Balloons • Softer, more flexible, and more susceptible to growth outside a hard lesion or metal stent. • Higher rate of balloon diameter growth and will typically grow in the areas of least resistance.

Monitor Catheters don’t kink, fall naturally onto the table Monitor Catheters prone to fall off table Patient Equipment table Patient Catheters kink

Assistant

Operator Operator

Assistant

Equipment table

A

B

Figure 23-2  Importance of table position while working with long wires and catheters. A, Implant equipment table is in its usual position behind the operator. Wires and catheters are bent 90 degrees as they exit the pocket, making them prone to fall off the table. The 90-degree bend makes open-lumen catheters prone to kink, resulting in collapse of the lumen, destroying the function of the catheter. The 90-degree bend also cuts torque control of the catheter by 50%, making it more difficult to cannulate the coronary sinus or target veins. Wire exchanges are difficult to perform. B, Table is perpendicular to the patient table. The catheters and wires fall naturally on the table. The operator and assistant are not distracted from the procedure by trying to keep the wires from falling off the table and becoming contaminated. Open-lumen catheters are less likely to kink, and torque control is optimal. Wire exchanges are easily performed by pinning the wire to the table and sliding the catheter back to the hand pinning the wire.

624

SECTION 3  Implantation Techniques

Over the wire

Suboptimal catheter control

Angioplasty wire exits at the hub

A A

Inflation port

Rapid exchange or monorail Operator can focus on catheter manipulation = better control Angioplasty wire exits 20-30 cm from the tip

B

Assistant injects

B Figure 23-3  How to torque an open lumen catheter and inject contrast. A, Operator is attempting to control the catheter and inject contrast simultaneously. B, Operator has both hands on the catheter. The assistant can inject contrast on request of the operator. Interventional principles dictate that both hands must be on the catheter for effective catheter manipulation. Using both hands spreads the torque over a larger area, reducing the chance the lumen will collapse, destroying the catheter. The addition of the Y adapter with hemostatic valve and rotating hub makes it much easier to hold the catheter in position and insert a wire when needed without loss of catheter position. When the operator attempts to inject contrast and manipulate the catheter, two events sabotage the result: the operator must redirect focus from the tip of the catheter to the syringe, and catheter position is compromised because the plunger hand no longer is in control of the catheter.

• Can grow in diameter outside the lesion and apply high pressure to healthy tissue. • Pressure tends to migrate to that area of the balloon with the least resistance. This can cause a “dog boning” effect, which could result in damage of healthy tissue outside the intended treatment area. Less Compliant Balloons • Typically stiffer, thicker, and less susceptible to growth outside a lesion. • Balloon holds its shape despite added pressure, exerting more force against a hard lesion, potentially increasing success. Technique Considerations.  For coronary vein venoplasty, a “noncompliant balloon” (midrange in compliance scale) is a good place to start. Such balloons track easily and relieve most stenotic areas. If the balloon will not advance across the stenosis, the first step is to reevaluate the guide support. After a guide with a size and shape suitable for the target vein is in place, the operator should consider downsizing the balloon, using one of the same composition (e.g., 3 mm to 2 mm), and changing to a more compliant balloon. Once the smaller balloon is inflated across the lesion, the balloon should be reinserted and inflated. If there is a residual “waist” (indentation in balloon created by obstruction) after full inflation of a noncompliant balloon, an ultranoncompliant balloon (Kevlar) can be tried. The addition of a second (stiff) angioplasty wire beside the balloon before inflation will focus the force of the balloon on the narrowing. Because it can be difficult to place a second wire across a lesion after initial attempts at dilation, we always place two wires across the lesion initially, one stiff and one floppy, before starting. The balloon goes over the floppy wire, and the stiff wire is used to concentrate forces at the site of stenosis.

Figure 23-4  Comparison of over-the-wire balloons with monorail balloons. A, The wire over which the balloon is tracked exits the catheter at the end of the catheter near the inflation port. B, The wire over which the balloon is tracked exits the side of the balloon 20 to 30 cm from the tip. The advantage of an over-the-wire balloon is better ability to push the balloon and change the wire, if needed, distal to the obstruction. The disadvantage is the wire over which the balloon tracks must be at least twice the length of the balloon. When working with short, peripheral balloons, the length of wire required is not problematic. Working with an over-the-wire coronary balloon (150 cm in length) requires a 300-cm wire, and thus the operator and assistant must cope with 150 cm outside the body. The disadvantage of the monorail (also referred to as rapid exchange) is that the balloon cannot be used to change wires distal to the obstruction, and there is less “pushability” because the wire does run the length of the balloon.

Compliant Balloon

Pressure

Degree deflection

A

Noncompliant Balloon Pressure

B

Degree deflection

Figure 23-5  Comparison of compliant to noncompliant balloons. A, Compliant balloon is inflated against an obstruction. B, Noncompliant balloon is inflated against the obstruction.



23  Interventional Techniques for Device Implantation

ATM pressure 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0

A

3.5-mm balloon 3.24 Compliant 3.29 3.35 3.40 3.45 Nominal 3.50 3.55 3.60 3.65 3.71 3.76 Rated* 3.81 3.86 3.91 3.96

ATM 3.5-mm pressure balloon 3.0 3.13 Noncompliant 3.17 4.0 5.0 3.21 6.0 3.25 7.0 3.29 8.0 3.33 9.0 3.38 10.0 3.42 11.0 3.46 12.0 3.50 Nominal 13.0 3.51 14.0 3.54 15.0 3.56 16.0 3.58 17.0 3.60 18.0 3.62 19.0 3.64 20.0 Rated 3.66* 21.0 3.67 22.0 3.72

B Figure 23-6  Compliance tables from compliant (A) and noncompliant (B) balloon. The material from which the compliant balloon is made is thinner than the noncompliant balloon; as a result the nominal atmospheric (ATM) pressure of the compliant balloon (A = 6 atmospheres) is lower than the noncompliant balloon (B = 12 atm). The rated burst pressure of the compliant balloon (A = 12 atm) is lower than the rated burst pressure of the noncompliant balloon (B = 20 atm). In addition, the size of the compliant balloon increases from 3.5 mm at nominal pressure to 3.81 mm at rated burst pressure (A), whereas the noncompliant balloon increases to only 3.66 mm at rated burst pressure. Thinner balloon material also makes the profile (outside diameter) of the compliant balloon smaller than that of the noncompliant balloon.

Profile of Balloon.  The outer diameter (OD) of the balloon in its wrapped, never-inflated state is referred to as the profile; the lower the profile, the easier it is to pass the balloon through the obstruction. Noncompliant balloons are made of thicker material; thus the OD of a 3-mm compliant balloon is less than OD of a noncompliant 3-mm balloon. Once a balloon is inflated, the profile is greater because of “winging” (Fig. 23-7). The balloon material is wrapped around the shaft, and once deflated, it remains unwrapped, increasing its profile. Diameter of Balloon.  When dealing with coronary arteries, the initial size of the balloon is based on the estimated size of the normal coronary artery proximal and distal to the stenosis. However, in the coronary veins, the size of the pacing lead determines the size of the balloon. In the coronary branch veins, a 3.0-mm balloon inflated to at least nominal pressure, or until the waist is eliminated, is satisfactory for 6-French (6F) leads, 2.5 mm for 5F Leads, and 2.0 mm for 4F leads. In the main body of the proximal coronary sinus (CS), a 6.0-mm balloon is used, while a 4.0- to 6.0-mm balloon is used for the mid to distal CS. Length of Balloon.  The length of noncompliant balloon suitable for coronary venoplasty is 15 to 21 mm. For enlargement of a straight, diffusely narrow vein segment, a longer balloon may be chosen. Longer balloons tend to be more difficult to advance because of their greater surface area of resistance in the stenotic vein segment. If a very tight, discrete stenosis is encountered, a shorter balloon with less resistance may be a better choice. However, longer balloons tend to be more stable in the vein as well. The composition of the balloon material also influences the length. When an ultra-noncompliant or a cutting balloon is required, 9 to 10 mm is usually the best starting length. The material

625

required to construct the ultra-noncompliant balloon is relatively thick and stiff, and thus it is difficult to track through any curved vein segments, particularly if the balloon is long. Inflation Pressure Reviewing the packing material included with the balloon gives the best indicator of the appropriate pressure, with the following definitions kept in mind: Nominal pressure: Pressure required for that balloon to achieve the rated size in an open system. If the balloon is not inflated to the nominal pressure, it will not reach the rated size. Overinflated: Balloon size when the nominal pressure is exceeded. Compliant balloons increase beyond nominal more than non­ compliant. The size of the balloon at pressures that exceed nominal is printed on the packaging along with the nominal pressure (see Fig. 23-6). Rated burst pressure: Pressure above which the balloon will burst (usually). Compliant balloons tend to have lower rated burst pressure (see Fig. 23-6). Effective pressure: Pressure required to relieve the obstruction. The effective pressure varies according to the nature of the stenosis. In patients with prior open-heart surgery, significant fibrosis or even suture material may be contributing to the obstruction. The effective pressure is judged from observation of the balloon. The pressure is effective when the balloon achieves a uniform size and the waist is eliminated. Box 23-4 summarizes major considerations in the preparation of a venoplasty balloon.

Crossing Obstructed or Occluded Vein in Patients with Preexisting Leads It is important to remember that “subclavian” is commonly used shorthand for the axillary/subclavian/innominate vein. Some degree of subclavian vein occlusion is common in patients with existing leads. The severity of the obstruction is often defined based on a venogram performed by contrast injection through an arm vein (peripheral venogram). When the peripheral venogram reveals an occlusion, it is best to enter the vein as far peripheral to the occlusion as possible to provide a stable access for approaching the occlusion (Fig. 23-8). A standard short J wire is then advanced to the occlusion and the needle exchanged for the dilator from a 5F sheath. The dilator is then connected to the

Effect of first inflation on balloon dilation catheter Never inflated Balloon material wrapped tightly around catheter

Deflated after first inflation Balloon material forms “wings”; increases profile

Figure 23-7  Balloon material unwraps after first inflation, increasing balloon profile. After the first inflation, a balloon designed for dilation will have a larger outside diameter, making it more difficult to place across an obstruction. The first inflation should be central, at the superior vena cava (SVC)–innominate junction, for subclavian obstructions and distal in the coronary veins.

626

SECTION 3  Implantation Techniques

Box 23-4 

PREPARATION OF VENOPLASTY BALLOON 1. Partially fill the syringe of the inflation device with halfstrength contrast. 2. Connect the inflation device to the balloon with a three-way stopcock. 3. Turn stopcock off to the balloon. 4. Clear air from the line with contrast from the inflation syringe. 5. Turn the stopcock off to the inflation device. 6. Connect a 30-mL (cc) syringe filled with half-strength contrast to the stopcock. 7. Draw back on the 30-mL syringe to remove air from the balloon. 8. With the 30-mL syringe vertical, tap bubbles to the top of contrast. 9. Release to fill the balloon with contrast from the 30-cc syringe. 10. Repeat the sequence: drawback, tap bubbles to the top, release. 11. Turn the stopcock off to the syringe and remove the syringe. 12. Draw back on the inflation device to clear residual bubbles from the line. 13. Holding the syringe of the inflation vertical, tap bubbles to the top. 14. Remove the protective cover from the balloon. 15. Proceed as ready for procedure. Important: Do not test-inflate the balloon before insertion.

Y adapter of the injection system (Fig. 23-9), and contrast is injected at the site of occlusion. The length and severity of the occlusion may be either overestimated or underestimated by the peripheral venogram. In Figure 23-10 the peripheral venogram reveals extensive collaterals, and the occlusion appears complete in A, whereas in B, contrast injected at the site of

Collaterals Needle

A

Central to obstruction

Peripheral to obstruction

Extension tubing

Stop cock

Dilator

Y adapter

Injection syringe

Figure 23-9  Injection system used to define the occlusion. The dilator is from a 5-French (5F) sheath. When the J wire provided with the access sheath will not advance, the dilator from a 5F sheath is advanced over the J wire and connected to the Y adapter. Contrast injection through the dilator at the site of occlusion will reveal openings in the occlusion. The glide wire can then be directed through the occlusion using a steering handle.

occlusion demonstrates an opening that was easily crossed with an angled glide wire and torque device. In Figure 23-11, despite collaterals, the peripheral venogram in A suggests an opening that will be easy to cross, whereas in B, with injection of contrast at the occlusion, there is a total occlusion over 2 cm. Although it is important to perform contrast injection at the site of obstruction, the true, clinically relevant severity of obstruction is ultimately determined by whether a wire will cross the obstruction. For example, the venogram may demonstrate a hopelessly long, total occlusion, but the wire may cross easily (Fig. 23-12). Conversely, the stenosis may be short but impossible to cross with a wire. Accordingly, we define the obstruction based on how difficult it is to deliver a wire across the occlusion, as follows: 1. Moderate: Glide wire is easily advanced, but catheters do not advance easily. 2. Severe: Glide wire does not easily cross. 3. Total: Despite aggressive manipulation with multiple wires and assist catheters, a wire will not cross. CROSSING AN OCCLUDED “SUBCLAVIAN” VEIN

Collaterals Needle

B

Reservoir syringe

Vein indented

Figure 23-8  Venous access peripheral to occlusion on brachial venogram. A, Thin-walled 18-gauge needle is positioned above the vein peripheral to the occlusion as 20 mL of contrast is injected in a brachial vein. B, As the needle is advanced into the vein, the column of contrast is seen to indent, confirming location. To ensure stable access from which to work, the needle should enter the vein as far peripheral to the occlusion as possible.

Based on the venogram, enter the vein peripheral to the obstruction, and advance the standard short, .035-inch J wire to the occlusion. Remove the needle and advance the dilator from a 4F to 5F sheath to the obstruction, and remove the J wire. Attach the injection system to the dilator, and inject contrast to define the extent of the occlusion. Often, an opening is apparent despite an apparent total occlusion on the peripheral venogram. The severity of the occlusion should never be based on the peripheral venogram. An angled .035-inch glide wire is then inserted through the Y adapter and a torque device attached. The wire is then directed into the opening defined by contrast injection. Additional puffs of contrast can be injected to define the opening, as needed. As the wire is advanced, the dilator is advanced to provide support for the wire. In some cases the axis of the dilator directs the wire away from the opening (Fig. 23-13; see also Fig. 23-18, A and B). Faced with this situation, we have evaluated a variety of catheters and catheter shapes and found a hydrophilic, left vertebral diagnostic catheter (vert slip-cath, vert) (Fig. 23-14), in conjunction with a torque device and angled glide wire (Fig. 23-15), to be most useful. The short tip of the “vert” can be turned in the vein peripheral to the occlusion, directing the glide wire toward the opening (Fig. 23-16). The hydrophilic coating on the



23  Interventional Techniques for Device Implantation

627

Opening for wire

Tip of dilator

A

B

Figure 23-10  Contrast injected at site of occlusion reveals opening. A, When contrast is injected through a vein in the left arm, the subclavian appears to be totally occluded with extensive collaterals on brachial venogram. B, When contrast is injected at the site of occlusion, it is apparent that the vein is stenotic, not occluded, and the opening to facilitate passing the wire is demonstrated.

catheter is important to ensure the catheter will advance as the glide wire is advanced; however, it can slip through the operator’s fingers and out of the vein. To avoid loss of venous access while using the vert, it is useful to exchange the dilator of the 5F sheath for the 5F sheath (Fig. 23-17). The sheath is more secure in the vein than the vert, even if only a few millimeters are in the vein. Once in place, the vert is connected to Y adapter of the injection system and advanced to the occlusion with puffs of contrast. Once at the occlusion, the vert is turned in

the direction of the opening and the glide wire advanced; the vert is useful for peripheral occlusions (Fig. 23-18) as well as central occlusions (Fig. 23-19). The support and direction of the vert can also be used to direct the wire through what appears to be a total occlusion (Fig. 23-20). In addition, the vert can be advanced without a guidewire using contrast and orthogonal views to confirm position (Fig 23-21). Figure 23-22 illustrates the synergism of the glide wire and the left vertebral catheter.

Collateral

A Leads Collaterals

End

Start

B Figure 23-11  Contrast injected at site of occlusion reveals total occlusion. A, Although there are collaterals, it appears that the vein is patent on brachial venogram, as indicated by black arrowheads.  B, Contrast injection through the dilator reveals that the vein is occluded, as indicated by the arrows marking where the occlusion starts and ends.

Total occlusion InnominateSVC junction

Figure 23-12  Total occlusion demonstrated by contrast injection at site of occlusion. Despite the extensive collaterals, this total occlusion was crossed with a .035-inch angled hydrophilic guidewire directed with a torque device in less than 1 minute. Currently, most implanting physicians do not attempt to cross the occlusion and resort to extraction or move to the other side, an unfortunate outcome for the patient.

628

SECTION 3  Implantation Techniques

Glide wire

Y adapter Tip of dilator Torque device

Dilator Opening in obstruction

A

A

Vert slip cath Glide wire Tip of dilator Dilator

B

Opening in obstruction

Figure 23-13  Dilator directs glide wire away from opening in occlusion. A, Glide wire follows the direction of the dilator. B, Working with the torque device, the tip of the wire is directed toward the opening but will not cross.

Glide wire

B Figure 23-15  System used to cross difficult subclavian/innominate occlusions. A, Glide wire is advanced through Y adapter, and the torque device is attached to the distal end of the glide wire. B, Direction of the glide wire can be determined by the left vertebral diagnostic catheter (vert). Contrast can be injected through the .038-inch lumen of the vert with the .035-inch glide wire in place.

Glide-cath

Tip of vert

10 mm

Vert slip-cath

A

12 mm

Figure 23-14  Two angled hydrophilic catheters that are useful for crossing an occluded vein. The short tip allows the catheter to be manipulated within the vein to direct and support the wire. Glide-cath (Angled Taper Radiofocus Glidecath, 5F 100 cm, Terumo Medical) is glide wire catheter 4 French (4F) in diameter with .038-inch lumen and 10-mm angled tip. Vert slip-cath (Vert Slip-Cath Beacon Tip; Cook) is left vertebral diagnostic catheter 5F in diameter with .038-inch lumen and 12-mm angled tip. The “vert” provides more support for the glide wire but may not advance as easily over the wire (5F) as the glide-cath (4F). Both catheters are available in 4F and 5F sizes.

Tip of vert

B

Glide wire through obstruction

Figure 23-16  Vert directing glide wire. A, Tip of the left vertebral diagnostic catheter (vert) is directed inferiorly toward the opening in the occlusion. B, Glide wire advances through the obstruction.



23  Interventional Techniques for Device Implantation

Glide wire

A

Glide wire

5F sheath filled with contrast

B

629

Prepectoral Wire under Insulation Technique Followed by Venoplasty.  The lead to be sacrificed is partially extracted and a wire inserted under the insulation (Figs. 23-23 and 23-24). Using a stiff stylet, the lead is advanced back into the circulation, carrying along the wire. The wire and lead are separated by advancing the lead and fixing the wire. The lead is then extracted, retaining the wire. The ability to readvance the lead into the circulation with a stiff stylet depends on (1) implant duration, which determines the extent of fibrous tissue encasing the lead; (2) size of the wire under the insulation; and (3) lubricity of the wire under the insulation. This method is usually reserved for leads in place less than 1 month but can be successful up to 2 years if a hydrophilic .014-inch angioplasty wire is placed under the insulation. Once the .014-inch angioplasty wire is free in the circulation, it is exchanged for a .035-inch extra-stiff J wire using a 4F to 5F hydrophilic catheter. When used for leads implanted for more than 1 month, venoplasty is usually required because of the fibrous sheath that develops around the lead. When the lead cannot be advanced back into the circulation, femoral extraction can be used. Femoral Extraction with Wire in Stylet Lumen Followed by Venoplasty.  When advancing the lead back into the circulation is not possible, the lead can be snared and extracted using the femoral route. With femoral extraction, the wire can be placed in the stylet lumen after the connector is removed, rather than under the insulation. Once the .014-inch angioplasty wire is free in the circulation, it is exchanged

Figure 23-17  Dilator exchanged for sheath to prevent loss of venous access. A, Glide wire is advanced deep into the collaterals before the dilator is removed. B, Contrast is injected in the sheath to ensure the tip of the sheath is in the vein before removing the glide wire.

Dilator

TOTAL OCCLUSION: UNABLE TO MANIPULATE WIRE In most cases, a wire can be manipulated across the obstruction and venoplasty safely performed.3 However, some are wire refractory. Most of the approaches to a wire-refractory total occlusion have limitations. A very proximal subclavian stick increases the risk of hemothorax, pneumothorax, and, if successful, the risk of clavicular crush. The supraclavicular approach carries the risk of insulation damage or lead fracture from contact with the clavicle.55 Tunneling requires a second incision (with associated risk of infection) and sacrifice of the other subclavian vein.56 In addition, the tunneled lead is prone to erosion and fracture. When a wire cannot be advanced across the occlusion, there are two options: sacrificing one of the leads or using specialized crossing tools (microdissection, laser wire, radiofrequency guidewire).

A Dilator

Glide wire

B

Establishing Venous Access By Sacrificing an Existing Lead Prepectoral Sheath Extraction (Powered or Mechanical).  Gula et al.57 report that “central venous occlusion is not an obstacle to device upgrade with the assistance of laser extraction.” Although extraction of a functional lead can be performed safely in some centers by experienced operators, it still carries a small risk of serious complications (including death), loss of the functional lead, and dislodgement of adjacent lead(s) tethered to the lead being extracted. In addition, the lead may be extracted without regaining venous access. When the lead dislodges prematurely during prepectoral sheath extraction, the lead can be snared and held in the circulation while the sheath is forced through the fibrous tissue over the lead. However, it might be easier and safer to cut off the connector, insert a wire in the lumen, and extract the lead using the femoral approach, followed by venoplasty (see later). If the lead is not functional, extraction is a more appealing option, but careful assessment of the risk/benefit of the extraction procedure and the experience of the operator must be considered.58 Before the development of the techniques described later, extraction was the only option for implantation of a new lead (see Chapter 26).

Vert

C

Vert

D Figure 23-18  Vert used to cross occlusion. A, Contrast is injected through the superiorly directed dilator of a 5F sheath, demonstrating an inferior opening. B, Dilator directs the glide wire away from the opening. C, Dilator is exchanged for a left vertebral diagnostic catheter (vert), which is directed toward the opening confirmed using contrast. D, Glide wire is easily advanced through the opening for subsequent venoplasty.

630

SECTION 3  Implantation Techniques

Collaterals

A

Total occlusion Tip of dilator

Tip of vert

A

Local venogram Glide wire through the occlusion

B

Wire Tip of vert

B

C

Figure 23-20  Vert directs glide wire through total occlusion despite no visible opening. A, Contrast injection at the site of occlusion fails to reveal an opening through which to advance the wire.  B, Left vertebral diagnostic catheter (vert) was used to provide direction and support for the glide wire, which was advanced through the occlusion.

Figure 23-19  Vert crossing central obstruction at peripheral end of proximal coil. A, Venography near the site of occlusion when a glide wire would not advance reveals the opening is located superiorly.  B, Left vertebral diagnostic catheter (vert) is directed to the site of occlusion. C, Glide wire is advanced across the occlusion, using the vert for direction and support. Peripheral vein venogram

Contrast injected at the obstruction

Collaterals Contrast

A

B

5F vert 5F vert

C

D

Figure 23-21  Vert can be used to cross occlusions without glide wire. A, Peripheral venogram suggests total occlusion with extensive collaterals. B, Contrast injection at the site of obstruction reveals an opening. C, 5-French left vertebral diagnostic catheter (5F vert) is directed along the leads with puffs of contrast to confirm position. D, Tip of the vert is along the leads. Contrast injected at this position refluxes back along the leads into the collaterals, confirming it is still intravascular. With long occlusions, it may be useful to advance the vert alone as far as possible before utilizing the glide wire.



23  Interventional Techniques for Device Implantation

Glide wire

Glide wire

Vert Stop vert advance

Start vert advance

Figure 23-22  Vert and glide wire used together to cross a total occlusion. A, Angled glide wire is advanced beyond the tip of the left vertebral diagnostic catheter (vert). The tip of the glide wire is off the axis of the leads. Once orthogonal views confirm the wire is along the lead, as it appears in the anteroposterior (AP) projection, the vert is advanced over the glide wire until the tip reaches the point where glide wire is off axis (stop vert advance). The glide wire is retracted and the tip  of the vert then directed to the leads, and the glide wire advanced further along the leads. B, Tip of the vert is advanced to where the glide wire goes off axis near the junction of the innominate vein and the superior vena cava (SVC). C, Glide wire was withdrawn into the vert, the vert then directed toward the SVC, and the glide wire advanced. D, Glide wire is in the SVC. To ensure proper position, the wire should be advanced to the pulmonary artery and its position confirmed in orthogonal views.

A

B Vert

Glide wire

Vert

Glide wire

C

D

Figure 23-23  Angioplasty wire inserted under insulation of 7F pacing lead. A, Thin-walled 21-gauge needle is inserted under the insulation (larger needles tear the insulation of 7-French leads) and the dry, extra-stiff, .014-inch hydrophilic angioplasty wire is inserted through the needle under the insulation then advanced beyond the tip of the needle as far as possible. The extra-stiff wire will advance further than a floppy wire. B, Needle is removed, retaining the wire under the insulation. It is important that the hydrophilic wire under the insulation is dry to maintain a high coefficient of friction.

Needle under the insulation

Pacing lead 21-gauge Cook needle

.014-in angioplasty wire under the insulation

A .014-in angioplasty wire under the insulation

B

631

632

SECTION 3  Implantation Techniques

Distal coil

Proximal coil

Snare

Sheath

RA lead

A

B .014-in wire

Distal coil

Wire under insulation

RA lead

RA lead Snare

C

Proximal coil

D

Figure 23-24  Snare and wire under insulation of sacrificed lead to gain venous access. A, Defective ICD lead in place for 18 months was unscrewed and withdrawn using traction alone, until the proximal coil reaches the pocket and the tip was in the right atrium (RA). B, A .014-inch extra-support hydrophilic wire was inserted 5 mm under the insulation starting 1 cm proximal to the proximal coil. C, Lead could not be advanced back into the circulation and thus was snared from femoral vein. D, Lead is pulled back into the circulation until the wire reaches the right atrium where the lead and wire are separated by holding the wire in place and continuing to pull the lead with the snare. Once the lead and wire are separated, the lead is extracted into the pocket. In retrospect, it makes more sense to remove the IS-1connector and extract via the femoral vein separating the lead from the wire. Further, once it becomes clear that the lead will not advance back into the circulation, a wire can be inserted into the stylet lumen rather than under the insulation.

for a .035-inch extra-stiff J wire using a 4F to 5F hydrophilic catheter, followed by venoplasty. Establishing Venous Access with Specialized Tools Using Leads for Direction Various mechanical devices have been utilized to cross wire-refractory total occlusions, including a flexible hollow tube with screwlike surface contour (Tornus), microdissection, and laser. We evaluated the Tornus, but after our first case, had very limited success.59 Microdissection.  The Frontrunner XP CTO Catheter (Cordis Endovascular, Miami) is a device designed for microdissection through total occlusions in interventional radiology (Fig. 23-25). For short, total venous occlusions, the Frontrunner is often very successful60,61 (Fig. 23-26), but in some cases the jaws will not engage the occlusion. Microdissection is a slow process; thus, although it is possible to open long, total occlusions, it requires a long procedure (Fig. 23-27). In addition to being a slow process, microdissection can result in the jaws of the device stuck in the fibrous tissue surrounding the lead beyond the total occlusion, unable to reenter the true lumen (Fig. 23-28). This is addressed with a directed needle reentry catheter62 (OutBack LTD Re-Entry Catheter, Cordis), a companion device of the Frontrunner

(Fig. 23-29). The OutBack is an open-lumen catheter with a curved, extendable, retractable 21-gauge needle on the distal end. The OutBack with needle retracted is advanced through the channel created by the Frontrunner catheter, until the tip is in the fibrous tissue outside the distal true lumen. The needle is advanced with the tip angled toward the true lumen. A .014-inch guidewire is then advanced into the distal true lumen, the OutBack catheter is withdrawn over the wire, and venoplasty is performed. Despite some success with microdissection, we found it timeconsuming. Further, in some cases where the Frontrunner was in the fibrous tissue beyond the occlusion, we were not able to redirect the catheter back into the lumen with the OutBack. Ultimately, we were successful in only 60% of patients, and despite experience, the procedure time did not diminish. Finally, there is no central lumen; thus, to determine if it has reached the true lumen, a 4.5F guide catheter (Micro Guide Catheter, Cordis) must be advanced and the Frontrunner removed, creating a 4.5F hole. Radiofrequency Guidewire.  Several groups report successful recanalization of a long-standing, complete left subclavian vein occlusion by radiofrequency (RF) perforation with use of an RF guidewire in dialysis patients, some of whom have had a pacemaker on the same side.62,63



23  Interventional Techniques for Device Implantation

A

633

B

Figure 23-25  Blunt microdissection tool. A, The Frontrunner with jaws closed (top) and open (bottom). The ruler provides a reference for the size of the device (Frontrunner XP CTO Catheter, Cordis Endovascular, Miami). B, The Micro Guide Catheter through which the Frontrunner is passed. The lumen of the Micro Guide easily tracks over a 0.014-inch guidewire, but the lumen is large enough to accommodate two 0.014-inch guidewires.

A

B

C

C

D

Figure 23-26  Blunt microdissection tool successfully crosses total occlusion. A, The length of the total occlusion (between two arrowheads) is short (3-5 mm). B, When the Frontrunner is advanced through the 6F sheath in the proximal axillary vein, it tends to be directed superior to the interface between the pacing leads and the occlusion. C, A short (65-cm) 6F multipurpose guide is advanced through the 6F sheath to direct the Frontrunner to the occlusion adjacent to the pacing leads. D, The Frontrunner (arrow) is across the lesion in the vein which is filled with contrast (C, arrow). The Micro Guide catheter (LuMend) is then advanced over the Frontrunner into the venous lumen, the Frontrunner is removed, a wire is advanced through the Frontrunner into the vein, and the Micro Guide is removed. Venoplasty is then performed.

634

SECTION 3  Implantation Techniques

Retrograde catheter

Antegrade catheter Unable to engage occlusion Occlusion

Large collateral

A

B Retrograde

Guide

Micro Snare

Micro Guide Frontrunner

Micro Guide

C

D

Figure 23-27  Retrograde microdissection of a long total occlusion. A, Both retrograde and antegrade catheters define the occlusion, which extends from the subclavian vein to the superior vena cava. B, Attempts to engage the occlusion are unsuccessful. Despite the use of various guide shapes, the microdissection catheter (Frontrunner XP CTO Catheter) repeatedly went into the collateral vein. C, Microdissection is successful in reaching the level of the open vein. However, on the first attempt, the microdissection catheter will not reenter the lumen. On the second try, starting at the inferior vena cava, the lumen of the vein is entered. A 4.5F straight braided guide with radiopaque tip (Micro Guide Catheter) through which the Frontrunner passes is advanced into the true lumen proximally. D, A microsnare is advanced through the sheath in the proximal vein. The wire originating in the femoral vein is snared into the sheath, providing access to the heart for lead placement.



23  Interventional Techniques for Device Implantation

Opened via micro dissection

Long total occlusion

A

635

B

Micro Guide Front runner

Unable to enter true lumen

RA

C

D

Figure 23-28  Failure of microdissection catheter to enter true lumen despite successful microdissection beyond the occlusion. A, The long total occlusion from the innominate vein to the superior vena cava (SVC) with extensive collateral vessels is shown. B, The long total occlusion is successfully crossed via antegrade microdissection along the inner curve of the leads. However, the Frontrunner does not cross into the true lumen, but remains in the fibrous tissue surrounding the pacing leads. C, The microdissection catheter and guide (Frontrunner XP CTO Catheter) are again advanced beyond the total occlusion, this time along the outer curve of the lead, but remain in the fibrous tissue surrounding the pacing leads.  D, Contrast material injected into the guide catheter shows that it is in the tissues outside the SVC. Attempts to direct the microdissection catheter into the true lumen of the SVC are unsuccessful. The contrast staining had no clinical impact.

Radiofrequency is also used as an alternative to needle puncture in cases of complete superior vena cava (SVC) occlusion after Mustard repair.64 Based on this experience, radiofrequency could be used to regain central venous access by adding a lead to an existing device. Although possible, it seems unlikely that the RF energy would be sufficient to damage the adjacent leads. As with microdissection, however, the RF wire does not have a central lumen; thus, to determine if it has reached the true lumen, a guide catheter must be advanced and RF wire removed. It is more comforting to have a device with a central lumen, where a wire can be advanced to confirm arrival in the central lumen. Direct Needle Puncture.  Honnef et al.65 report using a transjugular intrahepatic portosystemic shunt set (TIPS needle) followed by venoplasty and stent to recanalize the chronically occluded left brachiocephalic of a hemodialysis patient. Sadarmin et al.66 implanted an ICD despite chronic total occlusion of the SVC by directing a 21F Colapinto needle (Cook Medical) from the right internal jugular vein through the occlusion, followed by venoplasty and stent. The report was followed by an editor’s warning that insertion of a needle into a total occlusion is fraught with failure or complication, even with fluoroscopy. Concerns include perforating the vessel, then possibly reentering the true lumen distal to the occlusion.

Laser Crossing of Total Occlusions.  The open-lumen excimer laser can be used to cross total occlusions in the arterial system.67 The laser directs high-energy photons to cause molecular bond disruption at the cellular level (photoablation) without thermal damage to the surrounding tissue. The excimer laser transmits ultraviolet energy from the source (CVX-300TM Excimer Laser System, Spectranetics, Colorado Springs) to photoablate fibrous, calcific, and atheromatous material. Laser photons cause vaporization of contrast; thus residual contrast must be flushed from all catheters, the lasing site, and vascular structures adjacent to the lasing site prior to lasing. Laser catheters are indicated for treatment of both lower-extremity and coronary arteries when a total obstruction cannot be crossed with standard guidewires.16 The risk of perforation is greatest when the diameter of the laser catheter is close to the diameter of the vessel. In the subclavian, the 0.9-mm diameter laser is far smaller than the vessel. The laser must be advanced at less than 1 mm per second to allow time for the high-energy photons to disrupt the molecular bonds at the cellular level without thermal damage to the surrounding tissue. Our experience with the laser began when microdissection failed,68 but the laser was successful in crossing the total occlusion (Fig. 23-30). Subsequently, we have used the laser successfully,69 now in 15 of 17 consecutive cases; 16 on the left and one right. The acute angle where the right innominate enters the SVC could make it more difficult;

636

SECTION 3  Implantation Techniques

Total occlusion

Front runner

Front runner

A

B Outback needle withdrawn

C Outback needle advanced

Needle Needle

D

E

F

Figure 23-29  Directed needle catheter used to enter distal true lumen. A, The short total occlusion with proximal and distal true lumen (arrows). B, The jaws of the microdissection catheter are open in the proximal portion of the occlusion. C, A nylon catheter with stainless steel braid and radiopaque tip (Micro Guide Catheter) is advanced over the Frontrunner through the track created in the fibrous tissue by microdissection. Despite being beyond the true lumen, the catheter is not in the true lumen. D, The OutBack Re-Entry catheter with needle retracted is advanced to the proximal portion of the distal true lumen. E, The curved hollow needle is advanced into the true lumen, and a .014-inch guidewire into the distal true lumen. F, Final venoplasty is performed with an interventional radiology, 6-mm-diameter, 4-cm-long balloon over a .035-inch Amplatz wire; predilation was performed with a 3-mm-diameter, 23-mm-long coronary balloon over the 0.014-inch guidewire, which was then changed for the .035-inch wire using the Micro Guide catheter.



23  Interventional Techniques for Device Implantation

End Start

A

B

C

Occlusion

Single laser application

Single laser application

Figure 23-30  Peripheral and central extent of 10-mm occlusion well defined, and single application of laser energy successful. A, Antegrade contrast injection at the site of occlusion defines both the peripheral and central extent of the occlusion. B, Tip of the 0.9-mm open-lumen laser (Turbo Elite OTW laser ablation catheter, Spectranetics, Colorado Springs) is at the occlusion. C, After one application of laser energy, the tip is in the lumen central to the occlusion. A wire was passed through the laser into the pulmonary artery and venoplasty performed.

however, we used a 5F internal mammary artery (IMA) guide to successfully direct the laser. The clinical characteristics for our patients are shown in Tables 23-1. Sixteen of the 17 had existing leads; one patient presented with an infected system on the right and an occlusion on the left related to leads extracted 27 months previously for an infected system. Most of the upgrades were for an LV lead. Fifteen of the 17 cases were successful. The two unsuccessful laser-crossing cases both had long total occlusion where the lumen distal to the occlusion was stenotic, making it difficult to define as a target for the laser. There were no clinical complications, although contrast stains were observed in 11 of 17 patients. In six patients the stains were mild (<1 cm in diameter), in four moderate (1-2 cm), and one extensive (3.5 cm). Tables 23-1 and 23-2 present clinical and procedural details of the laser-crossing cases. As illustrated in Figure 23-30, when the peripheral and central extent of the occlusion is well defined by antegrade contrast injection and the occlusion is less than 10 mm, crossing the occlusion may require only a few applications of laser energy. However, peripheral contrast injection even at the site of occlusion may not define the central extent of the occlusion as well as it first appears (Fig. 23-31, A). When the laser did not reach the lumen central to the occlusion after four applications of energy, a femoral catheter was advanced to define this lumen (Fig. 23-31, B). In cases with known long total occlusions we start with both femoral and pectoral access (Fig. 23-32). The precise direction of the laser may not be apparent from the anteroposterior (AP) projection (Fig. 23-33). Thus, the tip position is always confirmed in orthogonal views before lasing. Depending on the length of the occlusion and position of the laser tip, forward lasing may be continued, or the laser withdrawn and redirected with the guide. Long total occlusions can be time-consuming and require multiple applications of laser energy. Before each subsequent application of laser energy, the tip is positioned firmly against the occlusion and its position confirmed in orthogonal views. When the lumen central to the occlusion is not well defined, it may be necessary to place a guide from the

TABLE

23-1 

Case # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Median Mean

637

Clinical and Patient Characteristics of Laser-Crossing Cases

Age (yr) Gender 65 Male 88 Male 77 Male 63 Male 67 Male 94 Male 65 Female 70 Male 72 Male 79 Female 79 Male 88 Female 85 Male 76 Female 72 Female 80 Male 66 Female 76.0 75.6

Number of Chronic Leads 2 3 3 2 4 2 3 0 4 5 4 4 3 2 2 3 2 3.0 2.8

Age of Chronic Leads (mo) 22 30 18 19 50 96 61 63 51 108 57 33 45 69 60 41 58 51.0 51.8

Total Length of Lead(s) Occlusion Added (mm) LV 10 LV 20 LV 15 LV 20 None 45 RA 120 RA 15 LV, ICD 120 RV 100 RV 10 LV 10 RV 100 RV 130 LV, ICD 15 LV 15 LV 20 RA, RV 10 20.0 45.6

Length of Laser Burn (mm) 7 20 15 20 45 4 15 3 80 10 10 10 135 15 15 20 7 15.0 25.4

ICD, Implantable cardioverter-defibrillator; LV, left ventricular; RA, right atrial; RV, right ventricle.

femoral in the central lumen and direct the laser into the lumen of the femoral guide (Fig. 23-34). When resistance decreases or the tip appears to be in the vein or guide central to the occlusion, the preloaded 300-cm, .014-inch angioplasty wire is advanced into the pulmonary artery (PA) or inferior vena cava (IVC) and venoplasty performed.7 If the wire does not advance freely to the PA, it must be assumed that the laser is not in the lumen; it is withdrawn and redirected with the guide. Figures 23-35 and 23-36 illustrate a right-sided implant with total occlusion of the SVC above the left innominate vein. The patient has an arteriovenous fistula for dialysis in the left arm. The existing leads were implanted 5 years previously via the internal jugular and tunneled TABLE

23-2 

Case # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Median Mean

Procedural Characteristics of Laser-Crossing Cases Pre Laser Time (min) 60.0 21.0 29.0 13.0 40.0 69.0 59.0 45.0 21.0 16.0 15.0 34.0 44.0 25.0 32.0 48.0 67.0 34.0 35.1

Laser Time (min) 7.0 6.0 13.0 23.0 23.0 6.0 11.0 7.0 11.0 4.0 54.0 14.0 134.0 32.0 56.0 62.0 3.0 13.0 27.4

Number of Laser Burns 2.0 3.0 7.0 7.0 6.0 1.0 2.0 2.0 5.0 2.0 5.0 1.0 13.0 5.0 5.0 10.0 3.0 5.0 4.6

Post Laser Time (min) 8.0 12.0 18.0 18.0 NA 30.0 19.0 18.0 28.0 8.0 8.0 10.0 4.0 7.0 27.0 NA 14.0 14.0 15.3

Total Access Time Success or (min) Failure 115.0 S 39.0 S 70.0 S 55.0 S NA F 105.0 S 89.0 S 70.0 S 60.0 S 34.0 S 77.0 S 48.0 S 182.0 S 64.0 S 115.0 S NA F 84.0 S 77.0 80.5

Pre laser time = from initial venous access until initiation of laser. Post laser time = from wire crossing to sheath placement, primarily the time required for venoplasty.

638

SECTION 3  Implantation Techniques

Antegrade venogram

1

2

Distal extent of occlusion

A Retrograde venogram

5F left vertebral Proximal extent of occlusion (2)

B

8F sheath

Figure 23-31  Antegrade and retrograde venogram of a wire refractory chronic total occlusion. A, Contrast injection at the site of occlusion clearly demonstrates the distal (peripheral) extent of the occlusion. From this venogram, it is not clear whether site 1 or site 2 is the proximal (central) extent of the occlusion. B, Central extent of the occlusion is defined via retrograde contrast injection. When the tip of the laser did not reach the central lumen after five laser applications, a 5F left vertebral catheter (Left Vertebral Slip-Cath with Beacon Tip, Cook, Bloomington, Ind) was advanced through an 8F braided sheath (Channel FX Transseptal Sheath, Bard Electrophysiology Division, Lowell, Mass) to site 2, the proximal (central) end of the occlusion. Site 1 is an out-of-plane collateral. Contrast injection defines the target lumen for the laser.

demonstration of laser operation, (4). hands-on training, and (5) a company representative to assist for a minimum of three cases. For physicians already trained in laser lead extraction, minimal additional training is required. Because a laser easily advances through tissue, it is possible to enter an artery, causing an arteriovenous fistula. Neurovascular structures, the chest cavity, or any other adjacent structure in the mediastinum could also be penetrated unless the tip location is confirmed in orthogonal views before and during lasing. A 1-mm opening created by laser perforation through a vein surrounded by fibrous tissue is very unlikely to have serious consequences, unless the perforation is not recognized and venoplasty is performed. Preventing Complications.  The laser catheter is used safely in the arterial system, where high pressure makes the consequence of perforation much worse than in the venous system. In addition, lasing is not really being performed in a vein, but rather into the extensive, dense fibrotic tissue surrounding the preexisting leads. To prevent barotrauma from laser vaporization of contrast, residual contrast must be flushed with saline from all catheters, the lasing site, and vascular structures adjacent to the lasing site before lasing. To prevent thermal damage to the surrounding tissue, the laser is advanced at less than 1 mm per second. To prevent perforation, the laser tip position is confirmed in orthogonal views before and during lasing, ensuring that the laser catheter remains in the fibrous tissue until it reaches the lumen proximal (central) to the occlusion. Although laser perforation is the complication most often considered, the real danger results from posterior deviation of the wire into a small branch vein or collateral that is not apparent on the AP projection. To ensure that the angioplasty wire is in the true lumen as it is advanced, the tip must move freely, remaining in proximity and parallel to the leads until it reaches the PA or IVC. Unrecognized wire deviation seems to occur most often at the innominate-SVC junction.

Collaterals

Dilator

to the left side after extraction of an infected system on the right. Although the failed right ventricular lead could have been extracted for access, the lead would need to be tunneled from the right internal jugular to the left side over the clavicle and across the sternum, resulting in the same stress factors that caused the lead to fail initially. One patient with a chronic total occlusion without leads to follow required a laser to cross the obstruction (see Figs. 23-39 to 23-41). This case is discussed in detail in the section on total occlusions without implanted leads to follow or extract. Limitations of Current Equipment and Procedure for Laser Crossing of Wire-Refractory Total Occlusions.  For the purposes of crossing an occlusion, then advancing a wire, the over-the-wire (not rapidexchange) laser catheter is required. The current 120-cm over-the-wire laser catheter is far too long for this application; the ideal length is 45 cm. Another limitation of the current equipment is the lack of an ideal companion guide. Keeping the laser advancing in the correct direction requires a guide catheter for support. To ensure that the guide can follow the laser, the lumen of the guide must match the outside diameter of the laser, and the guide should have a hydrophilic coating. On several occasions, the hole created in the fibrous tissue by the 0.9-mm laser was be too small to allow the guide to follow the laser, and we changed to the 1.3-mm-diameter laser. The ideal guide for this application would be 60 cm long, have a left vertebral shape, a hydrophilic coating, and an internal diameter (ID) of 1.0 mm. Finally, a means to better define and enlarge the lumen of the vein proximal (central) to the occlusion will make it easier to direct the laser. The requirements for operation of the laser include (1) training in laser safety and physics, (2) review of laser operation, (3)

Antegrade contrast injection

A

Dilator

5F catheter

B

8F guide

Retrograde contrast injection

Figure 23-32  Venograms of a wire refractory chronic total occlusion. A, Central extent of the occlusion is not defined by contrast injection at the site of occlusion through the dilator. B, Central extent of the occlusion is defined by a retrograde venogram. A 5F left vertebral catheter (Left Vertebral Slip-Cath with Beacon Tip, Cook) is advanced through an 8F guide (Channel FX Transseptal Sheath, Bard Electrophysiology) to probe for the innominate vein where the leads enter the superior vena cava. The tip of the left vertebral catheter is advanced and contrast injected to define the central extent of the occlusion.



23  Interventional Techniques for Device Implantation

1.3-mm laser 7F guide

.035-in J wire 8F guide

A

.035-in J wire 8F guide 7F guide 1.3-mm laser

B Figure 23-33  Demonstration of importance of orthogonal views for laser crossing of total occlusions. A, Tip of the 1.3-mm openlumen laser appears to be in the lumen of the vein distal to the occlusion. The tip of the braided 8F femoral guide is at the superior vena cava (SVC)–innominate junction, supported by the .035-inch J wire curled in the lumen of the vein central to the occlusion. The 7F axillary guide adjacent to the leads directs the 1.3-mm open-lumen laser. In this projection the tip of the laser appears to be in the lumen of the vein central to the occlusion, as defined by the curled J wire. B, When the camera is rotated, the tip of the laser appears to be in the SVC, however, the wire does not advance freely.

Fortunately, wire deviation is easily recognized when the wire fails to advance into the PA or femoral vein. Proper wire position is confirmed by panning along the length of the wire in the left anterior oblique (LAO) and right anterior oblique (RAO), as well as AP projection. The balloon should never be inflated (or progressively larger dilators be advanced) until the wire is in the femoral vein or PA and its position adjacent to the leads is confirmed by orthogonal projections. Unlike laser lead extraction, where catastrophic complications can occur despite experience and optimal technique, venoplasty following lasing should not result in a catastrophic complication, unless wire deviation/ perforation is unrecognized and followed by venoplasty. Thus, we do not require operating room backup or arterial pressure monitoring, as recommended for lead extraction. Summary.  We find laser crossing of wire-resistant total occlusions to be successful in a high percentage (15 of 17) of patients who needed device upgrades. The safety of the procedure remains to be established in a multisite evaluation. If directions are followed and precautions heeded, this technique for crossing wire-refractory total occlusion can be learned by physicians with training and experience in venoplasty and laser lead extraction and deserves further evaluation. Availability of a short (45-cm), over-the-wire laser and a 60-cm-long, left vertebral– shaped guide with hydrophilic coating and ID of 1.0 mm will facilitate the procedure. TOTAL OCCLUSIONS IN PATIENTS WITHOUT IMPLANTED LEADS Access to the central vasculature can be regained using interventional techniques. However, most EP physicians send patients with bilaterally occluded subclavian/innominate vein for an epicardial or a femoral

639

system. A variety of occlusions can be successfully opened, although the success rate is lower than in patients with retained pacing or defibrillation leads. The occlusion may be short (Fig. 23-37) or long (Fig. 23-38). There may be flush occlusion at the innominate-SVC junction (see Fig. 23-38), or the innominate may be patent and well reconstituted central to the occlusion (see Fig. 23-37). It may be possible to cross the obstruction with a wire, or it may require a laser (Figs. 23-39 to 23-41). When approaching a case with known occlusion and no leads to follow we start by evaluating the central extent of the occlusion. First, a long, 8F braided sheath (Preface Guiding Sheath, Cordis) is advanced to provide a stable supportive platform in the SVC. A 5F left vertebral diagnostic catheter is then advanced into the SVC and puffs of contrast used to locate the innominate (Fig. 23-37, B). To make the central extent of the occlusion easier to visualize for the prepectoral approach to the occlusion, a venogram balloon is inflated (see Fig. 23-37, C). Moving from the femoral to the prepectoral area, venous access is obtained in the axillary vein peripheral to the occlusion, and a 5F sheath inserted. Using the venogram as a target, the obstruction is crossed with a glide wire and a 5F left vertebral catheter (see Fig. 23-37, C). Venoplasty is performed once the wire is across the occlusion and position is confirmed in orthogonal views (Fig. 23-37, D). Figure 23-38 is an example of a long total occlusion without wires to follow where there is flush occlusion of the innominate as it enters the SVC. When it is not possible to cross into the innominate vein central to the occlusion with a wire, a laser can be used to bridge the gap. See Figures 23-39 to 23-41 for details of the procedure. Box 23-4 lists venoplasty equipment. Box 23-5 lists the equipment required for crossing an obstructed axillary/subclavian vein and performing venoplasty. Subclavian venoplasty is covered in the next section. John Gurley and the group from the Gill Heart Institute at the University of Kentucky described inside-out central venous access (IOCVA) Text continued on page 646

1.3-mm laser

.035-in J wire

7F guide

8F guide

A

.035-in J wire 1.3-mm laser 7F guide

B

8F guide

Figure 23-34  When orthogonal views confirm tip positions, laser enters femoral guide. A, Using the 7F guide, the tip of the laser is positioned at the tip of the 8F femoral guide. The femoral guide was advanced into the vein to provide a target for the laser. The .035-inch J wire is in position in the central portion of the innominate vein to keep the femoral guide in the vein. B, With application of laser energy, the tip of the laser entered the femoral guide.

640

SECTION 3  Implantation Techniques

Right axillary vein contrast injection

Femoral vein contrast injection

Occlusion SVC SVC occlusion

RA

A

Left innominate

B Simultaneous contrast injection

Simultaneous contrast injection

Occlusion

Occlusion

C

AP

D

RAO

Figure 23-35  Superior vena cava (SVC) occlusion with patent left innominate vein. A, Contrast injection in the right axillary vein reveals total SVC occlusion related to pacing leads that had been inserted in the right internal jugular vein and tunneled to the left pectoral area 5 years previously. B, Contrast injection at the site of occlusion through a catheter inserted in the leg demonstrates a patent left innominate vein. The patient has a left arteriovenous fistula for hemodialysis. C and D, In preparation for laser crossing, the extent of the occlusion is documented in the AP and RAO views via simultaneous contrast injection.



23  Interventional Techniques for Device Implantation

641

5F IMA guide

.9-mm laser 5F vert

5F IMA guide

Vert

8F sheath

Laser

8F sheath

A

B 8F sheath Waist Laser .014-in wire 6-mm x 4-cm Kevlar balloon 30 atm

C

D

Figure 23-36  Laser opening of occluded superior vena cava (SVC). A, The 0.9-mm laser is advanced through a 5F internal mammary artery (IMA) guide catheter (Sherpa NX Active IMA Medtronic Vascular, Danvers Mass). The IMA guide provides direction and support for the laser. The central extent of the occlusion is defined by the left vertebral catheter (“vert”) introduced through a braided 8F sheath (Preface Biosense Webster, Cordis, Miami). B, After three applications of laser energy, the tip is central to the occlusion. The 1.47-mm internal diameter of the IMA makes it difficult or impossible to track through dense fibrous tissue over the 0.9-mm laser. C, A 300-cm, .014-inch angioplasty wire is advanced through the central lumen and the laser removed. D, After venoplasty with a 3 × 15–mm coronary balloon, a vert is used to upsize to a .035-inch extra-stiff wire. A 6-mm × 4-cm Kevlar balloon is then advanced through the obstruction and inflated to 30 atm until the waist is eliminated and the pressure stable.

642

SECTION 3  Implantation Techniques

Left vertebral

Occlusion Occlusion

A

B

6-mm x 4-cm balloon

Left vertebral

Venogram balloon

C

Waist

D

Figure 23-37  Venous access despite total subclavian occlusion without pacing leads to provide direction. A, Brachial vein contrast injection demonstrates total occlusion of the subclavian vein. B, Central extent of the occlusion is defined by contrast injection from a catheter introduced from the left femoral vein. C, A venogram balloon is inflated to facilitate visualization of the central extent of the occlusion and the hydrophilic 5F left vertebral catheter (vert) is advanced across the occlusion. D, A .035-inch extra-support guidewire is advanced into the pulmonary artery through the vert, the vert is removed, the balloon is advanced across the occlusion and inflated to eliminate the obstruction.



23  Interventional Techniques for Device Implantation

643

Dilator SVC

Occlusion

A

B

6-mm x 4-cm balloon

Glide wire

C

D

Figure 23-38  Venous access despite long total subclavian occlusion without pacing leads to provide direction. A, Innominate/subclavian vein is seen to be occluded along its entire length. SVC, Superior vena cava. B, Dilator from a 5F sheath is advanced over a glide wire into the collaterals. C, Glide wire enters the SVC. D, Venoplasty is performed to open the innominate for lead placement.

644

SECTION 3  Implantation Techniques

TOTAL OCCLUSION WITH NO LEAD TO FOLLOW

Axillary vein

Vert from femoral vein

Needle

Vert in braided sheath

Central venogram

A

Peripheral venogram

B WIRE WILL NOT ADVANCE

Wire

Axillary vert

Wire

Femoral vert

C

Axillary vert

Femoral vert

LAO

D

AP

Figure 23-39  Total occlusion with no lead to follow or extract that required laser: part 1. A, Venogram central to the occlusion reveals the innominate is reconstituted and widely patent beyond the occlusion. Vert, Left ventricular diagnostic catheter. B, Peripheral venogram reveals collaterals and a small axillary vein. C, On left anterior oblique (LAO) view, the vert introduced in the axillary vein is advanced to the tip of the femoral vert. An angioplasty wire would not advance. D, Anteroposterior (AP) view confirms the position of the two catheters. Despite the direction and support of the vert, the wire would not cross the occlusion. Unsuccessful attempts were also made to advance wires from the vert central to the occlusion.



23  Interventional Techniques for Device Implantation

Axillary Rapido

Laser tip Axillary Rapido

Femoral vert

Femoral vert

Wire

Catheters appear aligned

A

645

Laser off axis

B FEMORAL AND AXILLARY CATHETERS REPOSITIONED IN ORTHOGONAL VIEWS

Rapido Rapido

Vert

Vert

C

D

Figure 23-40  Total occlusion with no lead to follow or extract that required laser: part 2. A, The 6F Rapido advanced from the axillary vein seems to be well aligned with the femoral vert. The inner diameter (ID) of the vert is too small for the laser to pass. A 6F sheath was placed and the 6F outer-diameter (OD) Rapido advanced. B, After advancing the laser under power to the tip of the vert, an angioplasty wire was advanced but did not reach the lumen of the vein central to the occlusion. The Rapido and vert were realigned and position confirmed in LAO (C), AP, and RAO (D) projections.

646

SECTION 3  Implantation Techniques

LASER ALIGNED AND WIRE ADVANCED INTO VERT

Rapido

Rapido

Tip of laser Wire

Tip of laser Vert

Laser advanced to femoral vert

A

Wire through central lumen of laser into lumen of vert

B VENOPLASTY AFTER WIRE POSITION CONFIRMED

Wire from central lumen of laser in 8F femoral sheath

C

Waist in 6-mm x 4-cm balloon

D

Figure 23-41  Total occlusion with no lead to follow or extract that required laser: part 3. A, After the tip of the Rapido from the axillary vein is realigned with the tip of the vert from the femoral vein, the laser is introduced and advanced toward the tip of the vert. As the laser is advanced, the tip of the vert is pushed back. B, A 300-cm, .018-inch extra-support angioplasty wire is advanced into the lumen of the vert. C, Angioplasty wire is clearly seen in the lumen of 8F femoral sheath when the vert is withdrawn. Using a 5F hydrophilic catheter (vert) the angioplasty wire is exchanged for a .035-inch Amplatz Extra Support Wire. D, A 6 mm × 4 cm, noncompliant peripheral balloon is advanced and inflated to eliminate the stenosis.

in eight patients.69a IOCVA is an important, well-reasoned new approach for central venous access that can be applied to patients with chronic total SVC and subclavian vein occlusions that cannot be recanalized with currently available technology. IOCVA is a new concept that reverses the approach by directing a needle outward from within the body. The authors reasoned that IOCVA can be performed safely because there are consistent anatomic relationships adjacent to the thoracic central veins. The central veins are bounded anteriorly by the clavicle, soft tissues, and skin. A needle directed anteriorly will not encounter arteries, nerves, or pleura, which lie posterior and lateral to the central veins. IOCVA allows the placement of conventional leads and devices in optimum locations.

Subclavian Venoplasty: Response to Stenosis between Axillary Vein and Right Atrium In this section we use the term subclavian venoplasty as shorthand to describe dilation of the axillary, subclavian, and/or innominate veins. Once the wire is successfully across the obstruction, the fibrous tissue surrounding the leads must be dilated to allow unfettered access to the

cardiac chambers. At this point the options are venoplasty or progressively larger dilators. The use of progressively larger dilators is an anachronism reflecting that surgeons, not cardiologists, initially implanted devices. In the late 20th century, when EP physicians took over device implantation from the surgeons, we followed their lead in part because the EP skill set did not include balloon dilation. The modern approach to vascular obstruction should favor balloon dilation over using progressively larger dilators. VENOPLASTY VS. PROGRESSIVELY LARGER DILATORS Progressive larger dilators have been used for many years to enlarge the opening of a focal subclavian stenosis but were often unsuccessful when the obstruction extended from the subclavian vein to the SVC. When a focal peripheral stenosis is opened, approximately 30% have a stenosis at the innominate-SVC junction that is more difficult to address with dilators. Even when a “subclavian” stenosis can be opened with dilators, the result is always incomplete. The frequency of this problem is increasing as we perform more device upgrades. In most cases with progressively larger dilators, the stenotic area continues to restrict sheath and lead manipulation. Implantation of a right atrial



23  Interventional Techniques for Device Implantation

Box 23-5 

EQUIPMENT FOR CROSSING AND DILATING STENOTIC/OCCLUDED SUBCLAVIAN VEINS Contrast injection system: injection syringe, stopcock, extension, reservoir syringe, Y adapter .018-inch angled-tip hydrophilic guidewire, 150 to 180 cm in length (Angled Zipwire, Boston Scientific) .035-inch angled-tip hydrophilic guidewire (Angled glide wire, Terumo, or Angled Zipwire, Boston Scientific) Steering handle for glide wire: torque device for .025- to .038-inch wires (Mallinckrodt) Extra-support wire = .035 inch, 145 cm, 3-mm tip curve (Amplatz Extra Stiff, Cook) Ultra-support wire = .035 inch, 260 cm, 3-mm tip curve (Amplatz Ultra Stiff, Cook) 4- to 5-French hydrophilic catheter with 10- to 12-mm angled tip, 100 cm (Vert Slip-Cath Beacon Tip, Cook, or Angled Taper GlideCath, Terumo) Noncompliant, 6 mm × 4 cm, subclavian venoplasty balloon For wires ≤0.035 inch (PowerFlex-P3, Cordis) For wires ≤0.018 inch (Sterling, Boston Scientific) Ultra-noncompliant, 6 mm × 4 cm, subclavian balloon for refractory stenosis (Conquest, Kevlar); rated burst = 30 atm (Bard) Inflation device Miscellaneous: Three-way stopcock 12-inch extension 30-mL syringe (to pull negative pressure for balloon preparation) Y adapter with Luer lock Small bowl for mixing contrast, 50/50 (contrast/saline) See Interventional Equipment List at the end of Chapter 22 and online for details and ordering information.

(RA) or right ventricular (RV) lead after incomplete innominate/ subclavian dilation is time-consuming and frustrating but often possible. However, it adds a significant degree of difficulty to a CRT implant that more frequently can result in failure. Restricted access makes it more difficult to cannulate the CS, and all subsequent manipulation of catheters and leads is impaired. Friction between the lead and catheters makes final sheath removal more likely to result in LV lead dislodgement. Drawbacks to Progressively Larger Dilators Prolonged Implant Time.  Use of dilators prolongs the case because it takes longer to dilate the occlusion with dilators than balloons. Also, catheter and lead manipulation is restricted, and thus each step in the implant procedure is more difficult and takes longer. Failed Implant.  Use of dilators (not balloons) reduces the chance of a successful implant because many obstructions, particularly those with a distal stenosis, cannot be dilated successfully with dilators, resulting in a right-sided implant that is more difficult and less likely to be successful. Also, restricted catheter manipulation makes the implant more difficult, increasing the risk of failure. Increased Risk of Infection.  Use of dilators (not balloons) increases the risk of infection because of the longer procedure times. Also, when the dilators fail and the other side is used, there are two incisions, each with its own risk of infection. When laser extraction is used for access, the pocket must be opened twice instead of once, if the laser and surgical backup are not immediately available during the initial procedure. Increased Cost.  Use of dilators (not balloons) increases the cost of the procedure. Dilator failure may result in lead extraction for access, requiring a second procedure with general anesthesia, and a surgical

647

consult. Prolonged implant time increases the staff and room costs and reduces the number of cases that can be performed. Suboptimal Clinical Result.  Use of dilators (not balloons) results in a suboptimal result because of increased risk of infection, loss of venous access from using the other side, increased risk of lead erosion if the lead is tunneled, and increased risk of death if extraction is employed for access. Increased mortality results if the patient has a failed implant and is sent for an epicardial lead, or if the patient has a failed lead implant and is not sent to surgery. Increased Risk of Complications with dilators.  Because venoplasty is new and many implanting physicians have no experience with balloons, there is a tendency to regard progressively larger dilators as safer than venoplasty. Paradoxically, the concern that venoplasty is dangerous probably makes it safer than dilators because more attention is paid to the wire position. Figures 23-42 and 23-43 illustrate a catastrophic vascular event during the use of progressively larger dilators. It is important to note the glide wire did not perforate the dilator but simply exited through a branch feeding the innominate vein. The branch vein is a thin-walled structure not encased in fibrous tissue; thus, advancing the dilator lacerated the vein. Wire position in the AP projection can be deceptive. To be certain the wire has not exited the vein, progressively larger dilators (and balloons) should never be advanced until the wire is in the PA or IVC and confirmed to be adjacent to the leads in orthogonal views. PERFORMING SUBCLAVIAN/INNOMINATE VENOPLASTY As previously discussed, it is important to define clearly the situation with contrast injection at the site of occlusion (Fig. 23-44). Before starting venoplasty, the implanting physician must consider which wire is across the occlusion and what level of support is required to advance the balloon beyond the obstruction. The .035-inch glide wire that is most frequently used does not provide optimal support. Thus, upsizing to a .035-inch extra-stiff wire using a 4F to 5F hydrophilic catheter is a worthwhile first step rather than first trying to advance the balloon. In patients with previously implanted leads, venoplasty may be required anywhere between the right atrium and the axillary vein (Fig. 23-45). The most common site of obstruction is in the area of the clavicle (Fig. 23-46). A central occlusion is encountered in approximately 30% of patients with a peripheral occlusion. An isolated central occlusion accounts for approximately 10% of venoplasties. The lumen of the balloon must be large enough to accommodate the wire across the stenotic area, usually a .035-inch angled glide wire (Terumo Medical, Somerset, NJ). In addition, the inflated diameter of the balloon must be large enough for the 9F sheath (9F ID/11F OD) to pass freely after dilation (6 mm). Lastly, the balloon must be long enough to dilate from the right atrium to the axillary vein with three to five inflations (4 cm). Initially, the balloon is inflated to the “nominal pressure” (listed on the package). At the nominal pressure, the balloon reaches the labeled diameter. The pressure is then increased until the “waist” opens or the balloon bursts. A balloon typically used by interventional radiologists is the PowerFlex P3, which is 6 mm × 4 cm with a .038-inch lumen (Cordis, Miami). If the stenosis does not submit to the initial balloon, an ultra-noncompliant (aramid fiber [Kevlar]), high-pressure balloon may be used (Conquest PTA Dilatation Catheter [Bard Peripheral Vascular, Tempe, Ariz.] or equivalent). Once the proximal stenosis is dilated, the balloon is advanced to the RA-SVC junction and inflated to nominal pressures from the right atrium back to the axillary vein in an overlapping manner. In this way, any occult distal stenotic areas are revealed and opened (Fig. 23-47). Balloons for Subclavian Vein Venoplasty Why not use coronary balloons for subclavian venoplasty? We switched from coronary balloons to peripheral balloons for several reasons,

648

SECTION 3  Implantation Techniques

AP

AP

SVC-innominate junction

A

B

AP

AP Sheath

Dilator

.035-in hydrophilic J guide wire

C

Contrast in the pleural space

D

Figure 23-42  Hemodynamic collapse during use of progressively larger dilators to open subclavian occlusion. A, Venogram produced by contrast injection in a peripheral vein reveals subclavian obstruction with collaterals. B, Venogram reveals obstruction at the superior vena cava (SVC)–innominate vein junction. C, Progressively larger dilators are advanced over the .035-inch angled-tip hydrophilic wire. The wire appears to be in the vein in the AP projection. D, With the development of hemodynamic collapse, contrast was injected through the sheath and flowed freely into the pleural space.

LAO

LAO Leads at SVCinnominate junction SVC-innominate junction Hydrophilic .035-in J wire

A

Contrast in pleural space

B

Figure 23-43  Left anterior oblique (LAO) projection reveals hydrophilic wire and contrast in pleural space. A, Hydrophilic wire is seen to exit the innominate vein into a branch vein off the innominate and into the pleural space. B, Contrast injected through the sheath flows freely into the pleural space through the laceration in the venous branch produced by the dilator. The wire exited the innominate vein through a branch vein peripheral to the obstruction at the SVC-innominate junction. It did not perforate the vein.



23  Interventional Techniques for Device Implantation

Local venogram

Arm venogram

A

649

B

Figure 23-44  Arm and local venograms of a typical high-grade stenosis at axillary-subclavian junction. A, From 15 to 20 mL of contrast material is injected into a vein in the distal left arm, revealing a stenosis at the junction of the axillary and subclavian veins. B, The contrast material is injected through a 5F sheath inserted in the axillary vein proximal to the stenosis. To create a flexible stable platform from which to approach the occlusion, one obtains venous access and inserts a 5F sheath percutaneously in the axillary vein as distal to the stenosis as possible. If venous access is too close to the occlusion, it will also be difficult to direct the wire to different potential routes through the stenosis.

A

B

Figure 23-45  Dilation of a proximal subclavian vein occlusion. A, Collateral vessels are seen (arrows) around the subclavian vein occlusion that developed in association with the leads of a previous implantable cardioverter-defibrillator (ICD). B, Despite what appeared to be a total occlusion, a 0.035-inch angled Glide wire (Terumo Medical, Somerset, NJ) crossed the occlusion and advanced through the heart into the pulmonary artery. A 6-mm-diameter, 4-cm-long balloon with a 0.038-inch wire lumen is across the occlusion and inflated to 15 atm, where two residual waists are seen. With inflation to 20 atm, both waists were eliminated.

650

SECTION 3  Implantation Techniques

61%

22%

17%

Figure 23-46  Most common sites of occlusion associated with device leads. Diagram of venous anatomy shows that the most common site of obstruction is in the area of the clavicle. A central occlusion is encountered in approximately 30% of patients with a peripheral occlusion. An isolated central occlusion accounts for approximately 10% of venoplasty procedures.

including the diameter of the wire across the stenosis. When dealing with stenotic subclavian veins, we usually start with a .035-inch angledtip glide wire. Coronary balloons track over wires .014 inch or less; thus, to use a coronary balloon, the wire must be downsized to .014 inch, where many peripheral balloons are designed to track over wires .038 inch or less. In addition, coronary balloons are less than 21 mm in

length. The number of head-to-tail inflations required for the 21-mm balloon (Fig. 23-48, A) to cover the vein from the SVC-innominate junction to the pocket is prohibitive compared to the 40-mm peripheral balloon (Fig. 23-48, B). Finally the diameter of most coronary balloons is less than 4 mm, which is too small for passing a 9F sheath. Although we do not know the optimal size of balloon, we started with a peripheral balloon 6 mm × 4 cm in diameter and have not found the need to change after experience with more than 300 cases. A coronary balloon may be necessary to predilate the lesion when the only wire to cross the occlusion is .014-inch or .018-inch angioplasty wire (Fig. 23-49). The Hi-Torque Cross-It 300XT (Guidant, Boston Scientific, Natick, Mass.) and the .014-inch Crosswire (Terumo Medical), among others, are specifically designed to cross total coronary occlusions. They may be used to cross a subclavian occlusion when the .035-inch wire will not advance. When the only wire that will cross the lesion is a .014-inch, we start with a 2- to 3-mm coronary balloon. Once the stenosis is dilated with the coronary balloon, our usual .038-inch lumen peripheral balloon may track over the .014- or .018-inch wire. We now have two choices: (1) a .018-inch lumen peripheral balloon, or (2) upsize to a .035-inch extra-stiff wire (Amplatz Extra Stiff Wire Guide, Cook Vascular, Leechburg, Pa.) and dilate with a “standard” peripheral balloon. Caution: When dealing with a peripheral stenosis, it is tempting to use a short dilator to upsize to a larger wire. Avoid this mistake at all cost. Over 30% of patients with a peripheral obstruction also have a central occlusion that the hydrophilic wire may cross without the obstruction becoming apparent. If the hydrophilic wire has crossed an unrecognized central stenosis and a short dilator is used, the extra-stiff J wire will not advance through the obstruction. Attempting to advance this J wire through an obstruction tends to disrupt the lumen, making it impossible to insert the hydrophilic wire back into the central circulation. When upsizing or exchanging a wire, always use a catheter long enough to reach the PA or IVC. A 4F to 5F hydrophilic catheter is ideal for this purpose. A nonhydrophilic catheter of the same size may not advance over the wire.

Proximal dilation

Distal dilation

Waist

A

B

Figure 23-47  Dilation of both proximal (peripheral) and distal (central) subtotal venous occlusions encountered in same patient. A, The balloon is inflated at the site of the proximal occlusion to 15 atm with elimination of the waist and proximal stenosis. When the sheath was advanced, we encountered an obstruction at the SVC-innominate junction. B, The balloon is advanced to the junction of the superior vena cava and innominate vein and inflated, demonstrating a waist in the balloon in the second stenotic location. If the stenosis is severe, winging of the balloon after the initial inflation may make it impossible to advance to the SVC-innominate junction. Because 30% of patients with a peripheral stenosis also have a central stenosis, we now start our dilation at the SVC-innominate junction.



23  Interventional Techniques for Device Implantation

A

651

B

Figure 23-48  Comparison of “long” to “peripheral” balloon for dilation of occlusion at superior vena cava (SVC)–innominate vein junction. A, Coronary balloon is inflated. B, Peripheral balloon is inflated. Note the difference in size. Consider the number of head to tail inflations required to go from the SVC-innominate junction to the pocket with the coronary balloon compared to the peripheral balloon.

.035-in angled Terumo Glidewire

A

.014-in Terumo Crosswire

B

3-mm x 23-mm coronary balloon

C

6-mm x 4-cm peripheral balloon

D

Figure 23-49  Predilation of subclavian occlusion with coronary balloon. A, The .035-inch angled Terumo Glide wire will not cross the total occlusion. B, The 0.014-inch Terumo Crosswire is successful in crossing the total occlusion. C, Coronary balloon is inflated at the site of occlusion. D, The 6-mm-diameter, 4-cm-long peripheral balloon with a .038-inch lumen is advanced over the .014-inch Terumo Crosswire and inflated. Peripheral balloons designed to track over .018-inch wires are now available if the .038-inch lumen peripheral balloon will not track over the .014-inch wire. Alternatively, the .014 wire can be upsized to a .035 extra-stiff wire using a 4F to 5F hydrophilic catheter (e.g., “vert”).

652

SECTION 3  Implantation Techniques

Balloon inflated

Balloon inflated

Distal occlusion

Wire through occlusion

A

B

Wire through occlusion

C

Figure 23-50  Dilation of a total occlusion on a bend with short balloons. A, The proximal subclavian vein is open, but the distal vein at the junction with the superior vena cava (SVC) is totally occluded. Collateral vessels have developed around the occlusion. B, Despite what appears to be chronic total occlusion, an angioplasty wire designed to cross total arterial occlusions is successfully advanced into the right atrium. A short (23-mm) balloon is inflated at the site of occlusion. C, The short balloon is again inflated, this time more distally. The short balloon is chosen because the occlusion occurs on a bend. Contrast material used to facilitate crossing of the total occlusion can be seen staining the tissues at the site of previous occlusion. No adverse clinical event occurred despite the contrast stain.

In the past, we usually upsized the wire rather than try to track the .038-inch lumen balloon over the .014- or .018-inch wire. Although the .018-inch lumen peripheral balloon is an option, our experience with these new balloons is minimal, and it is reassuring to have a .035inch extra-stiff wire across the occlusion. In summary, coronary balloons are too short, their diameters too small, and their lumens too narrow for the typical .035-inch access wire. Coronary balloons are used when a .014-inch wire is all that will cross the occlusion. As soon as the stenosis is partially dilated, the .014 wire is usually replaced with a .035 wire (see Fig. 23-49). Recent availability of .018-inch lumen peripheral balloons provides more options. Short Balloons for Central Stenosis (Superior Vena Cava–Innominate Vein Junction) As previously noted and shown in Figure 23-47, many patients with a peripheral stenosis also have a central stenosis. In these cases,

progressive dilation of the proximal occlusion leaves the distal stenosis untouched, further restricting lead manipulation. In some patients, only a distal occlusion is encountered. Initially, we used short balloons (<20 mm) for the SVC-innominate junction occlusion (Fig. 23-50), thinking there was too sharp an angle to accommodate a longer balloon. However, on further reflection we realized that the wire is not constrained with the lead but enters the SVC; thus the central end of the balloon is free and is not forced to follow the bend of the leads. Figure 23-50 shows a distal-only occlusion that appears to be on a sharp bend, dilated with a short balloon at multiple sites. Kevlar Balloons and Focused-Force Venoplasty In some patients, the stenosis is particularly resistant to dilation, requiring special balloons. In Figure 23-51, an angled .035-inch angled glide wire was manipulated across the stenosis, but the sheath would not advance. The stenosis was dilated with a 6 mm × 4 cm balloon Figure 23-51  Venoplasty of a stenotic subclavian vein that required an aramid fiber (Kevlar) balloon to eliminate the waist. A, The 6-mm-diameter, 4-cm-long peripheral balloon is inflated at the site of stenosis to rated burst pressure (16 atm) but the waist remained. At 20 atm the balloon burst. B, Kevlar balloon replaces the standard balloon. The waist is eliminated at 22 atm.

A

B



23  Interventional Techniques for Device Implantation

653

Waist Waist

6-mm x 4-cm PTA balloon inflated to 16 atm

A

6-mm x 4-cm Kevlar balloon inflated to 30 atm

B Wire beside balloon

Wire beside balloon

Waist

No waist

Kevlar balloon inflated to 20 atm

C

Kevlar balloon inflated to 30 atm

D

Figure 23-52  Focused-force venoplasty to resolve a focal obstruction. A, The waist remains despite inflating the PTA balloon to 16 atm. B, The waist remains despite inflating the Kevlar balloon to 30 atm. C, Kevlar balloon is inflated to 20 atm with an extra stiff .035-inch guidewire beside the balloon to focus the force of the inflated balloon on the residual waist (focused-force venoplasty). D, When Kevlar balloon is inflated to 30 atm against the wire, the obstruction opens.

delivered over the glide wire. Figure 23-51, A, demonstrates the balloon dilated at 16 atmospheres (atm); at 20 atm, the balloon ruptured without eliminating the stenosis. A Kevlar balloon (Conquest) was then advanced across the occlusion (Fig. 23-51, B). Once the second balloon was inflated to 22 atm, the stenosis was relieved, and the 9F sheath (9F ID/11F OD) passed easily. When the Kevlar balloon is not effective, a stiff wire is placed beside the balloon. This is a useful technique for a focal stenosis that does not respond, as seen in Figure 23-52. Focused-force venoplasty is also useful for an elastic obstruction,70 where the balloon inflates completely but rebounds as soon as the balloon is deflated (Fig. 23-53). “COMPLICATIONS” OF SUBCLAVIAN/INNOMINATE VENOPLASTY Despite our initial concerns, we find balloon dilation of venous structures remarkably safe as long as the balloon is never used until the wire is advanced successfully to the PA. Figure 23-54 illustrates the potentially catastrophic consequences of not heeding this axiom; in A the wire position appeared satisfactory, but it would not advance to the PA, the tip apparently stuck in the RA; the LAO view in B illustrates how deceptive wire position can be in the AP projection. Figures 23-42 and 23-43 illustrate the consequence of not abiding by the rule when using progressively larger dilators (not venoplasty). In the case of dilating at the site of stenosis associated with existing leads, concern with safety is understandable. Because the stenosis and

leads are surrounded by fibrous tissue, it is fibrous tissue, not a vein, that is being dilated. In addition, it is helpful to consider the relative trauma inflicted by extraction of a lead with a 14F to 16F laser sheath that vaporizes the tissue surrounding the lead. By comparison, balloon venoplasty in the same area is much less traumatic. We have seen contrast staining related to our attempts to manipulate a wire through the stenosis, but our patients have experienced no clinically significant complications (Fig. 23-55). When contrast staining occurs, we continue the procedure and perform venoplasty as long as we can move the wire across the stenosis. TRAINING REQUIRED TO PERFORM VENOPLASTY Given the advantages to patient care that accrue when venoplasty is performed, it is important that implanting physicians be trained. Because the procedure is new and involves balloons, most physicians overestimate the complexity of the procedure. Once the physician and staff become familiar with the equipment, the procedural aspects are quite simple. The procedure is safe provided the balloon is never advanced or inflated until the wire reaches the PA or femoral vein and is confirmed to be adjacent to the leads until it reaches the right atrium in orthogonal views. At our center, once the physicians become familiar with the equipment, usually with the help of the staff, they are observed by an experienced physician for two cases before they begin independent operation. This level of training seems adequate, as our 10-year experience with 375 cases without a complication affirms, particularly

654

SECTION 3  Implantation Techniques

.014-in wire Waist

.014-in wire

Contrast

4-mm x 15-mm coronary balloon 5F left vertebral

A

B .035-in extra-stiff wire beside balloon

No waist

6-mm x 4-cm peripheral balloon

C

D

Figure 23-53  Focused-force venoplasty for an elastic obstruction. A, Central stenosis appears complete, but a trickle of contrast is seen to cross (black arrowheads). The hydrophilic 5F left vertebral diagnostic catheter (vert) is redirected, placing the tip at the opening, and an angioplasty wire is advanced across the occlusion. B, Coronary balloon is placed across the obstruction and inflated until the waist is eliminated. The .014-inch wire is exchanged for a .035-inch extra-support wire using the hydrophilic 5F vert. C, A 6-mm × 4-cm balloon was inflated to 16 atm and the waist eliminated; however, the sheath would not advance. A Kevlar balloon was inflated to 30 atm, and still the sheath would not advance. D, Balloon was exchanged for a long 5F sheath. Two .035-inch extra-stiff wires were advanced into the right ventricle and the sheath removed. The balloon was advanced over one wire beside the other and inflated to 30 atm, after which the sheath advanced.



23  Interventional Techniques for Device Implantation

AP

655

LAO

Innominate vein SVC Device leads

Wire Wire

A

B

Figure 23-54  Location of the wire can be deceptive in the AP projection. A, Wire appears to enter the superior vena cava (SVC) from the innominate vein, but it would not advance beyond the right atrium, where it appeared to curl up. B, LAO projection reveals the wire has exited through a branch vein feeding the innominate vein. Either progressively larger dilators or venoplasty would be catastrophic.

when data include the learning curve of eight physicians, only two of whom had interventional experience. Box 23-6 lists key elements in crossing and dilating stenotic/occluded subclavian veins.

Coronary Venoplasty Techniques for Cardiac Resynchronization THE BUDDY WIRE TECHNIQUE The buddy wire technique is used to advance a pacing lead beyond a tortuous area without the need for venoplasty.71,72 With the buddy wire

A

technique, a stiff angioplasty wire (the buddy wire) is used to straighten a tortuous or looped vascular segment, allowing the LV lead to pass more easily.31,42 The ability to advance the stiff part of the wire through the tortuous vein segment requires a coronary sinus (CS) access catheter that provides a stable platform; otherwise, it will be displaced and the wire will not advance. After the vein is straightened, the stiff wire is left in place, and the lead is delivered over a second, softer wire (tracking wire) or with a stylet. The straightening wire should be an extra-support wire (e.g., Choice PT Extra Support or Platinum Plus ST), whereas the tracking wire should be a floppy wire (e.g., Choice PT Floppy). Figure 23-56 is a diagrammatic representation of the method; Figure 23-57 illustrates a patient in whom the lead would not

B

Figure 23-55  Extensive “stains” created with injection of contrast material during manipulation of wires to cross total occlusions seen at subclavian venoplasty. A, An extensive contrast stain can be seen in the tissue surrounding the subclavian occlusion. The stain developed as contrast material was injected to facilitate advancing the wire across the occlusion. B, A similar extensive contrast stain can be seen in the tissue surrounding the subclavian occlusion. As with the stain shown in A, this stain developed as contrast material was injected to facilitate advancing the wire across the occlusion. The contrast stain had no clinical effect in either case.

656

SECTION 3  Implantation Techniques

Box 23-6 

KEY ELEMENTS IN CROSSING AND DILATING STENOTIC/OCCLUDED SUBCLAVIAN VEINS 1. Obtain access laterally with a peripheral vein venogram. 2. Regardless of how difficult the situation appears on venogram, an attempt should always be made to “cross” the obstruction. 3. Inject contrast at the occlusion to determine severity and assess venous access. 4. Use angled-tip hydrophilic guidewires to cross the obstruction or occlusion. 5. Start with a .035-inch, angled-tip Glide wire or Zipwire. 6. Use torque device on the wire to probe channels. 7. Add a 4F to 5F angled-tip hydrophilic catheter to support and direct wire (see text). 8. Consider a .018-inch angled-tip hydrophilic guidewire. 9. Consider a .014-inch hydrophilic angioplasty wire. 10. For complete total occlusion that cannot be crossed, consider other options: extraction, laser, microdissection, or other techniques in which operator is experienced. 11. Upgrade to stiffer .035-inch wire, if needed, using a hydrophilic catheter. 12. Prepare peripheral balloon, use a noncompliant or ultranoncompliant balloon, typically 6 × 4 mm, 10-15 atm. 13. Consider focused-force venoplasty for diffuse narrowing. Never perform venoplasty until tip of wire is documented to be in the pulmonary artery or inferior vena cava (e.g., intravascular). 14. Typically, start centrally at subclavian/SVC junction with overlapping inflations to the pocket. 15. Continue to inflate until pressure stable, or to rated burst pressure or waist eliminated. 16. Upgrade to ultra-noncompliant Kevlar or forced venoplasty, if waist not eliminated.

revolutionizes the operator’s approach to LV lead placement. With venoplasty, the operator is much less dependent on the venous anatomy; leads are placed transvenously in areas that were previously accessible only with surgery. Despite the advantages of venoplasty, however, the technique is not yet widely used.1 We have performed PCV in 348 patients since our first CRT case in 1999. Initially, we used PCV as a last resort. As we became more comfortable with the safety and efficacy of the procedure, we used it more often. The importance of a specific LV location further increased use. The rate of first-attempt success in our most recent 300 patients with first-time implantations was 99%. Venoplasty is credited with success or ideal placement in 15%. Our first-attempt success rate in the last 50 patients with a previously failed attempt was 98%. Venoplasty is credited with successful/ideal lead placement in 40%. The majority of our patients undergoing coronary vein venoplasty (79%) had prior openheart surgery (OHS). The overall success rate for coronary vein venoplasty, defined as the ability to pass the lead beyond the stenosis, is 75%. Cine-review of our first 100 cases showed that venoplasty failed when a straight guide was used (Figs. 23-58 and 23-59), whereas failure was rare when guide support with a preshaped guide directed into the ostium of the target vein (Fig. 23-60). Other sources of venoplasty

pass beyond the tortuous area despite support from the CS access catheter and the delivery guide in the target vein. With a stiff wire straightening the vein, however, the pacing lead encountered less resistance and was advanced over the soft wire. BACKGROUND: CORONARY SINUS AND CORONARY VEIN VENOPLASTY A major issue is the importance of venoplasty to patient outcome. Venoplasty is infrequently if ever performed in many high-volume implant centers, reflecting either its lack of importance or its underutilization. It is well documented that venoplasty can safely achieve central venous access or LV lead placement that might not be possible otherwise.73-77 So why is venoplasty not used more frequently? Consider the current impediments to venoplasty during a device implant. First, the implanting physician may not think of or be aware of what can be accomplished with venoplasty. If the implanting physician does consider venoplasty, he or she may be deterred by assuming the risks and complications exceed the potential value, particularly in unpracticed hands. Typically, the implanting physician has no training in or experience with balloons; thus a consult is obtained from an interventional physician. Because the need for venoplasty is unpredictable, the case is delayed while an interventionalist is found. A stenotic lesion in the main body of the CS or the lateral wall target vein often prevents placement of the LV pacing lead in the ideal location on the lateral wall of the left ventricle. In other cases, the target vein may be too small or even occluded, preventing access to the desired area on the LV free wall. Venoplasty of the main CS, stenotic target veins, and collateral vessels between two veins can be performed, reducing the need to accept a suboptimal LV lead position.43,44 Percutaneous coronary venoplasty (PCV) is a safe and effective alternative to either implantation failure or accepting a less desirable lead position. The ability to confidently perform coronary vein venoplasty

Wire presses against vein

Not enough support to advance lead

Stiff wire straightens vein

Soft wire follows vein

A

B

Stiff wire straightens vein

Wire presses lead into vein

Lead on “soft” wire

Lead will not advance

C

D

Figure 23-56  Buddy wire used to straighten a tortuous vein segment. A, Vein segment is too tortuous to allow the lead to advance over the wire. B, “Stiff” angioplasty wire is advanced beyond the tortuous segment, straightening the vein. Dotted lines indicate the course of the vein before it was straightened by the stiff wire. C, The pacing lead is advanced over the stiff wire but becomes stuck as the lead is forced into the roof of the vein. D, The stiff wire is left in place to straighten the vein, becoming the buddy wire. The pacing lead is delivered over a second, softer wire, the tracking wire. To keep the tracking wire and lead centered, one must keep as much tension on the wire as possible without pulling it out of the vein.



23  Interventional Techniques for Device Implantation

657

GUIDE TO SUPPORT AND BUDDY WIRE TO ADVANCE LEAD

Tip delivery guide

Tortuous target vein

Tip of “old” guide cannot be advanced beyond tortuosity

A

B DELIVERY GUIDE PROVIDES THE SUPPORT REQUIRED TO ADVANCE THE LEAD WITH BUDDY WIRE

Buddy wire

Delivery guide

New soft-tip delivery guides can be advanced beyond tortuosity

CS access catheter

C

D

Figure 23-57  Buddy wire used to straighten vein for left ventricular (LV) lead placement. A, The midlateral wall target vein is demonstrated to be tortuous. B, A 9F OD/7F ID renal lateral vein introducer (LVI) is inserted into the target vein through a 9F sheath in the main coronary sinus (CS). A tortuous (or stenotic) segment remains beyond the tip of the guide, preventing the lead from advancing. C, A stiff buddy wire is advanced into and straightens the target vein. The pacing lead is tracked over a floppy angioplasty wire. Both wires are introduced directly into the target vein through the renal LVI. D, The combined effect of the buddy wire and the support provided by the LVI is enough to advance the lead beyond the tortuous area into a stable position.

658

SECTION 3  Implantation Techniques

VENOPLASTY FAILS WITHOUT GUIDE SUPPORT

CS access catheter 3-mm balloon across stenosis

Stenotic area

A

B No delivery guide Tip of CS access catheter not in vein

CS access catheter

Lead will not advance

Balloon inflated no waist

C

D

Figure 23-58  Venoplasty fails because of lack of guide support. A, The stenotic area of the vein is identified as vein selector delivers the wire. B, After the pacing lead fails to advance, a 3-mm balloon is placed across the narrowing. CS, Coronary sinus. C, The balloon is inflated to 15 atm with elimination of the waist, indicating that the stenosis is eliminated. D, Despite successful balloon dilation, the pacing lead does not advance. Venoplasty has failed because of the lack of delivery guide support. This situation requires a preformed directional guide for success.



23  Interventional Techniques for Device Implantation

659

VENOPLASTY FAILS WITHOUT TIP OF DELIVERY GUIDE IN THE VEIN

LV lead will not advance

Balloon fully inflated no waist

Target vein

No delivery guide

Tip of CS access catheter

A

B

C

Figure 23-59  Venoplasty using CS access catheter fails. A, The target vein is shown. B, There is no residual stenosis when the 3-mm balloon is inflated to 16 atm. C, The left ventricular lead (Attain 4193 pacing lead, Medtronic) will not advance from the coronary sinus (CS) access catheter over the wire into the target vein. Venoplasty fails to allow LV lead placement because a delivery guide is not inserted through the CS access catheter into the target vein.

Figure 23-60  Successful venoplasty of a tortuous stenotic vein with delivery guide support (hockey stick lateral vein introducer [LVI]). A, The origin of the vein is tortuous, as indicated by the double density of the coronary sinus (CS) near the origin of the vein (arrow) and the course of the vein beyond the CS. B, A thirdgeneration, preformed guide, selected to place the tip beyond the tortuous segment, is advanced over a wire into the CS above the vein. As the guide is withdrawn and contrast material puffed in, the vein is identified. The wire is advanced from the guide into the vein. Neither the guide nor the left ventricular (LV) lead advances into the vein. A stenosis is identified at the origin of the vein (arrow). C, A stiff second wire is added to straighten the vein (buddy wire). The lead still will not advance. A 30-mm balloon is centered at the os and inflated. As the balloon deflates, the preshaped guide advances into the vein.  D, The tip of the guide is beyond the tortuous and stenotic segment. The LV lead is easily placed.

VENOPLASTY WITH DELIVERY GUIDE SUPPORT

Delivery guide

Tortuous and stenotic vein

A

B Stiff wire beside balloon

LV lead in place

Delivery guide advanced into vein Delivery guide at os of vein

CS access catheter

Focused-force venoplasty

C

D

660

SECTION 3  Implantation Techniques

failure include swelling, edema, and clot formation as well as failure to eliminate the waist. PROCEDURES AND TECHNIQUES TO ENSURE SUCCESSFUL VENOPLASTY Edema vs. Clot Formation In some cases the lead will not advance after venoplasty, despite the absence of a waist, and the lead may not advance as far as it did before venoplasty (Fig. 23-61). If delivery guide position is lost, it may be impossible to reengage the target vein despite using the “push-pull” technique (Fig. 23-62). Long delay between balloon inflation and lead placement increases the risk of failure to deliver the lead. Optimizing Guide Support Optimal guide support is achieved when the tip of a delivery guide is deep in the vein and its back side is supported against the CS. Guide support is always more effective than wire support for advancing the balloon (and leads); thus the fine points of guidewire selection and balloon manipulation are less critical. To ensure the tip of the delivery guide enters the vein, the following procedure should be used: 1. Obtain stable CS access with a catheter lumen large enough to accept the delivery guide for the selected lead. The internal

diameter of the CS access catheter must be large enough to accept the outside diameter (OD) of the delivery guide: 4F leads require a 6F-OD delivery guide, 5F leads require a 7F-OD delivery guide, and 6F leads require a 9F-OD delivery guide. There are no 8F-OD delivery guides currently available. 2. A 5F vein selector is telescoped inside the delivery guide and the pair advanced into the CS until the tip of the delivery guide reaches the tip of the CS access catheter. 3. The vein selector is advanced beyond the tip of the CS access catheter/delivery guide and rotated laterally to locate and engage the target vein with puffs of contrast. 4. Using the vein selector for direction and support, two hydrophilic .014-inch angioplasty wires are advanced into the target vein and, if possible, into an adjacent vein through collaterals. The first wire is “floppy” (ChoICE PT Floppy #12160-01, Boston Scientific, Miami), followed by an extra-support wire (ChoICE PT Extra Support #12161-01, Boston Scientific). The floppy wire advances easily and provides direction for the extra-support wire. The hydrophilic coating makes it easier to advance the leads distally through collaterals to an adjacent vein. 5. The vein selector is advanced to a stable position over the two wires. 6. The delivery guide is advanced into the vein over the double-wirestabilized vein selector rail. It may be necessary to rotate the tip of

Phrenic pacing

Target vein

A

B

Venoplasty distal

C

Venoplasty proximal

D

Figure 23-61  Venoplasty fails because of edema or clot formation. A, Target vein is seen. B, A 5F left ventricular (LV) lead is placed, but there is phrenic pacing. C, Venoplasty of the distal vein is performed. D, “Push-pull” technique is used in an attempt to advance the guide further into the vein. Despite having the tip of the delivery guide well within the target vein, the lead would not advance. Attempts to advance the lead displaced the guide, which could not be inserted back into the vein despite “push-pull.” After venoplasty and loss of guide position, the tip of the lead would not even advance into the os of the vein, where prior to venoplasty, it easily advanced into the proximal vein (A).



23  Interventional Techniques for Device Implantation

Delivery guide “pushed” forward (advanced)

Balloon inflated with tail proximal to stenosis

Delivery guide

661

Balloon partially deflated and “pulled” into guide

Delivery guide in

Balloon tail

Guide tip

Balloon tail

Stenosis CS access

A

CS access catheter recoils back

B Delivery guide is “pushed” (advanced) as balloon is deflated and “pulled”

D

Continue to “push” delivery guide

C Delivery guide is “pushed” (advanced) as balloon is deflated and “pulled”

E

Delivery guide is “pushed” (advanced) as balloon is deflated and “pulled”

F

Figure 23-62  “Push-pull” technique to ensure tip of delivery guide beyond stenosis. A, Tip of the guide is proximal to the stenosis. The balloon is inflated with the tail proximal to the stenosis. B, Coronary sinus (CS) access guide is displaced back as the delivery guide is advanced (”pushed”) into the vein. C, Balloon is partially deflated as it is withdrawn (“pulled”) into the delivery guide. Forward pressure (“push”) is maintained on the delivery guide. D, Balloon is withdrawn into the delivery guide. E, Guide and balloon move forward into the vein. F, Tip of the delivery guide is deep in the target vein well beyond the obstruction.

the delivery guide slightly to ensure that it is coaxial as it enters the vein os. 7. With the delivery guide in place, the vein selector is removed, retaining the two wires. 8. The balloon is advanced over the floppy wire as far distally as the lead might need to be placed when inflated to rated burst. 9. The balloon is deflated and withdrawn until the tip overlaps the former position of the tail, then is reinflated to rated pressure. 10. The tip to tail deflation/inflation process is continued until the tail of the balloon reaches the tip of the guide. In some veins with difficult angulations, it may be necessary to use the balloon anchor technique to engage the delivery guide. Push-Pull Technique to Gain Guide Support.  It may not be possible to advance the tip of the delivery guide into very small veins or veins with a stenosis at the os before the balloon is advanced. The “pushpull” technique is used to advance the tip of the delivery guide into the target vein and is implemented as follows (see Fig. 23-62): 1. After venoplasty of the vein body as necessary, the balloon is withdrawn and the os dilated. 2. The balloon is then advanced until the tail of the balloon is at the os of the vein and inflated to nominal pressure. 3. While attempting to advance the guide (“push”) and keeping traction on the balloon (“pull”), the balloon is deflated gradually.

When the diameter of the balloon and internal diameter of the guide match, the balloon will pull into the guide and the guide will advance over the balloon. Step 3 may need to be repeated several times until the tip of the guide is secure within the vein (see legend of Fig. 23-62 for additional details). The tip of the guide serves as a temporary stent to ensure the lead will advance. Failure to advance the delivery guide into the vein using the “push-pull” technique greatly reduces the possibility of successful lead delivery. Focused-Force and Cutting-Balloon Venoplasty Because of the pericardial scar tissue and clips found in patients with prior cardiac surgery, it is not surprising to find stenotic coronary veins. However, one third of our venoplasty experience is in patients without prior surgery. Even more surprisingly, we found stenotic veins that resisted a noncompliant balloon taken to rated burst pressure in patients without prior cardiac surgery. Figure 23-63 is one of our PCV failures before we used focused-force venoplasty. When there is a persistent waist despite inflation to rated burst pressure (Fig. 23-64, A), a stiff wire is placed beside the balloon (Fig. 23-64, B) to augment the effect by forcing the wire into the tissue, eliminating the stenosis78 (Fig. 23-64, C). Inflating a balloon against a stiff wire is referred to as focused-force venoplasty (Figs. 23-64 and 23-65). Because it is impossible to predict when focused force will be needed, and because it may be difficult to add a second wire once a balloon has been inflated, we

662

SECTION 3  Implantation Techniques

Box 23-7 

KEY ELEMENTS OF CORONARY VEIN VENOPLASTY 1. Tip of guiding catheter must be in vein branch, must be secure, and must provide support to push balloon out. 2. Start with balloon as far distal as proximal. 3. Balloon should be noncompliant and rapid exchange.* 4. Typical length is 14 to 16 mm, and from 2 mm (4F leads) to 3 mm (6F leads) with duration of inflation until “waist” eliminated and pressure stable. 5. Balloon is sized to the lead, not the vein. 6. Focused-force venoplasty if waist does not go away. 7. Again, must perform a series of inflations moving the balloon proximally. 8. Tip of delivery guide must be in vein branch and must be secure to provide support to advance left ventricular (LV) lead. 9. Use “push-pull” technique to ensure tip of guide is in the vein.

Residual waist

*When using a balloon in the coronary sinus or coronary vein as an anchor, the balloon should be compliant.

USE OF CORONARY VENOPLASTY TO FACILITATE LEFT VENTRICULAR LEAD PLACEMENT Venoplasty of Main Coronary Sinus Figure 23-63  Persistent stenosis in a patient without prior openheart surgery. The 30 × 18–mm PowerSail balloon (Guidant, Boston Scientific, Natick, Mass) is inflated to 18 atm. The stenosis is not eliminated, as indicated by the residual indentation (arrow) in the balloon.

recommend always starting venoplasty with a stiff wire beside the balloon. In some cases, focused-force venoplasty is not effective, and a cutting balloon is required79 (Fig. 23-66). Although we use focusedforce venoplasty freely in patients without prior cardiac surgery, we have not used a cutting balloon. Box 23-7 outlines key elements of coronary vein venoplasty.

On occasion, a fixed stenosis in the main CS completely prevents advancement of the pacing lead. Balloon venoplasty is used to relieve the stenosis and permit lead placement. To move the wire past the stenosis, we use a 4F to 6F left vertebral catheter (“vert”) or multipurpose catheter passed through the CS access to provide additional wire support and direction. With the small catheter beyond the stenosis, contrast material is injected to confirm wire position before balloon dilation. Figure 23-67 shows a patient without prior OHS who has a high-grade stenosis in the proximal main CS that prevents the pacing lead from reaching the target vein. After dilation with a peripheral balloon 6 mm in diameter and 4 cm long, the CS access catheter is

FOCUSED FORCE VENOPLASTY 25 atm

20 atm

25 atm

2nd wire

Waist

Waist

A

B

Waist eliminated

C

Figure 23-64  Persistent waist eliminated by means of focused-force venoplasty and noncompliant balloon. A, Waist remains despite inflation of a noncompliant balloon to 20 atm (PowerSail, Guidant, Indianapolis) and then inflation of an ultra-noncompliant balloon to 25 atm (NC Monorail Balloon, Boston Scientific, Natick, Mass). B, Using a vein selected, a stiff second wire is advanced beyond the stenosis. The NC Monorail is then advanced and inflated on the softer wire. The stiff angioplasty wire beside the balloon augments the effect of the balloon on the waist. C, The waist is eliminated at 25 atm.



23  Interventional Techniques for Device Implantation

663

FOCUSED-FORCE VENOPLASTY OF COLLATERAL BETWEEN VEINS

2 wires Balloon wire

Collaterals to target vein

2nd wire beside balloon

A

B

Figure 23-65  Focused-force venoplasty of collaterals between veins. A, Collaterals are seen between a low posterior lateral vein and a lateral wall vein. Phrenic pacing prevented use of the lower vein, and it was not possible to enter the superior vein antegrade. B, Two wires are advanced into the upper vein and back into the coronary sinus (CS). The balloon is inflated on the floppy wire against the stiff wire. Because it can be difficult to advance a second wire after initial balloon inflation, and it is impossible to predict when focused-force venoplasty will be needed, it is wise always to place two wires before inflating the balloon.

CUTTING BALLOON FOR REFRACTORY CORONARY VEIN STENOSIS

Waist in 3-mm balloon

Waist in 3-mm balloon

A

B

Delivery guide

2-mm cutting balloon

C

LV lead

D

Figure 23-66  Cutting balloon used to open stenotic target vein. A, The only lateral wall target vein is selectively engaged with an improvised renal-shaped delivery guide (8F Vistabritetip RDC-1, Cordis). Contrast material is injected to confirm the location and proper position of the guide. B, The 3.5 × 23–mm PowerSail balloon (Guidant) is inflated to 20 atm without relief of the stenosis (arrow). C, A 2.5 × 10–mm cutting balloon (Boston Scientific) is inflated to 8 atm at the site of stenosis (arrow). D, With the PowerSail balloon inflated to 18 atm, the stenosis is no longer seen (arrow).

664

SECTION 3  Implantation Techniques

advanced beyond the occlusion and the lead delivered through a guide. Figure 23-68 is an example of venoplasty of the mid-CS in a patient with previous mitral valve replacement using a 4-mm coronary balloon. Venoplasty after Previous Left Ventricular Lead Placement Left ventricular lead fixation in a coronary vein may be the cause and result of thrombosis.80 Thus, venoplasty is often essential to avoiding the epicardial approach when a lead needs to be replaced and after dislodgement or extraction. Replacement of in situ Leads.  As with all leads, LV leads have a finite life span. When a lead fails after many years and the patient has responded, it is desirable to add a second lead to the same vein if possible. However, the vein is frequently occluded or stenotic (Fig. 23-69). Venoplasty enables the new lead to be placed in the same vein as the failed lead (Fig. 23-69, D). High thresholds or phrenic pacing also result in the need to replace the LV lead. During the first year after implant, it is tempting to extract the lead over a wire to preserve venous access; however, removing the lead will likely result in loss of the vein as a potential target. When the lead is left in place, it identifies the

location of the os. Once identified, a vein selector can probe the os around the lead to locate an opening to place a wire in the vein. When the lead is removed first, the vein usually occludes or is so stenotic that it may be impossible to locate the opening with a vein selector. Once a wire is down the vein, the lead can be removed to make way for a new lead and/or venoplasty performed. Replacement of Extracted or Dislodged Lead.  Left ventricular leads are often easy to extract. However, when leads have been in place for over 3 months, partial or total occlusion of the main CS and target veins is common.81 Using venoplasty, Zucchelli et al.82 reported successful LV lead implantation despite subtotal occlusion after lead extraction. Figures 23-70 to 23-73 illustrate the importance of venoplasty following lead extraction, where venoplasty of the main CS and the original target vein was required to avoid a surgical epicardial lead. Note that a 6-mm balloon was required to open the main CS. Venoplasty of Small or Stenotic Target Veins Figure 23-74 depicts the use of PCV to enlarge a diffusely small and stenotic vessel in a patient with prior heart surgery. Occlusive CS Text continued on page 671

6-mm x 4-cm balloon inflated to 10 atm

Vein selector

Stenosis

A

C

B

AP

LAO

D

Figure 23-67  Balloon venoplasty of the main coronary sinus without prior open-heart surgery. A, Contrast injection at coronary sinus (CS) cannulation reveals a high-grade stenosis in the proximal CS. A hydrophilic 5F left vertebral diagnostic catheter (vert) is advanced through the CS access catheter to the stenosis and used to direct a wire through the obstruction. B, LAO projection of the balloon is shown inflated to 10 atm in the proximal CS with elimination of the waist. C, AP projection of the same balloon position as in B. D, Balloon is inflated in the mid-CS. As the balloon is deflated and pulled back the CS access catheter is advanced (pushed) over the deflating balloon into the CS.



23  Interventional Techniques for Device Implantation

665

VENOPLASTY OF STENOSIS IN MID CS

Stenosis before venoplasty

Stenosis

A

B

4-mm balloon inflated

C

After venoplasty

D

Figure 23-68  Balloon venoplasty of main coronary sinus. A, The stenosis can be seen on the left anterior oblique projection. B, On anteroposterior projection, the lateral wall target vein is at the 2-o’clock position on the mitral valve ring (arrow). C, A 4-mm balloon is inflated at the site of the stenosis. The proximal and distal ends of the balloon are indicated by arrows. D, Site of stenosis after balloon angioplasty.

666

SECTION 3  Implantation Techniques

VENOPLASTY TO ADD LEAD TO SAME VEIN

Delivery guide

Stenosis Balloon

Old lead

A

CS access catheter

B

Tip of delivery guide Old lead New lead New lead

C

Old lead

D

Figure 23-69  Venoplasty to add second left ventricular lead to same target vein. A, Target vein containing the old LV lead is stenotic. No other veins are available for lead placement. B, Delivery guide is in the target vein over the balloon beyond the stenosis. C, Contrast injection through the delivery guide does not reflux around the guide. D, New LV lead is in the same target vein as the old LV lead.



23  Interventional Techniques for Device Implantation

667

LEAD DISLODGED 14 MONTHS AFTER INITIAL IMPLANT Initial implant

Target vein

A

B CS occluded beyond low posterior vein

CS fills retrograde from contrast injection in low posterior vein Previous target vein

Occlusion Guide

Phrenic pacing

C

D

Figure 23-70  Venoplasty of coronary sinus and target vein after left ventricular lead displacement: part 1. A, The occlusive coronary sinus (CS) venogram reveals the target vein. B, The LV lead is in place. C, At 14 months after implant, contrast injection reveals the CS is obstructed just distal to a large, posterior lateral branch. D, Contrast injection in the posterior lateral branch fills the CS retrograde. The original target vein is small and stenotic. The LV lead cannot be placed in the posterior lateral vein because of phrenic pacing.

668

SECTION 3  Implantation Techniques

VENOPLASTY OF THE CORONARY SINUS 3-mm x 21-mm balloon inflated to 18 atm

A

B VENOPLASTY OF THE CORONARY SINUS 6-mm x 4-cm balloon inflated to 14 atm

Waist

C

D

Figure 23-71  Venoplasty of coronary sinus and target vein after left ventricular lead displacement: part 2. A and B, Venoplasty was initially performed using a 3-mm coronary balloon; however, the coronary sinus (CS) access catheter would not advance into the CS. C and D, The CS was dilated with a 6-mm peripheral balloon, after which the CS access catheter was advanced.



23  Interventional Techniques for Device Implantation

669

DIFFICULT TO ADVANCE TO TARGET VEIN

Vein selector

Wire

Vein selector

Delivery guide

Delivery guide

Wire

A

CS access catheter

CS access catheter

B

Guide to the os of target vein

Inject contrast

Delivery guide Delivery guide

Wire CS access catheter

Stenotic target vein

CS access catheter

C

D

Figure 23-72  Venoplasty of coronary sinus and target vein after left ventricular lead displacement: part 3. A, The 5F vein selector and delivery guide are introduced into the coronary sinus (CS) after venoplasty. B, The original target vein was identified and cannulated using contrast injection through the 5F vein selector. C, Using the double-wire-stabilized vein selector as a rail, the delivery guide is advanced to ostium of the target vein and the vein selector removed. D, Contrast injection through the delivery guide demonstrates the target vein that is small and stenotic compared to before implant (see Fig. 23-70, A).

670

SECTION 3  Implantation Techniques

VENOPLASTY OF PREVIOUS TARGET VEIN

Waist

A

Start distal

B

Move proximal Guide support to deliver lead

Delivery guide Delivery guide

“Push-pull” until guide tip in vein

C

D

CS access catheter

Figure 23-73  Venoplasty of coronary sinus and target vein after left ventricular lead displacement: part 4. A, The 3 × 15–mm balloon is inflated to 18 atm as far distal as possible until the waist is eliminated and the pressure stable. B, Dilation must start distally because once the balloon is inflated its profile increases and it may not advance further. C, Balloon is inflated near the os. Once the os is dilated, the balloon is advanced a few millimeters back into the vein and inflated. As the balloon is deflated, the guide is pushed into the vein and the balloon pulled out in an attempt to advance the tip of the guide into the vein. The process may need to be repeated several times until the tip of the guide is secure in the vein. D, The LV lead is placed using support from the delivery guide.



23  Interventional Techniques for Device Implantation

671

Delivery guide Small stenotic vein

Waist in balloon

CS access catheter

A

B Delivery guide

Delivery guide Balloon up no waist

C

Vein after venoplasty

Wire

D

Figure 23-74  Diffusely small and stenotic vein enlarged with venoplasty in a patient with prior open-heart surgery. A, The only lateral wall target vein (arrow) is too small to permit placement of a left ventricular (LV) pacing lead. B, A 3.5 × 18–mm, noncompliant balloon is inflated in the target vein. A stenotic segment is signified by the indentation in the balloon (arrow) at 15 atm. C, The balloon is inflated to 20 atm, and the stenosis is eliminated (arrow). D, The enlarged target vein is filled with contrast material from the delivery guide in the vein.

venography showed extremely limited options for target veins. A delivery guide was placed at the os of the target vein. The lead would not follow despite the use of a buddy wire. A 3-mm balloon was advanced and inflated to 20 atm. The “bone” indicating residual stenosis was eliminated. Contrast injection showed that the target vein was large enough to accept the lead, which was easily placed and yielded a pacing threshold of 0.8 V at 0.5 msec without phrenic pacing. Figures 23-75 and 23-76 illustrate venoplasty of a diffusely small and stenotic vein in a patient without previous cardiac surgery. Given the size of the balloon (2.5 mm) relative to the vein (<1 mm), dissection of the vein is likely in such patients, but we have not observed adverse effects. In these cases the lead is presumably between the visceral pericardium and the myocardium. Venoplasty of Branch Veins to Avoid Phrenic Pacing When phrenic pacing and high thresholds are encountered along the length of the target vein, placement of the LV lead in a branch vein can solve the problem. However, in many cases the branch veins are too small to accept the lead. Fortunately, the branch veins can be dilated to accommodate the LV lead (Figs. 23-77 and 23-78). In some cases the LV lead may actually enter the pericardial space (Figs. 23-78 and 23-79).

Venoplasty of Collaterals Between Two Adjacent Veins for Retrograde Left Ventricular Lead Placement When a vein cannot be entered antegrade, it can often be entered retrograde by dilating the collaterals between an adjacent vein and the target vein.83 Hydrophilic angioplasty wires frequently pass from one vein to another through a collateral vessel and reenter the CS through the second vein. In patients with previous OHS, these collaterals are freely used to reach the target area. Figure 23-80 demonstrates the dilation of the venous collateral between the posterior lateral and midlateral coronary veins. Previous attempts to place an LV lead on the lateral wall in the patient had failed because of phrenic pacing, high pacing thresholds, and limited access. When the collateral is too small or stenotic (Fig. 23-81, A) that a 2.5- to 3.0-mm balloon will not advance (B), the vein is first dilated with a smaller, 1.5-mm balloon (C), followed by a balloon that is large enough to allow the lead to advance. When attempting to enter a vein retrograde through its collaterals, it is critical that the delivery guide be either in or close to the dilated collateral. Figures 23-82 to 23-85 illustrate the importance of advancing the tip of the delivery guide up to (and preferably into) the collateral. Although we primarily dilate collateral vessels in patients with previous heart surgery, there are situations in which the collaterals are large Text continued on page 681

672

SECTION 3  Implantation Techniques

VENOPLASTY OF SMALL STENOTIC VEIN NO PRIOR OHS

Vein selector Target vein

A

B

Delivery guide in target vein

6F LV lead in place

3-mm x 15-mm balloon

C

D

Figure 23-75  Diffusely small and stenotic vein enlarged with venoplasty in patient without prior open-heart surgery. A, Small target vein is too small for even a 4F lead. B, The vein selector is used to locate and cannulate the vein. C, The vein is dilated and the delivery guide advanced into the vein using the “push-pull” technique. D, The 6F left ventricular (LV) lead is in place.



23  Interventional Techniques for Device Implantation

673

Vein selector Target vein Target vein

Delivery guide Phrenic pacing Phrenic pacing

A

Delivery guide

C

B

Lead “in” target vein

2.5-mm x 15-mm balloon inflated to 18 atm

D

Figure 23-76  Venoplasty of very small target vein in a patient without prior heart surgery. A, Phrenic pacing was found in the two inferior lateral wall target veins. B, Upper lateral wall vein was engaged with a vein selector, and two wires advanced, followed by venoplasty (C) and insertion of the lead where there was no phrenic pacing (D).

674

SECTION 3  Implantation Techniques

Phrenic pacing

3-mm x 15-mm balloon 18 atm in branch vein Branch vein

A

B

Branch vein after venoplasty

C

Lead in branch vein no phrenic pacing

D

Figure 23-77  Venoplasty of branch vein to avoid phrenic pacing. A, Target vein and a small branch vein are seen. There is phrenic pacing along the target vein. The left ventricular (LV) lead is too large to fit in the branch vein. B, Venoplasty of the branch vein is performed to allow the LV lead to advance. C, Branch vein is larger after venoplasty. D, The LV lead is advanced into the branch vein where there is no phrenic pacing.



23  Interventional Techniques for Device Implantation

675

GUIDE USED TO STENT VEIN OPEN

LV lead

Delivery guide

Balloon Guide back

Guide pulled to balloon Lead stops despite full balloon inflation

A

B

Balloon

C

LV lead

Guide advanced into vein over balloon beyond resistance

“Push-pull” technique to advance guide

Guide in vein

D

E

F

Figure 23-78  Venoplasty to avoid phrenic requires “push-pull” technique to advance guide into small branch. A, The 3-mm balloon is inflated in a small branch to the lateral wall off the large posterior branch, with an Attain 6218 guide (Medtronic). B, Despite full balloon inflation in the small branch, the Attain 4193 pacing lead (Medtronic) will not track over the wire. Attempts to advance the lead caused the guide to back out.  C, The 3.5-mm balloon is inflated in the small branch and used as an anchor. The guide is pulled toward the balloon. D, Guide is pulled over the balloon into the dilated branch. E, Balloon is deflated and removed. The tip of the guide is turned up into the vein. F, With the tip of the guide beyond the area of difficulty, the larger lead (Attain 4194) will advance.

676

SECTION 3  Implantation Techniques

Retrograde filling into CS

Branch veins Branch vein

Phrenic pacing

A

B

Delivery guide

Vein selector

Wire retrograde into the CS

2.5-mm x 15-mm balloon

LV lead in place no phrenic pacing

Delivery guide

C

D

LAO

Figure 23-79  Venoplasty of branch vein to avoid epicardial lead in patient with previous implant failure. A, Phrenic pacing was found all along the target vein. B, The 5F vein selector is used to engage the branch vein and insert two .014-inch angioplasty wires. C, Branch vein is dilated with a 2.5-mm balloon. One of the angioplasty wires is seen to enter the coronary sinus (CS) retrograde through an adjacent vein, indicating that it is not intramuscular. The delivery guide is advanced into the branch vein as the balloon is deflated. D, The left ventricular (LV) lead is in place through the branch vein. The tip of the lead did not pace and appeared to be free in the pericardial space. The proximal pole was stable and captured at less than 1 volt without phrenic pacing.



23  Interventional Techniques for Device Implantation

New target

Phrenic pacing (P)

Contrast enters CS

P P

No phrenic

P Transit catheter insulates wire

Phrenic pacing

Inject contrast via delivery guide to find new target vein

A

677

Wire

Delivery guide

B

Test for phrenic pacing No phrenic pacing

Wire in CS

Delivery guide

Wire in new target LV lead

Balloon

Dilate collateral and new target vein

C

D

Delivery guide

Figure 23-80  Angioplasty of collateral vein in a patient with previous open-heart surgery. A, Selective injection reveals the collateral vein connecting the posterior lateral coronary vein to the lateral vein (arrows). Contrast material injected into the posterior lateral vein can be seen entering the coronary sinus (CS) through the lateral vein as a blush at the upper arrow. The lateral wall target vein could not be entered from the CS. Before proceeding with angioplasty of the collateral vein, the operator test-paced the target area with a Luge angioplasty wire insulated except at the tip (Pressure Products, San Pedro, Calif) and a Transit infusion catheter (Cordis, Miami). B, The Luge angioplasty wire (wire) covered with the Transit catheter is directed into the collateral vein to confirm pacing without phrenic stimulation before balloon dilation. The distal marker of the Transit catheter is indicated by the white arrow. The exposed, electrically active segment of the wire is distal to the tip of the Transit catheter. Pacing with this device establishes where phrenic pacing is a problem (indicated by P). The Transit catheter was then removed, leaving the angioplasty wire in place. C, The angioplasty wire (arrows) that starts in the posterior lateral vein returns to the CS through the lateral vein via collateral vessels. A 3.5-mm balloon is advanced into the collateral vein and inflated to 18 atm to create a channel for the pacing lead. The area of phrenic pacing, marked with a P, was not dilated. D, The left ventricular pacing lead is advanced into position, capturing at 0.5 V without phrenic pacing at 10 V.

678

SECTION 3  Implantation Techniques

Find new target CS

2.5-mm balloon will not advance New target Wires enter CS

Collateral Phrenic Delivery guide

Balloon

Contrast injected via delivery guide

A

B Predilate with 1.5-mm balloon

CS access 1.5-mm balloon

Dilate with 2.5-mm balloon

CS access

Delivery guide

Delivery guide

C

2 wires

D

Balloon

Figure 23-81  Small, low-profile (1.5 mm) balloon may be required to predilate a very small or stenotic vein to allow larger (2.5-3.0 mm) balloon required for leads to advance. A, Collaterals between the two veins are seen with contrast injection of the posterior lateral vein. The upper vein fills retrograde. B, Two wires, one stiff and one floppy, have been advanced retrograde into the coronary sinus (CS) from the posterior lateral vein to the upper vein through collaterals. The 2.5-mm balloon will not advance. C, A 1.5-mm balloon is advanced and inflated. D, The 2.5-mm balloon is inflated and the guide advanced to allow a 5F lead to be advanced.



23  Interventional Techniques for Device Implantation

679

UNABLE TO ADVANCE LEAD ANTEGRADE

Vein selector in target vein

Target vein

CS access catheter Delivery guide in CS access

Middle cardiac vein collaterals to target vein

A

B OPTIONS: 1. VENOPLASTY FOR RETROGRADE OR 2. SNARE FOR ANTEGRADE

Delivery guide in CS access

CS access catheter

C

Wire in target vein

Wire in CS retrograde can be snared for antegrade approach

D

Figure 23-82  Failed antegrade and difficult retrograde left ventricular lead placement; push-pull to advance delivery guide: part 1. A, Acute takeoff of the target vein is apparent. There are well-formed venous collaterals between the middle cardiac vein (MCV) and the target vein. B and C, Using the vein selector, a wire is advanced into the target vein. The 5F ID/7F OD delivery guide (SafeSheath Worley, Telescopic Braided Series, Renal LVI/75-5-66-55-RE) is within the 9F-ID CS access catheter (SafeSheath CSG, Braided Core Worley-STD/BCor-1-09, Pressure Products). Despite using the vein selector supported by two wires in the vein as a rail and balloon-anchoring technique, the LV lead will not advance. D, Vein selector in the MCV is used to advance wires through the collaterals into the MCV and out into the coronary sinus (CS). The tortuous collaterals from the MCV to the lateral wall target vein are well seen in A. With the wires in the CS, there are two options for placement of the LV lead: (1) use a snare to pull the distal end of the wire into the CS access catheter and advance the lead antegrade into the vein, or (2) dilate the collaterals and enter the vein retrograde. We were not familiar with the snare technique when this case was performed.

680

SECTION 3  Implantation Techniques

Target vein Collateral from MCV to target vein

A

Middle cardiac vein

Delivery guide will not advance Balloon in collaterals

Delivery guide

CS access catheter

B Figure 23-83  Failed antegrade and difficult retrograde left ventricular lead placement; push-pull to advance delivery guide: part 2. A, Well-developed collaterals between the middle cardiac vein (MCV) and the lateral wall target vein are well seen. B, A 2.5 × 14–mm, noncompliant coronary balloon is inflated in the collaterals between the two veins. The 5F ID/7F OD delivery guide (SafeSheath Worley) is telescoped out of 9F-ID coronary sinus (CS) access catheter (SafeSheath CSG) is in the proximal MCV. Despite using a double-wire-supported vein selector as a rail and balloon-anchoring techniques, the delivery guide will not advance farther into the vein. After focused-force head-to-tail venoplasty, without a visible waist between the middle of the target vein and the middle of the MCV, the LV lead will not advance.

“PUSH-PULL” TECHNIQUE TO ADVANCE GUIDE Guide “pushed” as deflating balloon “pulled”

A

Delivery guide

Guide “pushed” as deflating balloon “pulled”

Balloon

B

Balloon

Deflated balloon now “pulled” into guide

Delivery guide “pushed”

C

Delivery guide

Deflating balloon “pulled”

Delivery guide advanced

D

Balloon inside delivery guide

Figure 23-84  Failed antegrade and difficult retrograde left ventricular lead placement; push-pull to advance delivery guide: part 3. To provide better support for advancing the LV lead through the collaterals the “push-pull” technique is used to advance the delivery guide deep into the middle cardiac vein (MCV). A, The 7F OD/5F ID delivery guide in the proximal MCV will not advance into the MCV. The balloon is inflated immediately in front of the guide. B, As the balloon is gradually deflated, the guide is advanced and traction maintained on the balloon. C, When the diameter of the deflating balloon matches the guide’s internal diameter, the guide advances. D, Delivery guide is at the tip of the deflating balloon. The process is repeated until the tip of the guide reaches the collaterals.



23  Interventional Techniques for Device Implantation

Delivery guide serves as a temporary stent of MCV and collateral

Balloon

Delivery guide CS access catheter

A

Wire in CS Lead Delivery guide

B

CS access catheter

Figure 23-85  Failed antegrade and difficult retrograde left ventricular lead placement; push-pull to advance delivery guide: part 4. A, Tip of the delivery guide is advanced into the collaterals using the “push-pull” technique. CS, Coronary sinus. B, The left ventricular (LV) lead is advanced. The delivery guide serves as a temporary stent for the middle cardiac vein (MCV) and collateral vein.

enough to be dilated in patients without prior cardiac surgery (Fig. 23-86). Venoplasty with Stent Placement A stent can be placed in a vein beside the lead to trap the lead against the wall of the vein, preventing repeated dislocation.84,85 Stents can also be deployed in the coronary veins if the LV lead will not advance because of vessel occlusion or dissection after venoplasty.86,87 A tortuous vein segment can usually be overcome by advancing the delivery guide over the rail created by two wires (buddy wire) and a vein selector. However, in some cases the vein may be folded back on itself because of prior surgery, particularly mitral valve ring, repair, or replacement. In these cases, a stent may be required to straighten the vein long enough to allow the pacing lead to pass. Figures 23-87 and 23-88 demonstrate a case in which the target vein was folded back on itself and required a stent to place the lead. A frequently asked question is, “What happens to the vein after venoplasty?” In the patient shown in Figure 23-89, initial placement of the LV lead required PCV with a 3.0-mm balloon. The LV lead became dislodged. Six days later, a second occlusive CS venogram demonstrated a widely patent vein. With the use of a delivery guide (9F “renal” lateral vein introducer), a larger, more stable LV lead was placed. Loss of Venous Integrity Associated with Venoplasty The process of delivering a lead using venoplasty can result in loss of venous integrity through the following mechanisms: 1. The vein can tear when the balloon size exceeds the ability of the vein to expand. 2. The vein can be perforated when a balloon is overinflated and ruptures.88 3. The vein can be torn or perforated in the process of advancing the delivery guide into the vein. 4. The vein can be perforated by advancing the lead through a vein stretched by venoplasty.

681

Clinical significance depends on the size and location (proximal or distal) of the disruption, as well as the pressure gradients. Unless there is a clinical event or contrast is injected, venous disruption will go undetected. Contrast injection after venoplasty reverses the normal venous pressure gradient, potentially forcing contrast through a clinically insignificant opening in the vein. In our early experience with venoplasty, we occasionally injected contrast and in some cases found the vein intact but enlarged (Fig. 23-90), and in other cases, contrast exited the vein. In patients with previous cardiac surgery, adhesions limited the spread of contrast, as expected (Fig. 23-91). When a balloon bursts from exceeding the rated burst pressure, the contrast in the balloon defines the dissection or rupture (Fig. 23-92), even if contrast is not injected; in this case the lead was successfully placed without hemodynamic consequence as well. The scar tissue that develops around the heart after cardiac surgery limits the bleeding from the low-pressure venous system. We have not seen tamponade in any patient with OHS undergoing coronary vein venoplasty. We do not routinely inject contrast following coronary venoplasty in patients with previous cardiac surgery; forcing contrast into a vein after venoplasty may create or exacerbate loss of venous integrity. In patients without prior cardiac surgery, loss of venous integrity usually allows contrast to be forced freely into the pericardial space (Fig. 23-93); however, development of tamponade is rare. In our experience, one patient without prior cardiac surgery developed tamponade, and we are aware of a second case at another institution. In both cases the pericardium was drained successfully, and the patients had no lasting adverse effects. When injected after venoplasty, contrast may be contained under the visceral pericardium (Fig. 23-94), rather than flowing freely into the pericardial space. As with OHS patients, we do not routinely inject contrast after coronary venoplasty in patients without previous cardiac surgery; again, forcing contrast into a vein after venoplasty may cause or expand loss of venous integrity. Inflation of Balloon in Myocardium When a hydrophilic wire is advanced beyond the body of the vein, it usually stays in the collaterals on the pericardial surface. In one case the wires did not remain on the surface, and the balloon was advanced and inflated in the myocardium, resulting in pain and increased cardiac enzymes (Fig. 23-95). To ensure they have remained on the epicardium, the wires should enter the CS via an adjacent vein through surface collaterals. Conclusion As illustrated in Figures 23-96 and 23-97, with the persistent use of vein selectors, delivery guides, and the venoplasty techniques described here, successful placement of the LV lead on the lateral wall is possible in virtually every patient. Although some risk of complication is associated with venoplasty, it seems to be low, with one case of tamponade and one intramyocardial balloon inflation in more than 356 cases. When the risk of venoplasty is compared to the risk of an epicardial lead placement, the risk/benefit ratio for venoplasty seems favorable in many patients. Box 23-8 lists equipment for coronary vein venoplasty. USING ANCHOR BALLOONS TO FACILITATE LEFT VENTRICULAR LEAD IMPLANTATION In the process of implanting a CRT device, the coronary venous anatomy can make a successful implant difficult or impossible. Balloons are used to dilate obstructions in the main CS and in small and/ or stenotic coronary veins to facilitate LV lead implantation. This section describes how balloons can be used as anchors to facilitate initial CS cannulation, assist LV lead placement, and recover venous and CS as well as target vein access.89 Successful implementation of the procedures described next requires the physician to adopt an Text continued on page 693

682

SECTION 3  Implantation Techniques

Contrast injection in adjacent vein Wire back in CS Wire enters CS Target vein

Vein selector directs wire into collateral

Collateral between veins

Delivery guide

A

Collateral before venoplasty

Delivery guide

B Venoplasty of collateral between veins

C Contrast injection via delivery guide

Alternative: snare wire for antegrade approach

LV lead in place

3-mm balloon

Collateral after venoplasty

Delivery guide

D

Contrast enters CS

E

F

Figure 23-86  Angioplasty of collateral vein in patient without previous open-heart surgery. A, Collateral venous structure connects the posterior lateral wall coronary vein to the midlateral vein (arrows). B, Angioplasty wire is placed in the collateral vein using a 5F Bernstein catheter inserted through a 7F ID/9F OD multipurpose lateral vein introducer (MP LVI). C, The 5F catheter is removed over the wire, leaving the LVI in place. Contrast material injected into the posterior lateral vein enters the coronary sinus (CS) retrograde through the lateral vein (the blush at upper arrow labeled CS). D, A 3.0 × 15–mm, noncompliant balloon (PowerSail, Guidant, Boston Scientific) is advanced into the collateral vein and inflated to 12 atm to create a channel for the pacing lead. E, Injection of contrast material shows that the collateral vessel has been enlarged. F, Attain OTW 4193 LV pacing lead (Medtronic) is advanced into position. The lead captured at 0.5 V without phrenic pacing at 10 V.



23  Interventional Techniques for Device Implantation

Tortuous vein

683

Lead will not advance

Delivery guide

A

B Delivery guide Waist in balloon

Lead will not advance after first 3-mm x 18-mm stent

Insertion of 2nd 3-mm x 18-mm stent more proximal in vein

C

D

Figure 23-87  Stent to straighten folded cardiac vein: part 1. A, The tortuous target vein is seen folded back on itself (arrow). B, Despite the use of a buddy wire (see Fig. 23-57) and advancing the 9F OD/7F ID delivery guide (SafeSheath Worley, Renal LVI/75-5-62-07-RE) into the proximal vein, the left ventricular (LV) lead (Quickflex Model 1156T, St. Jude Medical) will not advance. C, Despite placement of a 3-mm × 18-mm stent, the LV lead will not advance. D, Thus, a second 3-mm × 18-mm stent is placed.

684

SECTION 3  Implantation Techniques

“Push” guide as balloon deflates Delivery guide Lead would not advance after second stent; re-dilate with 3.5-mm balloon

A

“Pull” balloon while deflating

B

2 stents

Balloon Delivery guide advances over the balloon into stent

C

D

Figure 23-88  Stent to straighten folded cardiac vein: part 2. When the left ventricular (LV) lead would not advance after placement of the second stent, a 3.5-mm balloon is inflated in the stent (A) and the “push-pull” technique used to advance the tip of the delivery guide into the proximal stent (B and C), after which the LV lead advances (D).

Before venoplasty

A

Before venoplasty

RAO

B

6 days after venoplasty

AP

C

AP

Figure 23-89  Coronary vein before and 6 days after venoplasty. Right anterior oblique (A) and anteroposterior (B) occlusive venograms showing small, stenotic vein (arrow). C, AP occlusive venogram taken 6 days after venoplasty, showing the same vein.



23  Interventional Techniques for Device Implantation

685

CONTRAST INJECTION FOLLOWING VENOPLASTY

Delivery guide Balloon Target vein CS access catheter

A

B Start contrast injection

Guide tip

Guide tip LV lead

Tip of LV lead CS access catheter

C

D

Figure 23-90  Contrast injection after venoplasty in patient with previous cardiac surgery: part 1. A, Target vein is injected selectively. B, When the lead would not advance despite delivery guide support, venoplasty was performed. C, With the tip of the guide advanced into the vein using “push-pull” technique, the LV lead is placed and contrast injected (D), which exits the vein into the pericardial space.

686

SECTION 3  Implantation Techniques

Tip of delivery guide

Guide tip

LV lead

Ring electrode

Tip of lead

CS access catheter

A

B

Guide tip

Ring electrode

Tip of lead

C

D

LAO

Figure 23-91  Contrast injection after venoplasty in patient with previous cardiac surgery: part 2. A, Contrast is injected with the left ventricular (LV) lead in the vein just distal to the tip of the delivery guide. B and C, Contrast spread in the pericardial space is limited by adhesions from previous cardiac surgery. D, Contrast is visible in the left anterior oblique projection when final films were taken. The patient had no apparent acute or late effects from disrupting the integrity of the vein. Contrast is not routinely injected following coronary venoplasty.



23  Interventional Techniques for Device Implantation

687

BALLOON RUPTURE FROM EXCEEDING RATED BURST PRESSURE No clinical consequence

No clinical consequence

Stenotic segment

A

Waist despite exceeding burst pressure

B

Delivery guide beyond stenosis Contrast from balloon rupture

C

D

Figure 23-92  Angioplasty balloon bursts at 24 atm. A, The only viable target vein (arrow) is identified. An improvised, third-generation, renalshaped telescoping guide (8F, 55-cm Vistabritetip RDC-1, Cordis) cannulates the vein. Neither a 4193 nor an Attain 2187 lead (Medtronic) could be advanced into the target vein. B, A 3.5-mm × 18-mm, noncompliant PowerSail balloon (Guidant, Boston Scientific) is inflated to 24 atm without relief of the stenosis (arrow). C, The balloon ruptures from overinflation. Contrast material (arrows) can be seen in the pericardial space, limited by adhesions from prior open-heart surgery. D, After inflation of an NC Monorail Balloon (ultra-noncompliant) (Boston Scientific) to atmospheric pressure, the tip of the guide advances farther into the target vein. An Attain 4193 lead was initially placed, but it was removed because of high pacing thresholds. With the tip of the guide in the vein, an Attain 2187 lead is advanced, yielding a pacing threshold lower than 2 V.

688

SECTION 3  Implantation Techniques

Delivery guide Wire 2

Contrast free in pericardial space

Waist Wire 1

No tamponade CS access

A

B Delivery guide Balloon Contrast free in pericardial space CS access

Tamponade

C

D

Figure 23-93  Rupture of coronary vein without and with hemodynamic sequel. A, There is a residual waist (white arrow) despite focused-force venoplasty (two wires defined by black arrows) at rated burst pressure. CS, Coronary sinus. B, When rated burst was exceeded, the balloon ruptured, and contrast injection through the guide revealed free flow into the pericardial space. There was no hemodynamic consequence, and the lead was placed in a low posterior lateral vein. C, Balloon is taken to rated burst pressure without rupture or residual waist. D, Contrast injection through the guide reveals vein rupture with extensive contrast (between white arrowheads and black arrowheads) in the pericardial space. The patient recovered uneventfully after pericardial drainage.



23  Interventional Techniques for Device Implantation

689

CONTRAST INJECTION FOLLOWING VENOPLASTY

Start injection

Delivery guide in target vein via “push-pull”

Target vein

A

B

Tip of delivery guide

C

Stop injection

1 second after stop injection

D

Figure 23-94  Contrast injection following venoplasty in a patient without previous cardiac surgery. A, Occlusive coronary sinus (CS) venogram reveals a target vein with acute takeoff and a stenosis near its os, in a patient without prior cardiac surgery. B, Contrast is injected, with the tip of the guide advanced into the vein using “push-pull” technique after venoplasty of the stenotic segment. C, With injection, contrast appears outside the vein (arrowheads). D, When contrast injection is terminated, it appears to be contained (arrowheads). The pacing lead was subsequently placed without incident, and the patient had no apparent acute or late effects from disrupting the integrity of the vein. Contrast is not routinely injected after coronary venoplasty.

690

SECTION 3  Implantation Techniques

Phrenic pacing

Phrenic pacing

Branch

A

B Delivery guide

Balloon intramuscular

Vein selector

C

D

Wire intramuscular

Figure 23-95  Inflation of balloon in myocardium. Phrenic pacing was found in both the inferior (A) and the superior (B) lateral wall veins. C, Vein selector was used to advance hydrophilic wires into a branch vein. D, The wires did not pass through collaterals to enter the coronary sinus (CS) through an adjacent vein. When the balloon was inflated, the patient developed pain, and when the lead was returned to the target vein, the thresholds that had been less than 1 V were greater than 10 V. After the procedure, the patient’s cardiac enzymes were elevated, but no abnormalities were visible on echocardiography or cardiac computed tomography.



23  Interventional Techniques for Device Implantation

691

9F delivery guide Vein #2 5F vein selector Hydrophilic wire will not advance

Vein #1

Unable to place lead in vein #1

A

B

C

Delivery guide Wire advanced with vein selector despite total occlusion

Vein #2 total occlusion

3-mm balloon

D

E

F

Figure 23-96  Placement of left ventricular lead despite virtual absence of target veins and presence of phrenic pacing: part 1. A, The occlusive coronary sinus (CS) venogram shows only two lateral wall target veins. The lower of the two (Vein # 1) is small with an acute takeoff. There is a subtotal occlusion in the higher lateral wall branch (Vein # 2). B, The lower branch (Vein # 1) is cannulated with a 5F internal mammary artery (IMA) catheter inside the 9F “renal” lateral vein introducer (LVI) but a hydrophilic wire will not advance deep into the vein. C, The 9F renal LVI (9F delivery guide) is advanced into Vein #1 over the rail created by a vein selector (5F vein selector) stabilized with two angioplasty wires. Despite guide support and attempts at using the balloon anchoring technique the lead would not advance. D, The renal LVI is advanced to the mouth of the higher target vein (Vein # 2). Injection of contrast material confirms the tortuous course of the vein and the subtotal occlusion. E, A 5F Bernstein catheter, used as a vein selector, is inserted through the 9F delivery guide into the vein, and an angioplasty wire is advanced deep into the vein beyond the stenosis. F, The preformed shape of the delivery guide directs the tip laterally into the target vein but is stopped by the stenosis. A 3-mm balloon is advanced across the occlusion and inflated.

692

SECTION 3  Implantation Techniques

Venoplasty #1

Phrenic pacing Branch vein

Tip advanced as balloon deflated

3-mm balloon Delivery guide

Attain 4194

LV lead not stable in branch vein

A

B

C

Venoplasty #2 branch vein

Branch vein after venoplasty

3-mm balloon

LV lead now stable in branch vein

Enlarge branch vein for LV lead

D

E

F

Figure 23-97  Placement of left ventricular lead despite virtual absence of target veins and presence of phrenic pacing: part 2. A, The balloon is inflated in the proximal stenosis with the tip of the “renal” lateral vein introducer (LVI) (guide) directed into the os of the target vein. Because of the shape of the guide, there is lateral pressure at the tip of the guide directing it into the vein. The guide will not advance because of the stenosis. B, Lateral pressure at the tip of the guide (resulting from its preformed shape) advances it into the target vein as the balloon deflates. Injection of contrast material confirms that the tip of the guide is beyond the stenotic segment. C, The Attain 4194 pacing lead (Medtronic) is advanced through the guide into the target vein. Phrenic pacing at outputs of less than 2 V is found in the vein. D, A 3-mm balloon is inflated in the small branch seen in B, black arrow. E, Injection of contrast material confirms that the small branch seen in B is enlarged. F, Left ventricular (LV) pacing lead, an Attain 4193 lead (Medtronic) is placed in the dilated branch vein, where phrenic pacing is not encountered.



23  Interventional Techniques for Device Implantation

Box 23-8 

CORONARY VEIN VENOPLASTY EQUIPMENT 6-French (6F) left ventricular (LV) leads: 3.0 × 15 mm, noncompliant balloon dilation catheter (NC Sprinter or Voyager NC or Quantum Apex Monorail) 4F-5F LV leads: 2.5 × 15 mm, noncompliant balloon dilation catheter (NC Sprinter or Voyager NC or Quantum Apex Monorail) Inflation device Miscellaneous: Three-way stopcock 12-inch extension 30-mL syringe (to pull negative pressure for balloon preparation) Y adapter with Luer lock Small bowl for mixing contrast, 50/50 (contrast/saline) See Interventional Equipment List at the end of Chapter 22 and online for details and ordering information.

interventional approach to device implantation and pay attention to the ergonomics of the implant, as described earlier in the chapter.

693

as an anchor to augment the rail formed by the 6F guide for CS cannulation. The 3 × 21–mm coronary balloon is advanced through the 6F guide and inflated in the distal CS with the 9F sheath is in the right atrium. Gentle traction is applied to the balloon, and the sheath is advanced into the CS. To summarize, once the angioplasty balloon is in place, proceed as follows: 1. Inflate the balloon as far distal in the CS or branch vein as possible. 2. Place gentle traction on the balloon with the right hand to change the angle of approach to the CS. 3. While maintaining traction on the balloon, advance the sheath/ guide over the balloon into the CS. If resistance is encountered, maintain traction and gentle forward pressure while carefully applying clockwise and counterclockwise torque, to more favorably align the tip of the sheath and body of the balloon. Do not force the sheath/guide. Left Ventricular Lead Placement Using Coronary Balloon as Anchor Coronary balloons are used as anchors to facilitate LV lead placement in one of two ways: (1) anchoring the pacing lead wire in the vein, preventing dislodgement as the LV lead is advanced (Fig. 23-100), or

Coronary Sinus Cannulation Using Balloon as Anchor When the angulation of the CS makes access difficult, it can usually be overcome by creating a progressively supportive rail over which the guide/sheath can be advanced. When a rail cannot be created or is ineffective, a CS venogram balloon can be used as an anchor to prevent buckling and to change the angle of approach to the CS (Fig. 23-98). CS cannulation is facilitated by applying traction to the inflated venogram balloon, which changes the angle of approach to the CS. Initially unsuccessful attempts to advance the sheath over the guide may be caused by the inferior angle of approach to the vertically oriented CS. Traction is placed on the inflated CS venogram balloon to change the angle of approach of the sheath to the CS. The sheath is then advanced into the CS. Coronary Sinus Venogram Balloon.  When using an occlusive CS venogram balloon as an anchor (see Fig. 23-98), it is useful to consider (1) compliance of the occlusion balloon, (2) how well the balloon tracks over a wire, and (3) size of the central lumen. Although all venogram balloons are relatively compliant (tendency of balloon to be distorted to fit anatomy), compliance varies with the vendor. Ideally, the most compliant balloon is used. The ability of the balloon to track over a wire and the size of lumen are also important. When a .035-inch glide wire will advance into the CS, the lumen of the venogram balloon must be adequate. However, venogram balloons are not designed for tracking over a wire and may not advance distally into the CS. By comparison, venogram balloons with small, central lumens tend to track well, and their balloons are more compliant. Although any occlusive venogram balloon will likely suffice for anchoring in the CS, we prefer the 6-French CS Balloon Venography Catheter (Pressure Products, San Pedro, Calif). The soft catheter body seems to track better, and the balloon seems more compliant than venogram balloons provided by the device manufacturers. Coronary Balloon.  Coronary balloons are designed to track over a wire. Specifically, they have a hydrophilic coating, low profile (small diameter), and stiff proximal section. As a result, coronary balloons advance easily into the CS when none of the occlusive venogram balloons will pass. However, all coronary balloons are noncompliant by comparison to venogram balloons. When used as an anchor, a coronary balloon should be long (>20 mm) and relatively compliant (rated burst <10 atm). The diameter should be 3 to 4 mm, depending how far distal the angioplasty wire and balloon are advanced into the CS. Figure 23-99 demonstrates the technique for using a coronary balloon

Catheters buckle when advanced

Angle of approach to CS results in buckeling

Tip of CS access catheter

A Traction on inflated venogram balloon

Venogram balloon inflated

Tip of CS access catheter Angle of approach changed by traction

B Catheter advances into the CS

Venogram balloon inflated

Tip of CS access catheter

C Figure 23-98  Traction on inflated venogram balloon to cannulate coronary sinus. A, Attempts to advance the coronary sinus (CS) access catheter (Worley-STD) resulted in buckling despite creating progressively supportive rails. Note the angle of approach to CS. B, Traction is placed on the inflated venogram balloon changing the angle of approach to the CS. C, CS access catheter is advanced into the CS while traction is maintained on the balloon. There was no visible CS trauma identified at the time of occlusive CS venography.

694

SECTION 3  Implantation Techniques

Inflate balloon to hold position in CS

6F guide

A

Balloon

(Cook). However, if the CS has a difficult angulation, the angioplasty wire may be displaced as the 5F catheter approaches the OS. To ensure CS access, a long (21 mm), noncompliant (rated burst <10 atm), 3- to 4-mm balloon is backloaded over the wire and a 5F guide. The balloon is then tracked over the wire into the CS or a distal branch vein and inflated. The 5F guide is then advanced over the secured wire and balloon, with subsequent substitution of the balloon for an extrastiff wire.

Tip of CS access catheter

Traction on balloon straightens bends

Balloon traps second wire

Tip of CS access catheter

Extra stiff wire

Balloon 6F guide

Second wire

B

Tip of CS access catheter Allowing CS access catheter to advance

Balloon wire

A

Lead advanced on second wire

CS access catheter 6F guide

Balloon

Balloon

Lead buckels as it is advanced

C Figure 23-99  Traction on coronary balloon for coronary sinus (CS) cannulation. A, Despite the formation of progressively supportive rails, the CS access catheter could not be advanced into the CS. A 3 × 21–mm balloon was advanced deep into the anterior interventricular vein and the balloon inflated. Using the rail created by traction on the inflated balloon, a 6F multipurpose guide (6F guide) is advanced from the proximal CS deep in the CS while the 9F CS access sheath (Worley-STD) is in the right atrium (RA). B, The 9F CS access catheter is advanced to the CS os over the rail created by the combination of the anchored balloon and the 6F guide. When the sheath reaches the CS os, it may not advance. Additional traction is applied to the balloon, straightening the approach to the CS and changing the angle of approach, and the sheath is advanced into the CS.

(2) anchoring the wire in the vein to allow the guide to be pulled into the vein for subsequent lead placement (Fig. 23-101). Although LV lead placement is facilitated in both cases, using the balloon to advance the guide in the vein allows selective contrast injection to locate options in event that phrenic pacing or high thresholds are encountered. Further, guide support allows easy repositioning of the lead in the alternative branch, if necessary. Recovering Access Using Anchored Balloon Recovering Coronary Sinus Access.  When phrenic pacing, high threshold, or lead instability develops after the guides and sheaths are removed, a coronary balloon can be used to regain access. Removing the lead over an angioplasty wire preserves venous access. In some cases, CS access can be preserved by advancing a 65-cm, soft, 5F hydrophilic angiographic catheter (Vert [left vertebral] Slip-Cath [hydrophilic coating]) with Beacon-Tip, Cook; or Angled Taper, Radiofocus Glidecath, Terumo], over the wire into the CS and exchanging for an Amplatz Extra Stiff Wire Guide, .035 inch, 145 cm, 3-mm tip curve

Balloon wire

B Tension second wire

Lead advanced Trapped wire is not displaced by tension

C Figure 23-100  Coronary balloon anchors pacing lead wire, preventing dislodgement as left ventricular lead advanced. A, Amplatz Extra Stiff Wire in the coronary sinus (CS) maintains the tip of the 9F sheath CS access catheter, (SafeSheath CSG, Pressure Products) at the CS os. Two wires were inserted into the target vein by vein selector. A 3 × 14–mm coronary balloon (balloon) is inserted on one of the wires (balloon wire) and inflated trapping the second wire in the vein. B, As the pacing lead is advanced over the second wire, it buckles (arrowheads) as it reaches the takeoff of the target vein. The sheath, Amplatz wire, CS access catheter, and the inflated balloon are again seen.  C, Gentle traction on the pacing lead wire (second wire) straightens the lead (arrowheads), allowing it to be advanced into the vein. The trapped wire is not dislodged by the tension required to straighten the lead, allowing it to advance. With the tip of the CS access catheter at the CS os, the .035-inch extra-stiff wire is important to maintain a stable platform throughout the procedure. In this case, a 14-mm balloon was used; however, a 21-mm balloon provides more anchoring surface area.



23  Interventional Techniques for Device Implantation

Target vein with acute takeoff near CS os

Nothing would advance except an angioplasty wire

A

Inflated balloon anchors wire to support advancing guide

CS access

Delivery guide

B Delivery guide advanced back into target vein

Coronary balloon

Balloon

CS access catheter

C

Delivery guide

Figure 23-101  Anchored coronary balloon to pull delivery guide into target vein. A, Acutely angulated vein to the midlateral wall is demonstrated (arrowheads) on the occlusive coronary sinus (CS) venogram. Nothing could be advanced into the CS beyond the vein. The only wires that could be advanced without displacing catheters from the CS were angioplasty wires. Attempts to advance a pacing lead displaced the wire from the vein. B, Two .014-inch angioplasty wires and a 3 × 15–mm, noncompliant angioplasty balloon (coronary balloon) is deep in the target vein. The anatomically shaped, 9F peel-away sheath (CS access) is above the CS os. The 9F “renal” delivery guide (delivery guide) is at the ostium of the target vein. Traction on the balloon straightens the acute angle of the vein, creating a stable rail over which to advance the delivery guide. C, The 9F sheath (CS access catheter) and 9F renal-shaped delivery guide (delivery guide) are coaxial with the lateral vein. The tip of the guide is within the vein beyond the acute angle. The inflated balloon remains distal in the vein, maintaining a stable rail for the delivery guide. Once the delivery guide is stable in the vein, the balloon is deflated and removed, retaining the wire. The lead is then easily delivered through the delivery guide over the wire.

Recovering Target Vein Access.  An attempt to recover the target vein with a retained angioplasty wire usually fails unless a balloon is used as an anchor to keep the wire in place. The anchor technique is performed as follows: 1. The guiding catheter is loaded into the sheath. 2. The angioplasty wire is backloaded into the tip of the guide (Fig. 23-102, A). 3. A noncompliant, rapid-exchange angioplasty balloon is loaded onto the wire and inserted into the hub of the guide (Fig. 23-102, B). 4. With the tip of the guide close the pocket (Fig. 23-102, C), the balloon is advanced over the wire into the target vein as far distal as possible (Fig. 23-103). 5. With the balloon inflated, the guide/sheath is advanced into the venous circulation.

695

Figure 23-103 illustrates the technique for regaining target vein access subsequent to backloading the balloon and guide over the wire and advancing the balloon into the target vein. As previously mentioned, the angioplasty wire is advanced as deep as possible into the vein, and the pacing lead is removed. The guide and a 3 × 21–mm coronary balloon are loaded onto the wire as shown in Figure 23-102. The balloon is advanced over the wire into the vein (see Figs. 23-102, B and C, and 23-103, A) and inflated, securing position in the vein (see Fig. 23-103, B). Gentle traction is held on the balloon while the guide is advanced to the CS os, where it may become difficult to advance. Maintaining gentle traction on the balloon and gentle forward pressure on the guide, the guide is rotated 30 to 60 degrees clockwise and/or counterclockwise until the tip is coaxial with the CS, at which point it advances without additional application of forward pressure. Maintaining gentle traction on the balloon, the guide advances to the target vein os with gentle forward pressure. Two related potential complications of using balloons as anchors are vein rupture and vein “laceration.” Vein rupture results from the anchoring balloon exceeding the ability of the vein to expand and is an important consideration. The potential for balloon inflation to rupture the vein is reduced by using a compliant (deformable) balloon. In addition, balloons that conform to the anatomy are likely to anchor more securely. The compliance of venogram balloons varies with the manufacturer. However, even the most noncompliant venogram balloon is much more compliant than a coronary balloon. Remember that venogram balloons inflate (like a party balloon) whereas coronary balloons “fill” to a predetermined size (like a beach ball). Compliant coronary balloons are identified by a nominal pressure of 8 atm or less. In patients with previous remote OHS, inadvertent venous rupture is unlikely to have clinical consequence because of the adhesive scar tissue between the visceral and parietal pericardium. In patients without prior OHS, the consequence of venous rupture can be, but is not always, significant.4 Vein laceration may occur with or without rupture. If excess traction is placed on the balloon, it usually pulls out of the vein without a clinically significant event other than loss of wire position. Conceivably, however, rather than slipping free, the balloon may tear the vein. As with venous perforation, vein laceration is much less likely to have a clinical impact on the patient with prior OHS. To avoid excess traction and the potential for laceration, it is important to adjust the tip of the advancing catheter to a coaxial position if resistance is encountered, avoiding brute force. We have not seen either perforation or laceration in our use of balloons as anchors. Figure 23-104 shows a coronary balloon used as an anchor for CS cannulation. Despite moderate traction, there is no visible trauma to the vein. However, the author (SW) has witnessed a case of tamponade resulting from venoplasty (possibly with addition of traction) of a proximal stenotic segment in one patient without previous OHS. Tamponade was managed successfully with pericardiocentesis without subsequent surgery. In more than 200 patients with OHS in whom dilation of one to four veins was performed for LV lead placement, we have not encountered tamponade, and there are no reported cases. We now use the methods described more frequently because experience has demonstrated their safety and utility. Rather than spending time trying techniques less likely to be successful, we tend to move more quickly to an anchoring technique. Anchoring techniques are successful approximately 90% of the time when “standard” techniques fail. Over time, anchoring techniques are becoming our “standard” technique for difficult coronary sinus anatomy. Box 23-9 lists balloon anchor equipment. SNARE FOR LEFT VENTRICULAR LEAD PLACEMENT Loss of wire position is a common problem during LV lead placement and venoplasty. Although guide support is often sufficient, in some cases the only solution is to gain control of the distal end of the wire. The ability to control the distal end of the guidewire is another important advance in implant technique. The distal end of the

696

SECTION 3  Implantation Techniques

Angioplasty wire backloaded into delivery guide

Balloon over wire into hub of delivery guide Hub

A

Wire Tip of delivery guide

Wire Balloon

B

Balloon advanced into the subclavian through the RA and CS out into the target vein

Wire

Balloon

Tip of delivery guide

C

Pacing lead removed over wire Balloon advanced over wire into target vein

A

All catheters out pacing lead only access

Delivery guide entering CS

B

Inflated balloon

Anchored balloon serves as rail to regain access Delivery guide

Inflated balloon

C

Delivery guide advanced back into target vein

Figure 23-102  Loading coronary balloon and delivery guide on angioplasty wire to regain target vein access. A, Back end of the angioplasty wire (wire) that remains in the target vein is introduced into the tip of the 9F “renal” delivery guide (delivery guide) (SafeSheath Worley Telescopic Braided Series, Renal Lateral Vein Introducer, Pressure Products). The delivery guide will eventually be advanced into the target vein. B, A 3 × 21–mm coronary balloon (balloon) is loaded on the back end of the angioplasty wire (wire) and inserted into the hub of the renal-shaped delivery guide (hub). C, Balloon is advanced out the tip of the 9F renal delivery guide into the subclavian vein. The balloon is then advanced over the wire into the right atrium (RA) through the coronary sinus (CS) into the target vein and inflated. The coronary balloon requires much less wire support than a pacing lead or catheter. Once in place and inflated in a suitably small vein, the anchored balloon provides a stable rail over which to advance the lead.

Figure 23-103  Anchored coronary balloon to regain venous, coronary sinus (CS), and target vein access. A, After all catheters were removed, the pacing thresholds increased and could not be improved with a wire or stylet. A hydrophilic wire was advanced as far as possible and the lead removed. A delivery guide was loaded into a CS access sheath. The delivery guide/CS access sheath was backloaded onto the angioplasty wire. The 3 × 21–mm coronary balloon was then inserted through the delivery guide into the target vein (see Fig. 23-102). B, Balloon is inflated securing position in the vein. Gentle traction is held on the balloon while the 9F “renal” delivery guide (delivery guide) is advanced to the CS os, where it may become difficult to advance. Maintaining gentle traction on the balloon and gentle forward pressure on the delivery guide, the guide is rotated 30 to 60 degrees clockwise and/or counterclockwise until the tip is coaxial with the CS, at which point it advances without additional application of forward pressure. C, Maintaining gentle traction on the balloon, the guide advanced to the target vein os with gentle forward pressure. At the os of the target vein, the guide may “hang up” and become difficult to advance. While maintaining gentle traction on the balloon and gentle forward pressure on the guide, the guide is rotated 30 to 60 degrees clockwise and/or counterclockwise until the tip is coaxial with the target vein, at which point it advances into the vein without application of additional forward pressure.



23  Interventional Techniques for Device Implantation

697

EFFECT OF ANCHORED BALLOON ON VEIN

LAO balloon anchored

LAO venogram after anchor

A

B

LAO balloon anchored AP venogram after anchor

C

D

Figure 23-104  Effect of anchored balloon for coronary sinus (CS) cannulation on vein in patient without prior open-heart surgery. A, Position of the anchored balloon is shown in the left anterior oblique (LAO) view. B, Occlusive venogram balloon after traction on the anchored balloon for CS cannulation in the LAO view. C, Balloon is anchored in the anteroposterior (AP) view. D, Occlusive venogram balloon after traction on the anchored balloon for CS cannulation in the AP view. There is no visible trauma to or dissection of the vein despite moderate traction on the balloon during a difficult CS cannulation.

Box 23-9 

BALLOON ANCHOR EQUIPMENT 3 mm × 20-30 mm, compliant balloon: wire lumen .014 inch, rapid exchange, rated burst = 14 atm, diameter = 3 mm, length = 20 mm or 30 mm Inflation device Miscellaneous: Three-way stopcock 12-inch extension 30-mL syringe (to pull negative pressure for balloon preparation) Y adapter with Luer lock Small bowl for mixing contrast See Interventional Equipment List at the end of Chapter 22 and online for details and ordering information.

guidewire can be snared if it reenters the CS by passing through the collaterals between two adjacent veins.90 To accomplish this, a snare system is introduced through the sheath already located in the CS. Using a snare system to retrieve an object loose in the circulation is time-consuming and difficult. Snaring a wire in the CS is much easier because the wire is confined within the CS, and the snare opens perpendicular to the long axis of the CS.91 There are two types of snare systems for control of the distal end of the wire (Fig. 23-105): the single-loop snare (Amplatz Goose Neck Snare eV3, Plymouth, Minn.) and the triple-loop snare (EN Snare, Merit Medical, South Jordan, Utah). A snare system consists of the snare and the snare catheter (Fig. 23-106). When using a 9F sheath (9F lumen), the snare system must be 4F or less. An 8-mm to 10-mm snare will almost fill the CS; thus a wire advanced past the snare usually passes through the loop. The 10-mm gooseneck snare system is 4F, while the 4-mm to 8-mm tripleloop snare is 3F. The French size of larger snares prohibits simultaneous passage of catheters and leads through a single CS access. Once the

698

SECTION 3  Implantation Techniques

10 mm

A

8 mm

B Figure 23-105  Types of snares available to assist in left ventricular lead placement. A, Single-loop snare (Amplatz Goose Neck Snare eV3, Plymouth, Minn). The loop size is 10 mm; the snare catheter is 4F.  B, Triple-loop snare system (EN Snare, Merit Medical Systems, South Jordon, Utah). When the three individual 4-mm loops are deployed, the effective coverage area is 8 mm. The 3.2-mm catheter has a radiopaque tip marker. The size of the snare catheter needs to carefully considered when inserting in a CS access catheter with a lead or other catheter. The lumen of a 7F CS access catheter is too small to accommodate any snare catheter and an LV at the same time. When using the Orthodromic Snare technique, the distal end of the wire must be snared and pulled out of the hub of the CS access catheter before the lead is advanced.

target vein. If the wire pulls back as attempts are made to dilate the collaterals and place a lead retrograde, the snare can be used to secure the lead as follows. Once in the target vein, the wire can usually be advanced retrograde out into the CS where it is snared. With the tip secured, the wire will not pull back as tension is placed to dilate the collaterals and advance the pacing lead retrograde into the target vein (Fig. 23-108). In our experience, venoplasty of collaterals between two veins is safe in patients with prior OHS.3-5 However, inserting the lead retrograde into the target vein can be difficult and is not always successful despite venoplasty. Further, extensive dilation and disruption of collaterals in patients without previous OHS to place the lead retrograde may result in tamponade. These issues lead to the next option. Antidromic Snare for LV Lead Implantation: Insert the LV Pacing Lead over the Distal End of the Wire in Difficult Anatomy Where the Wire Cannot Be Delivered into Target Vein Antegrade, But Still Want to Insert Lead into Target Vein Antegrade.  This technique requires a 300-cm wire. Select an adjacent vein, and direct the wire through the collaterals into the target vein. Once in the target vein, the wire can usually be advanced retrograde out into the CS where it is snared. Pull the distal end of the wire out of the target vein into the tip of the sheath and out into the pocket (Fig. 23-109). Be certain to advance the wire into the adjacent vein as the wire is pulled up into the sheath. Continue to advance the stiff end, and pull the distal (floppy) end until 80 cm of wire is on the field. Trim the tip of the wire, and backload the lead onto the distal (floppy) end of the wire. While holding the proximal (stiff) end of the wire, advance the lead into the target vein (Fig. 23-110). If the internal diameter of the CS access catheter is ≤7F, the vein selector (if used to advance the wire) will need to be removed (5F vein selector will not fit beside any LV lead). If the internal diameter of the CS access catheter is 9F, the vein selector may be left in the adjacent vein (5F vein selector will fit beside a 5F LV lead). If the lead will not advance, venoplasty of the target vein can be performed.

Snare catheter

wire is within the loop(s) of the snare, the loop is closed by either withdrawing the loop into the snare catheter or advancing the snare catheter over the loop (see Fig. 23-106). Orthodromic and Antidromic Snare Techniques Orthodromic Snare for LV Lead Implantation: Stabilization of the Distal End of the Wire for LV Lead Placement in Difficult Anatomy.  If the wire pulls out of the target vein when the delivery guide and leads are advanced, the distal end of the wire can be secured by a snare as follows. Using a floppy hydrophilic wire, advance the wire into the target vein into the collaterals of an adjacent vein. From there, the wire can often be advanced into the adjacent vein, then retrograde into the CS. The distal end of the wire is snared as it reenters CS from the adjacent vein (Fig. 23-107). The distal end of the wire is stabilized either internally (in the CS or in the catheter) or externally (at the hub) depending on the internal diameter of the CS access catheter. The 7F internal diameter of the CS access catheter will not accept the snare catheter and LV lead at the same time. With the distal end of the wire secured by the snare, traction can be placed on the wire as the delivery guide and lead are advanced. When a wire cannot be advanced into the target vein antegrade, it is often possible to enter the target with a wire retrograde by selecting an adjacent vein and directing the wire through the collaterals into the

Snare

Wire

Sheath

A Snare catheter

Snare

Sheath

B

Wire

Figure 23-106  Use of 10-mm single-loop system to snare distal end of wire. A, The snare, snare catheter, and delivery sheath are shown. The snare is advanced out of the snare catheter, deploying the loop perpendicular to the long axis of the system. A wire is within the loop of the snare. B, Snare catheter is held in place and the snare withdrawn into the snare catheter, collapsing the loop around the wire. Traction is maintained on the snare at the hub of the snare catheter to keep the wire trapped within the loop.



23  Interventional Techniques for Device Implantation

699

Snare holds wire in place Before snare wire pulls back

Delivery guide

Wire Tip of delivery guide

CS access Target vein

MCV

Snare MCV

Wire

A

Tip of delivery guide

CS access and snare

B

Figure 23-107  Orthodromic snare technique in which gooseneck snare is used to stabilize the distal end of the wire. A, Tip of the coronary sinus (CS) access sheath (9F SafeSheath CSG Worley, Braided Core) is just inside the CS os. The tip of the 7F guide (SafeSheath Worley, Renal Lateral Vein Introducer, LVI/75-5-66-5.5-RE, Pressure Products) is at the ostium of the target vein, but the lead will not advance. The guidewire is advanced from the target vein through the collaterals into the middle cardiac vein (MCV) and back into the CS. The snare is deployed from the access sheath to engage the tip of the guide, where it reenters the CS. B, Tip of the guidewire is snared and secured just inside the sheath. Holding tension on the tip of the wire with the snare tip, the guide is advanced deep into the target vein, from which the lead can now be advanced.

Summary When using the snare, the angioplasty wire must be advanced through collaterals to reenter the CS. This is best done using the direction and support of a vein selector and a hydrophilic polymer-tip wire (Choice PT Floppy, Boston Scientific, others) to advance through collaterals more readily than “standard” wires. Further, a floppy hydrophilic wire advances through the collaterals more readily than a wire with extra support. Because the support required is obtained by traction, a floppy wire can be used without concern about lack of support. As mentioned previously, “T-bone” table position is important for successful application of this technique. When using the Antidromic Snare Technique, the angioplasty wire (see Figs. 23-109 and 23-110) must be long

enough to make the round trip to and from the target vein, with enough excess to advance a pacing lead, and still control the proximal end. A 300-cm wire is necessary for this purpose. In addition, to prevent the wire from damaging the veins as it is pulled into the sheath, the proximal end must be advanced as the distal end is pulled into the sheath. When a snared wire is pulled out of the hub of the sheath, the kinked section (see Fig. 23-109, B) must be trimmed before a lead or balloon is advanced. Backloading the floppy end of the angioplasty wire into a pacing lead or a balloon is slightly more difficult but is readily accomplished. Finally, the wire must be removed by traction on the proximal (stiff) end of the wire. Box 23-10 lists the two approaches for using the snare to assist LV lead placement.

Snare to control distal end of wire Snared guide wire Snared guide wire Target vein

Target vein

Snare

Snare

Lead CS access

A

CS access

Balloon Delivery guide

B

Delivery guide

Figure 23-108  Orthodromic snare technique in which gooseneck snare is used to control distal end of guidewire for retrograde approach to target vein. A, Snare prevents the wire from pulling back as the balloon is advanced into the collaterals between the middle cardiac vein (MCV) and the target vein. The tip of the 9F peel-away sheath (CS access) is at the coronary sinus (CS) os. The 4F gooseneck snare (snare) is advanced superiorly into the CS to secure the guidewire. The 5F-ID delivery guide (renal 7F OD/5F ID) is in the MCV. The 2.5 × 14–mm angioplasty balloon (balloon) is inflated in the collaterals between the two veins. Before the guide was snared, the wire pulled back when the balloon was advanced into the collateral. B, Snare stabilizes the guidewire as the lead is advanced into the collaterals between the MCV and the target vein. Tip of the 9F peel-away sheath (CS access) is at the CS os. The 4F gooseneck snare is advanced superior into the CS to secure the guidewire. The 5F-ID delivery guide (delivery guide) is in the MCV. The 5F left ventricular (LV) pacing lead (lead) is advanced into the distal target vein. Before snaring, the guidewire pulled back when attempts were made to advance the lead through the collaterals. If the lumen of the CS access catheter is 7F, the distal end of the wire must be snared and pulled out the hub before the lead is advanced. The 7F lumen is too small to accommodate the snare catheter and the LV at the same time.

700

SECTION 3  Implantation Techniques

Distal end of wire pulled out of hub

Distal end of wire pulled into sheath

Stiff end of wire

Wire direction Snare Distal end of wire Snare

Vein selector in middle cardiac vein

CS access

Distal end wire

B

A

Figure 23-109  Antidromic snare technique in which gooseneck snare is used to pull distal end of guidewire into sheath and out of hub. A, Tip of the 9F peel-away sheath (CS access) is just inside the coronary sinus (CS) os. A 5F vein selector is deep in the middle cardiac vein (MCV). A 300-cm, floppy, .014-inch hydrophilic angioplasty (Choice PT Floppy, Boston Scientific) is advanced through the vein selector into collaterals, then retrograde into the CS via the target vein. The 10-mm gooseneck snare (snare) is open in the proximal CS. The wire passes through the open snare. B, Distal tip of the wire is pulled through the sheath and out of the hub. The proximal end of the wire enters the hub. The distal tip is in the closed loop of the snare.

Backload lead on distal end wire Stiff end of wire

Lead advanced on distal end of wire

Box 23-10 

APPROACHES FOR USING THE SNARE TO ASSIST IN LEFT VENTRICULAR LEAD PLACEMENT Orthodromic Snare for LV Lead Implantation: Stabilization of the distal end of the wire for LV lead placement in difficult anatomy. Antidromic Snare for LV Lead Implantation: Insert the LV pacing lead over the distal end of the wire in difficult anatomy. See Interventional Equipment List at the end of Chapter 22 and online for details and ordering information.

A Lead in over distal end of wire

Wire coming out CS access into MCV CS access

B

Wire direction

Figure 23-110  Antidromic Snare Technique in which the pacing lead is advanced over distal end of wire into target vein. A, Pacing lead has been backloaded onto distal (floppy) end of the wire and into the hub while gentle tension is placed on both the proximal and the distal end of the wire. B, Tip of the sheath is just inside the coronary sinus (CS) os (CS access). The angioplasty wire enters the middle cardiac vein (MCV) passes through the collaterals into the target vein, then into the lead. The pacing lead enters the target vein over the distal end of the wire. This approach is very valuable because placing leads retrograde (see Fig. 23-109), although valuable, has significant limitations.

TRANSSEPTAL LEFT VENTRICULAR LEAD IMPLANTATION In the rare cases when transvenous LV lead implantation is unsuccessful despite persistent application of intervention implant techniques, the LV lead can be implanted transseptally. The transseptal approach can be technically difficult and is associated with the risk of thromboembolism from the lead in the LV cavity.92 The interest in this approach was renewed by recent studies, two in animals and one in humans, which found a superior hemodynamic performance associated with endocardial compared with epicardial stimulation.93 However, Spragg et al.94 conclude that endocardial CRT improved the response to CRT by allowing access to previously inaccessible pacing sites (not endocardial stimulation per se). Clinical trials are underway to better define the value of endocardial CRT. Jaïs et al.95 first described a combined femoral/prepectoral approach where a long wire is placed across the septum from the femoral vein after using a conventional transseptal approach from the leg. The long guidewire is stabilized in the left atrium with a large, hand-formed loop. The wire is then snared in the right atrium and pulled into a sheath in the innominate vein. The left atrium is then entered over the wire from above for lead placement. Since then, several other groups have described methods for left-sided lead placement, including direct transseptal puncture from both the right internal jugular96 and the left axillary vein.97 Van Gelder et al.98 described successful endocardial LV lead placement in 9 of 10 patients using a combined femoral/axillary vein approach with balloon dilation of the septum following femoral transseptal puncture to allow entry from above.



23  Interventional Techniques for Device Implantation

Transseptal

701

Snare around transseptal sheath Screw-in lead in transseptal sheath

Snare

A

B

C

D

Figure 23-111  Transseptal left ventricular lead placement as described by Elencwajg and Lopez-Cabanillas: part 1. A, The 12F sheath is advanced through a snare basket/snare introducer into the inferior vena cava from the pacemaker pocket (Check-Flo Performer Introducer, Mullins Design [G09171 RCFW-13.0-38-65-RB-MTS 13F ID, .038-inch wire lumen, 65 cm long], Cook Medical). The transseptal sheath passed through the snare, then across the interatrial septum. B, Transseptal sheath is positioned across the mitral valve on the lateral free wall of the left ventricle. The screw-in lead is advanced through the transseptal sheath and screwed in place. Once in place, the lead is pushed out of the transseptal sheath as it is withdrawn. C and D, Anteroposterior and lateral chest radiographs show the left ventricular lead in place. (Images for production of the figure courtesy Drs. Elencwajg and Lopez-Cabanillas.)

Elencwajg et al.99 described an approach where the lead was screwed in place from the femoral vein, then pulled up to the prepectoral area with a snare. To accomplish this, the snare is introduced from the prepectoral area to the distal IVC or right iliac vein. The transseptal sheath is then advanced through the snare, across the interatrial septum, and into the left ventricle (Fig. 23-111, A). An active-fixation 110-cm lead is then advanced through the transseptal sheath (Figs. 23-111, B, and 23-116, A) and screwed in place from the leg. Once in place, the stylet is removed, an angioplasty wire inserted into the lumen of the lead, and a suture attached to the IS-1 connector (see Fig. 23-116, B). A 6F guide is advanced over the suture and angioplasty wire (Fig. 23-112, B) until the IS-1 connector enters the tip of the sheath (Fig. 23-112, C). The sheath and angioplasty wire are used to push the IS-1 connector through the hemostatic hub and hold the lead in place as the sheath is withdrawn (Fig. 23-112, D). When the tip of the transseptal sheath is just above the snare, the IS-1 connector is pushed out of the transseptal sheath into the IVC, with the 6F catheter and the sheath withdrawn further. When the 6F catheter is withdrawn, the snare is closed around the exposed suture attached to the IS-1 connector and pulled into the axillary sheath.

Figure 23-111, C and D, shows the posteroanterior (PA) and lateral chest radiographs of the result. By combining the prepectoral and femoral methods just described, we developed the Selectsite snare method described in Figures 23-113 to 23-116; this was successful in four cases but failed with a right-sided implant. Recently, Lau described success with essentially the same approach in four patients.99a It was almost impossible to insert the Attain Deflectable 6226 DEF catheter into the left atrium, and then it fell out and we lost access. The failed Selectsite implant was successfully accomplished with a modification of the Elencwajg-Cardinali femoral approach; Figures 23-117 to 23-122 provide details of this approach. We perform transseptal LV lead placement in patients receiving coumadin with an international normalized ratio (INR) of 2 to 3 and those receiving heparin with an ACT of greater than 300, because we observed thrombus formation by intracardiac echo during our initial case with an INR of 2.6. Box 23-11 lists equipment for prepectoral transseptal and femoral transseptal left ventricular lead placement. Text continued on page 711

702

SECTION 3  Implantation Techniques

Lead positioned and screwed in from leg

Suture attached to IS-1 connector

Suture

85-cm screw in lead

6F catheter

A

13F transseptal sheath

Angioplasty wire

B

Lead pushed into transseptal sheath

Lead pushed out transseptal sheath into snare

6F catheter

6F catheter

IS-1 Transseptal connector sheath

C

5-mm section 4F catheter

D

Figure 23-112  Transseptal left ventricular lead placement as described by Elencwajg and Lopez-Cabanillas: part 2. A, The LV lead is positioned and screwed into place through the 13F transseptal sheath (Check-Flo). Transeptal access was initially obtained using an SL1 8.5F transseptal guiding introducer (St. Jude Medical) sheath through a basket snare placed in the inferior vena cava (IVC). The basket snare was placed using a 13F introducer in the device pocket. The transseptal sheath was then upsized to 13F using an ultra-stiff .035-inch guidewire. B, A 5-mm section of a braided 4F catheter “fixing ring” is force-fit over a long, 3.0 nylon suture onto the pin of the IS-1 connector. Cianmetacrilate contact cement was added to the pin/”fixing ring”/nylon suture interface to insure that the suture was securely attached to the IS-1 connector. After 15 minutes of drying time, a .014-inch angioplasty wire was inserted into the lumen of the pacing lead. The suture and angioplasty wire were advanced into the lumen of a 6F multipurpose catheter. C, The 6F multipurpose catheter was advanced to the IS-1 connector to push the pacing lead into the transseptal sheath. D, As the transseptal sheath was withdrawn through the basket snare, the pacing lead was pushed through the sheath, forming a loop in the left atrium (LA). With the tip of the transseptal sheath above (superior) to the proximal extent of the snare, the IS-1 connector (with suture attached) was pushed out of the sheath into the IVC using the 6F multipurpose catheter. Using the angioplasty wire to stabilize the lead, the 6F catheter and transseptal sheath were withdrawn below the distal extent of the snare and the angioplasty wire removed. The snare was closed around the suture attached to the IS-1 connector (not the pacing lead) and pulled into the 13F introducer and out into the pocket. The trailing suture was cut in the pocket and withdrawn from the femoral access. The suture was detached from the IS-1 connector by carefully cutting the “fixing ring” from the lead pin with a scissor. The transseptal sheath and catheter were removed and hemostasis obtained. (Images for production of the figure courtesy Drs. Elencwajg and Lopez-Cabanillas).



23  Interventional Techniques for Device Implantation

Selectsite deflectable catheter

Snare catheter

25-mm loop snare

25-mm loop snare

A

B

Wire

Wire

25-mm loop snare

Intracardiac echo

Wire

C

703

25-mm loop snare

D

Figure 23-113  Coupled Selectsite snare approach to transseptal left ventricular lead placement: part 1. A, The 25-mm loop snare is shown inside the 6F snare catheter included with the kit (Amplatz Goose Neck Snare Kit [120-cm loop snare and 102-cm snare catheter] EV3, Plymouth, Minn). B, The 25-mm loop snare is shown in the Selectsite deflectable catheter (304-XL74, Medtronic). The snare catheter included with the kit is replaced with the Selectsite deflectable catheter. C (ex vivo version of D), Snare alone (Selectsite catheter is too short and remains high in the inferior vena cava (IVC) near the right atrium (RA). [RA]) is extended beyond the Selectsite into the distal IVC. The .035-inch wire is advanced through the loop. D (in vivo version of C), The 120-cm-long loop snare is advanced from the deflectable catheter to the IVC–right common iliac junction after the intracardiac echo probe is deployed in the RA. The .035-inch wire for the transseptal sheath is advanced through the open snare.

704

SECTION 3  Implantation Techniques

SNARE WITHDRAWN UP TRANSSEPTAL SHEATH

Selectsite

Transseptal sheath Loop snare

Selectsite

Loop snare Transseptal sheath

A

B SHEATH WITHDRAWN OVER WIRE

Wire

Selectsite

Selectsite advanced to close loop around wire

Loop snare

C

D

Figure 23-114  Coupled Selectsite snare approach to transseptal left ventricular lead placement: part 2. A, After transseptal puncture, the loop snare is withdrawn up over the sheath (Preface 8F 307803M, Biosense Webster, Diamond Bar, Calif) into the Selectsite catheter, closing the loop. B (in vivo version of A), After transseptal puncture, an extra-support wire is advanced into the left atrium (LA) and the transseptal sheath withdrawn into the right atrium (RA). The snare is withdrawn from the femoral vein into the Selectsite catheter positioned in the mid-RA, closing the loop around the sheath. C, Positions of the dilator and Selectsite catheter are adjusted in the RA until the snare can be closed around the wire. D (in vivo version of C), Transseptal sheath is withdrawn until the wire is exposed in the RA. The Selectsite snare is advanced and the loop closed around the wire. The snare is closed tightly enough so as not to slide over the dilator, but loose enough to allow the wire to slide through the loop.



23  Interventional Techniques for Device Implantation

705

SELECTSITE AND TRANSSEPTAL DILATOR AT SEPTUM Snare closed on wire Snare closed on wire

Selectsite flexed

Selectsite flexed

A

B DILATOR ADVANCED ACROSS THE SEPTUM

Dilator

Selectsite

Snare loose enough to allow dilator to advance over the wire

C

Contrast injected through Selectsite confirms location

D

Figure 23-115  Coupled Selectsite snare approach to transseptal left ventricular lead placement: part 3. A, Selectsite snare is flexed to align with the transseptal sheath. The wire can move through the closed snare. A clamp is placed on the proximal end of the snare where it enters the Selectsite to keep the loop tight. B is the in vivo version of A. The Selectsite and dilator are at the interatrial septum. C, The dilator is advanced over the wire across the septum as the attached Selectsite catheter is advanced into the LA. D, Before the catheters are separated, contrast is injected through the Selectsite to confirm LA position.

706

SECTION 3  Implantation Techniques

Transseptal sheath

Contrast injection confirms the Selectsite is in the LV

Selectsite separated from transseptal in LA

A

B

Endocardial LV lead

Endocardial LV lead

CS LV lead

C

CS LV lead RAO

D

LAO

Figure 23-116  Coupled Selectsite snare approach to transseptal left ventricular lead placement: part 4. A, Transseptal sheath and Selectsite catheters are separated. The loop snare is advanced out the tip of the Selectsite over the wire, then withdrawn once free of the wire. B, Selectsite catheter is manipulated across the mitral valve into the left ventricle and its position confirmed with contrast injection. C, Right anterior oblique (RAO) projection of the left ventricular (LV) lead screwed in place. D, Left anterior oblique (LAO) projection of the LV lead screwed in place on the endocardium.



23  Interventional Techniques for Device Implantation

12F transseptal sheath Hemostatic valve removed 11F hemostatic peel away sheath Figure 23-117  Modified Elencwajg & Lopez-Cabanillas femoral approach to transseptal left ventricular lead placement: part 1. A, The 11F hemostatic peel-away sheath (SafeSheath Long HLS2511, Pressure Products) is shown with a 12F transseptal sheath with the hemostatic valve removed (Check-Flo Performer Introducer, Mullins Design, Cook; 12F ID, .038-inch wire lumen, 75 cm long). B, When the 11F peel-away sheath is inserted in the 12F transseptal sheath, the fit is tight enough to prevent backbleeding. The modified 12F transseptal sheath is advanced across the interatrial septum. C, Suture sleeve is removed from the lead before it is advanced into the transseptal sheath. The tip of a 4F sheath is used as a fixing ring (Avanti Plus, Cordis, Miami Lakes, Fla) Two 30-inch lengths of 0-braided polyester suture (Ethibond Excel, Ethicon) are attached to the IS-1 connector. The suture is attached by placing a half-hitch around the sealing ring of the connector, then holding hitch tight by passing both ends through the “fixing ring,” which is force-fit over the pin. With this arrangement, glue is not required.

A 11F sheath in 12F transseptal sheath

Suture attached to IS-1 connector

Tip of 4F sheath

B

Figure 23-118  Modified Elencwajg & Lopez-Cabanillas femoral approach to transseptal LV lead placement: part 2. A, Suture is attached at the proximal and distal sealing rings on the IS-1 connector using a half-hitch. To demonstrate the knot, the half-hitch around the distal sealing ring has not been tightened. B, The ends of the 0 Ethibond suture are fed into an 8-mm segment of a 4F sheath. C, The 8-mm segment of the 4F sheath (fixing ring) is force-fit over the suture material onto the pin of the IS-1 connector, which keeps the half-hitch tight.

C

Half-hitch around sealing ring

Suture sleeve removed

Half-hitch

A 8-mm segment of 4F sheath

B 8-mm segment of 4F sheath force fit over suture onto IS-1 pin

C

707

708

SECTION 3  Implantation Techniques

Slice and withdraw transseptal sheath on top of peel-away sheath Lead Sheath tip

Snare catheter

Snare

A

B

30-cm segment of 8F guide

Use 8F guide to push lead through sheath

Suture attached to IS-1 into guide

C

D

Figure 23-119  Modified Elencwajg & Lopez-Cabanillas femoral approach to transseptal LV lead placement: part 3. A, Transseptal sheath is sliced as it is withdrawn from the left side of the heart by fitting the slicing tool on the surfaces of the peel-away sheath such that the blade engages the transseptal sheath. The transseptal sheath is then sliced as it is withdrawn against the blade. The suture sleeve is removed from the pacing lead. B, When the transseptal sheath is withdrawn to the low inferior vena cava (IVC), the snare is positioned 1 cm distal to the tip. The stylet is withdrawn from the tip of the lead to the left atrium (LA). The pacing lead is advanced and the stylet withdrawn, forming a loop in the LA until the IS-1 connector reaches the hub, at which point the stylet is withdrawn completely. C, Proximal 30 cm (including the hub) of an 8F guide is used to push the IS-1 connector and lead through the 11F sheath. The suture is advanced into the 8F sheath and a hemostatic cap placed on the hub. D, Distal end of the 8F guide is advanced over the fixing ring and used to push the IS-1 connector into the peel-away sheath and out of the transseptal sheath.



23  Interventional Techniques for Device Implantation

709

Remainder of transseptal sheath withdrawn over slicer

IS-1 Snare catheter

8F guide

Snare

A

B Transseptal sheath removed Suture attached to IS-1

IS-1

8F guide

Snare

Guide withdrawn

C

D

Figure 23-120  Modified Elencwajg & Lopez-Cabanillas femoral approach to transseptal LV lead placement: part 4. A, Using the 8F guide, the IS-1 connector is pushed out of the transseptal sheath. B, Remainder of the transseptal sheath is withdrawn over the slicer positioned on the peel-away sheath. The 8F guide remains in the 11F peel-away sheath, holding the lead in place. C, With the transseptal sheath removed, the snare is around the 8F guide, which contains the suture. D, The 8F guide is withdrawn, exposing the suture to the snare.

710

SECTION 3  Implantation Techniques

8F guide withdrawn Tip of 4F sheath force fit on pin of IS-1 connector

Snare closed around suture

Suture attached to pacing lead

A

B

Snare Snare pulled into 11F sheath

Fixing ring

Suture Snare lead pulled up from the IVC toward pocket

C

IS-1 connector with attached suture

D

Figure 23-121  Modified Elencwajg & Lopez-Cabanillas femoral approach to transseptal LV lead placement: part 5. A, Snare catheter is advanced to close the snare around the suture. The tip of the snare catheter abuts the fixing ring (4F sheath segment) on the IS-1 connector. A hemostat is clamped to the snare at the hub of the snare catheter to ensure the snare does not come loose from the suture. B, The guide is withdrawn out of the hemostatic hub, exposing the suture attached to the IS-1 connector. C, Snare and lead are pulled up through the right atrium and superior vena cava (RA/SVC). IVC, Inferior vena cava. D, Snare/fixing ring/IS-1 connector is pulled into the prepectoral 11F-12F peel-away sheath.

LEAD PULLED THROUGH PRE-PECTORAL 11F SHEATH

Snare closed around suture

Tip of 11F sheath

Tip of 4F sheath force fit on pin of IS-1 connector

IS-1 connector

A

B

Figure 23-122  Modified Elencwajg & Lopez-Cabanillas femoral approach to transseptal LV lead placement: part 6. A, IS-1 connector with attached suture is pulled into the 11F-12F prepectoral sheath. B, Snare and IS-1 connector are pulled into the pacemaker pocket. The suture is pulled into the pocket, and the fixing ring and suture removed from the IS-1 connector.



23  Interventional Techniques for Device Implantation

Box 23-11 

TRANSSEPTAL LEFT VENTRICULAR LEAD PLACEMENT EQUIPMENT Prepectoral Transseptal 25-mm loop snare: Amplatz Goose Neck Snare (eV3) 45-cm deflectable sliceable catheter: Selectsite 304-XL74 (Medtronic) Slicing tool: Universal II slitter (Medtronic) 8-French (8F) transseptal sheath: Preface (Biosense Webster) Transseptal needle: Brockenbrough curved needle (Medtronic) 69-cm 4.1F active-fixation lead, 69 cm: SelectSecure 3830 (Medtronic) Femoral Transseptal 25-mm loop snare: Amplatz Goose Neck Snare (eV3) 8F transseptal sheath: Preface (Biosense Webster) Transseptal needle: Brockenbrough curved needle (Medtronic) 12F transseptal sheath: Check-Flo Performer Introducer, Mullins Design (Cook) 4F sheath (fixing ring): AvantiPlus (Cordis) 11F long hemostatic sheath: SafeSheath Long (Pressure Products) 0 suture, 30-inch length (braided polyester): Ethibond Excel (Ethicon) 6F multipurpose guide: Mach 1 MP2 (Boston Scientific) 100-cm 7F screw-in lead Slicing tool: Universal II slitter (Medtronic) See Interventional Equipment List at the end of Chapter 22 and online for details and ordering information.

INTERVENTIONAL APPROACH TO HIGH DEFIBRILLATION THRESHOLDS The addition of a subcutaneous coil or subcutaneous array for high defibrillation thresholds (DFTs) was the surgical approach to high DFTs when one or more coils were tunneled in the subcutaneous (SC) tissue around the left chest. However, placement of a subcutaneous lead may require a second procedure to position the patient properly. This is particularly challenging for the nonsurgeon, can be painful for the patient, and involves the risk of traumatic perforation of skin and pleura. A defibrillator coil designed for intravascular implantation is available (Transvene, CS/SVC Unipolar, endocardial CS/SVC lead for

711

cardioversion and defibrillation, Model 6937A), with coil length of 5 cm, surface area 125 mm2, 58-cm and 65-cm lengths, and requiring a 9F introducer (Medtronic, Minneapolis). It has no fixation mechanism and a DF1 connector. The supplemental transvenous lead can be placed in the CS, used to replace a proximal coil that is displaced to the right atrium, or added to an existing proximal coil with an adapter (Fig. 23-123, A). When high DFTs are encountered with a right-sided implant, placement of the transvenous coil in the left subclavian vein can be effective (Fig. 23-123, B). Of the transvenous approaches described, we find placement in the azygos vein to be the most effective supplemental ICD coil location for high DFTs.100 However, Nilsson et al.101 suggest that the hemiazygos vein may be superior for right-sided implants. Cooper et al.102 describe a typical EP skill set approach to azygos coil placement.2,3 A JR-4 catheter is loaded onto a Wholey wire and advanced wire first into the SVC. Working in the anteroposterior (AP) view, the JR-4 and Wholey wire are positioned above the superior margin of the right main-stem bronchus. From there the JR-4 catheter is directed straight-posterior and the area probed with the wire to identify the azygos vein as it empties into the posterior SVC. The EP skill set approach “typically … takes less than 15 min to complete and uses less than 5 min of additional fluoroscopy.”102 The authors state that they rarely find it necessary to inject contrast while searching for the azygos vein os, although with this method they have placed a coil anterior to the heart in an internal thoracic vein that had to be repositioned in the azygos. INTERVENTIONAL APPROACH TO AZYGOS VEIN COIL PLACEMENT Using the approach of Cooper et al.,102 intravenous contrast is rarely used when searching for the azygos vein os, but this approach takes 15 minutes and can be complicated by anterior coil placement. The interventional approach described next relies on specific catheter shapes, catheter manipulation with two hands, and contrast injection by the assistant. Using the interventional skill set approach, locating the os and advancing a wire into the azygos vein takes 10 mL of contrast and less than 1 minute. Total implant time is usually less than 5 minutes, and the interventional approach eliminates the possibility of anterior coil placement (Box 23-12). In the process of developing the interventional approach we evaluated a variety of catheter shapes and found a 5-French Judkins Left 3.5

Coil at innominate SVC junction Coil in left subclavian Proximal coil in SVC

A

B

Figure 23-123  Addition of transvenous supplementary transvenous coil for high defibrillation thresholds (DFTs). A, Supplementary coil (Medtronic 6937A) is placed at the superior vena cava (SVC)–innominate junction for high DFTs when the proximal coil of the ICD lead was in the SVC/high right atrium (RA). B, Supplementary coil is placed in the left subclavian because of high DFTs with a right-sided implant. The coil was connected to the proximal coil input, and the ICD “can” was removed from the circuit, in effect creating a single-coil ICD with the supplemental coil acting as the can.

712

SECTION 3  Implantation Techniques

Box 23-12 

Catheters designed for azygos vein cannulation

AZYGOS VEIN CANNULATION Contrast injection system: injection syringe, stopcock, extension, reservoir syringe, Y adapter Cannulation of azygos vein from the left (Azygous Left Catheter, Merit) Cannulation of azygos vein from the right (Azygous Right Catheter, Merit) Hydrophilic guidewire: .035 inch, 180 cm (Angled Glide Wire or Angled Zipwire) Extra-support wire: .035 inch, 180 cm (Amplatz Extra Stiff or Amplatz Ultra) Long, 9-French peel-away sheath (Standard SafeSheath CSG Worley or SafeSheath Long)

Azygous Left Impress (JL-3.5 shape)

See Interventional Equipment List in Chapter 22 for details and ordering information.

(JL-3.5) to be the most effective when cannulating the azygos vein from the left and the Amplatz Left 1 (AL-1) most effective from the right. Because standard diagnostic catheters are stiff and excessively long, we designed catheters specific for the procedure. The 5F Impress Azygous Left Angiographic Catheter (Azygous Left Wirebraid) is a softer shorter version of a JL-3.5 diagnostic catheter. The 5F Impress Azygous Right Angiographic Catheter (Azygous Right Wirebraid) is a softer shorter version of an AL-1 diagnostic catheter (Merit Medical) (Fig. 23-124). Figure 23-125 demonstrates the approach for reliably locating the azygos vein. The procedure is performed in 30- to 45-degree LAO projection; thus posterior structures are to the right. Figure 23-125

Azygous Right Impress (AL-1 shape)

Figure 23-124  Catheters designed for azygos vein cannulation from axillary vein. The Impress Azygous Left Angiographic Catheter (Azygous Left Wirebraid Ref/#1628-044, Merit Medical, New Jordan, Utah) is identical to a Judkins Left 3.5 (JL-3.5) coronary diagnostic catheter. The Impress Azygous Right Angiographic Catheter (Azygous Right Wirebraid Ref/#1628-043) is identical to an Amplatz Left 1 (AL-1) coronary diagnostic catheter. Both catheters are 5 French (5F). They are softer and shorter and track better over a glide wire than their standard diagnostic counterparts.

RAPID CANNULATION OF THE AZYGOS IN LAO PROJECTION WITH JL-3.5 AND CONTRAST

Tip of JL-3.5

Tip of 5F JL-3.5 Advance JL-3.5 over a wire into SVC

A

Withdraw tip to innominate SVC junction

B

Contrast in azygous

Tip of JL-3.5

Tip of JL-3.5

Apply counterclockwise torque and advance

C

Inject 2-4 mL of contrast to confirm location

D

Figure 23-125  Rapid cannulation of the azygos vein with 5F Azygous Left Impress catheter. The Impress Azygous Left (JL-3.5) catheter has the shape of a standard JL-3.5 diagnostic catheter but is better suited for azygos vein cannulation. The Impress Azygous Left catheter has a softer tip, is shorter, and tracks better over a glide wire. All four views are in the 37-degree left anterior oblique (LAO) projection; thus posterior structures are to the right. A, Tip of the JL-3.5 is advanced into the superior vena cava (SVC) over a wire. B, Tip of the catheter is withdrawn to the innominate-SVC junction. C, Counterclockwise torque is applied to direct  the tip posteriorly while the catheter is advanced. D, Injection of 2 to 4 mL of contrast confirms the catheter is in the azygos vein.



23  Interventional Techniques for Device Implantation

illustrates the method for locating the azygos vein from the left using a JL-3.5–shaped catheter. Figures 23-126 and 23-127 describe the technique of advancing a sheath into the azygos vein and placing the coil from the left. Figure 23-128 illustrates the method of locating the azygos vein from the right using an AL1-shaped catheter. Figure 23-129 describes the method for advancing a sheath and placing a coil into the azygos vein from the right. In the case where it is not possible to advance the coil into the azygos vein, a subcutaneous coil placed transvenously can improve

713

DFTs substantially (subcutaneous unipolar lead with defibrillator coil electrode, 6996SQ, coil length of 25 cm, surface area 500 mm2, introducer size 10F-10.5F, Medtronic) (Fig. 23-130, A and B). In the event a transvenous azygos coil is not effective in reducing DFTs of a right-sided implant, as suggested by Nilsson et al.,101 a subcutaneous coil placed in the azygos vein can be effective (Fig. 23-130, C and D). A disadvantage of these approaches is the potential difficulty removing one of these leads in the case of systemic infection.

EXCHANGE GLIDE WIRE FOR EXTRA-STIFF WIRE

Glide wire

Impress Azygous left over glide wire Advance Impress Azygous (JL-3.5 shape) over glide wire

A

Catheter tip below diaphragm glide out, extra-stiff in

B ADVANCE LONG SHEATH WITH DILATOR

Sheath tip

Dilator

Sheath tip

Extra stiff wire

Dilator

Keep dilator in as sheath enters azygos

C

Extra-stiff wire

Slide dilator in and out if difficult to advance

D

Figure 23-126  Azygos vein catheter advanced over glide wire, exchanged for extra-stiff wire, and sheath inserted. A, Glide wire is down the azygos vein with the tip below the diaphragm. Tip of the JL-3.5 (Impress Azygous Left) catheter is entering the azygos vein. This catheter is softer and easier to advance over a glide wire than a standard diagnostic JL-3.5. The Impress Azygous is also not as long as a diagnostic catheter, avoiding the need for exchange-length wires. B, Tip of the JL-3.5 is below the diaphragm, the glide wire is removed, and the extra-stiff guidewire is inserted, placing its tip as far below the diaphragm as possible; the catheter is then removed. C, The long, 9F-OD peel-away sheath (Worley-STD) is advanced with the dilator in over the glide wire. The tip of the dilator can be curved in anticipation of the bend from the innominate to the azygos vein. D, If there is difficulty advancing around the bend, the dilator can be withdrawn and advanced as the sheath rounds the bend. If the problem persists, the extra-stiff wire can be exchanged for super-stiff wire.

714

SECTION 3  Implantation Techniques

WITH THE DILATOR BELOW THE DIAPHRAGM, ADVANCE THE SHEATH OFF DILATOR

Sheath tip

Sheath tip Dilator

Dilator

A

B

Wire

ADVANCE THE COIL BELOW THE DIAPHRAGM COIL RETRACTS AS SHEATH IS REMOVED

Sheath tip

Coil

Coil Sheath tip

C

D

Figure 23-127  Advance sheath and insert coil in azygos vein from left side. A, Dilator and sheath are advanced deep into the azygos vein. B, Tip of the wire and dilator are below the diaphragm. From here, the sheath is advanced over the dilator until the tip is below the diaphragm. The dilator and wire are removed. C, With the tip of the sheath below the diaphragm, the coil is advanced through the sheath until its tip is below the diaphragm. D, With the stylet in place and the tip of the coil held as far below the diaphragm as possible, the sheath is peeled away. As the sheath is removed, the coil will retract. The coil can always be withdrawn if desired, but will not advance without the sheath.



23  Interventional Techniques for Device Implantation

715

RAPID CANNULATION OF THE AZYGOS IN LAO PROJECTION WITH AL-1 AND CONTRAST

Tip of AL-1 AL-1 in SVC withdrawn and turned counterclockwise to the innominate

A

From innominant advance counterclockwise torque

B

Tip of AL-1

Tip of AL-1

Contrast in azygos

Inject contrast; confirm location; withdraw slightly

C

Tip of AL-1 engages azygos

D

Figure 23-128  Cannulation of azygos vein from the right side. A, Impress Azygous Right (AL-1) catheter is advanced into the superior vena cava (SVC) over a wire. This catheter is the same shape as an AL-1 diagnostic catheter but has a softer tip, is shorter, and tracks better over a glide wire. B, The AL-1 is posterior and at or just above the level of the azygos vein. C, The AL-1 is advanced until the tip is in or just below the azygos. D, The AL-1 is withdrawn slightly, and the tip extends deep into the azygos vein.

716

SECTION 3  Implantation Techniques

EXCHANGE GLIDE WIRE FOR EXTRA STIFF WIRE WITH AL-1 AND ADVANCE SHEATH

Sheath tip Dilator

AL-1 Wire

A

B ADVANCE THE SHEATH OFF THE DILATOR TO PLACE TIP BELOW DIAPHRAGM

Sheath tip

Sheath tip

Dilator

C

D

Figure 23-129  Inserting sheath in azygos vein from right axillary vein. A, Impress Azygous Right catheter (AL-1) is deep in the azygos vein. From here a glide wire is advanced to a position below the diaphragm and the tip of Azygous Right catheter is advanced over the glide wire. Once the tip of the Azygous Right catheter is below the diaphragm, the glide wire is exchanged for the extra-stiff wire. The Impress Azygous Right has  the same shape as an AL-1 diagnostic catheter, but it has softer tip, is not as long, and tracks better over a glide wire. B, With the dilator in place, the sheath (Worley-STD) is advanced over the extra-stiff glide wire. C, Tip of the dilator is below the diaphragm. The dilator is held in place and the sheath advanced until its tip is below the diaphragm. D, Tip of the sheath is below the diaphragm. The coil is advanced and the sheath removed, keeping the tip below the diaphragm.



23  Interventional Techniques for Device Implantation

717

TRANSVERSE IMPLANTATION OF SUBCUTANEOUS COIL FOR HIGH DFTS

Coil

Coil

A

B

PA erect

L

Coil

C

Coil

D

Figure 23-130  Transvenous placement of the 25 cm subcutaneous coil to reduce high defibrillation thresholds (DFTs). A and B, Posteroanterior (PA) and lateral chest radiographs demonstrate placement of the 25-cm unipolar coil designed for subcutaneous placement (SQ coil) (Model 6996SQ Medtronic, Inc, Minneapolis, Minn) from the left subclavian vein, reducing DFTs from greater than 35 joules (J) using the integrated SVC coil, to less than 15 J with the SQ coil in the superior vena cava (SVC) port. C and D, PA and lateral chest radiographs show placement of the 25-cm SQ coil in the azygos vein. The 25 cm coil was placed in the azygos vein when a 50-mm unipolar coil electrode (Transvene—CS/SVC 6937A Medtronic, Inc, Minneapolis, Minn) (Transvene coil) did not reduce the DFTs. When connected alone to the SVC input, neither the integrated coil in the SVC nor the 50-mm Transvene coil in the azygos vein reduced the DFTs which remained greater than 45 J. With the 25-cm coil in the azygos vein the DFTs were less than 26 J.

REFERENCES 1. Moss AJ, Hall WJ, Cannom DS, et al: Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361:1329, 2009. 2. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation 117:2820, 2008. 3. Linde C, Daubert C: Cardiac resynchronization therapy in patients with New York Heart Association Class I and II heart failure: an approach to 2010. Circulation 122:1037, 2010. 4. Lubitz SA, Leong-Sit P, Nowell Fine N, et al: Effectiveness of cardiac resynchronization therapy in mild congestive heart failure: systematic review and meta-analysis of randomized trials. Eur J Heart Fail 12:360, 2010. 5. Levy D, Kenchaiah S, Larson MG, et al: Long-term trends in the incidence of and survival with heart failure. N Engl J Med 347:1397, 2002. 6. Lickfett L, Bitzen A, Arepally A, et al: Incidence of venous obstruction following insertion of an implantable cardioverterdefibrillator: a study of systematic contrast venography on patients presenting for their first elective ICD generator replacement. Europace 6:25, 2004. 7. Spittell P, Vleietstra R, Hayes D, Higano S: Venous obstruction due to permanent transvenous pacemaker electrodes: treatment with percutaneous transluminal balloon venoplasty. Pacing Clin Electrophysiol 13:271, 1990. 8. McCotter CJ, Angle JF, Prudente LA, et al: Placement of transvenous pacemaker and ICD leads across total chronic occlusions. Pacing Clin Electrophysiol 28:921, 2005.

9. Worley SJ: Implant venoplasty: dilatation of subclavian and coronary veins to facilitate device implantation: indications, frequency, methods, and complications. J Cardiovasc Electrophysiol 19:1004, 2008. 10. Tauras JM, Palma EC: Venoplasty of innominate bridge during implantation of single-chamber ICD in a patient with a persistent left-sided superior vena cava. Pacing Clin Electrophysiol 31:1077, 2008. 11. Kowalski O, Lenarczyk R, Prokopczuk J, et al: Effect of percutaneous interventions within the coronary sinus on the success rate of the implantations of resynchronization pacemakers. Pacing Clin Electrophysiol 29:1075, 2006. 12. Ailawadi G, LaPar D, Swenson B, et al: Surgically placed left ventricular leads provide similar outcomes to percutaneous leads in patients with failed coronary sinus lead placement. Heart Rhythm 7:619, 2010. 13. Poole JE, Gleva MJ, Mela T, et al: Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures results from the REPLACE Registry. Circulation 122:1553, 2010. 14. Aggarwal R, Darzi A: Technical-skills training in the 21st century. N Engl J Med 355:25, 2006. 15. Cleland JGF, Daubert JC, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539, 2005. 16. Solomon R, Werner C, Mann D, et al: Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 331:1416, 1994. 17. Rihal CS, Textor SC, Grill DE, et al: Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105:2259, 2002.

18. Cowburn P, Patel H, Pipes R, Parker J: Contrast nephropathy post cardiac resynchronization therapy: an under-recognized complication with important morbidity. Eur J Heart Fail 7:899, 2005. 19. Marenzi G, Assanelli E, Marana I, et al: N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 354:2773, 2006. 20. Boerrigter G, Costello-Boerrigter L, Abraham W, et al: Cardiac resynchronization therapy improves renal function in human heart failure with reduced glomerular filtration rate. J Card Fail 14:539, 2008. 21. Adelstein E, Shalaby A, Saba S: Response to cardiac resynchronization therapy in patients with heart failure and renal insufficiency. PACE 33:850, 2010. 22. Dixon S, Grines C, O’Neill W: The year in interventional cardiology. J Am Coll Cardiol 55:2272, 2010. 23. McCullough P, Tumlin J: Prostaglandin-based renal protection against contrast-induced acute kidney injury. Circulation 120:1749, 2009. 24. Mautone A, Brown J: Contrast-induced nephropathy in patients undergoing elective and urgent procedures. J Interv Cardiol 23:78-85, 2010. 25. Brown JR, DeVries JT, Robb JF, et al: Serious renal dysfunction after percutaneous coronary intervention can be predicted. Am Heart J 155:260, 2008. 26. Mueller C, Buerkle G, Buettner HJ, et al: Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 162:329, 2001. 27. Solomon R, Werner C, Mann D, et al: Effects of saline, mannitol, and furosemide on acute decreases in renal function

718

SECTION 3  Implantation Techniques

induced by radiocontrast agents. N Engl J Med 331: 1416, 1994. 28. Merten GJB, Burgess W, Gray LV, et al: Prevention of contrastinduced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 291:2328, 2004. 29. Brown JR, Block CA, Malenka DJ, et al: Sodium bicarbonate plus N-acetylcysteine prophylaxis: a meta-analysis. J Am Coll Cardiol Interv 2:1116, 2009. 30. Zoungas S, Ninomiya T, et al: Systematic review: sodium bicarbonate treatment regimens for the prevention of contrastinduced nephropathy. Ann Intern Med 151:631, 2009. 31. Brar SS, Hiremath S, Dangas G, et al: Sodium bicarbonate for the prevention of contrast induced acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol 4:1584, 2009. 32. Brar SS, Shen AY, Jorgensen MB, et al: Sodium bicarbonate vs. sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA 300:1038, 2008. 33. Ozcan EE, Guneri S, Akdeniz B, et al; Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrastinduced nephropathy: a comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures—a single-center prospective controlled trial. Am Heart J 154:539, 2007. 34. Masuda M, Yamada T, Mine T, et al: Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure. Am J Cardiol 100:787, 2007. 35. Briguori C, Airoldi F, D’Andrea D, et al: Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation 115:1211, 2007. 36. Maioli M, Toso A, et al: Sodium bicarbonate versus saline for the prevention of contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. J Am Coll Cardiol 52:599, 2008. 37. Schwab S, Hlatky M, Pieper K, et al: Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent. N Engl J Med 320:149, 1989. 38. Jo S, Youn TJ, Koo BW, et al: Renal toxicity evaluation and comparison between Visipaque (Iodixanol) and Hexabrix (Ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial. J Am Coll Cardiol 48:924, 2006. 39. Aspelin P, Aubry P, Fransson S-G, et al: Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 348:491, 2003. 40. Solomon R, Natarajan M, Doucet S, et al: Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 115:3189, 2007. 41. Swartz RD, Crofford LJ, Phan SH, et al: Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure. Am J Med 114:563, 2003. 42. Yerram P, Saab G, Karuparthi PR, et al: Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure: role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. Clin J Am Soc Nephrol 2:258, 2007. 43. Durant TM, Stauffer HM, Oppenheimer MJ, Paul RE: The safety of intravascular carbon dioxide and its use for roentgenologic visualization of intracardiac structures. Ann Intern Med 47:191, 1957. 44. Heye S, Maleux G, Marchal GJ: Upper-extremity venography: CO2 versus iodinated contrast material. Radiology 241:291, 2006. 45. Winters S, Curwin J, Sussman J, et al: Utility and safety of axillosubclavian venous imaging with carbon dioxide (CO2) prior to chronic lead system revisions. PACE 33:790, 2010. 46. Tepel M, van der Giet M, Schwarzfeld C, et al: Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 343:180, 2000. 47. Shyu K-Gi, Cheng J-J, Kuan P: Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol 40:1383, 2002. 48. Thiele H: Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. J Am Coll Cardiol 55:2201, 2010. 48a.  ACT Investigators. Acetylcysteine for the Prevention of Contrast Induced Nephropathy (ACT) Trial. Paper Presented at the Annual Meeting of the American Heart Association; November 16, 2010; Chicago, IL. 49. Spargias K, Alexopoulos E, Kyrzopoulos S, et al: Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation 110:2837, 2004. 50. McCullough P, Tumlin J: Prostaglandin-based renal protection against contrast-induced acute kidney injury. Circulation 120:1749, 2009.

51. Spargias K, Adreanides E, et al: Iloprost prevents contrastinduced nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation 120:1793, 2009. 52. Marenzi G, Marana I, Lauri G, et al: The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 349:1333, 2003. 53. Lee PT, Chou KJ, Liu CP, et al: Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis: a randomized controlled trial. J Am Coll Cardiol 50:1015, 2007. 54. Kagan A, Sheikh-Hamad D: Contrast-induced kidney injury: focus on modifiable risk factors and prophylactic strategies. Clin Cardiol 33:62, 2010. 55. Antonelli D, Freedberg NA, Rosenfeld T: Lead insertion by supraclavicular approach of subclavian vein puncture. Pacing Clin Electrophysiol 24:379, 2001. 56. Fox DJ, Petkar S, Davidson NC, Fitzpatrick AP: Upgrading patients with chronic defibrillator leads to a biventricular system and reducing patient risk: contralateral LV lead placement. Pacing Clin Electrophysiol 29:1025, 2006. 57. Gula LJ, Ames A, Woodburn A, et al: Central venous occlusion is not an obstacle to device upgrade with the assistance of laser extraction. Pacing Clin Electrophysiol 28:661, 2006. 58. Venkataraman G, Hayes D, Strickberger SA: Does the riskbenefit analysis favor the extraction of failed sterile pacemaker and defibrillator leads? J Cardiovasc Electrophysiol 20:1413, 2009. 59. Worley SJ, Gohn DC, Pulliam RW: Opening an occluded subclavian vein with a screw-like flexible hollow guide-wire and venoplasty. Pacing Clin Electrophysiol 30:1290, 2007. 60. Worley SJ, Gohn DC, Smith TL: Micro-dissection to open totally occluded subclavian veins. EP Lab Digest September 2003. 61. Worley SJ, Gohn DC, Pulliam RW: Needle directed re-entry to cross a subclavian occlusion following failed microdissection. Pacing Clin Electrophysiol 30:1562, 2007. 62. McGuckin JF, Gosnear AM, Williams RL: A new pathway for central venous occlusion after the failure of conventional techniques: a radiofrequency energy guidewire may be a useful treatment option. Endovasc Today July 2009. 63. Baerlocher MO, Asch MR, Myers A: Successful recanalization of a longstanding complete left subclavian vein occlusion by radiofrequency perforation with use of a radiofrequency guidewire. J Vasc Interv Radiol 17:1703, 2006. 64. Asgar AW, Joaquim Miro J, Ibrahim R: Recanalization of systemic venous baffles by radiofrequency perforation and stent implantation. Catheter Cardiovasc Interv 70:591, 2007. 65. Honnef D, Wingen M, Günther RW, et al: Sharp central venous recanalization by means of a TIPS needle. Cardiovasc Interv Radiol 28:673, 2005. 66. Sadarmin PP, Uberoi R, Tomlinson DR, Betts TR: ICD lead implantation following sharp cannulation of a blocked superior vena cava. PACE 33:1-3, 2010. 67. Bittl J, Sanborn T: Excimer laser-facilitated coronary angioplasty: relative risk analysis of acute and follow-up results in 200 patients. Circulation 86:71, 1992. 68. Worley SJ, Gohn DC, Pulliam RW: Excimer laser catheter to cross a subclavian occlusion after failed microdissection. Heart Rhythm 5:469, 2008. 69. Worley SJ, Gohn DC, Pulliam RW: Excimer laser to open refractory subclavian occlusion in 12 consecutive patients. Heart Rhythm 7:634, 2010. 69a.  Elayi CS, Allen CL, Leung S, et al: Inside-out access: A new method of lead placement for patients with central venous occlusions. Heart Rhythm 8:851-857, 2011. 70. Worley SJ, Gohn DC, Pulliam RW: Over the wire lead extraction and focused force venoplasty to regain venous access in a totally occluded subclavian vein. J Interv Card Electrophysiol 23:135137, 2008. 71. Chierchia G-B, Geelen P, Rivero-Ayerza M, Brugada P: Double wire technique to catheterize sharply angulated coronary sinus branches in cardiac resynchronization therapy. Pacing Clin Electrophysiol 28:168, 2005. 72. Perzanowski C, Gilliam FR: The buddy wire technique: accessing lateral coronary veins while maintaining coronary sinus position. J Interv Card Electrophysiol 13:231, 2005. 73. Sandler DA, Feigenblum DY, et al: Cardiac vein angioplasty for biventricular pacing. Pacing Clin Electrophysiol 25:1788, 2002. 74. Soga Y, Ando K, Yamada T, et al: Efficacy of coronary venoplasty for left ventricular lead implantation. Circ J 71:1442, 2007. 75. Luedorff G, Grove R, Kranig W, Thale J: Different venous angioplasty manoeuvres for successful implantation of CRT devices. Clin Res Cardiol 98:159, 2009. 76. Osman F, Kundu S, Tuan J, Pathmanathan RK: Use of coronary venous angioplasty to facilitate optimal placement of left ventricular lead during CRT. Pacing Clin Electrophysiol 3:281, 2009. 77. Chauhan K, Sayad D, Bowerman R, Barold SS: Coronary vein angioplasty with noncompliant balloon for resistant coronary vein stenosis during left ventricular lead implantation. Pacing Clin Electrophysiol 31:251, 2008.

78. Worley SJ, Gohn DC, Pulliam RW: Focused force coronary venoplasty to eliminate a refractory stenosis preventing LV lead placement in two patients. Pacing Clin Electrophysiol 31:1503, 2008. 79. Lopez JA, Hernandez E: Transvenous implantation of a coronary sinus lead for left ventricular pacing after cutting balloon angioplasty. Pacing Clin Electrophysiol 30:568, 2007. 80. Breuls N, Res JC: LV lead fixation in a coronary vein may be the cause and result of thrombosis. Pacing Clin Electrophysiol 31:1506, 2008. 81. Burke MC, Morton J, Lin AC, et al: Implications and outcome of permanent coronary sinus lead extraction and reimplantation. J Cardiovasc Electrophysiol 16:830, 2005. 82. Zucchelli G, Soldati E, Segreti L, et al: Cardiac resynchronization after left ventricular lead extraction: usefulness of angioplasty in coronary sinus stenosis. Pacing Clin Electrophysiol 31:908, 2008. 83. Abben RP, Chaisson G: Traversing and dilating venous collaterals: a useful adjunct in left ventricular electrode placement. J Invasive Cardiol 22:93, 2010. 84. Cesario DA, Shenoda M, Brar R, Shivkumar K: Left ventricular lead stabilization utilizing a coronary stent. Pacing Clin Electrophysiol 29:427, 2006. 85. Szilagyi S, Merkely B, Roka A, et al: Stabilization of the coronary sinus electrode position with coronary stent implantation to prevent and treat dislocation. Pacing Clin Electrophysiol 18:303, 2007. 86. Gutleben KJ, Nölker G Marschang H, et al: Rescue-stenting of an occluded lateral coronary sinus branch for recanalization after dissection during cardiac resynchronization device implantation. Europace 10:1442, 2008. 87. Van Gelder BM, Meijer A, Basting P, et al: Successful implantation of a coronary sinus lead after stenting of a coronary vein stenosis. Pacing Clin Electrophysiol 26:1904, 2003. 88. Worley SJ, Gohn DC, Pulliam RW: Coronary vein rupture during venoplasty for LV lead placement. Pacing Clin Electrophysiol 31:904, 2008. 89. Worley SJ: How to use balloons as anchors to facilitate cannulation of the coronary sinus left ventricular lead placement and to regain lost coronary sinus or target vein access. Heart Rhythm 6:1242, 2009. 90. Kranig W, Grove R, Lüdorff G, Thale J: Successful implantation of a left ventricular lead for cardiac resynchronization therapy in extremely unfavourable coronary venous anatomy: “over the wire” technique. Herzschr Elektrophys 15:211, 2004. 91. Worley SJ, Gohn DC, Pulliam RW: Goose neck snare for LV lead placement in difficult venous anatomy. Pacing Clin Electrophysiol 32:1577, 2009. 92. Bordachar P, Nicolas Derval N, Ploux S, et al: Left ventricular endocardial stimulation for severe heart failure. J Am Coll Cardiol 56:747, 2010. 93. Derval N, Steendijk P, Gula LJ, et al: Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. J Am Coll Cardiol 55:566, 2010. 94. Spragg DD, Dong J, Barry J, et al: Optimal left ventricular endocardial pacing sites for cardiac resynchronization therapy in patients with ischemic cardiomyopathy. J Am Coll Cardiol 56:774, 2010. 95. Jaïs P, Douard H, Shah DC, et al: Endocardial biventricular pacing. Pacing Clin Electrophysiol 21:2128, 1998. 96. Leclercq F, Hager FX, Macia JC, et al: Left ventricular lead insertion using a modified transseptal catheterization technique: a totally endocardial approach for permanent biventricular pacing in end-stage heart failure. Pacing Clin Electrophysiol 22:1570, 1999. 97. Sen JI, Cesario DA, Swerdlow CD, Shivkumar K: Left ventricular endocardial lead placement using a modified transseptal technique. J Cardiovasc Electrophysiol 15:234, 2004. 98. Van Gelder BM, Scheffer MG, Meijer A, Bracke FA: Transseptal endocardial left ventricular pacing: an alternative technique for coronary sinus lead placement in cardiac resynchronization therapy. Heart Rhythm 4:454, 2007. 99. Elencwajg B, Cabanillas Nl, Cardinali El, Trainini JC: Ventricular resynchronization: a new technique and device for endocardial left ventricular lead placement. Rev Argent Cardiol 78:143, 2010. 99a.  Lau EW: Yoked Catheter Positioning in Transseptal Endocardial Left Ventricular Lead Placement. Pacing Clin Electrophysiol 34:884-893, 2011. 100. Cooper J, Latacha, M , Soto G, et al: The azygos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series. Pacing Clin Electrophysiol 31:1405, 2008. 101. Nilsson K, Jackson K, et al: Hemiazygous coil placement for high-defibrillation thresholds in a patient with a rightsided implantable cardioverter-defibrillator. PACE 33, 2010. 102. Cooper J, Smith TW, et al: How to implant a defibrillation coil in the azygous vein. Heart Rhythm 6:1677, 2009.

24  24

Approach to Pulse Generator Changes STEVEN P. KUTALEK  |  BHARAT K. KANTHARIA

R

eplacement of the pulse generator of a pacemaker or a defibrillator may occur at any time in the life of a patient with an implanted device. Although this need is most often the result of the finite life span of the battery, replacement of the device may also be precipitated by such diverse causes as infection,1-12 erosion,13-16 trauma,17-23 component failure,24-29 and migration of the device.30-34 In recent years, the need for system upgrade has become an increasingly important indication for pulse generator replacement and associated lead revision.35-43 This is the result of the increasing number of devices being implanted for newer indications in a broader patient population, the generally younger age at which patients receive implants, and patients living longer after device implantation because of advances in medical treatment as well as the device’s life sustaining effects. Indications for device replacement have evolved with the development of new technologies and greater understanding of cardiac physiology. These more recent requirements for replacement may involve upgrade of a pacemaker to a defibrillator, but more importantly and with greater complexity, upgrade to a biventricular cardiac resynchronization device through the addition of new leads, including a coronary sinus electrode44,45 (Box 24-1). Generator change may also be required secondarily from the need for lead replacement or revision,46-51 including lead advisories and recalls,52-57 especially if the generator is already near end of service. Chronic lead malfunction, in particular low lead impedance, may also require premature battery replacement because of high current drain. The success of the replacement procedure depends on accurate preoperative evaluation and planning as well as good surgical technique. This chapter addresses preoperative evaluation of the patient and the pacing/defibrillation system, as well as the indications for device replacement and revision and the surgical process. Because of the variety of indications for replacement of pacemaker or defibrillator generators, the approach to generator change or lead revision begins at the initial implantation of the system. Meticulous technique in the positioning of endocardial leads allows optimal programming of the pulse generator to reduce long-term battery drain, thereby prolonging the life of the generator.58 Careful lead positioning also reduces the likelihood of lead dislodgment that would require reoperation.49,50,59,60 Care with venous entry, lead fixation, leadgenerator connection, pocket location, appropriate surgical plane, and handling of components enhances long-term pacing and sensing function. Ensuring that leads in the generator pocket are placed posterior to the pulse generator improves the likelihood of expeditious pulse generator replacement without lead damage. Bulkier defibrillator leads or lead headers may be placed in the same surgical plane next to the device instead of behind it. Ensuring that the pocket is of adequate size to accommodate easily the pulse generator and lead coils reduces the risk of damage to the leads in the pocket caused by excessive bending, which itself may result in lead fractures in a location separate from the anchoring sleeve, usually the most vulnerable area for lead breakage. Thus, the primary implanting physician prepares the stage for successful reoperation (Box 24-2).

Special Considerations for Implantable Cardioverter-Defibrillators Since the first surgical placement of an implantable cardioverterdefibrillator (ICD) in 1980,61 the role of ICDs in the management of

patients with life-threatening ventricular tachyarrhythmias has become well established. Advanced indications have enabled widespread use of ICDs in clinical practice. Many patients outlive the life span of their first ICD generator. As with pacemakers, ICDs are prone to complications such as infection and malfunction, necessitating replacement or revision of the generator or leads. Although the approach to ICD generator change, lead evaluation, and reoperation can be extrapolated from the approach to pacemaker revision, certain aspects of ICD generator change and revision deserve special consideration. These include the need to upgrade to more complex lead systems or pacing modes (including cardiac resynchronization), lead malfunction in more complex lead systems that involve defibrillation as well as pacing, inadequate defibrillation thresholds, change of implantation site, and interchangeability of older devices and leads to newer models, or the interchangeability of components from various manufacturers. Each of these issues is addressed in this chapter in relation to special considerations for ICD devices.

Patient Evaluation NONINVASIVE EVALUATION Before performing a surgical procedure for pacemaker or defibrillator revision or generator replacement, the physician must document the need for intervention. Specific indications are approached with a welldefined plan of evaluation. Documentation of Pacemaker Pulse Generator Battery Depletion Most bradycardia pacemaker pulse generators provide direct or indirect indicators of battery depletion, documenting the need for enhanced follow-up, elective generator replacement, or incipient battery failure (end of service). Additionally, certain nonspecific indicators may alert the physician to early signs of battery wear (Box 24-3). Because most pacemaker patients are followed by remote monitoring systems more frequently than by full evaluation in the physician’s office, it is not surprising that battery depletion for permanent pacemaker patients is most often detected through remote recordings.62-65 Remote evaluation of defibrillator systems also allows interrogation of device function and arrhythmic events, as well as battery capacity.66-73 A change in magnet-activated paced rate remains the most common indicator of reduced battery output voltage for pacemakers (Box 24-4). Some pacemaker pulse generator models respond to declining voltages through a gradual reduction in magnet-activated pacing rate; reduced rates indicate the need for enhanced follow-up, with even slower rates indicating elective or obligatory replacement. Other models demonstrate an abrupt shift in the magnet-activated paced rate at the enhanced follow-up period or at the time of elective replacement. A demand mode switch from DDD to VVI (or a magnet mode switch from DOO to VOO) may occur at the elective replacement time or as an obligate replacement indicator for dual-chamber systems before complete battery failure. Inability to reprogram the device, inaccurate measurement of lead impedances, and an automatically reprogrammed reduction in data storage capabilities to preserve battery life may also occur as the generator approaches end of service. Other, secondary parameters suggest gradual battery depletion and can be interrogated remotely. The usual battery impedance in a new pulse generator is less than 1000 ohms (Ω). As pulse generator batteries deplete, internal battery impedance increases, providing a

719

720

SECTION 3  Implantation Techniques

Box 24-1 

INDICATIONS FOR PACEMAKER OR ICD GENERATOR REPLACEMENT Primary Indications Generator battery depletion: Elective replacement indication (ERI) End of service, i.e., complete battery failure (EOS or EOL) Loss of output Sensing malfunction caused by component failure Generator upgrade: Single chamber to dual chamber Pacemaker to ICD Pacemaker to BiV pacemaker Pacemaker to BiV ICD Single-chamber ICD to dual-chamber ICD ICD to BiV ICD Need for high-energy ICD Unipolar to bipolar (pacemaker) Pocket twitch (caused by): Lead insulation break Current leak from header or set-screw seal Unipolar system Unanticipated generator failure Device recall Secondary Indications* Pocket issues Generator migration Persistent pain Pronounced pocket effusion or hematoma Erosion or pre-erosion Infection of the pacing system Trauma Lead Issues Need for lead revision High pacing or sensing thresholds High defibrillation threshold Lead conductor fracture Lead insulation break Loose lead-generator connection Myopotential sensing Diaphragmatic pacing or sensing Twiddler’s syndrome Change bifurcated bipolar to unipolar because of malfunction of one conductor (rare) *Caused by factors other than the pulse generator itself. Patients with these indications require reoperation but may or may not require generator replacement. BiV, Biventricular; ICD, implantable cardioverter-defibrillator.

secondary indicator of the impending need for replacement (Fig. 24-1). Replacement is not required, however, until more definitive indicators appear, such as a change in magnet-activated pacing rate, a specific elective replacement indicator voltage, or mode switch. The patient’s dependence on the pacing functions of the device needs to be considered when timing the generator replacement. For example, a patient with complete heart block may not tolerate a mode switch to an asynchronous VVI pacing mode at the elective replacement time. Telemetered battery depletion curves or battery status screens (Fig. 24-2), internal calculations of anticipated device longevity at current programmed settings, and a general knowledge of the expected performance of various generators all assist in anticipating a pacemaker generator’s end of service. Ultimately, loss of sensing and pacing capabilities occurs with battery exhaustion. The rate of battery depletion may accelerate as the device reaches end of service, making timely replacement in dependent patients very important. Indicators for Replacement of ICD Generators Precise longevity of ICD battery systems is more difficult to predict because the rate of defibrillator generator depletion depends on the (1)

Box 24-2 

FACTORS TO REDUCE NEED FOR REOPERATION Technical Issues of Device Implantation Appropriate connections of leads in the generator header Gentle treatment of tissues Hemostasis Secure closure of muscle, subcutaneous tissues, and skin Pocket large enough for generator and leads, without tension Generator set screws secure Appropriate pocket location, not intruding on clavicle and not too lateral in axilla Lead Issues Meticulous care in positioning for pacing, sensing, and defibrillation thresholds Fixation Lead selection appropriate for patient Integrity of lead insulation maintained Gentle handling of stylets Anchoring sleeve secured with nonabsorbable suture Placement of lead coils posterior to, or beside, pulse generator Appropriate connections: A or V to generator Proximal and distal high-energy coils, array, patch Secure adapters, if required Leads fully advanced into generator head Adapters secure and not kinked Set screws sealed

frequency of bradycardia pacing, (2) delivery of high-energy shocks to terminate tachyarrhythmias, and (3) data storage. Nevertheless, documentation of ICD battery drain remains crucial to evaluation of the safe function of the defibrillator system. Manufacturers have developed relatively straightforward methods to document impending ICD battery depletion, which fall into three major categories: (1) a measurable reduction in battery voltage (V) or remaining charge (mAh, milliamphours) that can be acquired through telemetry, (2) an increase in measured charge time to a level that indicates the need for elective replacement, and (3) various device-specific markers that indicate a particular degree of pulse generator depletion. Measurement of charge time to a maximal voltage on the device capacitors is the earliest method used for estimating the remaining longevity of an ICD. Most early systems included such markers. However, this method of determining elective replacement time requires fully charging the capacitors, which may necessitate an office visit, or determining the charge time from a capacitor recharge that may have occurred weeks earlier because of programmed automatic capacitor Box 24-3 

INDICATORS OF BATTERY DEPLETION Primary Indicators Pacemaker Abrupt decrease in magnet-paced rate Gradual decrease in magnet-paced rate Mode switch (DDD to VVI, or DOO to VOO magnet mode) Battery depletion indicator Abrupt loss of pacing or sensing capability Defibrillator Reduction in battery voltage Battery depletion indicator Secondary Indicators Pacemaker Rise in internal battery impedance Drop in battery voltage Defibrillator Increased charge time



24  Approach to Pulse Generator Changes

721

Box 24-4 

GENERAL MAGNET RESPONSES OF PULSE GENERATORS Pacemaker Battery depletion indicators: Mode switch (to DOO or VOO) Rate change—gradual or abrupt Magnet rate: Fixed Variable First few complexes faster Last few complexes faster Output: Fixed Variable Voltage or pulse width decremented in first or last few complexes for threshold margin test, or pulse width reduced after magnet withdrawal Duration: Continuous as long as magnet is applied Fixed number of paced complexes Defibrillator Inhibition of sensing—especially useful to avoid initiation of tachyarrhythmia with magnet application Reset of tachyarrhythmia sensing Activation/inactivation of device (if this function is programmed “on”)

maintenance. Charge times can also be obtained if the device spontaneously charges and delivers therapy at maximum output, but this process does not always occur opportunely between office visits. Reduced battery voltage provides a readily useful method of determining generator depletion; the value can be obtained telemetrically. This method is now the most common for marking elective replacement time and end of service for ICDs. Specifically, telemetered voltage can be obtained on initial interrogation of the device and is remotely retrievable in most ICD devices. Some specific ICD models use battery voltage to produce labels that indicate the beginning, middle, or end of service for pulse generators. MEASURED DATA Date last programmed ................................ June 15, 2006 10:37 Magnet rate ..................................................................... 91.5 Ventricular: Pulse amplitude ............................................................. 0.9 Pulse current ................................................................. 1.8 Pulse energy ................................................................. 0.9 Pulse charge ......................................................................1 Lead impedance ............................................................ 528 Battery data ....................... (W.G. 9438-nom. 0.95 Ah) Voltage ......................................................................... 2.61 Current .............................................................................. 9 Impedance .................................................................... 15.7

am ppm V mA µJ µC Ω V µA kΩ

Figure 24-1  Pacemaker battery depletion. Acquired telemetry data from St. Jude Medical Affinity SR Model 5130 single-chamber (VVI) pacemaker programmed to the unipolar pacing and bipolar sending mode to enable the autothreshold function. Cell impedance has increased to 15,700 Ω, a secondary indicator of battery depletion, concomitant with a reduction in cell voltage to 2.61 volts (V). Pulse amplitude and pulse width are maintained, with the device minimizing ventricular output by reducing pacing voltage through autothreshold to 0.9 V with a threshold of 0.75 V. Ventricular lead impedance is acceptable. Pulse energy is low at 0.9 microjoule (µJ) per impulse, which has enabled its long battery life from implant in March 2000 until the most recent interrogation in September 2010. Magnet rate has dropped to 91.5 beats per minute (bpm) from an initial magnet rate of 98.6 bpm. Elective replacement indicator (ERI) occurs at a magnet rate of 86.3 bpm.

Figure 24-2  Battery status indicator. Visual graphic of the battery status screen from a Boston Scientific pacemaker is clear, giving a “fuel gauge” depiction of remaining battery life, which here is “full.” The screen depicts the measured magnet rate and an estimate of the remaining longevity of the device at current programmed settings. Elective replacement indicator (ERT) and end of life (EOL) magnet rates are also indicated. Changes in programming or use of pacing affect battery longevity.

These labels can be obtained directly through interrogation of the device in the office. End of service may also be clearly indicated graphically (see Fig. 24-2). Regardless of the method used by the device to document end of service, the clinician has the responsibility to increase the frequency of follow-up visits as the unit nears elective replacement time, to ensure continued safe function of the system, protection of the patient from tachyarrhythmias, and bradycardia support if required. In the event that the patient receives frequent shocks just before the anticipated need for device replacement, elective replacement may occur earlier than originally planned. Documentation of Lead Malfunction A variety of causes of lead malfunction require reoperation,51-57,74 from primary lead dysfunction to premature battery depletion as a result of excessive current drain (see Box 24-1). Primary lead malfunction may result from outer insulation break,75-81 inner insulation break in a bipolar coaxial lead,82,83 lead conductor fracture,17,19,84-86 or lead dislodgment.49,50,59,60,87 Current drain may be increased by (1) high pacing thresholds46,88-90 through a need to increase output voltage, (2) failure to optimize generator output for long-term pacing after lead maturation, or (3) inner insulation break with a resultant low pacing impedance. All these scenarios can result in premature battery depletion. Before reoperation for lead malfunction is performed in these patients with primary lead malfunction, the physician should consider upgrading or replacing the pulse generator, especially if the battery is old. Lead malfunction can usually be documented by noninvasive telemetric evaluation or remote monitoring.63,66-73,91 A measured bipolar pacing lead impedance less than 200 Ω suggests an inner insulation break between the two coaxial pacing coils. An outer insulation break may be the result of lead wear or may have been inadvertently caused during surgery, especially with generator replacement; an inner insulation break between the two coils of a bipolar system occurs most often at the subclavian insertion site as the result of crush injury to the lead, especially with leads inserted into the subclavian vein and tied securely in a medial position in patients with a tight clavicular–first rib space. Telemetry for lead diagnostics may demonstrate markedly low bipolar pacing impedance in patients with an inner lead insulation break. The impedance may vary with manipulation of the pacemaker, which causes intermittent short-circuiting of the two lead conductors (Fig. 24-3). High pacing lead impedance (generally >1200 Ω) may be the result of lead conductor fracture or an incomplete circuit caused by a loose lead pin–pulse generator connection. Rarely, this may occur with fractures of conductors inside the pulse generator header. The introduction of high-impedance leads makes it essential to compare the

722

SECTION 3  Implantation Techniques

Pacing rate Pacing interval Average cell voltage Cell impedance Sensitivity Lead impedance Pulse amplitude Pulse width Output current Energy delivered Charge delivered Tachycardia detected

68 873 2.63 1.00 8 41 7.42 0.45 96.5 173.2 42.85 No

ppm ms volts KOhms mV ohms volts ms mA UJ UC

Figure 24-3  Inner insulation fracture. Acquired telemetry data from an early, Intermedics Intertach 262-14 VVICP antitachycardia pacemaker, connected through a bipolar coaxial lead to the right ventricular apex. Battery voltage and cell impedance are normal; however, measured lead impedance of 41 Ω is extremely low. In this patient, measured lead impedance was normal in the supine position but decreased with sitting or when the device was pulled inferiorly This behavior indicates a break in the inner insulator between the coaxial conductor strands in the area of the clavicle. With movement, the conductors contact each other, resulting in low impedance and preventing delivery of electric current to the heart. Because output voltage is fixed, the low lead impedance results in a high delivered current (96.5 mA) and high delivered energy and charge per pulse.

impedance at implantation with follow-up impedance measurements and with established acceptable impedance ranges for each lead. Depending on the point of discontinuity, lead impedance may vary with manipulation of the pulse generator or with respiration. Lead conductor fractures may be evident on chest radiographs or fluoroscopy; however, absence of visual evidence does not exclude conductor 25 mm/s

S 70

VS 650 VP 857

VF 176 VS 648

fracture. A break in the connection of the lead to the generator, or within the lead itself, can produce intermittent loss of energy delivery to the heart, which in turn results in absence of pacemaker spikes. Undersensing, or oversensing caused by lead “chatter,” may also occur with lead conductor fracture (Fig. 24-4). Most recently, this scenario has occurred with a recalled high-energy ICD lead system.92 Lead dislodgment produces intermittent noncapture or failure to sense that may be related to respiration. Pacing thresholds needed to achieve consistent capture may rise significantly. Lead impedance increases or remains unchanged. Fluoroscopy may demonstrate a loose or displaced lead tip but is not always diagnostic. Special Issues for ICD Leads The ICD lead remains the weak link in the ICD system. Oversensing caused by diaphragmatic impulses or extraneous signals may inhibit pacing therapy or lead to inappropriate delivery of “treatment” for presumed ventricular tachyarrhythmias that actually represent noise sensing.93,94 Further, although fracture and degradation of leads have become less common with transvenous (vs. epicardial) ICD lead systems, these problems nevertheless occur with some frequency, necessitating reprogramming or reoperation.95 Conductor fractures resulting from specific lead design issues have led to recalls and the need for reoperation in patients who experience a lead fracture92 (Fig. 24-5). Depleted battery status is readily evident on routine ICD follow-up both in the office and remotely (as described previously), and integrity of the ICD high energy coils can be evaluated easily in most current devices. High shocking-electrode impedance measurements may indicate lead conductor fracture or a lead-generator interface problem. Measuring high-energy electrode impedance in early devices required delivery of a shock, either to treat a clinical tachyarrhythmia 07-AUG-98 16:43

VF 146 VS 729

Surface ECG Rate EGM Markers

VP 857 VP 857

VP 857

Figure 24-4  Oversensing in antitachycardia device. Sensing of diaphragmatic myopotentials during periods of deep inspiration can lead to inappropriate triggering of the antitachycardia functions of an implantable cardioverter-defibrillator (ICD). These tracings are recorded from an ICD placed with a passive-fixation Endotak endocardial lead that incorporates integrated bipolar sensing and pacing between the right ventricular apical (RVA) high-energy shocking coil and the lead tip (Boston Scientific). Surface electrocardiogram (ECG), rate-sensing electrograms (EGMs), and marker channels all record spurious signals that represent inappropriate sensing of extracardiac electrical potentials. The frequency of these signals is high, and they occur after paced events as well as after sensed events. Pacing increases the gain of the device to avoid undersensing of low-amplitude signals of ventricular fibrillation, but it also increases the possibility of sensing extraneous noise. An underlying paced rhythm exists at a cycle length of 857 msec, but even this is altered by oversensing. The first paced complex (VP 857) is followed by two inappropriately sensed events (VS 650 and VS 648) that inhibit ventricular pacing output. Because the next native QRS complex occurs close to an inappropriately sensed signal, it is interpreted by the device to represent sensing in the ventricular fibrillation zone (VF 176). After that, another myopotential is inappropriately sensed (VS 729), and the native QRS is again sensed in the VF zone (VF 146). Finally, three sequential paced events occur at intervals of 857 msec, despite the presence of spurious electrical signals, which are not of sufficient amplitude to trigger sensing. Repetitive events such as these could lead to inappropriate antitachycardia therapies or prolonged periods of inhibition of pacing. This lead was extracted and replaced with an active-fixation endocardial Defibrillation (DF) lead positioned distally on the lower interventricular septum.



24  Approach to Pulse Generator Changes

V F F F F V V V V V VV V V VV V V V 0 0 8 8 0 8 8 8 8 8 88 8 8 88 8 8 8 2 1 1 1 1 1 2 1 1 1 1 1 2 1 11 2 2 1 5 6 5 3 3 7 4 6 3 2 6 1 4 23 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 0 0 VF VF Rx 1 Defib

4 0 0

V 8

6 6 6 6 0 0

V 8

2 6 0

C V VVV E 8 888 2 11 1 3 22 2 7 0 00 0 6 0

V V C 8 8 D 1 1 6 5 6 2 0 0 0 25.1J

VF 8 8 1 2 0

7 6 0

V 8

1000

V 8

7 6 0

V 8

6 2 0

V F 8 8 1 3 0

6 6 0

V F 8 8 2 0 0

723

8 6 0

V 8

Figure 24-5  Lead fracture and inappropriate shock. Conductor fracture with intermittent contact of the broken ends of the lead wire may result in inappropriate sensing of noise chatter, as demonstrated here in a Medtronic 6949 ICD lead with a fracture of the rate/sense conductor. Underlying native QRS complexes are easy to discern in the far-field intracardiac recordings in the top two tracings. Despite regular sinus rhythm, marker channels show a large amount of noise sensing; intracardiac recordings of noise are also evident on the right side of the tracing. Noise sense intervals vary from 120 to 500 msec. The high degree of variability of sensed intervals, as well as frequent nonphysiologic intervals shorter than 200 msec, lead to the diagnosis of noise sensing. In this example, the number of sensed intervals in the ventricular fibrillation zone is great enough to trigger the VF detection algorithm of the device. Ventricular fibrillation therapy was inappropriately delivered (VF Rx 1 Defib, 21 J). Lead replacement is recommended; alternatively, placement of a new high-energy lead may be indicated in some instances where extraction is not feasible.

or as part of a noninvasive testing protocol. As a result, about 10% of patients undergoing ICD generator replacement because of battery depletion were found to have a previously undetected sensing or defibrillation system failure.96,97 Noninvasive indicators of lead malfunction almost always occur before surgery; nevertheless, the operator should always test the lead system carefully during a battery replacement procedure and must be prepared to deal with malfunctioning leads at the time of generator change. Manipulation of a lead in a pocket may uncover a previously undetected conductor fracture. Newer systems automatically measure high-energy lead impedance at office or remote device interrogation, similar to standard pacing and sensing electrodes. The lower-energy impulses delivered by these devices may be more sensitive to the detection of microfractures than higher-energy shocks. Determination of Pulse Generator-Lead Interface Malfunction Pulse generator–lead interface problems may be grouped into three categories: (1) loose, incomplete, or uninsulated connections; (2) reversal of atrial and ventricular leads in the pulse generator connector block (for ICDs, reversal of shocking electrode polarity may also occur); and (3) pulse generator–lead mismatch.98,99 A loose pace/sense lead connection is apparent with noninvasive testing. The device may fail to deliver pacing spikes when appropriate, may intermittently fail to sense, or may oversense as a result of chatter caused by intermittent contact with the set screw. Oversensing can result in inappropriately high tracking rates or inhibition of ventricular output. Capture or sensing problems may be exacerbated by manipulation of the device. An uninsulated connection most often produces current leakage (an electrical short circuit in the system) that inhibits pacing or sensing. Leakage can occur if a set screw is not properly insulated or tightened, or if sealing rings on the lead header do not prevent body fluid from oozing into the pulse generator connector block around a loosely fitting lead. Leakage around lead header sealing rings may result from a loose lead connection or lead–pulse generator mismatch. Lead impedance in pulse generator–lead interface problems varies, depending on the specific situation. A loose, unconnected lead that remains in the pulse generator connector block, so that lead header sealing rings prevent fluid from entering, causes a break in the electric circuit and a very high impedance. If fluid enters the pulse generator connector block around a loose lead or at the level of a set screw and maintains contact with body fluids, the short circuit can produce very

low measured impedance. As with lead fractures, impedance can vary with manipulation of the device. Reversed lead connections (atrial lead in ventricular port, or vice versa) should be evident before the patient leaves the implantation laboratory, allowing immediate correction. Some atrial and ventricular leads are marked to enable easy identification, especially preformed, passive atrial J leads and straight, passive ventricular leads; however, “generic” leads may be placed into both chambers, especially straight screw-in leads, which may not be so labeled. Likewise, most atrial, left ventricular (LV), and right ventricular (RV) lead pace/sense headers for insertion into ICD ports are all of the International Standard IS-1, so the implanter must exercise care in placing these leads properly into the appropriate locations in the ICD generator connector block. It is also possible, in patients whose pacemaker or ICD remains inhibited because of native electrical activity, to see no pacing spikes initially after implantation. To be certain that the pulse generator–lead system functions appropriately immediately after implantation, the device should be programmed to an atrioventricular (AV) delay shorter than the intrinsic P-R interval, and the device should be checked with a programmer after the leads are attached to document appropriate function. Caution exercised at implantation should avoid reversed leads; for example, we always connect the ventricular lead first to ensure pacing in the proper chamber. Beyond ensuring the presence of adequate and appropriate lead connections to the pulse generator, the battery connector block and leads must be compatible (see later).98-102 This issue is less important with the standardization of new lead models used for device upgrades or generator replacements. However, incompatibility can result in fluid leakage or loose connections, with resultant loss of pace/sense or shocking capabilities, requiring reoperation. Detection of Need for Reoperation for Other Reasons Other indications for pacemaker or ICD generator replacement or lead revision generally become apparent through careful patient evaluation (see Box 24-1). Abrupt pulse generator failure with no antecedent sign of battery depletion is rare but can occur, producing symptoms in pacemaker-dependent patients. In others, abnormal pacing output or rate, lack of pacing output, or inappropriate sensing from generator malfunction may be detected by remote interrogation or in the office.27 Of particular importance to patients with ICDs are the risks of no output when required to terminate tachyarrhythmias, inappropriate shocks from oversensing of diaphragmatic or lead chatter artifact (see Fig. 24-5), and oversensing of extraneous electromagnetic signals, such

724

SECTION 3  Implantation Techniques

as surveillance systems or high-voltage generators, which can be sensed as ventricular fibrillation or can inhibit ventricular pacing output. Cellular telephones rarely present substantial interference because of variations in signal frequency.103-106 Development of pacemaker syndrome in patients with implanted ventricular demand (VVI), ventricular rate-responsive (VVIR), or atrial rate-responsive (AAIR) pacemakers presents another indication for device revision. This need should be apparent from history and physical examination, although confirmatory blood pressure or cardiac output measurements may be required. Pacemaker syndrome occurring with an implanted functioning dual-chamber pacemaker with normal lead function must be managed by reprogramming.107-110 Interchangeability of Products from Different Manufacturers Early ICD leads from different manufacturers were compatible only with ICD pulse generators from the same manufacturer. This is especially evident when replacing generators that used LV-1 leads (Fig. 24-6). For later models, manufacturers have adhered to standard header designs for ICDs, including IS-1 ports for both atrial and ventricular pace/sense leads. Defibrillation ports now also follow a standard for defibrillation lead headers, DF-1, a 3.2-mm unipolar lead head with sealing rings (Fig. 24-7). The newest agreed-on IS-4 standard, which provides four electrical connections combining the functions of a bipolar pace/sense connection with up to two high-voltage connections, should reduce some of the confusion. However, there are two approved IS-4 connections with limited distribution at this time, one for devices with and one for devices without high-voltage (defibrillation) capacity. Eventually, this situation should simplify connections, except when extra leads for defibrillation are required in individual patients, which would require an adapter to connect to the IS-4 lead111 (Fig. 24-8). For procedures involving early, nonstandard ICD connector blocks, however, the operator must be familiar with the existing system of leads and generator in the patient before surgery, and technical support from the manufacturer may be required at operation. A full range of adapters, or various pulse generator header designs, to mate a replacement generator to the existing leads, must be available. Ensuring tight and proper connections between the generator and the lead, and with any adapters and lead extenders, avoids malfunction and current leak. Although early adapters used an uncured medical adhesive to seal set

Figure 24-6  Lead upgrade to adapter. Right, An LV-1 lead (Boston Scientific), which remains in a coronary sinus branch at generator replacement. Left, An adapter to upsize the LV-1 lead to an IS-1 standard header to fit into the new pulse generator. The LV-1 lead header contains a 3.2-mm pin with no sealing rings and would not fit into an IS-1 generator header without this upsizing adapter. The end of the adapter that connects to the LV-1 lead is bulky, containing electrical contacts, sealing rings, and a set screw.

Figure 24-7  Typical trifurcated high-energy ICD lead header at generator replacement. The most inferior electrode is the coaxial IS-1 standard bipolar rate/sense electrode, with the proximal and distal defibrillation (DF-1) standard electrodes above that, carrying red insulation over the high-energy wires (Boston Scientific). The structural integrity of the lead headers and the trifurcation can be readily examined at generator replacement. The bulk of the trifurcation and the three lead headers are replaced by a single lead head in the DF-4 configuration (see Fig. 24-8).

screws in the connector block of the device, some newer adapters use set-screw seals similar to those found in pacemaker pulse generators. Special Indications for Replacement of ICD Generators As outlined in Box 24-1, the ICD generator may need to be replaced for other reasons, as discussed here. Malfunction of Generator with or without Lead Malfunction.  Hardware or software errors in the ICD generator, or more often malfunctioning ICD leads, may result in the need to revise the ICD system. The overall reported incidence of lead-related complications has ranged from 2% to 28%.112,113 These complications typically manifest as inappropriate shocks resulting from oversensing of noise; noise sensing from chatter caused by a fractured conductor has led to inappropriate shocks and pacing inhibition in some patients implanted with specific Medtronic high-energy electrodes (see Fig. 24-5). Alternatively, ineffective shocks caused by shunting of defibrillation energy from an inner insulator breach may lead to a low impedance route for high energy to be delivered directly back to the pulse generator and can cause pulse generator failure. Replacement of the ICD pulse generator may be indicated in each of these scenarios, in conjunction with lead revision or extraction, because of premature battery depletion, pulse generator failure, or to avoid another operation in the near future if the battery is already partially depleted. Upgrading to Higher-Energy Device or Addition of Hardware for Inadequate Defibrillation Threshold.  An elevated defibrillation threshold (DFT) detected through noninvasive testing or at elective generator replacement may require a change in hardware configuration. Options include placing a generator capable of delivering higher defibrillation energy to respond to an elevated DFT (although most current devices can do this), waveform adjustments,114 repositioning the right ventricular apical (RVA) shocking electrode, or the addition of various other lead systems, including superior vena cava or azygos vein coils, or subcutaneous coils, arrays, or patches to better distribute current around the heart to reduce the DFT,115-122 lowering shock electrode impedance for higher current delivery. Reoperation may be required for antiarrhythmic drug changes that lead to substantial alterations in the DFT, although elimination of the offending medication provides a more straightforward solution.123,124



24  Approach to Pulse Generator Changes

Low

Low

High

725

High-voltage lead

High

High-voltage cavity

Low

Low

Low

Low

Low-voltage lead

High-voltage cavity No contact Figure 24-8  Schematics of quadripolar high-voltage and low-voltage lead pin configurations. Top, Combined pacing/shocking, high-voltage defibrillation (DF-4) header configuration. Bottom, Low-voltage standard (IS-4) header configuration. The specifications for the pins and the header are extremely precise, permitting the interchange of leads between models and manufacturers. Although both configurations are quadripolar,  the low-voltage IS-4 lead tip will not fit into a high-voltage DF-4 receptacle cavity, enhancing safety. Although both lead heads are 3.2 mm in diameter, the diameter of the distal pin is larger for the low-voltage leads. (From Proposed IS-4 Standard; American Association of Medical Instrumentation presentation at Cardiostim, Nice, France, 2004; and ISO Standard: Active implantable medical devices: four-pole connector system for implantable cardiac rhythm management devices—dimensional and test requirements. Geneva, 2009, International Standards Organization— E:\ISO FDIS 27186 (E) 25June2009.doc STD Version 2.1c2.)

Also, the drug may be changed to an agent that lowers DFT, or a class III medication may be added to reduce DFT.125

removed some time after implantation of the new system, preferably during a separate procedure.

Upgrading to Incorporate Dual-Chamber Pacing Capability.  Although the DAVID trial and substudies indicated that there was detriment to RV pacing in ICD patients, the DAVID-II trial indicated that atrial pacing to maintain chronotropic competence does not increase heart failure or mortality. This is especially important in patients with congestive heart failure or coronary artery disease who require beta blockers. Upgrading to a dual-chamber device along with generator change can require considerable deliberation when substantial hardware is already in place. Several scenarios may be encountered, each with unique potential solutions. The patient may have a previously implanted abdominal singlechamber ICD with an epicardial or endocardial lead system. In this situation the operator has two options: (1) place an endocardial atrial pacing lead through the subclavian system and tunnel the lead subcutaneously to the abdominal pocket, while upgrading the device to a dual-chamber ICD, or (2) abandon the abdominal ICD, and place an entirely new AV sequential ICD system in the pectoral area. The advantage of long-term stability of thresholds for endocardial pace/sense leads favors the approach of adding an endocardial atrial lead and tunneling it to the abdomen. However, this also requires that the lead be long enough to tunnel to the abdominal site, making manipulation and positioning of the lead in the atrium more challenging. Alternately, a lead extender may be attached to a shorter lead, but the adapter adds another weak link. Further, this approach requires opening both the abdominal pocket and the subclavian site simultaneously, which could raise the risk for cross-infection of the abdominal site, eventually requiring extraction of a very old endocardial or epicardial ICD lead system. We clearly prefer not to have two pockets open at the same time, especially when one involves an epicardial lead system, where infection could be disastrous. Abandoning the abdominal site altogether is preferable. The new pulse generator and lead system are placed in the pectoral area, preferably on the opposite side to avoid any chance of infecting a preexisting chronic endocardial lead, and DFT testing is performed at implantation. The previous abdominal pocket remains closed during this operation, eliminating the possibility of cross-infection between sites. The abdominal generator may be turned off and left in place, or it can be

Upgrade to Biventricular, Cardiac Resynchronization System.  Upgrade to a biventricular (BiV) cardiac resynchronization system has become one of the most common indications for ICD reoperation, either as a de novo device upgrade or at the time of generator replacement.35-43,126 Upgrade requires generator replacement and insertion of a new coronary sinus (CS)/LV electrode. We perform venography to ensure patency of the vasculature for the new lead if any difficulty is encountered in accessing the axillary vein. Understanding the venous anatomy is critical to making the correct surgical decision. If the subclavian/axillary venous system is occluded, options include lead extraction to produce a conduit or placing the CS lead on the opposite side and tunneling it across the chest to the pulse generator. Implantation of the new lead and device often requires a pocket revision to accommodate the larger generator. Surgical aspects for upgrade to a BiV system are addressed later.127-131 Complications of Pacemaker or ICD Implantation That Require Reoperation.  Reoperation may be required for complications resulting from the initial implantation procedure.13,132-139 Indications include large pocket hematomas or effusions, cardiac chamber perforation by a lead, or a need to reposition the pulse generator. Most small to moderate hematomas resolve; the risk of secondarily introducing infection through reoperation or aspiration should be avoided as much as possible. Large hematomas or effusions that do not resolve and that compromise the blood supply through pressure on the overlying skin require evacuation followed by primary closure, because the pocket cannot be left open with a device in place. Bolus dosing of heparin, use of enoxaparin, and large loading doses of warfarin should be avoided to reduce hematoma risk. We continue warfarin at full anticoagulant levels for all generator replacements and for lead revisions on patients in whom there is an increased risk of discontinuing anticoagulation.140 Pocket twitch (due to lead insulation break, loose lead-generator connection, or exposed set-screw), diaphragmatic pacing, or skeletal muscle stimulation or myopotential inhibition141 may require surgical intervention if such problems cannot be solved by reprogramming.

726

SECTION 3  Implantation Techniques

Box 24-5 

IDENTIFICATION OF PULSE GENERATOR Manufacturer code and serial number code Implantation data Identification card Transtelephonic or remote monitoring records Manufacturer’s implantation records Monitoring physician’s records Noninvasive testing Size, shape, thickness Magnet response (pacemakers) Interrogation (if manufacturer identified) Fluoroscopy Size, shape Connector block shape Unipolar or bipolar (pacing) Single or dual chamber Number of ports for implantable cardioverter-defibrillator leads Identifying markings/codes Lead Unipolar or bipolar (pacing) Active or passive fixation Number of high-energy coils Shape of fixation mechanism Invasive Testing Direct identification of pulse generator through interrogation Lead: manufacturer code and serial number code Type of connector Size of lead header

Identification of Pulse Generator Make and Model The most straightforward means of identifying a pulse generator is to obtain information directly from the patient (Box 24-5). An identification card specifies the type of device, model and serial number, implantation date, name of implanting or monitoring physician, and lead model and serial numbers. This information may also be obtained from records from the manufacturer, implanting or monitoring physician, transtelephonic or remote service that monitors the patient, or institution where device was placed. If none of these is helpful, alternative methods must be used to identify the pulse generator. Identification of the make and model of the existing pulse generator is crucial to determining its true functional status and, with earlier leads, to have the necessary information to select a compatible replacement or upgraded device. In the rare case of a pulse generator that cannot be identified before surgery, the implanting physician must have a full array of leads, generators, and adapters available at reoperation. Magnet Response.  The response of a bradycardia pacemaker pulse generator to placement of a magnet can assist in the identification of its manufacturer (see Box 24-5). Pacemaker pulse generators respond to magnet application by entering a fixed-rate, single-chamber or dualchamber pacing mode corresponding to the type of generator and the programmed mode. Magnet rates vary among manufacturers and may provide a clue to the origin of the device. To undergo a magnetactivated test, the patient must be connected to an electrocardiographic recorder before the magnet is applied and must remain connected until after the magnet is removed. The first few paced complexes after magnet application may occur at a rate or output other than that seen later in the recording, providing identification data as well as information regarding the integrity of the pulse generator and lead system; for example, the delivered pulse width may be reduced during the first few paced complexes to ensure that capture still occurs with an adequate safety margin, the “threshold margin test.” Furthermore, with constant magnet application over the pacemaker, some devices continue to pace at a fixed rate, whereas others cease pacing after a programmed number of intervals. Devices temporarily reprogrammed to a backup mode by

electrical interference (e.g., electrocautery during surgery) may exhibit unusual magnet responses. Radiographic or Fluoroscopic Identification of Pulse Generator.  Pacemaker and ICD pulse generators can be identified from their appearance under radiography, the most helpful method for identifying unknown devices. The shape and size of the generator may characterize a particular manufacturer (e.g., square, oval, elongated ellipsoid, round), although pulse generator shape can vary significantly from one model to another, even in those by the same manufacturer. Considering that the life span of some pacemaker devices may exceed 10 or 12 years, various shapes and sizes will be encountered. More specific to identification of the pulse generator are radiopaque markings placed near the connector block that code for manufacturer and device model. These markings appear most clearly under magnified fluoroscopic or radiographic examination when the device is positioned perpendicular to the x-ray beam (Fig. 24-9). The shape and orientation of internal components, which can often be identified radiographically, provide further clues to the device type, manufacturer, and model. Comparison of these radiographic features (size/ shape, identification markings, internal components) with compiled x-ray photographs available from manufacturers facilitates identification of the pulse generator. Finally, an attempt to interrogate a pulse generator with a cadre of different programmers may identify the pulse generator, unless the battery is so depleted that telemetry communication is not possible. Radiographic or Fluoroscopic Identification of Leads.  Radiographic examination of leads serves two purposes.142 First, it allows the physician to ascertain the presence of unipolar versus bipolar distal electrodes and the fixation mechanism. Distal active-fixation screws may often be seen directly on radiography, whereas passive-fixation leads have a bulbous tip. Second, radiographic examination may identify lead conductor fractures in which the conductor has clearly separated, leaving a gap, especially with magnified views (Fig. 24-10). Lead information of this sort is important for programming, for selecting an appropriately compatible generator, and for identifying leads for extraction. Fluoroscopy also gives some indication of the degree of fibrosis evident through the real-time motion of the lead and

Figure 24-9  Radiographic identification of a pulse generator. The unit is clearly connected to two leads, and each lead has only a single, electrically active pole (i.e., unipolar). Although the shape and arrangement of electronic components assist in identification, the specific radiopaque code block inside the pulse generator provides the primary means of identifying the device. Here, a Medtronic logo, followed by S W 2, indicates that the pulse generator is a Medtronic Synergyst II Model 7071 DDDR unit with a connector block that will accept two (atrial and ventricular) 5-mm or 6-mm unipolar leads.



24  Approach to Pulse Generator Changes

727

the new battery. Surgery for lead repair or revision itself involves extensive testing of chronic leads to confirm the lead as the source of malfunction, ensure normal operation of other leads, and evaluate new leads for optimal positioning inside the heart. After the pacemaker or ICD pocket is opened, the pulse generator is disconnected from the leads to enable testing of lead sensing and pacing functional capacity.143 The lead must be disconnected from the pulse generator cautiously in pacemaker-dependent patients. To avoid prolonged ventricular asystole, the operator must be prepared to connect the lead immediately to a cable attached to a functioning external pacing system (Fig. 24-12). The external device should be activated and should be delivering pacing impulses before the ventricular lead is disconnected from the pulse generator in a pacemakerdependent patient. Alternatively, although usually unnecessary, a temporary pacing wire may be placed before disconnecting a lead in a pacemaker-dependent patient; however, such additional instrumentation may increase the risk of infection. As always, the operator must exercise care not to cut the lead. Testing the Sensing and Pacing Capabilities of Long-Term Leads

Figure 24-10  Fractured pacemaker leads. Cine-radiograph shows two coradial atrial and ventricular pacing leads fractured just inside the first rib–clavicular junction. The conductors of one lead are completely, through-and-through fractured, whereas those of the other lead are stretched and uncoiled, with obvious damage to the lead insulation as well. The partially fractured lead was extracted using the subclavian approach, whereas removal of the completely fractured lead required a femoral approach.

Another crucial aspect of invasive testing involves measurement of pacing and sensing thresholds in long-term implanted pacemaker and ICD leads. Most leads show some deterioration in pacing and sensing thresholds during the first 4 to 8 weeks after implantation, then reach a relatively stable level for the long term.46,88 However, thresholds may continue to increase over time, a change that may now be recognized by remote monitoring. The change in threshold from baseline was greatest with active-fixation, non-steroid-eluting leads; threshold

surrounding calcification, information that could be useful if extraction is required. Radiography of leads involves an examination of the insertion site (e.g., subclavian, axillary, cephalic, jugular, or epicardial), acute bends or fractures in the lead, the location of lead coils beneath the pulse generator (in the event they need to be freed for lead repositioning or extraction), the position of the pulse generator connector block, and a general preview of the character of the connector block–lead interface (Fig. 24-11; see also Fig. 24-9). The lead should be examined fluoroscopically throughout its course for kinking, fracture, or excessive tension as well as for fixation at the distal tip. A thorough radiographic examination of lead integrity and pulse generator–lead interface before reoperation in pacemaker and ICD patients can save much distress when the pocket is opened. INVASIVE EVALUATION After as much information as possible has been gathered noninvasively about the hardware of the pacing system and the functional status of all its components, further invasive evaluation occurs at the time of reoperation. Invasive evaluation does not supplant noninvasive analysis but adds to it. Invasive evaluation involves (1) measuring the functional capacity of implanted leads, (2) examining the structural integrity of leads and the lead-generator interface, and (3) venography. Measuring Functional Capacity of Implanted Leads One of the most crucial parts of invasive analysis during reoperation involves measurement of pacing and sensing capabilities in existing leads. Vigorous noninvasive evaluation should provide the operator with valuable information on lead viability and functional status,51,58,64,79,91 although verification of lead integrity and precise DFT determination must be performed at the surgical procedure. If surgery is undertaken for pulse generator replacement, demonstrating viability of existing leads is vital to the appropriate long-term performance of

Figure 24-11  Pulse generator with vascular overload and abandoned lead. Cine-radiograph shows ICD with five transvenous leads through the left subclavian venous system in a chronically implanted patient. Behind the pulse generator can be seen a mass of lead coils, which will require much dissection in the operating room to loosen them sufficiently to allow connection to a new pulse generator. One of the proximal poles is clearly not connected to the generator, indicating that it is not in current use and is, in fact, capped. The thinnest lead in the upper right corner of the figure is a unipolar lead that had been placed through left brachiocephalic vein cutdown for the patient’s original pacemaker, which had subsequently been upgraded to an ICD. Lead pins can be seen to be appropriately inserted into the header. Upgrading or placing a new lead in this situation would require extraction to debulk the vasculature. With the current bulk of leads already in place, the likelihood of venous occlusion is already high.

728

A

SECTION 3  Implantation Techniques

B

C

Figure 24-12  Reattaching pulse generator in pacemaker-dependent patient. A, Unipolar pacing. Connection of the ventricular lead to temporary pacing cables at generator replacement. This is the unipolar configuration to allow pacing off the distal tip electrode with a ground to the subcutaneous tissues, particularly useful in pacemaker dependent patients. The positive pacing cable (red) can be already connected to a stable grounding location at the time the ventricular lead is removed from the generator; the distal tip of the lead is then quickly connected to the negative pacing cable (black) to prevent prolonged asystole. Following this connection, the red cable can then be repositioned on the proximal electrode of the lead to check bipolar pacing parameters. B, Reconnecting ventricular lead. After the bipolar lead is tested, the red cable is again attached to the grounding location. The torque wrench is inserted into the distal port of the ventricular channel of the new pulse generator to be ready to tighten. After disconnecting the black cable, an assistant quickly inserts the lead electrode into the header of the pulse generator, and the torque wrench is tightened. Even if there are two set screws, there is enough contact with the proximal electrode in the header of the pulse generator to enable bipolar pacing. C, Tightening torque wrench on distal electrode. After tightening the distal set screw, the proximal set screw is tightened, and the red cable is no longer required. Placing the atrial lead in the atrial port and tightening those set screws completes the connections to the pulse generator.

increases are reduced with passive fixation and steroid elution on all lead types. Noninvasive testing should alert the operator to the usefulness of long-term leads, but invasive testing and inspection confirm their functional utility. Both atrial and ventricular leads must be tested. If bipolar, leads should be evaluated in both unipolar and bipolar configurations. After connecting the external pacing analyzer to the lead, the clinician determines pacing and sensing thresholds and lead impedance. The voltage pacing threshold at a fixed pulse width is recorded as the threshold that produces reliable capture. Pacing lead impedance is best determined at an increased output voltage (e.g., 5 V) to ensure accuracy. Low-voltage pacing thresholds are desirable for long-term leads. This allows programming of the pulse generator output to a reduced level, enhancing battery longevity. For chronic leads that have been in place for several years, the operator may decide to accept a pacing threshold (at 0.5-msec pulse width) of up to 2.5 V because this still allows two times the pacing safety margin for most pulse generators. However, a pacing threshold of 2.5 V that occurs early after implantation (e.g., within 6 months) may not be acceptable. This suggests excessive early fibrosis around the lead tip and possible exit block and noncapture in the future if the pacing threshold continues to increase. Care at initial implantation helps ensure lower long-term pacing thresholds and improved sensing capabilities. Higher chronic thresholds may be more acceptable in patients with implanted autothreshold devices. Thresholds for sensing likewise tend to increase after lead implantation but less so for newer steroid-eluting leads. Acceptable measurable intracardiac electrogram (EGM) amplitudes and slew rates depend on the maximum programmable sensitivity of the new pulse generator. For most systems, P-wave amplitude of 1 mV or more and R-wave amplitude of 3 mV or more constitute minimally acceptable long-term values. Such low amplitudes, however, leave little room for further deterioration in lead function. P waves of 1.5 mV or more and R waves of 5 mV or more provide an additional safety margin. If atrial or ventricular ectopy is present, the operator should determine EGM amplitude of ectopic complexes to ensure appropriate sensing by the pacemaker. In patients with paroxysmal atrial fibrillation, excellent atrial sensing may be required to detect atrial fibrillation reliably without signal dropout. Higher-amplitude EGMs are required for chronic unipolar leads to allow programming of lower sensitivities to avoid myopotential sensing.

Inadequate sensing or pacing thresholds at generator replacement are indications for placement of a new lead in the affected chamber. This may entail either capping an old lead and leaving it in place or removing it. The new lead can usually be placed through the same subclavian or axillary vein; although it is preferable to avoid having too many leads, especially more than four, pass through the same vessel, to reduce the chance of venous occlusion and thrombosis.144 A single new lead may also be placed through the internal jugular vein, external jugular vein, the contralateral subclavian or axillary vein, or deep into the innominate vein.145 The proximal tip can be tunneled to the original pocket to meet a second, functional long-term lead for a dualchamber pacemaker system if required. Alternatively, an entirely new generator or lead system may be placed on the contralateral side.146 Lead extraction allows placement of new leads through a conduit produced by lead removal. Testing Defibrillation Threshold of Long-Term High-Energy Leads The DFT testing of ICD leads can be performed after evaluation of the pace/sense functions of these multifunctional leads, according to standard DFT testing techniques. Stability of the EGM recording should be ensured, and visual inspection should demonstrate no significant abnormalities in lead appearance, consistent with lead structural integrity. Examining Structural Integrity of Leads and Lead-Generator Interface Visual inspection at surgery provides clues to lead integrity. Fluid inside the lead body suggests an outer insulation break but, especially in coradial pacing leads, does not necessarily mandate lead replacement. Fluid can be identified routinely in CS leads with an open lumen. Undue tension on the lead near the fixation site may cause kinking, conductor uncoiling, conductor fracture, or thinning of the electric insulator. A hazy appearance of the insulator surrounding an area of tension or repeated stress is common in earlier leads. This appearance represents surface erosion of the lead insulator and does not itself imply lead malfunction. However, the finding should alert the operator to potential lead damage in areas of stress to the insulation. An examination of the suture location ensures that the ligature remains around the suture sleeve, and gentle tension on the lead body ensures its fixation at the venous entry site. Visual inspection of the specific course



Figure 24-13  Twiddler’s syndrome. The patient had been noncompliant and had not returned for office evaluation of his ICD for more than a year. Because the pulse generator had reached end of service, lead integrity could not be evaluated noninvasively before the operation to replace the pulse generator. The device was found to be in a subpectoral location. There were two leads, a high-energy ventricular ICD lead and an atrial lead. The leads were wrapped around each other 21 times; on unwrapping them, it was clear that both conductors had been fractured. A preprocedure chest radiograph might show coils under the generator, but they are so tightly entwined that a single film may not delineate all the twisting. In this patient, lead extraction was used to remove the failed leads, and two new leads were placed. The new pulse generator was tacked to the fascia with nonabsorbable suture to prevent it from being twirled.

of a coiled lead in the pocket may be hampered by a significant thickness of overlying capsule scar; fluoroscopy can assist in this regard.75-78 Be ready for any surprise, such as a “twiddled” lead (Fig. 24-13). Direct examination of the lead connector can assist in the identification of the lead model if not previously known.100-102 This is particularly important for lead models that have excessive premature failure rates; such leads in the ventricular position should routinely be replaced in pacemaker-dependent patients.

24  Approach to Pulse Generator Changes

729

indeed present and, if so, its site. Chronic venous occlusion may occur asymptomatically in conjunction with the development of collateral venous circulation around the shoulder. Delineation of the location and length of occlusion indicates to the operator an appropriate needle insertion site for placement of a new lead. It also ensures patency of the SVC. Dye is injected directly into the subclavian vein through the insertion needle; this local venogram gives the best opacification. Occlusion of the brachiocephalic system proximal to the junction of the internal jugular vein excludes the ipsilateral jugular system as an alternative site for a new lead. Alternatively, if the subclavian vein is occluded and the internal jugular vein remains patent, a new lead may still be placed using the jugular approach. Occlusion of the SVC precludes the use of any new endocardial lead placed from a superior site unless leads are extracted to produce a conduit.157 Although venoplasty is acceptable, stents should never be placed into veins without removal of preexisting leads, so as to avoid trapping the leads between a stent and the vein wall (Fig. 24-14). A persistent SVC (which usually drains into the coronary sinus) makes placement of RV endocardial leads difficult or impossible.158,159 In some cases of venous occlusion, it may facilitate placement of a lead system.130 Venography defines the anatomy of the venous system in such a situation, which may be suggested by an unusual intravascular guidewire course. Finally, leakage of venography dye into perivascular tissues or into the pericardial space suggests vessel or cardiac chamber perforation, respectively. The technique is performed by injection of 10 to 20 mL of radiopaque dye (a 50% dilution generally suffices) into a vein peripheral to the occlusion site. Fluoroscopy with permanent storage of cine images is necessary to evaluate flow.

Surgical Considerations Device replacement or revision in a tertiary care institution, with an active electrophysiology service following the patient for the long term, accounts for 30% to 40% of all pacemaker and ICD procedures. The timing of intervention depends on the specific indication. Most patients require reoperation for elective battery replacement or battery

Venography Venography is usually required as part of the device replacement procedure. It plays an important role when insertion of replacement leads into the subclavian vein is difficult. Venography can ensure patency of the subclavian and superior vena cava (SVC) systems, demonstrate points of venous occlusion, and show the course of the axillary venous system for direct access. Venography is indicated when the subclavian, axillary, or cephalic veins cannot be accessed (to demonstrate their locations), when the veins are accessed but a guidewire cannot be passed into the SVC, and when lead upgrade is required in the presence of long-standing prior lead implant durations. Inability to access the subclavian vein that carries a previously implanted lead suggests either an incorrect needle insertion angle or an occluded subclavian or brachiocephalic venous system.127-131,147-151 Finding an appropriate location to insert the access needle can be facilitated by advancing the needle fluoroscopically in the direction of the chronic electrode under the clavicle, with care not to damage the implanted lead. The vein should be approached with the bevel of the needle facing the implanted lead. If access is not possible, venography may provide better delineation of the course of the axillary or subclavian vein. In this situation, radiopaque dye must be injected distal to the veins to be visualized, that is, into the basilic or median cubital vein. Occasionally, access to the axillary or subclavian vein is possible, but the guidewire will not pass freely to the SVC. If needle placement in the vessel is adequate, failure to pass a wire suggests proximal venous occlusion.128,147,152-156 Venography demonstrates whether occlusion is

Figure 24-14  Venous occlusion. Venography of left upper extremity demonstrates complete occlusion of the left subclavian vein around a previously existing transvenous ICD lead tunneled to the abdomen. The occlusion occurs at the level of the subclavian vein as it enters the left brachiocephalic vein. Collateral vessels branch off at the first point of occlusion and will eventually reconstitute at the level that the occlusion ends. The left internal jugular vein is clearly patent. If access from the left side is required, extraction of the lead to maintain a conduit would be the only option to pass a new lead to the superior vena cava from this side.

730

SECTION 3  Implantation Techniques

or lead revision, whereas 1% to 6% of patients return to the laboratory for other problems, such as pocket hematoma, pocket twitch, diaphragmatic pacing, and pocket relocation (see Box 24-1). ELECTIVE DEVICE REPLACEMENT OR REVISION Most reimplantation procedures are either elective or performed for repair or replacement of prior devices. Preoperative blood analysis is performed. Aspirin and clopidogrel are not stopped before the procedure unless a compelling medical reason exists; stopping these medications can lead to myocardial infarction. Warfarin may be discontinued for 3 to 5 days for procedures in which the major vessels will be instrumented, although more frequently, patients receiving warfarin undergo implantation and revision, because the risk of hematoma development is much higher with heparin and enoxaparin than with warfarin.140 The patient fasts from midnight and receives preoperative antibiotics, usually being admitted on the day of the procedure. Elevated coagulation times may be corrected with fresh-frozen plasma if necessary. Procedures are routinely performed with local or regional anesthesia, supplemented by intravenous (IV) conscious sedation. For ICDs, the patient is given general anesthesia for ventricular fibrillation induction and DFT testing. Most institutions use a combination of a short-acting, amnestic benzodiazepine such as midazolam together with an IV narcotic for analgesia. Continuous electrocardiographic monitoring, pulse oximetry, and sterile preparation and draping are standard procedures. Preoperative antibiotics are administered intravenously. Midazolam provides excellent amnesia for the procedure.160 General Guidelines and Techniques There is no substitute for careful surgical planning in approaching the established pacemaker pocket and gentle handling of the tissues. Perfect hemostasis, avoidance of a tight-fitting pacemaker or ICD pocket, and multilayered incision closure are the basic principles that help prevent future difficulties. These principles are similar to those required at initial implantation (see Box 24-2). To avoid induction of ventricular fibrillation, development of fibrosis at the lead tip, and damage to the generator itself, electrocautery must not be used directly over an implanted pulse generator with unipolar leads. This issue has become much less of a problem with the current exclusive implantation of bipolar leads. Electrocautery can be used safely during battery changes as long as the leads are not grounded to the patient, to avoid current shunting directly to the heart. Hemostasis at reoperation can usually be secured with electrocautery or direct ligature. Use of surgical absorbable cellulose or topical thrombin assists in treating persistently oozy pockets. Clinical judgment should be used in the application of various technical approaches (Fig. 24-15). Specific Techniques Local anesthesia is administered most frequently as 1% lidocaine infiltrated into the scar line from the previous procedure. Additional

A

lidocaine may be given under direct vision once the capsule of the pocket has been defined. The surgical incision is placed directly over the previous incision. The skin and subcutaneous tissues are opened with sharp dissection, which is required to penetrate the tough scar tissue and dermal layer. Deeper dissection with Metzenbaum scissors or electrocautery is carried out to delineate the pacemaker capsule. Once the pocket is reached, the fibrous capsule is sharply incised and then extended under direct visualization of the implanted pulse generator and leads. The capsule must be opened far enough to allow extraction of the pulse generator and lead connector assembly without undue force. The posterior capsule should be carefully dissected away from the leads to allow mobility. Access to leads and generator may be facilitated through the use of self-retaining retractors. Extreme care is required throughout the procedure to preserve the integrity of the leads and lead connectors; they must not be punctured with anesthetic needles or cut with blades or scissors. If electrocautery is used to remove tissue from the leads in dissecting them from scar tissue in the posterior capsule, the probe must keep moving over the lead so as to not overheat the lead insulation and thereby damage it. Leads with very thin insulation, including coradial leads and most coronary sinus electrodes used with BiV systems, are more prone to heat damage from electrocautery because of their thin outer insulators (Fig. 24-16). Once the generator is delivered out of the pocket, the leads are disconnected and analyzed. Leads from pacemaker-dependent patients need to be expeditiously reconnected to an external pacemaker (see Fig. 24-12). Unipolar pacemaker leads require direct grounding to subcutaneous tissue; the active part of the unipolar generator must remain in contact with the patient before the lead is disconnected. Grounding can best be accomplished through a large-surface-area ground electrode placed directly into the open pocket. Making contact with this electrode onto the active surface of a unipolar pulse generator allows the generator to be removed safely from the pocket before the lead is disconnected, even in a pacemaker-dependent patient. After being secured to temporary pacing cables, leads can be completely freed of adhesions up to their entry point into the subclavian vein, if necessary, to examine lead integrity or for extraction. We use low-energy electrocautery sparingly to dissect the leads free of adhesions, because the scar tissue could be especially tough and adherent to lead structures. If lead replacement or repair is not necessary, and if the function of previously implanted leads is adequate, dissection of the complete course of each lead may not be necessary, as long as lead connector mobility is sufficient to attach it to a new pulse generator without tension (Fig. 24-17). Lead malfunction or upgrade from a single-chamber to a DDD pacemaker system or to a BiV system may require placement of an additional lead. If a previously implanted lead is extracted through an occluded vessel using a dilating sheath, a guidewire can usually be inserted into the vascular system through the extraction sheath to maintain a conduit for replacement. In other cases, repeat axillary or

B

Figure 24-15  Pacemaker and ICD basic instrument and equipment trays. A, Instrument tray. A selection of basic surgical instruments is essential, including hemostats, retractors, anesthetic and needles, sutures, and sponges. B, Introducers and cables. Equally important are tools used for venous access and testing of the leads. These include a variety of sizes of introducers, sheaths/guidewires, and testing cables. Suction is especially important to maintain hemostasis and to flush the pocket, and sterile drapes cover the image intensifier and lights. Strict sterile technique is essential.



24  Approach to Pulse Generator Changes

A

B

731

C

Figure 24-16  Replacement of pulse generator. A, Incision of capsule. The initial incision to replace the pulse generator has been carried to the capsule surrounding the metallic “can,” which is clearly visible. Hemostasis has been maintained. The capsule around the device is incised and opened carefully to avoid damage to the leads; occasionally, a lead will be found overlying the generator. B, Delivering the generator. The pulse generator is delivered through the skin. Note that the incision is just long enough to fit the device removed and the new device to be placed in the pocket. Skin edges are intact and hemostasis is meticulous. C, Dissecting scar from leads. After delivery of the pulse generator, tension on the leads demonstrates that they are heavily fibrosed into the pocket. Electrocautery over the lead insulators proceeds cautiously to avoid insulator damage; the cautery pen must be kept in motion and not linger over any one location on the lead body. This figure depicts the proper method to remove scar tissue from leads. Gentle traction is applied to the leads and, when possible, to the scar tissue also. Capturing scar tissue must be done carefully to avoid damage to underlying leads.

subclavian venipuncture, brachiocephalic cutdown, or an internal jugular approach provides an alternative means of inserting a new lead. If new leads are placed through the same subclavian system by direct puncture, the operator must be careful to avoid lead damage. After the old pulse generator has been detached from leads and lead integrity and functional status have been ascertained, a new pulse generator can be attached. The principles of generator-lead

A

B

D

E

compatibility must be maintained. Redundant lead coils are placed posterior to the pulse generator, and the pocket is closed with at least three layers of absorbable suture—two subcutaneous and one subcuticular. ICD leads may be tested for defibrillation threshold before, or concomitant with, final pocket closure. At generator replacement or revision, the old capsule should be incised or removed. We open the capsule in a medial and inferior

C

Figure 24-17  Debridement of ICD pocket. A, Debriding the scar. Debridement of scar tissue from the posterior aspect of an ICD capsule. The scar tissue is thick, dense, and relatively avascular. Cautery is a safer method to remove scar from the leads than is sharp dissection or the use of surgical scissors. Removing dense scar tissue increases the vascularity of the pocket, enabling white blood cells to enter if required and allowing absorption of serous fluid to prevent the development of a seroma, which would make an excellent culture medium. B, Posterior capsule scar. Leads from the same patient as in A, embedded in scar tissue of the posterior capsule of the ICD pocket. Debriding this area improves pocket vascularization and reduces pocket bulk. It also allows for a connection of the leads to the new pulse generator with reduced tension. Finally, it is not possible to place an identical-size pulse generator in a preexisting pocket without expanding it; otherwise, excess tension can occur on the borders of the pocket and lead to erosion. C, Posterior capsule. Debriding scar tissue from over the leads seen in B. Gentle electrocautery directly over the lead insulators can be performed safely. D, Caution: crossing leads. Caution must be maintained to watch for crossing leads. Thus, the cautery pen needs to keep moving, with any resistance to motion being recognized as a possible crossing lead. E, Total capsule scar removed. The total amount of scar tissue is removed from the debrided pocket. It is avascular and dense and does not contribute to healing.

732

A

SECTION 3  Implantation Techniques

B

C

Figure 24-18  Opening the capsule. A, Fresh avascular capsule. The glistening capsule of a healthy pocket from a patient with a single-chamber ICD generator receiving generator replacement. The avascular nature of the capsule is clear. Hemostasis of the skin edges is maintained. The posterior aspect of the pocket is visible. This area deep in the pocket is anesthetized and then incised on the inferior and medial borders.  B, Incising inferomedial border. Electrocautery being used to incise the inferior and medial internal edges of the ICD capsule to expose fresh, vascular tissue. Hemostasis in the incised region is necessary to prevent the development of a pocket hematoma. C, Capsule opened internally for new blood flow. The final incised inner borders of the ICD capsule. There is good hemostasis after cautery. Some operators remove the entire capsule, but no evidence indicates this is required, and doing so can lead to more bleeding in the pocket. The pocket will now be flushed, the new generator attached to the lead, and the generator placed in the pocket with the lead posterior. The capsule and skin will be closed with at least three running layers of absorbable suture.

direction because (1) a new device, even if an identical model to the one removed, will never fit perfectly in the original pocket without tension, and (2) doing so allows for absorption of fluid and fresh blood flow, which are not possible if the relatively avascular capsule is left intact. This reduces the risk of infection, which is higher at generator replacement than at initial device implantation161 (Fig. 24-18). In very thin patients, subpectoral or axillary locations may be required. The physician can access the subpectoral plane by locating the junction between the sternal and clavicular heads of the pectoralis major muscle and making entry at that point, taking care to avoid damage to penetrating neurovascular bundles. As a secondary approach, the deltopectoral groove can be similarly approached. Alternatively, the muscle fibers of the pectoralis major can be teased apart longitudinally to allow entry to the subpectoral plane. Axillary subcutaneous placement of a pacing device is generally avoided because of the possibility of lateral migration of the device, which can be uncomfortable for the patient and, especially with larger ICDs, can lead to erosion. When required, however, the axillary location can be entered through direct extension from a subclavian pocket or through a separate axillary incision.162 The device may be secured in placed in a subpectoral location at that site for more stability (Fig. 24-19). The

abdominal wall, subcostal, intrathoracic, and transiliac positions represent other alternatives for a replacement pulse generator.163 Nevertheless, a subcutaneous prepectoral approach is appropriate in most patients for both pacemaker and ICD reimplantation.

Figure 24-19  Lateral subpectoral device placement. A healing lateral subpectoral incision (2 weeks since surgery) for placement of a pacemaker. The axillary vein is accessed for entry to the vasculature, and the device is placed in a subpectoral location. The muscle layer is closed over the device with interrupted sutures before closing the subcutaneous tissues.

Managing Venous Stenosis

UPGRADE TO BIVENTRICULAR SYSTEM Upgrading to a BiV pacemaker or ICD involves the addition of at least one lead to a system that already contains one or two leads, sometimes more if there are abandoned leads. Venous access and patency are the first issues. Venous Access The need for adding a CS lead to a preexisting pacing or ICD system requires venography to document venous patency. Discovering that the ipsilateral vessel of choice is occluded after the pocket is opened, and not being prepared to extract a lead to form a conduit for implantation or have the other shoulder prepped for access and tunneling, may compromise sterility when these course adjustments need to be made during the procedure. Despite advances in lead technology, a substantial proportion of implant vessels occlude chronically, often unrecognized before revision. A prominent subcutaneous venous pattern may be a marker for reduced flow, but venography is required to document the degree, length, and location of stenosis or occlusion and local options for venous access, if any. Current lead extraction guidelines recommend that no more than four leads pass through either subclavian vein, and that no more than five leads pass through the SVC.144 Lead extraction is indicated to prevent vascular overload and occlusion. After extraction, with fewer leads in place, standard axillary or brachiocephalic access techniques can be used to place an additional CS lead. In the event of upgrade from a pacemaker to a BiV ICD, an additional high-energy lead is also needed, so extraction of the preexisting ventricular pacemaker electrode may be indicated. The simple addition of a CS lead in a patient with a patent ipsilateral vessel is straightforward. Rarely are the other leads affected or dislodged; placing straight stylets down each of the existing leads while the CS lead is added gives the preexisting leads additional security, especially if relatively new. Venous stenosis in the entry vessel can be addressed in three ways. (1) The stenotic vessel can be accessed and the stenosis up dilated using standard venous introducers. (2) The stenosis can be up dilated using angioplasty catheters. (3) Entry to the vessel can be made proximal to



24  Approach to Pulse Generator Changes

the site of stenosis, for example, deep to the clavicular head in the subclavian/brachiocephalic vein junction. Use of a hydrophilic curved tip introducer wire facilitates entry to the central vasculature. In no event should pre-existing leads be stented into the vessel wall. Stents do not reliably maintain patency of major veins due to the low pressure of the venous system. Stenting pre-existing leads into the walls of blood vessels makes them very difficult, if not impossible, to remove should they become infected. Special Precautions All the additional manipulation required to place a CS lead or upgrade any system to a BiV device adds time and complexity to the revision procedure. This poses an additional infective risk to a procedure (generator replacement) that already carries an increased risk of infection compared to an initial device implantation. Thus, a meticulously sterile approach is mandatory, despite all the additional time and tools required.161

Generator Lead Adaptability LEAD CONNECTORS Replacing a pulse generator onto one or more chronic leads requires that the pulse generator connector block be compatible with the proximal lead tip.100-102 Through years of development by multiple manufacturers, pacemaker leads have evolved to an International Standard (IS-1) proximal lead connector configuration, which consists of (1) a 3.2-mm lead connector with a short pin that is electrically connected to the distal electrode tip, (2) a lead connector ring wired to the proximal pacing pole, and (3) sealing rings. The proximal lead connector configuration is the same for unipolar and bipolar leads, except that the ring is inactive in unipolar leads. Modern pulse generators have connector block specifications that conform to IS-1 leads; some also fit the prior Voluntary Standard (VS-1) lead type. Thus, generator replacement onto implanted leads of either of these two types poses no difficulty because of the wide array of compatible pulse generators from multiple manufacturers. Before the availability of IS-1 and VS-1 lead connector configurations,100,101 the most common pacemaker leads were 3.2-mm lowprofile leads (unipolar or linear bipolar), 5-mm or 6-mm unipolar and linear bipolar leads, and bifurcated bipolar systems. Pacemaker pulse generators available from some manufacturers remain compatible with

A

B

733

each of these lead models, especially 3.2-mm and 5- or 6-mm linear bipolar and unipolar leads. Precise compatibility, however, is essential to ensure that no fluid leaks into the pulse generator connector block and that electrical continuity to proximal and distal poles remains intact. The implanting physician must be particularly cautious to ensure that sealing rings are located either on the lead connector or in the pulse generator connector block, because not all early lead models had sealing rings placed on the lead connector itself. Similarly, ICD leads have evolved to incorporate IS-1 pace/sense connectors with concomitant IS-1 atrial and ventricular ports in the generator connector block to attach these leads. Early-generation ICDs, however, used a wide variety of lead port sizes and configurations, requiring the operator to have available generators with various header port sizes, adapters, and upsizing sleeves for reoperation of early ICD generators implanted before the adoption of a uniform standard. Even CS lead ports have evolved from an LV-1 configuration without sealing rings to the IS-1 configuration (Fig. 24-20). High-energy defibrillation lead headers have also evolved into a standard Defibrillation configuration (DF-1) which consists of (1) a lead pin that is electrically connected to the corresponding high-energy coil or patch, (2) sealing rings, and (3) a single lead head for each coil of an endocardial lead to allow various hardwire configurations. A single DF-1 connector attaches to all three coils of a subcutaneous array or to a single patch. As with pace/sense leads, defibrillator lead heads had a variety of different end configurations before the adoption of the DF-1 standard, resulting in greater complexity at the time of generator or lead replacement. Because a variety of other lead connector configurations had previously been developed, and because early models of implanted leads may remain useful for many years and still exist, although in a gradually decreasing percentage of patients, a number of these older lead connector configurations remain in use (Table 24-1). If sensing and pacing thresholds are adequate, early leads with such configurations may be used, but a pacemaker or ICD pulse generator with a compatible connector block needs to be selected. As with pacemakers, ICD generator connector blocks from some manufacturers are available in a variety of configurations and port sizes to attach directly to existing implanted leads (Fig. 24-21). An alternative (but less desirable) approach involves using an adapter to fit odd-sized lead connectors into available ports on the ICD header block. Review of manufacturers’ specifications of devices provides the necessary details regarding lead and pulse generator compatibility. Because

C

Figure 24-20  Older-model leads and adapters. A, Bifurcated bipolar 5-mm and 6-mm high-energy leads. An older-model ICD pulse generator attached to early-style leads. Posterior (white header) is a bifurcated bipolar rate/sense electrode with 5-mm lead head configurations. Anterior are two separate high-energy electrodes (red and black) with 6-mm lead head configurations. Generator replacement in this patient would require selection of a generator to fit this lead configuration or placement of multiple lead adapters, which add weak links in the system. Lead adapters would be required if an atrial or coronary sinus lead upgrade were also planned. B, Upsizing sleeves and corresponding leads. Some of these may still be seen on devices removed for replacement today. Top, Seven pacemaker lead connectors, clockwise from bottom left, Intermedics 6-mm linear bipolar, Intermedics 6-mm unipolar, Medtronic 5-mm unipolar, Cordis 3.2-mm linear bipolar, Pacesetter IS-1, Medtronic atrial 5-mm unipolar, and Medtronic IS-1. Bottom, Nonconducting adapters (bottom right five) and lead caps (bottom left two). Lead caps are 5-mm cap (bottom left) and 3.2-mm low-profile or IS-1/VS-1 (bottom left, center). Upsizing sleeves are 5-mm to 6-mm (top left, center), 3.2-mm to 5-mm (top right, center), and 3.2-mm to 6-mm (bottom right, center). Unipolarizing sleeves for 6-mm bipolar leads are shown on bottom right. C, Lead caps. A variety of lead caps must be available. Depicted are caps for 5-mm and 6-mm lead heads, common sizes for older-model, bifurcated, transvenous high-energy leads.

734

TABLE

24-1 

SECTION 3  Implantation Techniques

Common Configurations for Endocardial Lead Connectors

Designation IS-4 DF-4 IS-1 DF-1 VS-1 3.2-mm low-profile 5-mm 5-mm 6-mm

Unipolar (U) or Bipolar (B)? U or B B U or B U U or B U or B U B U or B

Linear (L) or Bifurcated (B)? L L L — L L L B L or B

Pin L/S S L S S S or L L L L S or L

Connector Diameter (mm) >3.2 3.2 3.2 3.2 3.2 3.2 5.4 5.4 6.4

Sealing Rings? (Y/N) Y Y Y Y Y Y or N Y Y Y

Fixation (A/P) A or P A or P A or P — A or P A or P A or P A or P A or P

Atrial J Available? (Y/N) N N Y N Y Y Y Y Y

A/P, Active or passive; DF-1 and DF-4, Standard for high-energy defibrillator lead connectors; IS-1 and IS-4, International Standard for pacemaker lead connectors; L/S, Long or short; VS-1, voluntary Standard for pacemaker lead connectors; Y/N, yes or no.

the lead model may not always be known before reoperation, and because it may not be determined even with visual inspection, careful evaluation of the lead connector configuration may be required in the laboratory after the old pulse generator has been removed. Although the lead and pulse generator should have been compatible at the initial implantation, the implanter cannot assume this without visual inspection of the type of lead connector at reoperation. Lead-generator incompatibility may be the cause of presumed lead malfunction or premature generator depletion. Defibrillator (high voltage) and pacemaker (low voltage) standards have continued to progress with the development of a quadripolar 3.2-mm standard. This has been introduced as DF-4 for combined pacing and shocking applications and is under development as IS-4 for dedicated low-voltage applications (see Fig. 24-8). The terminal pin and first ring carry low-voltage impulses in both applications and for all four poles in the low-voltage application. The most anticipated application, DF-4, replaces the trifurcated ICD lead combining the function of one IS-1 and up to two DF-1 connectors (Fig. 24-22). The new DF-4 lead header simplifies connection to the pulse generator. At reoperation, it eliminates the need to dissect out the trifurcation of the high-energy lead for mobility in the pocket. However, the introduction of this connector creates new problems, with the need for new adapters in the event that a separate ratesensing lead or an additional high-energy lead is required. Extra care P+/S,P–/S (IS-1 or 3.2mm)

is appropriate during intraoperative evaluation to connect testing cables correctly.111 ADAPTERS The two general categories of adapters available are (1) electrically conducting units that change the size or configuration of lead connectors to fit specific pulse generators and (2) upsizing sleeves that allow IS-1 or 3.2-mm, low-profile leads to fit into 5- or 6-mm pulse generator connector blocks while maintaining a fluid seal, or a similar sleeve to upsize an LV-1 header to an IS-1 header for a CS lead (Table 24-2 and Fig. 24-23). Electrically conducting adapters necessarily contain wires attached on one end to a lead pin to enter the new pulse generator and a socket on the other to accept the old lead as well as a mechanism to connect the old lead, generally a set screw. Produced by most manufacturers, adapters are available in an array of types (see Table 24-2). The most common pacemaker adapters downsize 5- or 6-mm leads to IS-1 unipolar or bipolar configurations or adapt 3.2-mm low-profile connectors to the IS-1 variety. Adapters are also available to convert bifurcated bipolar leads to the linear IS-1 bipolar configuration. Adapters for ICD leads may be used either for the rate-sensing (pace/sense) leads or for the high-energy leads, patches, or arrays (Fig. 24-24). These small units are most helpful for adapting epicardial lead

HVB = Common P+/S,P–/S (6.5mm) (IS-1)1 HVA = Pulse 2 HVA (6.5mm) (Device case)

HVX=Pulse 1 (6.5mm)

B-style connector HVX (DF-1)

C-style connector

HVA (DF-1)

P+/S,P–/S (IS-1)

HVB (DF-1)

D-style connector

HVB (DF-1)2

P–/S (5.0mm)

P+/S (5.0mm)

HVB (6.5mm)

HVA (6.5mm) E-style connector

HVX or plug (DF-1) IS-1 P+/S P–/S HVA (Device case)

HVB (DF-1) Cx-style connector

HVX or plug (DF-1) P+/S,P–/S (IS-1) HVA (Device case)

HVB (DF-1) Cx-style connector

Figure 24-21  Implantable cardioverter-defibrillator header connector block configurations. These various styles of ICD header configurations are designed to connect directly to different types of implanted rate-sensing and pacing leads (pace and sense, P/S) and to high-voltage lead connectors (HVA, HVB, HVX). All rate/sense lead ports are of the IS-1 or 5-mm configurations. This means that any rate/sense leads that are of different connector configurations must be adapted to fit into these ports. Likewise, high-energy lead ports are of the DF-1 or 3.2-mm configuration. Adapters may be required here as well to provide a direct connection into the ICD header. Many forms of adapters are available for pace and sense leads. A variety of adapters for high-energy leads are also available. (From ICD replacement guide. Medtronic, Minneapolis.)



24  Approach to Pulse Generator Changes

735

High Voltage DF4-LLHH Low

Low

High

High DF4-LLHO

Low

Low

High

Open DF4-OOHH

Open

Open

High

High

Low Voltage IS4-LLLL Low

Low

Low

Low IS4-LLLO

Low

Low

Low

Open

Figure 24-22  Configurations for DF-4 and IS-4 leads. Three highvoltage (DF-4) and two low-voltage (IS-4) lead configurations as proposed by the American Association of Medical Instrumentation. In all configurations, the connections flow from the distal end of the lead and connect at the pin, most distal to most proximal, and so forth. In all configurations, the pin and next electrode are reserved for low-voltage functions. Each pole is labeled either L or H, depending on its function. (From Proposed IS-4 Standard; American Association of Medical Instrumentation presentation at Cardiostim, Nice, France, 2004; and ISO Standard: Active implantable medical devices: four-pole connector system for implantable cardiac rhythm management devices— dimensional and test requirements. Geneva, 2009, International Standards Organization—E:\ISO FDIS 27186 (E) 25June2009.doc STD Version 2.1c2.)

connectors found in an abdominal pocket to newer-generation ICD batteries, that is, attaching nonstandard lead connectors to IS-1 pacing and DF-1 shocking ports in an ICD header block. The adapters may also be used when older transvenous leads must be attached to newer, standard-connect ICD pulse generators. One additional special use for ICD lead adapters involves connecting high-energy leads in parallel to enable them to function as a single unit with the same polarity. For example, a subcutaneous patch or array

TABLE

24-2 

Figure 24-23  Pacing lead adapters and sleeves. Left, Four conducting adapters are (top to bottom) 6-mm lead pin replacement; 3.2-mm low-profile linear bipolar (to accept a lead connector without sealing rings) to VS-1 linear bipolar; 6-mm linear bipolar to 3.2-mm linear bipolar; and 3.2-mm low-profile linear bipolar to VS-1 linear bipolar. Right, Four nonconducting adapters are (top to bottom) unipolarizing sleeve for 6-mm bipolar lead; upsizing sleeve from 5 to 6 mm; upsizing unipolarizing sleeve from 3.2 to 6 mm; and upsizing unipolarizing sleeve from 3.2 to 5 mm.

may have to be added to a system because of a high DFT. This additional hardware can be connected in parallel with a proximal highenergy coil located in the SVC. Lead connectors from both the subcutaneous lead and the proximal coil are inserted side by side into an adapter, which then attaches to a single port in the ICD header. This lead system thereby functions as a single, electrically connected unit with the same polarity. Despite the available variety of electrically conducting adapters, these units prove bulky in the pacemaker or ICD pocket (Fig. 24-25) Furthermore, they provide another electrical weak link, that is, one additional set of connections in the pacing circuit for delivery of current to the patient and for sensing, increasing the chance of malfunction, compared with direct attachment of a lead into a pulse generator connector block. Some adapter set screws must be sealed with medical adhesive after being fastened to the lead; a poor seal can result in a short circuit in the system. Because of internal connections, not all adapters have the reliability inherent in most pacemaker or ICD leads directly connected to the generator. TOOLS Several specially designed tools assist the operator in replacing pacemaker and ICD pulse generators and repairing leads (Box 24-6 and Fig. 24-26). Most important are wrenches to loosen set screws in the

Common Configurations for Pacemaker or Defibrillator Adapters

From (Lead) To (Generator) Conducting Adapters 6-mm UNI 5-mm UNI 6-mm BIF 3.2-mm LP BI 6-mm BI 3.2-mm LP BI 5-mm BIF 3.2-mm LP BI 5-mm BIF IS-1 BI 5-mm UNI IS-1 UNI 3.2-mm LP BI 5-mm BIF 3.2-mm LP IS-1 BI DF-1* DF-1 + DF-1 Nonconducting Upsizing Sleeve Adapters 3.2-mm LP BI 5-mm or 6-mm UNI (+ pin extender) IS-1 UNI or BI 5-mm or 6-mm UNI 5-mm UNI 6-mm UNI LV-1 IS-1 *Used for the addition of a subcutaneous lead, patch, or array to an endocardial highenergy lead. BI, Linear bipolar; BIF, bifurcated bipolar; LP, low profile; UNI, unipolar.

Box 24-6 

COMMON TOOLS* Set-screw torque wrench Set screws Anchoring sleeves Lead repair kit: insulating sleeve, medical adhesive Lead end-caps: 6.5-mm; 5-mm; 3.2-mm LP; IS-1 Probes (to unlock lead connector block in some devices) Allen wrenches†: 0.035-inch (No. 2); 0.050-inch (No. 4); 0.062-inch (No. 6); 0.093-inch (No. 10) Screwdrivers: 0.100-inch; 0.200-inch *Used for generator replacement, lead replacement, lead revision, or lead repair. †Specific torque wrenches may be available from some manufacturers; these are especially important for tightening set screws with appropriate force. Wrench numbers are standardized for ease of identification.

736

SECTION 3  Implantation Techniques

AICD Lead adapters

pulse generator connector block to allow the old lead to be withdrawn. Set-screw sizes are now standardized, but if the original generator manufacturer and model are known, a specific wrench may be required. Some early pulse generators had to be removed from the lead with a small, flat screwdriver. Some pulse generators were connected to the lead without set screws through pressing of an attachment unit into place; loosening this unit required that a small probe be inserted into the side of the connector block to push open the locking mechanism. It is unusual to lose set screws because they are generally held in place by a seal. It is advisable, however, to have additional set screws available in a busy pacing laboratory. Occasionally, repair can salvage an old lead, as long as the conductor fracture or insulation break is accessible at least several centimeters from the point at which the lead enters the vascular system. Lead insulation breaks can be repaired by gluing on a polymeric silicone (Silastic) sleeve with medical adhesive. The sleeve should also be tied in place with nonabsorbable suture. Repair of polyurethane leads can prove functionally inadequate because adhesive may not bond properly with the lead insulator, as it does with silicone. A more viable approach in any of these situations may be to extract or cap the culprit lead and replace it entirely.

Model 6024 (16 cm) 4.75-mm

IS-1

Model 6833 (15 cm) 6.1-mm

DF-1

Model 6835 (15 cm) 3.2-mm

DF-1

Model 6836 (15 cm) 6.1-mm

6.1-mm

Model 6931 (14 cm) 6.1-mm

DF-1

AICD Lead extender Model 6952 (60 cm) DF-1

APPROACH TO THE ERODING DEVICE DF-1

IS-1 DF-1

IS-1

Figure 24-24  Implantable cardioverter-defibrillator lead adapters. A variety of ICD lead adapters. As indicated, several different sizes of lead connectors can be inserted side by side to be adapted to the appropriate size to fit directly into the ICD header port. Additionally, linear adapters to change the size of a lead connector may also be required. Lead extenders are used to attach rate-sensing and highenergy leads placed through the subclavian system to an ICD pulse generator inserted in the abdomen. As the size and weight of ICDs have been reduced, however, the need to place the ICD pulse generator in the anterior abdominal wall has greatly diminished. (From Multiple options for customized therapy. Guidant, St Paul, Minn.)

A

Although relatively uncommon, chronic erosion through the skin by the pulse generator or lead can occur.1,13,135 Incipient erosion manifests as localized erythema in an area of thinned skin that is adherent to the underlying device. The area gradually becomes necrotic and may drain serosanguineous fluid. Outright erosion and drainage necessarily imply that the pacemaker pocket is no longer sterile;1,164 the system (generator and leads) should be removed in such cases.5,8,9 Occasionally, the pocket heals with removal of the pulse generator alone, but only when skin integrity has not been breached. However, even a nearerosion is more often a manifestation of a chronic indolent infection and rarely is adequately treated without removal of the leads as well as the device (see Chapter 26). After removal of the pulse generator and leads, eroded pockets can be fully debrided and closed primarily, leaving a drain in place for 2 to 3 days; pockets rarely need to be packed for closure by secondary intention. IV antibiotics are administered for 1 week up to 6 weeks, if bacteremia is present. A new device should be implanted on the contralateral side only after all signs of infection have resolved at the original pacemaker site,

B

Figure 24-25  Pocket bulk from adapters. A, Bulk in pocket with transvenous lead. Lead header connections from the same patient as in Figure 24-20, A. It is clear that adding adapters increases pocket bulk. In the center of the figure is a linear adapter that takes a long, IS-1 pace/ sense electrode to adapt it to a bifurcated, bipolar, 5-mm side-by-side lead, to allow its connection to the pulse generator. The side-by-side pace/ sense portion of the original trifurcating, high-energy lead has two 5-mm caps in place, likely because of pace/sense malfunction at the previous generator change. Two 6-mm high-energy lead heads attach from the high-energy lead directly into the pulse generator. Options for replacement here include obtaining a pulse generator that adapts directly to these leads, which is the best option. Alternatively, the pace/sense adapter could be removed (not always possible) and the high-energy lead heads adapted to DF-1. If upgrade is required, new adapters to DF-1 would be necessary. B, Adapter mass in pocket. Multiple lead adapters deigned to maintain use of existing leads and connect them to a new pulse generator. The degree of bulk in the pocket is extreme, which can lead to discomfort and an increased risk of erosion.



24  Approach to Pulse Generator Changes

A

737

B

Figure 24-26  Common tools required for reoperation of new and old devices. A, Top left, Three nondeformable Allen wrenches of various sizes. Top right, Pinch-on tool (Medtronic) to extend and retract the distal screw of an active-fixation lead. Bottom left, Three wrenches. Bottom right, Two torque wrenches (Medtronic and CPI/Guidant) on either side of a probe (Intermedics) used to unlock a pacemaker connector block. Some wrenches are deformable or ratchet configuration to avoid placing excess torque on the set screw, whereas others are not; caution is required in use of the various systems (see text). B, Left to right, Intermedics ratchet torque wrench; Intermedics flat-bladed ratchet torque screwdriver; Cordis No. 6 Allen wrench; unlocking probe; two Allen wrenches with handles (not deformable).

and if the patient has not experienced recurrent fever, the white blood cell count has not increased, and no tricuspid valve vegetation is seen. Two to five days of IV antibiotics appears sufficient before device replacement, as long as bacteremia has resolved and there are no large, intracardiac vegetations. Replacement of the pulse generator on the original side is not recommended; however, this may be possible if complete erosion did not occur, if the pocket could be closed after primary removal of the generator, and if there are no signs of active infection after discontinuation of antibiotics. Alternative approaches are discussed in Chapter 21. ANTIBIOTIC PROPHYLAXIS Compared with pacemaker generator change, the overall procedure time for ICD generator change may be longer. This is because of the larger size of the ICD device and greater extent of dissection, especially to dissect out the trifurcating lead header; the frequent need for upgrade; and the added time for DFT testing during the procedure. Therefore the surgical wound may be open longer, although closure may be started before all testing is complete. Furthermore, the generator change could involve even a larger incision in an abdominal site. The use of broad-spectrum antibiotics for antimicrobial prophylaxis during all procedures involving generator or lead revision is essential. This is especially crucial because these procedures use combinations of previously implanted hardware with new equipment, and because the incidence of infection is increased with generator change or pocket revision. Controversy surrounds whether and how long to use postoperative antibiotic prophylaxis.10,164

Intervention for Acute Problems Indications for acute intervention include primary complications of pacemaker or ICD implantation (e.g., pocket hematoma, infection,1-3 or cardiac perforation126-135) as well as other, less crucial indications, such as iatrogenic lead damage and lead dislodgment. Pocket hematomas occur most often in patients receiving anticoagulants, especially heparin and enoxaparin, and in patients with platelet dysfunction, which is common in those undergoing long-term hemodialysis. The range in hematoma size varies from a contained, small amount of fluctuance and ecchymosis to a large hematoma that may drain through the skin. A minor hematoma requires only observation, whereas a breach of skin integrity after operation may require evacuation of the hematoma or, if it has become secondarily infected, complete removal of the generator and lead system. If the patient remains

pacemaker dependent, a temporary wire must be placed when the original system is removed; after an appropriate course of IV antibiotic therapy, a new device can be placed on the contralateral side. Prolonged antibiotic therapy may be required in some cases. Antibiotic therapy alone and conservative surgical approaches other than complete removal of an eroded or infected generator and leads prove unsatisfactory.5-8,10 Immediate reoperation may also be required for cardiac perforation.132-137 Perforation is suggested by curvature of the lead beyond the confines of the right ventricular apex, an abrupt rise in pacing threshold or deterioration of sensing, precordial pain that increases with inspiration, hypotension, and hemodynamic collapse. Although most perforations close spontaneously, development of a large, pericardial bleed or tamponade requires immediate intervention.137 Pericardiocentesis usually suffices, but occasionally, a subxiphoid approach to pericardial drainage is necessary. Proper lead selection to match the patient’s anatomy and gentle technique are vital to avoiding acute perforation. Subcostal placement of epicardial screw-in leads has been associated with a higher-than-expected incidence of serious or fatal ventricular perforations; chronic perforation by endocardial leads is distinctly rare. Early surgical exploration is indicated to confirm the diagnosis of iatrogenic lead insulation damage. This is an uncommon complication that manifests early in the form of “pocket twitch,”141 failure to capture, or failure to sense, often with associated low measured lead impedance.91 Chronic lead damage has been associated with excessively tight anchoring sutures, especially if they are placed around the lead and not the anchoring sleeve. The damaged lead, whether passive or active fixation, should be removed and replaced, if possible; alternatively, it may be repaired, although repair is difficult if damage has occurred near the venous insertion site. Lead dislodgment occurs most frequently during the first 24 to 48 hours after system implantation.49,50 It can occur later, however, as a result of a loose anchoring sleeve, incomplete fixation of the distal lead tip, excessive diaphragmatic motion, or patient manipulation of the device (i.e., twiddler’s syndrome).87 Before the development of leads with active fixation or a finlike mechanism at the distal tip, the incidence of lead dislodgment ranged as high as 5% to 18%. With careful technique and selection among a variety of active-fixation and passivefixation leads, the incidence should range no higher than 1% to 2%.59,60 Most spontaneous dislodgments occur with atrial passive-fixation leads. The diagnosis may be facilitated by chest radiography or fluoroscopy; pacing analysis reveals an increased pacing threshold, usually with normal lead impedance. The operator has the option of

738

SECTION 3  Implantation Techniques

Figure 24-27  Explanted Parsonnet Pouch. This explanted Dacron pouch was removed with the proximal portion of a dual-chamber pacemaker lead system at the time of device explant and lead extraction. The pouch is heavily fibrosed around the lead coils in the pocket. This holds them firmly in place, but it also makes for a difficult dissection, even if only for a generator change, to free up the leads sufficiently and allow them to be connected to a new generator.

Figure 24-28  Explanted antibiotic-impregnated pouch. Although the degree of fibrosis is significant, this pouch (Tyrx, Monmouth Junction, NJ), unlike the Dacron pouch from Figure 24-27, has a glistening internal surface because it is less predisposed to embed itself around the lead coils in the pocket. Nevertheless, removal of the pouch is difficult because of extensive scarring to the capsule inside the device pocket.

repositioning or replacing the lead. If a distinct cause cannot be identified, placement of an active-fixation lead may avoid a second dislodgment. To prevent recurrent lead dislodgment in twiddler’s syndrome, leads must be sutured to prepectoral fascia or firm, fibrous, pacemaker pocket tissue with nonabsorbable sutures around anchoring sleeves at more than two points; the pacemaker connector block may also need to be anchored to the pectoralis fascia. A polyester (Dacron) pouch has been used in the past to improve device stability in twiddler’s syndrome and in patients with very loose subcutaneous tissue,165 but it is rarely required at present. Removal of the pouch may be difficult at generator replacement (Fig. 24-27). Newer, antibiotic-impregnated, nonabsorbable pouches may be even more difficult to remove166,167 (Fig. 24-28).

diaphragmatic pacing,141 lead insulation break or lead fracture,17,19,22,23 premature generator failure (which could be caused by intrinsic component failure or externally induced failure, as caused by electrocautery, irradiation, or cardioversion),29 and the need for system upgrade.35-43,126 The device clinic or remote monitoring may prove particularly useful in recognizing early surgical or functional problems.63-73 Evaluation and technique follow the principles described earlier.

INTERVAL OR UNSCHEDULED INTERVENTION In the course of pacemaker or ICD follow-up and before the patient requires elective replacement, interval intervention may be needed to correct other complications. These include pulse generator migration,30 lead dislodgment,* high pacing thresholds,46,88 pocket twitch or *References 31-33, 46, 49, 50, 60, 87.

Conclusion Successful pacemaker or ICD replacement is the result of accurate preoperative evaluation and careful surgical intervention. Complication rates of pulse generator replacement and lead revision exceed those of initial implantation.161 The preoperative status of the pulse generator battery and the lead pace/sense function, as well as the appropriateness of both to future pacing or defibrillating systems, needs to be determined to enable surgical planning. There should be no surgical surprises, and all the tools, adapters, leads, and generators should be ready for the intervention. The goal should be to avoid reoperation for as long as possible with careful initial implantation and programming. When properly planned, surgery is likely to proceed smoothly.

REFERENCES 1. Bonchek LI: New methods in the management of extruded and infected cardiac pacemakers. Ann Surg 176:686, 1972. 2. Corman LC, Levison ME: Sustained bacteremia and transvenous cardiac pacemakers. JAMA 233:264, 1975. 3. Wohl B, Peters RW, Carliner N, et al: Late unheralded pacemaker pocket infection due to Staphylococcus epidermidis: a new clinical entity. Pacing Clin Electrophysiol 5:190, 1982. 4. Prager PI, Kay RH, Somberg E, et al: Pacemaker remnantsanother source of infections. Pacing Clin Electrophysiol 7:763, 1984. 5. Ruiter JH, Degener JE, Van Mechelen R, Bos R: Late purulent pacemaker pocket infection caused by Staphylococcus epidermidis: serious complications of in situ management. Pacing Clin Electrophysiol 8:903, 1985. 6. Vilacosta I, Zamorano J, Camino A, et al: Infected transvenous permanent pacemakers: role of transesophageal echocardiography. Am Heart J 125:904, 1993. 7. Ruttmann E, Hangler HB, Kilo J, et al: Transvenous pacemaker lead removal is safe and effective even in large vegetations: an analysis of 53 cases of pacemaker lead endocarditis. Pacing Clin Electrophysiol 29:231-236, 2006. 8. Sohail MR, Uslan DZ, Khan AH, et al: Management and outcome of permanent pacemaker and implantable cardioverter-defibrillator infections. J Am Coll Cardiol 49:18511859, 2007.

9. Klug D, Balde M, Pavin D, et al: Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. PEOPLE Study Group. Circulation 116:1349-1355, 2007. 10. Baddour LM, Epstein AE, Erickson CC, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Interdisciplinary Council on Quality of Care; American Heart Association: Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 121:458-477, 2010. 11. Grammes JA, Schulze CM, Al-Bataineh M, et al: Percutaneous pacemaker and implantable cardioverter-defibrillator lead extraction in 100 patients with intracardiac vegetations defined by transesophageal echocardiogram. J Am Coll Cardiol 55:886894, 2010. 12. Voigt A, Shalaby A, Saba S: Continued rise in rates of cardiovascular implantable electronic device infections in the United States: temporal trends and causative insights. Pacing Clin Electrophysiol 33:414-419, 2010. 13. Garcia-Rinaldi R, Revuelta JM, Bonnington L, SolteroHarrington L: The exposed cardiac pacemaker: treatment by

subfacial pocket relocation. J Thorac Cardiovasc Surg 89:136, 1985. 14. Gold MR, Peters RW, Johnson JW, Shorofsky SR: Complications associated with pectoral cardioverter-defibrillator implantation: comparison of subcutaneous and submuscular approaches. Worldwide Jewel Investigators. J Am Coll Cardiol 28:1278-1282, 1996. 15. Tsai V, Chen H, Hsia H, et al: Cardiac device infections complicated by erosion. J Interv Card Electrophysiol 19:133-137, 2007. 16. Hamid S, Arujuna A, Ginks M, et al: Pacemaker and defibrillator lead extraction: predictors of mortality during follow-up. Pacing Clin Electrophysiol 33:209-216, 2010. 17. Kronzon I, Mehta SS: Broken pacemaker wire in multiple trauma: a case report. J Trauma 14:82, 1974. 18. Tegtmeyer CJ, Bezirdjian DR, Irani FA, Landis JD: Cardiac pacemaker failure: a complication of trauma. South Med J 74:378, 1981. 19. Grieco JG, Scanlon PJ, Pifarre R: Pacing lead fracture after a deceleration injury. Ann Thorac Surg 47:453, 1989. 20. Catanzaro JN, Makaryus AN, Jadonath S, Jadonath R: Pacemaker ventricular lead microdislodgement following a motor vehicle accident. Eur J Emerg Med 14:224-227, 2007. 21. Hai AA, Kalinchak DM, Schoenfeld MH: Increased defibrillator charge time following direct trauma to an ICD generator: blunt consequences. Pacing Clin Electrophysiol 32:1587-1590, 2009.



24  Approach to Pulse Generator Changes 22. Chen WL, Chen YJ, Tsao YT: Traumatic pacemaker lead fracture. J Trauma 69:E34, 2010. 23. Fernández-González AL, García Bengochea JB, Cortés Laíño J, et al: Fracture of epicardial resynchronization lead caused by deceleration injury. Asian Cardiovasc Thorac Ann 18:77-78, 2010. 24. Wallace WA, Abelmann WH, Norman JC: Runaway demand pacemaker: report, in vitro reproduction, and review. Ann Thorac Surg 9:209, 1970. 25. Austin SM, Kim CS, Solis A: Electrical alternans of pacemaker spike amplitude: an unusual manifestation of permanent pacemaker generator malfunction. Pacing Clin Electrophysiol 4:313, 1981. 26. Campo A, Nowak R, Magilligan D, Tomlanovich M: Runaway pacemaker. Ann Emerg Med 12:32, 1983. 27. Lewinn AA, Serago CF, Schwade JG, et al: Radiation-induced failures of complementary metal oxide semiconductor containing pacemakers: a potentially lethal complication. Int J Radiol Oncol Biol Phys 19:1967, 1984. 28. Venselaar JL, Van Kerkeorle HL, Vet AJ: Radiation damage to pacemakers from radiotherapy. Pacing Clin Electrophysiol 19:538, 1987. 29. Maisel WH: Pacemaker and ICD generator reliability: metaanalysis of device registries. JAMA 295:1929-1934, 2006. 30. Bello A, Yepez CG, Barcelo JE: Retroperitoneal migration of a pacemaker generator: an unusual complication. J Cardiovasc Surg 15:256, 1974. 31. Kim GE, Haveson S, Imparato AM: Late displacement of cardiac pacemaker electrode due to heavyweight pulse generator. JAMA 228:74, 1974. 32. Lorsheyd A, De Boeck BW, Guyomi SH, Klöpping C: A wandering defibrillator lead. Eur J Echocardiogr 10:156-159, 2009. 33. Tay JK, Dweck MR, Francis CM, Grubb NR: Unusual complication of a migrant pacemaker lead. Europace 11:1122-1124, 2009. 34. Hörer T, Vidlund M, Lindell P, Jansson K: A rare case of pacemaker electrode perforation of the heart with intra-abdominal migration. Clin Cardiol 33:E20, 2010. 35. Korley VJ, Hallet N, Daoust M, Epstein LM: A novel indication for transvenous lead extraction: upgrading implantable cardioverter defibrillator systems. J Interv Card Electrophysiol 4:523528, 2000. 36. Baker CM, Christopher TJ, Smith PF, Langberg JJ, et al: Addition of a left ventricular lead to conventional pacing systems in patients with congestive heart failure: feasibility, safety, and early results in 60 consecutive patients. Pacing Clin Electrophysiol 25:1166-1171, 2002. 37. Höijer CJ, Meurling C, Brandt J: Upgrade to biventricular pacing in patients with conventional pacemakers and heart failure: a double-blind, randomized crossover study. Europace 8:51-55, 2006. 38. Leclercq C, Cazeau S, Lellouche D, et al: Upgrading from single chamber right ventricular to biventricular pacing in permanently paced patients with worsening heart failure: the RD-CHF Study. Pacing Clin Electrophysiol 30:S23-S30, 2007; erratum 30:1424, 2007. 39. Duray GZ, Israel CW, Pajitnev D, Hohnloser SH: Upgrading to biventricular pacing/defibrillation systems in right ventricular paced congestive heart failure patients: prospective assessment of procedural parameters and response rate. Europace 10:48-52, 2008. 40. Lin G, Rea RF, Hammill SC, et al: Effect of cardiac resynchronisation therapy on occurrence of ventricular arrhythmia in patients with implantable cardioverter defibrillators undergoing upgrade to cardiac resynchronisation therapy devices. Heart 94:186-190, 2008. 41. Foley PW, Muhyaldeen SA, Chalil S, et al: Long-term effects of upgrading from right ventricular pacing to cardiac resynchronization therapy in patients with heart failure. Europace 11:495501, 2009. 42. Vatankulu MA, Goktekin O, Kaya MG, et al: Effect of long-term resynchronization therapy on left ventricular remodeling in pacemaker patients upgraded to biventricular devices. Am J Cardiol 103:1280-1284, 2009. 43. Fröhlich G, Steffel J, Hürlimann D, et al: Upgrading to resynchronization therapy after chronic right ventricular pacing improves left ventricular remodeling. Eur Heart J 31:1477-1485, 2010. 44. Halperin JL, Camunas JL, Stern EH, et al: Myopotential interference with DDD pacemakers: endocardial electrographic telemetry in the diagnosis of pacemaker-related arrhythmias. Am J Cardiol 54:97, 1984. 45. Den Dulk K, Lindemans FW, Brugad P, et al: Pacemaker syndrome with AAI rate-variable pacing: importance of atrioventricular conduction properties, medication, and pacemaker programmability. Pacing Clin Electrophysiol 11:1226, 1987. 46. Aris A, Shebairo RA, Lepley D, Jr: Increasing myocardial thresholds to pacing after cardiac surgery. Surg Forum 24:167, 1973. 47. Gaidula JJ, Barold SS: Elimination of diaphragmatic contractions from chronic pacing catheter perforation of the heart by conversion to a unipolar system. Chest 66:86, 1974. 48. Contini C, Papi L, Pesola A, et al: Tissue reaction to intracavitary electrodes: effect on duration and efficiency of unipolar pacing in patients with A-V block. J Cardiovasc Surg 14:282, 1973. 49. Holmes DR, Jr, Nissen RG, Maloney JD, et al: Transvenous tined electrode systems: an approach to acute dislodgement. Mayo Clin Proc 54:219, 1979. 50. Hauser RG, Hayes DL, Kallinen LM, et al: Clinical experience with pacemaker pulse generators and transvenous leads: an

8-year prospective multicenter study. Heart Rhythm 4:154-160, 2007. 51. Alt E, Volker R, Blomer H: Lead fracture in pacemaker patients. Thorac Cardiovasc Surg 35:101, 1987. 52. Maisel WH: Pacemaker and ICD generator reliability: metaanalysis of device registries. JAMA 295:1929-1934, 2006. 53. Gula LJ, Massel D, Krahn AD, et al: Survival rates as a guide to implanted cardioverter-defibrillator replacement strategies for device recalls: adding statistical insight to clinical intuition. Am Heart J 153:253-259, 2007. 54. Kapa S, Hyberger L, Rea RF, Hayes DL: Complication risk with pulse generator change: implications when reacting to a device advisory or recall. Pacing Clin Electrophysiol 30:730-753, 2007. 55. Costea A, Rardon DP, Padanilam BJ, et al: Complications associated with generator replacement in response to device advisories. J Cardiovasc Electrophysiol 19:266-269, 2008. 56. Gould PA, Gula LJ, Champagne J, et al: Outcome of advisory implantable cardioverter-defibrillator replacement: one-year follow-up. Heart Rhythm 5:1675-1681, 2008. 57. Priori SG, Auricchio A, Nisam S, Yong P: To replace or not to replace: a systematic approach to respond to device advisories. J Cardiovasc Electrophysiol 20:164-170, 2009. 58. Woscoboinik JR, Maloney JD, Helguera ME, et al: Pacing lead survival: performance of different models. Pacing Clin Electrophysiol 15:1991, 1992. 59. Morse D, Yankaskas M, Johnson B, et al: Transvenous pacemaker insertion with a zero dislodgment rate. Pacing Clin Electrophysiol 6:283, 1983. 60. Hakki AH, Horowitz LN, Reiser J, Mundth ED: Improved pacemaker fixation and performance using a modified finned porous surfaced tip lead. Int Surg 69:291, 1984. 61. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322, 1980. 62. Mond H, Twentyman R, Smith D, Sloman G: The pacemaker clinic. Cardiology 57:262, 1972. 63. Starr A, Dobbs J, Dabolt J, Pierie W: Ventricular tracking pacemaker and teletransmitter follow-up system. Am J Cardiol 32:956, 1973. 64. Janosik DL, Redd RM, Buckingham TA, et al: Utility of ambulatory electrocardiography in detecting pacemaker dysfunction in the early postimplantation period. Am J Cardiol 60:1030, 1987. 65. Mugica J, Henry L, Rollet M, et al: The clinical utility of pacemaker follow-up visits. Pacing Clin Electrophysiol 9:1249, 1986. 66. Joseph GK, Wilkoff BL, Dresing T, et al: Remote interrogation and monitoring of implantable cardioverter defibrillators. J Interv Card Electrophysiol 11:161, 2004. 67. Hauck M, Bauer A, Voss F, et al: “Home monitoring” for early detection of implantable cardioverter-defibrillator failure: a single-center prospective observational study. Clin Res Cardiol 98:19-24, 2009. 68. Varma N, Johnson MA: Prevalence of cancelled shock therapy and relationship to shock delivery in recipients of implantable cardioverter-defibrillators assessed by remote monitoring. Pacing Clin Electrophysiol 32(Suppl 1):S42-S46, 2009. 69. Theuns DA, Rivero-Ayerza M, Knops P, et al: Analysis of 57,148 transmissions by remote monitoring of implantable cardioverter defibrillators. Pacing Clin Electrophysiol 32(Suppl 1):S63-S65, 2009. 70. Ip J, Waldo AL, Lip GY, et al: Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: rationale, design, and clinical characteristics of the initially enrolled cohort. The IMPACT study. Am Heart J 158:364370, 2009. 71. Varma N, Epstein AE, Irimpen A et al: Efficacy and safety of automatic remote monitoring for implantable cardioverterdefibrillator follow-up: the Lumos-T Safely Reduces Routine Office Device Follow-up (TRUST) trial. Circulation 122:325332, 2010. 72. Burri H, Quesada A, Ricci RP, et al: The Monitoring Resynchronization Devices and Cardiac Patients (MORE-CARE) study: rationale and design. Am Heart J 160:42-48, 2010. 73. Varma N, Michalski J, Epstein AE, Schweikert R: Automatic remote monitoring of ICD lead and generator performance: the TRUST Trial. Circ Arrhythm Electrophysiol 3:428-436, 2010. 74. Kertes P, Mond H, Sloman G, et al: Comparison of lead complications with polyurethane tined, silicone rubber tined, and wedge tip leads: clinical experience with 822 ventricular endocardial leads. Pacing Clin Electrophysiol 6:957, 1983. 75. Van Gelder LM, El Gamal MI: False inhibition of an atrial demand pacemaker caused by an insulation defect in a polyurethane lead. Pacing Clin Electrophysiol 6:834, 1983. 76. Sanford CF: Self-inhibition of an AV sequential demand (DVI) pulse generator due to polyurethane lead insulation disruption. Pacing Clin Electrophysiol 6:840, 1983. 77. Timmis GC, Westveer DC, Martin R, Gordon S: The significance of surface changes on explanted polyurethane pacemaker leads. Pacing Clin Electrophysiol 6:845, 1983. 78. Chawla AS, Blais P, Hinberg I, Johnson D: Degradation of explanted polyurethane cardiac pacing leads and of polyurethane. Biomater Artif Cells Artif Organs 16:785, 1988. 79. Van Beek GJ, den Dulk K, Lindemans FW, Wellens HJ: Detection of insulation failure by gradual reduction in noninvasively measured electrogram amplitudes. Pacing Clin Electrophysiol 9:772, 1986.

739

80. Stokes KB, Church T: Ten-year experience with implanted polyurethane lead insulation. Pacing Clin Electrophysiol 9:1160, 1986. 81. Phillips R, Frey M, Martin RO: Long-term performance of polyurethane pacing leads: mechanisms of design-related failures. Pacing Clin Electrophysiol 9:1166, 1986. 82. Barold SS, Gaidula JJ: Demand pacemaker arrhythmias from intermittent internal short circuit in bipolar electrode. Chest 63:165, 1973. 83. Adler SC, Foster AJ, Sanders RS, Wuu E: Thin bipolar leads: a solution to problems with coaxial bipolar designs. Pacing Clin Electrophysiol 15:1986, 1992. 84. Barold SS, Scovil J, Ong LS, Heinle RA: Periodic pacemaker spike attenuation with preservation of capture: an unusual electrocardiographic manifestation of partial pacing electrode fracture. Pacing Clin Electrophysiol 1:375, 1978. 85. Fortescue EB, Berul CI, Cecchin F, et al: Patient, procedural, and hardware factors associated with pacemaker lead failures in pediatrics and congenital heart disease. Heart Rhythm 1:150-159, 2004. 86. Olgun H, Karagoz T, Celiker A, Ceviz N: Patient- and leadrelated factors affecting lead fracture in children with transvenous permanent pacemaker. Europace 10:844-847, 2008. 87. Bayliss CE, Beanlands DS, Baird RJ: The pacemaker-twiddler’s syndrome: a new complication of implantable transvenous pacemakers. Can Med Assoc J 99:371, 1968. 88. Starr DS, Lawrie GM, Morris GC, Jr: Acute and chronic stimulation thresholds of intramyocardial screw-in pacemaker electrodes. Ann Thorac Surg 31:334, 1981. 89. Biffi M, Spitali G, Silvetti MS, et al: Atrial threshold variability: implications for automatic atrial stimulation algorithms. Pacing Clin Electrophysiol 30:1445-1454, 2007. 90. Rosenthal LS, Mester S, Rakovec P, et al: Factors influencing pacemaker generator longevity: results from the complete automatic pacing threshold utilization recorded in the CAPTURE Trial. Pacing Clin Electrophysiol 33:1020-1030, 2010. 91. Ferek B, Pasini M, Pustisek S, et al: Noninvasive detection of insulation break. Pacing Clin Electrophysiol 7:1063, 1984. 92. Maytin M, Love CJ, Fischer A, et al: Multicenter experience with extraction of the Sprint Fidelis implantable cardioverterdefibrillator lead. J Am Coll Cardiol 56:646-650, 2010. 93. Sandler MJ, Kutalek SP: Inappropriate discharge by an implantable cardioverter defibrillator: Recognition of myopotential sensing using telemetered intracardiac electrograms. Pacing Clin Electrophysiol 17:665, 1994. 94. Santos KR, Adragão P, Cavaco D, et al: Diaphragmatic myopotential oversensing in pacemaker-dependent patients with CRT-D devices. Europace 10:1381-1386, 2008. 95. Korte T, Jung W, Spehl S, et al: Incidence of ICD lead related complications during long-term follow-up: comparison of epicardial and endocardial electrode systems. Pacing Clin Electrophysiol 18:2053, 1995. 96. Schwartzman D, Callans DJ, Gottlieb CD, et al: Early postoperative rise in defibrillation threshold in patients with nonthoracotomy defibrillation lead systems: attenuation with biphasic shock waveforms. J Cardiovasc Electrophysiol 7:483, 1996. 97. Goyal R, Harvey M, Horwood L, et al: Incidence of lead system malfunction detected during implantable defibrillator generator replacement. Pacing Clin Electrophysiol 19:1143, 1996. 98. Schuchert A, Voitk J, Liu B, et al: Autocapture compatibility in patients with the MembraneEX lead and Affinity pulse generators. Europace 3:332-335, 2001. 99. Kucukosmanoglu O, Celiker A, Ozer S, Karagoz T: Compatibility of automatic threshold tracking pacemakers with previously implanted pacing leads in children. Pacing Clin Electrophysiol 25:1624-1627, 2002. 100. Calfee RV, Saulson SH: A voluntary standard for 3.2-mm unipolar and bipolar pacemaker leads and connectors. Pacing Clin Electrophysiol 9:1181, 1986. 101. Doring J, Flink R: The impact of pending technologies on a universal connector standard. Pacing Clin Electrophysiol 9:1186, 1986. 102. Tyers GF, Sanders R, Mills P, Clark J: Analysis of setscrew and sidelock connector reliability. Pacing Clin Electrophysiol 15:2000, 1992. 103. Hayes DL, Wang PJ, Reynolds DW, et al: Interference with cardiac pacemakers by cellular telephones. N Engl J Med 336:1473, 1997. 104. Fetter JG, Ivans V, Benditt DG, Collins J: Digital cellular telephone interaction with implantable cardioverter-defibrillators. J Am Coll Cardiol 31:623, 1998. 105. Calcagnini G, Censi F, Floris M, et al: Evaluation of electromagnetic interference of GSM mobile phones with pacemakers featuring remote monitoring functions. Pacing Clin Electrophysiol 29:380-385, 2006. 106. Ismail MM, Badreldin AM, Heldwein M, Hekmat K: Thirdgeneration mobile phones (UMTS) do not interfere with permanent implanted pacemakers. Pacing Clin Electrophysiol 33:860-864, 2010. 107. Torresani J, Ebagosti A, Allard-Latour G: Pacemaker syndrome with DDD pacing. Pacing Clin Electrophysiol 7:1183, 1984. 108. Cunningham TM: Pacemaker syndrome due to retrograde conduction in DDI pacemaker. Am Heart J 115:478, 1988. 109. Farmer DM, Estes NA, 3rd, Link MS: New concepts in pacemaker syndrome. Indian Pacing Electrophysiol J 4:195-200, 2004. 110. Pascale P, Pruvot E, Graf D: Pacemaker syndrome during managed ventricular pacing mode: what is the mechanism? J Cardiovasc Electrophysiol 20:574-576, 2009.

740

SECTION 3  Implantation Techniques

111. ISO Standard: Active implantable medical devices: four-pole connector system for implantable cardiac rhythm management devices—dimensional and test requirements. Geneva, 2009, International Standards Organization (ISO) Copyright Office (ISO TC 150/SC 6, 2009-2006-25). 112. Schwartzman D, Nallamothu N, Callans DJ, et al: Postoperative lead-related complications in patients with nonthoracotomy defibrillation lead system. J Am Coll Cardiol 26:776, 1995. 113. Lawton JS, Wood MA, Gilligan DM, et al: Implantable cardioverter defibrillator leads: the dark side. Pacing Clin Electrophysiol 19:1273, 1996. 114. Swartz JF, Fletcher RD, Karasik PE: Optimization of biphasic waveforms for human nonthoracotomy defibrillation. Circulation 88:2646, 1993. 115. Neuzner J, Pitschner HF, Huth C, et al: Effect of biphasic waveform pulse on endocardial defibrillation efficacy in humans. Pacing Clin Electrophysiol 17:207, 1994. 116. Natale S, Sra J, Axtell K, et al: Preliminary experience with a hybrid nonthoracotomy defibrillating system that includes a biphasic device: comparison with a standard monophasic device using the same lead system. J Am Coll Cardiol 24:406, 1994. 117. Block M, Hammel D, Bocker D, et al: A prospective randomized cross-over comparison of mono- and biphasic defibrillation using nonthoracotomy lead configuration in humans. J Cardiovasc Electrophysiol 5:581, 1994. 118. Gold MR, Foster AH, Shorofsky SR: Lead system optimization for transvenous defibrillation. Am J Cardiol 80:1163, 1997. 119. Bardy GH, Dolack GL, Kudenchuck PJ, et al: Prospective comparison in humans of a unipolar defibrillation system with that using an additional superior vena cava electrode. Circulation 89:1090, 1994. 120. Jacob S, Lieberman RA: Percutaneous epicardial defibrillation coil implantation: a viable technique to manage refractory defibrillation threshold. Circ Arrhythm Electrophysiol 3:214-217, 2010. 121. Reynolds CR, Nikolski V, Sturdivant JL, et al: Randomized comparison of defibrillation thresholds from the right ventricular apex and outflow tract. Heart Rhythm 7:1561-1566, 2010. 122. Kroll MW, Schwab JO: Achieving low defibrillation thresholds at implant: pharmacological influences, RV coil polarity and position, SVC coil usage and positioning, pulse width settings, and the azygous vein. Fundam Clin Pharmacol 24:561-573, 2010. 123. Almassi GH, Olinger GN, Wetherbee JN, et al: Long-term complications of implantable cardioverter-defibrillator lead system. Ann Thorac Surg 55:888, 1993. 124. Brode SE, Schwartzman D, Callans DJ, et al: ICD-antiarrhythmic drug and ICD-pacemaker interactions. J Cardiovasc Electrophysiol 8:830, 1997. 125. Simon RD, Sturdivant JL, Leman RB, et al: The effect of dofetilide on ventricular defibrillation thresholds. Pacing Clin Electrophysiol 32:24-28, 2009. 126. Baker CM, Christopher TJ, Smith PF, et al: Addition of a left ventricular lead to conventional pacing systems in patients with congestive heart failure: feasibility, safety, and early results in 60 consecutive patients. Pacing Clin Electrophysiol 25:166, 2002. 127. Breuls NP, Res JC: Acute subclavian or axillary vein occlusion during biventricular pacemaker implantation. Pacing Clin Electrophysiol 29:1170-1173, 2006. 128. Haghjoo M, Nikoo MH, Fazelifar AF, et al: Predictors of venous obstruction following pacemaker or implantable cardioverterdefibrillator implantation: a contrast venographic study on 100 patients admitted for generator change, lead revision, or device upgrade. Europace 9:328-332, 2007.

129. Kamdar RH, Schilling RJ: Percutaneous permanent pacemaker implantation via the azygous vein in a patient with superior vena cava occlusion. Pacing Clin Electrophysiol 31:386-388, 2008. 130. Imran N, Grubb B, Kanjwal Y: Persistent left superior vena cava: a blessing in disguise. Europace 10:588-590, 2008. 131. Worley SJ, Gohn DC, Pulliam RW: Over-the-wire lead extraction and focused force venoplasty to regain venous access in a totally occluded subclavian vein. J Interv Card Electrophysiol 23:135137, 2008. 132. Peters RW, Scheinman MM, Raskin S, Thomas AN: Unusual complications of epicardial pacemaker: recurrent pericarditis, cardiac tamponade and pericardial constriction. Am J Cardiol 45:1088, 1980. 133. Phibbs B, Marriott HJ: Complications of permanent transvenous pacing. N Engl J Med 312:1428, 1985. 134. Villaneuva FS, Heinsiner JA, Burkman MH, et al: Echocardiographic detection of perforation of the cardiac ventricular septum by a permanent pacemaker lead. Pacing Clin Electrophysiol 59:370, 1987. 135. Hill PE: Complications of permanent transvenous cardiac pacing: a 14-year review of all transvenous pacemakers inserted at one community hospital. Pacing Clin Electrophysiol 10:564, 1987. 136. Pizzarelli G, Dernevik L: Inadvertent transarterial pacemaker insertion: an unusual complication. Pacing Clin Electrophysiol 10:951, 1987. 137. Sandler MA, Wertheimer JH, Kotler MN: Pericardial tamponade associated with pacemaker catheter manipulation. Pacing Clin Electrophysiol 12:1085, 1989. 138. Mueller X, Sadeghi H, Kappenberger L: Complications after single- versus dual-chamber pacemaker implantation. Pacing Clin Electrophysiol 13:711, 1990. 139. Bailey SM, Wilkoff BL: Complications of pacemakers and defibrillators in the elderly. Am J Geriatr Cardiol 15:102-107, 2006. 140. Robinson M, Healey JS, Eikelboom J, et al: Postoperative lowmolecular-weight heparin bridging is associated with an increase in wound hematoma following surgery for pacemakers and implantable defibrillators. Pacing Clin Electrophysiol 32:378382, 2009. 141. Ekbom K, Nilsson BY, Edhag O, Olin C: Rhythmic shoulder girdle muscle contractions as a complication in pacemaker treatment. Chest 66:599, 1974. 142. Chun PK: Characteristics of commonly utilized permanent endocardial and epicardial pacemaker electrode systems: method of radiologic identification. Am Heart J 102:404, 1981. 143. Angello DA: Principles of electrical testing for analysis of ventricular endocardial pacing leads. Prog Cardiovasc Dis 27:57, 1984. 144. Wilkoff BL, Love CJ, Byrd CL, et al: Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management (endorsed by the American Heart Association). Heart Rhythm 6:1085-1104, 2009. 145. Aleksic I, Kottenberg-Assenmacher E, Kienbaum P, et al: The innominate vein as alternative venous access for complicated implantable cardioverter-defibrillator revisions. Pacing Clin Electrophysiol 30:957-960, 2007. 146. Kemler RL: A simple method for exposing the external jugular vein for placement of a permanent transvenous pacing catheter electrode. Ann Thorac Surg 26:266, 1978. 147. Sethi GK, Bhayana JN, Scott SM: Innominate venous thrombosis: a rare complication of transvenous pacemaker electrodes. Am Heart J 87:770, 1974.

148. Fritz T, Richeson JF, Fitzpatrick P, Wilson G: Venous obstruction: a potential complication of transvenous pacemaker electrodes. Chest 83:534, 1983. 149. Sharma S, Kaul U, Rajani M: Digital subtraction venography for assessment of deep venous thrombosis in the arms following pacemaker implantation. Int J Cardiol 23:135, 1989. 150. Antonelli D, Turgeman Y, Kaveh Z, et al: Short-term thrombosis after transvenous permanent pacemaker insertion. Pacing Clin Electrophysiol 12:280, 1989. 151. Spittell PC, Vlietstra RE, Hayes DL, Higano ST: Venous obstruction due to permanent transvenous pacemaker electrodes: treatment with percutaneous transluminal balloon venoplasty. Pacing Clin Electrophysiol 13:271, 1990. 152. Wertheimer M, Hughes RK, Castle CH: Superior vena cava syndrome: complication of permanent transvenous endocardial cardiac pacing. JAMA 224:1172, 1973. 153. Toumbouras M, Spanos P, Konstantaras C, Lazarides DP: Inferior vena cava thrombosis due to migration of retained functionless pacemaker electrode. Chest 82:785, 1982. 154. Blackburn T, Dunn M: Pacemaker-induced superior vena cava syndrome: consideration of management. Am Heart J 116:893, 1988. 155. Goudevenos JA, Reid PG, Adams PC, et al: Pacemaker-induced superior vena cava syndrome: report of four cases and review of the literature. Pacing Clin Electrophysiol 12:1890, 1989. 156. Mazzetti H, Dussaut A, Tentori C, et al: Superior vena cava occlusion and/or syndrome related to pacemaker leads. Am Heart J 125:831, 1993. 157. Pace JN, Maquilan M, Hessen SE, et al: Extraction and replacement of permanent pacemaker leads through occluded vessels: use of extraction sheaths as conduits-balloon venoplasty as an adjunct. J Interv Cardiol Electrophysiol 1:271, 1997. 158. Chaithiraphan S, Goldberg E, Wolff W, et al: Massive thrombosis of the coronary sinus as an unusual complication of transvenous pacemaker insertion in a patient with persistent left, and no right superior vena cava. J Am Geriatr Soc 22:79, 1974. 159. Kennelly BM: Permanent pacemaker implantation in the absence of a right superior vena cava: a case report. S Afr Med J 55:1043, 1979. 160. Schuster MM, McCauley K, Kutalek S: Learning retention in patients receiving midazolam during permanent pacemaker implantation. J Cardiovasc Nurs 14:27-34, 1999. 161. Poole JE, Gleva MJ, Mela T, et al: Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results from the REPLACE Registry. Circulation 122:1553-1561, 2010. 162. Al-Bataineh M, Sajadi S, Fontaine JM, Kutalek S: Axillary subpectoral approach for pacemaker or defibrillator implantation in patients with ipsilateral prepectoral infection and limited venous access. J Interv Card Electrophysiol 27:137-142, 2010. 163. Ching CK, Elayi CS, Di Biase L, et al: Transiliac ICD implantation: defibrillation vector flexibility produces consistent success. Heart Rhythm 6:978-983, 2009. 164. Wade JS, Cobbs CG: Infections in cardiac pacemakers. Curr Clin Topics Infect Dis 9:44, 1988. 165. Parsonnet V: A stretch fabric pouch for implanted pacemakers. Arch Surg 105:654, 1972. 166. Agostinho A, James G, Wazni O, et al: Inhibition of Staphylococcus aureus biofilms by a novel antibacterial envelope for use with implantable cardiac devices. Clin Transl Sci 2:193-198, 2009. 167. Bloom HL, Constantin L, de Lurgio DB, et al: Implantation success and infection in cardiovascular implantable electronic device procedures utilizing an antibacterial envelope. Cooperative Multicenter Study Monitoring a CIED Antimicrobial Device (COMMAND). Pacing Clin Electrophysiol 34:133-142, 2011.

25  25

Prevention and Management of Procedural Complications OUSSAMA WAZNI  |  BRUCE L. WILKOFF

The cardiac implantable electronic device (CIED) has become an

integral part of both cardiology and the overall practice of medicine. The indications for CIED implantation have expanded in particular as a result of the documented mortality benefit from implantable defibrillators and cardiac resynchronization therapy (CRT) in complementary population studies in multicenter, randomized clinical trials. With the increasing number of indications for CIED implantation, the need to recognize the adverse effects associated with these devices and to develop methods to minimize complications and patient morbidity are greater than ever. This chapter addresses the issues surrounding implantation techniques and proposes strategies to reduce CIED-related morbidity. The acute management of implant complications is also addressed.

Choice of Physician A primary issue regarding morbidity associated with CIED implantation is which medical professional should implant and follow up in these patients. As the indications for CIEDs have broadened, and an increasing number of patients are considered for implantation, physicians of various specialties are being called on to implant the devices and manage the postimplantation care of these patients. Curtis et al.,1 using data from the National Cardiovascular Device ICD Registry, found that the rates of overall complications and major complications were lowest among procedures carried out by electrophysiologist (EP) physicians (3.5% and 1.3%, respectively) and highest among those performed by thoracic surgeons (5.8% and 2.5%). Importantly, EP physicians had the lowest rates of major complications, including cardiac arrest, lead dislodgment, and pneumothorax. In this study, the choice of device was also influenced by the specialty of the physician performing the procedure. Non–EP physicians failed to recommend implantation of an indicated cardiac resynchronization implantable cardioverter-defibrillator (ICD) device (CRT-D).1 In a different study, Al-Khatib et al.2 also identified implantation by non–EP physicians as being associated with an increased incidence of complications.2

Implantation-Related Complications Implantation technique is an important determinant of subsequent complications. In most centers a pocket for the generator is made, after which venous access is obtained. However, the formation of the pocket is a crucial part of the procedure, and several principles are useful to prevent future device complications. Through this venous access, a lead is placed, then connected to a device placed in the pocket. Some implantation techniques result in excessive stress on the lead and premature lead failure. Depending on the physical characteristics of the lead, in terms of both materials and construction, certain approaches to subclavian vein access have been associated with subclavian crush, where the lead is compressed in the space between the clavicle and the first rib. This entrapment of the lead in the subclavius muscle, in the periosteum of the clavicle, or just through the very narrow space that occurs with medial subclavian vein puncture is completely dependent on the proceduralist’s approach to accessing the central circulation. In addition, management of suture tie-down sleeves with overly tight ligatures can

damage the outer insulation, inner insulation, or conductor coils, particularly in coaxial leads with a polyurethane inner insulation.3,4 In response to the concerns about medial access of the subclavian system, physicians began to use more lateral access techniques. Unfortunately, extreme lateral access places different stresses on the lead body. Recently popularized implantation techniques within the last 10 years employ access to the subclavian venous system at the point where the axillary vein crosses the first rib, immediately lateral to the clavicle. However, if a more lateral approach into the axillary vein over the second or third rib stresses the leads by a different mechanism. The extreme angle of the lead on entry to the axillary vein at this lateral but also more posterior position, as well as the resultant acute anterior bend following the trajectory of the vein, exacerbated by the suture tie-down sleeve fixing the lead to the muscle, places a torque and compression fatigue stress on the lead conductors. This is most often observed with leads constructed with a thin body, coaxial construction, and active-fixation inner coils (Figs. 25-1 and 25-2). The more medial axillary vein puncture, over the first anterior rib, avoids both subclavian crush and second-rib fatigue fractures.5 The axillary vein can be accessed under fluoroscopy over the first rib and the area probed posterolaterally until the vein is punctured. Alternatively, venography or ultrasound can be used to guide lead implantation6 (see Chapter 21). At implantation, the lead must be treated gently, and any mechanical stress should be avoided. Even overuse of the helical screw mechanism can place additional stress on the conductor. It is usually difficult to nail down the precise trauma that later causes a lead failure, but the time of implantation is a relatively dangerous time for a lead and is often a contributor to the ultimate failure. Prolapsing of the lead on itself should not be performed unless absolutely necessary. Again, although difficult to prove, this practice has been implicated in early lead failure, particularly with lower-profile ICD leads.7-12 In addition to placing the lead in the heart and affixing the suture sleeve, making the connections to the CIED is another potential problem. Utmost vigilance should be exercised when the leads are connected to the device, to avoid the need for surgical revision, reentering the pocket and increasing the risk of infection. In the Replace trial, five patients needed revision because of generator-lead interface problem, such as loose set screw or misconnected leads.13 With the introduction of the DF-4 ICD leads, in which the two DF-1 and one IS-1 connectors are replaced with a single connector, the incidence of connection error should be significantly reduced.14 Currently, an SJ-4 lead is available and is in clinical use (Fig. 25-3).

Procedural Complications LEAD DISLODGMENT Lead dislodgment is the most common complication associated with CIEDs (1.6%-4.4% of cases), with atrial lead dislodgment accounting for most cases. In the MOST trial of more than 2000 patients, Ellenbogen et al.15 found atrial dislodgment in 1.7% of patients in the first 30 postimplant days.15 To prevent dislodgment, it is important to have an adequate intrinsic signal and to ensure contact to the myocardial wall. This is partly assessed by viewing a modest current of injury in

741

742

SECTION 3  Implantation Techniques

Thoracic inlet approaches Lateral approach • Introducer technique • Pneumothorax • Transpulmonary implant • Hemothorax • Lead • Safe

Medial approach • Introducer technique • Safe • Lead • Binding–conductor coil fracture • Crush–insulation failure

Misdirection

Figure 25-1  Intrathoracic (thoracic inlet) introducer approaches. Two introducer approaches, medial and lateral, demonstrate the issues associated with inserting introducers in the intrathoracic portion of the subclavian vein. The medial approach is safe, but the leads are subjected to crush (insula­ tion failure) and binding (conductor coil fracture). The lateral approach is free from lead crush and binding, and it is  safe when the needle is properly directed. Because of vari­ ation in chest wall anatomy, extensive experience is needed to avoid misdirection with the introducer needle and  potentially lethal complications (e.g., transpulmonary vein implantation).

the unfiltered electrogram, in addition to the appearance on fluoroscopy. This has the appearance of a QRS complex with ST-segment elevation before fixation of the active helix into the myocardium. Appropriate slack on the lead is also important, to allow for settling of the device when the patient is upright. There may be micro- or macrodislodgment. Micro-dislodgment has been defined as when there is loss of capture and sensing without radiographic evidence of dislodgment. Macro-dislodgment can be detected by radiography. Lead dislodgment requires reopening the pocket and repositioning of the dislodged lead to ascertain satisfactory function. However, it is best to reaccess the vein, remove the dislodged lead, and ensure that there is no clot or tissue or damage to the lead before reinsertion.

level of difficulty obtaining access. This complication can be mitigated by using an extrathoracic approach with the introducer technique, accessing the axillary vein over the first rib, which acts as a barrier against entering the lung. Pneumothorax should not occur when using the cephalic vein cutdown technique. Most patients with pneumothorax are asymptomatic and are diagnosed on the postimplant chest radiograph. In patients with a sizable pneumothorax, cardiothoracic surgery should be consulted for possible chest tube insertion, in addition to administering high-flow oxygen. Tension pneumothorax should be recognized as a potential cause of sudden hemodynamic compromise during device implantation. Tension pneumothorax should be treated immediately with a chest tube.

PNEUMOTHORAX

HEMOTHORAX

Inadvertent entrance into the pleural space, especially with the introducer access technique, can lead to pneumothorax (0.7%-2% of cases).1,2 This is related to the experience of the implanter and also the

Hemothorax is rare and is usually caused by injury to the great vessels. If arterial access is obtained, pressure should be applied for several minutes. Advancing the wire into the inferior vena cava (IVC) below

Inner coil fracture theory Vein entry site

R2

R1 <
R1

As R↓, stress ↑.

A

As stress ↑ past design limit, the inner coil can fracture.

B

Figure 25-2  Lead stress and fracture. A, With a turning radius less than 0.5 inches (R1), there is increased cyclic bending stress on the lead compared with a turning radius greater than 0.5 cm (R2). B, Note vein and medial access causing fracture of lead.



25  Prevention and Management of Procedural Complications

Four-pole connector...

...replaces (1) IS-1 and (2) DF-1 connectors! Figure 25-3  ICD lead connector. Single DF-4 connector replaces three-pole connector of an ICD lead.

743

Most cases of perforation manifest after the procedure with complaints of chest pain, pleurisy, and at times extracardiac pacing. Perforation also may manifest as a change in sensing and pacing characteristics. Delayed perforation has been a concern with the smallprofile ICD and pacemaker leads, although careful analysis did not confirm the incidence of perforation.11,17-19 However, when there is a delayed perforation, days to months after implantation, the lead should be extracted with surgical backup in the unlikely event of acute tamponade. According to most reported cases and from experience at our institution, extraction of such perforating leads is uneventful, and reimplantation can be performed at the same time.18 Implantation at the right ventricular septum is associated with less risk of perforation.20 This can be achieved using a stylet with a posteriorly angulated bend.21 POCKET HEMATOMA

the diaphragm before enlarging the defect in the vessel with the introducer ensures that the artery is not cannulated. Surgical intervention will depend on the degree of injury and hemodynamic instability. Axillary access is always extrathoracic and therefore amenable to manual compression. A more medial needle stick, especially if arterial, can cause uncontrollable bleeding, especially if the site is intrathoracic. This is another reason that the extrathoracic approach to access is recommended. PERFORATION Perforation of the great vessels is very rare during implantation and is more common with lead extraction. Ventricular perforation is rare and reported to occur in 0.3% to 1% of CIED cases7,11,16,17 (Fig. 25-4). Most are self-limited with no sequelae. Acute tamponade is extremely rare but should be quickly recognized as a cause of hemodynamic compromise and easily diagnosed by bedside echocardiography or with fluoroscopy; the enlarged cardiac silhouette is associated with minimal contraction. Immediate pericardiocentesis should be performed and surgical intervention sought if bleeding does not stop. H

Pocket hematoma usually occurs acutely after implantation. The source of bleeding may be the pocket itself or backbleeding from the vein around the lead entry site. Hemostasis may be achieved using electrocautery while creating the pocket. Digital pressure at the lead entry site usually controls backbleeding; otherwise, purse-string or figure-of-eight suture placement may be needed. The risk of hematoma is higher in anticoagulated patients, especially when heparin is restarted after the procedure. The use of antiplatelet therapy and anticoagulation may increase the risk of hematoma. In one study, only 4.2% of patients with no antiplatelet or anticoagulation developed hematoma, whereas up to 18% of patients with uninterrupted clopidogrel developed hematoma at the pocket site. Patients taking warfarin (Coumadin) only had a 6.9% risk. Combinations of these increased the risk drastically;22 24% of patients with ongoing aspirin and clopidogrel treatment developed hematoma.23 The use of periprocedural heparin (enoxaparin) was associated with increased risk of bleeding compared with continuation of warfarin (INR >1.5).24 The use of dual-antiplatelet therapy presents a challenge, particularly in that it is difficult to stop these agents in patients with drug eluting stents. Warfarin use seems to be less of an issue. Giudici et al revealed that discontinuation of warfarin was associated with same risk as continuation of anticoagulation with a mean international normalized ratio (INR) of 2.5.25 Most hematomas are treated conservatively. Evacuation of hematoma may be needed with continued bleeding, severe tension, and pain. The optimal approach to patients undergoing therapy with the new factor X antagonists, such as dabigatran, has not been directly approached in those with planned device procedures, but it may provide an alternative pathway to a bridging anticoagulation approach. VEIN THROMBOSIS

R

L Lead tip is in epicardial fat Pericardium 10.00 mm/div RV epicardium

Symptomatic venous thrombosis occurs in up to 5% of patients.26,27 However, the incidence of superior vena cava (SVC) obstruction with symptomatic SVC syndrome is rare, approximating 2 per 1000 implants. Treatment is usually based on symptom relief. Acute deep vein thrombosis (DVT) after implantation can occur in up to 40% of cases, but most are asymptomatic. When subclavian occlusions have not presented with symptoms, they are usually detected when a new lead is required because of lead dysfunction or mode-upgrade procedures. In patients with symptoms, arm elevation is advised and, depending on the severity, anticoagulation started with either warfarin alone or with heparin. Again, the use of factor X antagonists has not been explored.

Pain F

10.00 mm/div

Figure 25-4  ICD lead perforation. The tip is in the epicardial fat.

Occasionally, patients complain of pain in or near the implant pocket. History and physical examination are the only diagnostic tools available. Regardless of the cause, pain is a difficult complication to manage. Acutely, some patients heal with no complaints of pain; others have

744

SECTION 3  Implantation Techniques

severe pain. The cause of pain may be nerve entrapment, inflammation of the scar tissue, migration, or injury to the musculoskeletal system. Pain associated with no physical signs may be related to nerve entrapment; the best approach for successful treatment is to remove the generator and leads, abandon the site, and reimplant on the opposite side. Chronic pain or pain that starts after implantation is often an indication of infection and should be treated accordingly.

Infection Increased implantation of CIEDs has led to a greater awareness of implant infection. The increasing incidence of CIED infections, now reported at 1% to 7%, presumably is a result of the increasing number of nonprimary implantations (e.g., generator changes, upgrades). Infection occurs in 1.9 to 2.11 per 1000 device-years, with most infections being pocket infections.28 CIED infection is a serious problem with high morbidity and mortality. In the LExICon study the all-cause in-hospital mortality in infected patients was 3%, with the highest mortality associated with device-related endocarditis (4.3%).29 Tarakji et al.30 demonstrated all-cause mortality as high as 4.6% in infected patients. After extraction of the infected device, mortality remained high in that cohort, with 1-year mortality after removal of 17%. Oneyear mortality was significant in both the pocket infection group (12%) and the endovascular infection group (25%). RISK FACTORS Patient-associated risk factors for infection include diabetes mellitus, renal failure, and heart failure. In one study, oral anticoagulation with the development of pocket hematoma increased the risk of infection, although this has not been confirmed in larger studies.31 Procedural factors associated with infection are reoperation, prolonged procedure time, and previous temporary pacing. In the long term, generator changes and device upgrades continue to pose significant risk for increasing rates of infection.28 PREVENTION Because of the high morbidity and mortality associated with CIED infection, especially in the heart failure population, who also tend to have comorbidities, prevention of infection is probably the most important aspect of device therapy. Universal infection prevention techniques, including hand scrubbing, procedure room and instrument preparation, and double gloving should be observed during CIED implantation. Skin preparation is crucial, but even with skin preparation and periprocedural antibiotics, the overall infection rate during replacement procedures was 1.4% in the Replace Registry.13 Preimplantation antibiotic administration is standard care and has been recently reinforced. In a randomized double-blind study of 649 patients, de Oliveira et al.32 demonstrated that 1.0 g of cefazolin given before CIED implantation was associated with an 80% decrease in infections at 6-month follow-up. The infection rate was 0.64% in the cefazolin group and 3.28% in the control group (P = .016). All infections were caused by Staphylococcus species, with about two-thirds being S. aureus.32 The choice of antibiotic agent depends on the patterns of infections and antibiotic resistance in individual treatment centers. Approximately half of all device-related infections are caused by methicillinresistant S. aureus (MRSA). At our institution, we recommend the use of vancomycin for preoperative antibiotic prophylaxis. We also screen patients for MRSA using nasal swabs and, if the test is positive, pretreat patients with mupirocin. Although not proven in the literature on CIED use, several studies of patients undergoing cardiac surgery have shown that treatment of carriers of MRSA with mupirocin decreases the rate of postoperative infection.33 No matter what antibiotic is used, it is important to have the infusion completed by the time of the surgical incision and initiated within 1 hour if agent is not vancomycin and within 2 hours if vancomycin.34-36 Not only is this important to reduce

the incidence of postsurgical infections. but it is a U.S. national quality measure.37 PRESENTATION The most common presentation of infection continues to be pocket infection with a variety of appearances (Figs. 25-5 to 25-9). In a recent study by Tarakji et al.,30 89% of patients presented with pocket infection compared to patients with systemic signs of infection with an intact pocket. This is in line with historical data. Patients with pocket infection tend to present earlier, whereas patients with systemic infection have more comorbidities, such as heart failure, renal failure, diabetes, or previous episodes of endocarditis. Pocket infection has a diverse and continuum of presentation. Although frank, purulent discharge is the obvious presentation, pocket infection should be considered present with warmth, erythema, dehiscence, and skin adherence. Erosion of the overlying skin is by definition a pocket infection. It is important to recognize that patients with pocket infection can also harbor endovascular vegetations (Fig. 25-10), Tarakji et al.30 reported that vegetations were detected in almost half the patients (56) in whom transesophageal echocardiography (TEE) was performed in a group of 241 patients with pocket infection. Klug et al.35,38,39 reported evidence of intravascular system involvement in at least 88% of patients with pocket infection. As such, as deduced by the Cleveland Clinic group, pocket infections should be considered a manifestation of an infected system encompassing endovascular infection, rather than only a localized phenomenon.30 CIED infection can also have systemic manifestations, including fever, chills, endocarditis, and persistent bacteremia. BACTERIOLOGY Staphylococcus species cause most implant infections, with some series reporting 80%. In cases of coagulase-negative staphylococcal infection, it is important to rule out contamination by repeat cultures. Organisms such as Pseudomonas, Klebsiella, Proteus, and Enterococcus are seen less frequently (8%). Fungi and acid-fast mycobacteria are present on rare occasions. Some of these organisms may have caused the infection, and

Figure 25-5  Erythema and fluctuance. These are signs of infection, not an allergic reaction.



25  Prevention and Management of Procedural Complications

745

Figure 25-8  Erosion of leads through the implant pocket.

Figure 25-6  Fat necrosis. This presentation of infection occurs even in the absence of erythema or discharge. Compromised blood supply to the subcutaneous tissue and skin causes a decrease in the supply of nutrients to the cells. In the early stages (pre-erosion), the fatty tissue begins to lose mass.

Figure 25-9  Purulent discharge from implant-induced infection.

Figure 25-7  Tissue pocket erosion. During the latter pre-erosion stages, the tissue becomes ischemic, and skin changes occur. The last stage before erosion is adhesion of the skin to the fibrous tissue pocket. Complete loss of blood supply to the skin results in gangrene of the skin before erosion.

Figure 25-10  Transesophageal echo revealing a large vegetation.

746

SECTION 3  Implantation Techniques

some may be secondary contaminants (e.g., yeast). Infections caused by a mycobacterium are rare, dangerous, and difficult to treat.40-47 Patterns of antibiotic resistance differ among patient situations or series, with up to 50% of Staphylococcus spp. being methicillin resistant. Infection with gram-negative bacteria, Candida, and fungi is rare compared to Staphylococcus spp. The most plausible pathogenesis is introduction of the microorganisms during the procedure, whether during the primary implantation or subsequent instrumentation. The most likely source is the patients’ skin flora.

antibiotics according to susceptibility is necessary but is not sufficient. Because most infections are caused by staphylococci, empiric therapy with vancomycin should be started until antibiotic susceptibility on blood cultures are available. If there is only pocket erosion with no frank purulence, treatment for 1 week to 10 days may be sufficient. All other cases should be treated with parenteral antibiotics for at least 2 weeks. Treatment with antibiotics alone may pose significant risk to patients, since this would expose them to longer periods of uncontrolled infection, spread, and possible seeding of distant structures.

MANAGEMENT

Measuring Outcomes and Quality Improvement

Superficial infection usually presents as a stitch abscess or a superficial incisional infection that does not seem to involve the device. This may be treated with oral antibiotics that cover staphylococci, for 1 week to 10 days. Staphylococcal bacteria are the most common pathogen on entering the pocket and form a protective biofilm that adheres to the insulation and metal of the devices. This makes these infections resistant to the patients’ immune system and antibiotics. In certain cases, when a patient is not a candidate for extraction, long-term suppression with antibiotics may be warranted. In most patients the definitive treatment of CIED infection is extraction of all the CIED system. Treatment with

Clearly, it is essential that every EP laboratory have a practical quality assurance program in place. This program will help in tracking and measuring outcomes. The program could entail a procedural database that will capture complications and possibly a registry that will follow the patients after discharge. Also, such a program should include the capability of remote monitoring of the implanted devices. The goal should be continuing quality improvement in procedures and in follow-up of patients with implantable cardiac devices. Attention to detail, measuring outcomes, and continuous improvement in techniques are the fundamentals that ensure consistent quality care.

REFERENCES 1. Curtis JP, Luebbert JJ, Wang Y, et al: Association of physician certification and outcomes among patients receiving an implantable cardioverter-defibrillator. JAMA 301:1661-1670, 2009. 2 Al-Khatib SM, Greiner MA, Peterson ED, et al: Patient and implanting physician factors associated with mortality and complications following implantable cardioverter-defibrillator implantation, 2002-2005: Al-Khatib—patient and physician factors and ICD outcomes. Circ Arrhythm Electrophysiol 1:240249, 2008. 3. Magney JE: Anatomical mechanisms that cause lead and catheter damage. Pacing Clin Electrophysiol 19:257-258, 1996. 4. Roelke M, O’Nunain SS, Osswald S, et al: Subclavian crush syndrome complicating transvenous cardioverter defibrillator systems. Pacing Clin Electrophysiol 18:973-979, 1995. 5. Ramza BM, Rosenthal L, Hui R, et al: Safety and effectiveness of placement of pacemaker and defibrillator leads in the axillary vein guided by contrast venography. Am J Cardiol 80:892-896, 1997. 6. Belott P: How to access the axillary vein. Heart Rhythm 3:366-369, 2006. 7. Ellis CR, Rottman JN: Increased rate of subacute lead complications with small-caliber implantable cardioverter-defibrillator leads. Heart Rhythm 6:619-624, 2009. 8. Hauser RG, Hayes DL: Increasing hazard of Sprint Fidelis implantable cardioverter-defibrillator lead failure. Heart Rhythm 6(5):605-610, 2009. 9. Farwell D, Green MS, Lemery R, et al: Accelerating risk of Fidelis lead fracture. Heart Rhythm 5:1375-1379, 2008. 10. Krahn AD, Champagne J, Healey JS, et al: Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: a report from the Canadian Heart Rhythm Society Device Advisory Committee. Heart Rhythm 5:639-642, 2008. 11. Wilkoff BL: Lead failures: dealing with even less perfect. Heart Rhythm 4:897-899, 2007. 12. Hauser RG, Kallinen LM, Almquist AK, et al: Early failure of a small-diameter high-voltage implantable cardioverterdefibrillator lead. Heart Rhythm 4:892-896, 2007. 13. Poole JE, Gleva MJ, Mela T, et al: Complication rates associated with pacemaker or implantable cardioverter-defibrillator generator replacements and upgrade procedures: results From the Replace Registry. Circulation 122:1553-1561, 2010. 14. Association for the Advancement of Medical Instrumentation: AAMI DF-4 Standard. 2010. 15. Ellenbogen KA, Hellkamp AS, Wilkoff BL, et al: Complications arising after implantation of DDD pacemakers: the MOST experience. Am J Cardiol 92:740-741, 2003. 16. Danik SB, Mansour M, Singh J, et al: Increased incidence of subacute lead perforation noted with one implantable cardioverterdefibrillator. Heart Rhythm 4:439-442, 2007. 17. Epstein AE, Baker JH, 2nd, Beau SL, et al: Performance of the St. Jude Medical Riata leads. Heart Rhythm 6:204-209, 2009.

18. Khan MN, Joseph G, Khaykin Y, et al: Delayed lead perforation: a disturbing trend. Pacing Clin Electrophysiol 28:251-253, 2005. 19. Porterfield JG, Porterfield LM, Kuck KH, et al: Clinical per­ formance of the St. Jude Medical Riata defibrillation lead in a large patient population. J Cardiovasc Electrophysiol 21:551-556, 2010. 20. Burri H, Sunthorn H, Dorsaz PA, et al: Thresholds and complications with right ventricular septal pacing compared to apical pacing. Pacing Clin Electrophysiol 30(suppl 1):75-78, 2007. 21. Rosso R, Medi C, Teh AW, et al: Right ventricular septal pacing: a comparative study of outflow tract and mid ventricular sites. Pacing Clin Electrophysiol 33:1169-1173, 2010. 22. Thal S, Moukabary T, Boyella R, et al: The relationship between warfarin, aspirin, and clopidogrel continuation in the periprocedural period and the incidence of hematoma formation after device implantation. Pacing Clin Electrophysiol 33:385-388, 2010. 23. Kutinsky IB, Jarandilla R, Jewett M, et al: Risk of hematoma complications after device implant in the clopidogrel era. Circ Arrhythm Electrophysiol 3:312-318, 2010. 24. Tompkins C, Cheng A, Dalal D, et al: Dual antiplatelet therapy and heparin “bridging” significantly increase the risk of bleeding complications after pacemaker or implantable cardioverterdefibrillator device implantation. J Am Coll Cardiol 55:2376-2382, 2010. 25. Giudici MC, Paul DL, Bontu P, et al: Pacemaker and implantable cardioverter-defibrillator implantation without reversal of warfarin therapy. Pacing Clin Electrophysiol 27:358-360, 2004. 26. Barakat K, Robinson NM, Spurrell RA: Transvenous pacing leadinduced thrombosis: a series of cases with a review of the literature. Cardiology 93:142-148, 2000. 27. Oginosawa Y, Abe H, Nakashima Y: The incidence and risk factors for venous obstruction after implantation of transvenous pacing leads. Pacing Clin Electrophysiol 25:1605-1611, 2002. 28. Baddour LM, Epstein AE, Erickson CC, et al: Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 121:458-477, 2010. 29. Wazni O, Epstein LM, Carrillo RG, et al: Lead extraction in the contemporary setting: the LExICon study: an observational retrospective study of consecutive laser lead extractions. J Am Coll Cardiol 55:579-586, 2010. 30. Tarakji KG, Chan EJ, Cantillon DJ, et al: Cardiac implantable electronic device infections: presentation, management, and patient outcomes. Heart Rhythm 7:1043-1047, 2010. 31. Lekkerkerker JC, van Nieuwkoop C, Trines SA, et al: Risk factors and time delay associated with cardiac device infections: Leiden device registry. Heart 95:715-720, 2009. 32. De Oliveira JC, Martinelli M, Nishioka SA, et al: Efficacy of antibiotic prophylaxis before the implantation of pacemakers and

cardioverter-defibrillators: results of a large, prospective, randomized, double-blinded, placebo-controlled trial. Circ Arrhythm Electrophysiol 2:29-34, 2009. 33. Trautmann M, Stecher J, Hemmer W, et al: Intranasal mupirocin prophylaxis in elective surgery: a review of published studies. Chemotherapy 54:9-16, 2008. 34. Sohail MR, Uslan DZ, Khan AH, et al: Management and outcome of permanent pacemaker and implantable cardioverterdefibrillator infections. J Am Coll Cardiol 49:1851-1859, 2007. 35. Klug D, Balde M, Pavin D, et al: Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation 116:1349-1355, 2007. 36. Da Costa A, Kirkorian G, Cucherat M, et al: Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation 97(18):1796-1801, 1998. 37. Centers for Medicare and Medicaid Services (CMS): Specifications manual for national hospital inpatient quality measures, version 3, 2009. 38. Klug D, Wallet F, Kacet S, et al: Detailed bacteriologic tests to identify the origin of transvenous pacing system infections indicate a high prevalence of multiple organisms. Am Heart J 149(2):322-328, 2005. 39. Klug D, Wallet F, Kacet S, et al: Involvement of adherence and adhesion Staphylococcus epidermidis genes in pacemaker leadassociated infections. J Clin Microbiol 41:3348-3350, 2003. 40. Sharma S, Tleyjeh IM, Espinosa RE, et al: Pacemaker infection due to Mycobacterium fortuitum. Scand J Infect Dis 37:66-67, 2005. 41. Verghese S, Mullaseri A, Padmaja P, et al: Pacemaker implant site infection caused by atypical mycobacteria. Indian Heart J 50(2):201-202, 1998. 42. Toda H, Sato K, Iimori M, et al: [A case of Mycobacterium goodii infection with isolation from blood and a pacemaker lead]. Kansenshogaku Zasshi 80:262-266, 2006. 43. Tam WO, Yew WW, Yam WC, et al: Pacemaker infections due to rapidly growing mycobacteria: further experience. Int J Tuberc Lung Dis 11:118, 2007. 44. Kestler M, Reves R, Belknap R: Pacemaker wire infection with Mycobacterium tuberculosis: a case report and literature review. Int J Tuberc Lung Dis 13:272-274, 2009. 45. Kessler AT, Kourtis AP: Mycobacterium abscessus as a cause of pacemaker infection. Med Sci Monit 10:CS60-CS62, 2004. 46. Cutay AM, Horowitz HW, Pooley RW, et al: Infection of epicardial pacemaker wires due to Mycobacterium abscessus. Clin Infect Dis 26:520-521, 1998. 47. Chrissoheris MP, Kadakia H, Marieb M, et al: Pacemaker pocket infection due to Mycobacterium goodii: case report and review of the literature. Conn Med 72:75-77, 2008.

26  26

Techniques and Devices for Lead Extraction OUSSAMA WAZNI  |  BRUCE L. WILKOFF

Lead extraction is increasingly required and is directly related to the

increased numbers of cardiac implantable electronic devices (CIEDs). The number of extractions has increased because of expanded indications, such as the need to upgrade to newer technology in patients with occluded veins or lead-device safety alerts, and improved access to extraction providers. The components of the CIED, the leads and pulse generators, have a limited functional life. As the population and the devices age, components of the system require removal for a variety of reasons, including infection, lead malfunction, venous stenosis/occlusion, and safety alerts. This chapter discusses the indications, techniques, and devices for lead extraction in detail, using definitions and information from the 2009 Heart Rhythm Society (HRS) Expert Consensus on Facilities, Training, Indications, and Patient Management for transvenous lead extraction.1

Definitions Implant lead removal technically means removal of a CIED lead using any technique. However, leads with short implantation duration can usually be removed with simple traction, and this is defined as a “lead removal procedure.” However, with prolongation of the duration of implantation, segments of chronically implanted leads are encased in encapsulating fibrous tissue and may be bound to the vein and/or heart wall, bound to another lead, or both (Figs. 26-1 to 26-4). Removal of chronically implanted leads from these binding sites becomes very difficult and potentially hazardous with traction alone. The tensile strength of encapsulating fibrous tissue is greater than that of the surrounding tissue, and thus leads cannot easily be removed without risking a tear or avulsion of the vein or heart wall. In such cases the removal, separation, and freeing of leads from encapsulating fibrous tissue are defined as lead extraction. As a rule, if one or more of the leads implanted in the patient that require removal are more than 1 year old or require extraction tools for removal, the procedure is labeled as a “lead extraction procedure,” and if not, then a “lead removal without extraction.” Extraction techniques include traction, countertraction, counterpressure, and tissue disruption, cutting locally with an instrument, laser, or electrosurgery unit. Lead extraction techniques are designed to free the lead from the encapsulating fibrous tissue (countertraction) or to free the encapsulating fibrous tissue (counterpressure) from the vein or heart wall.2-4 Telescoping sheaths are used remotely to apply countertraction and counterpressure at the selected binding sites. Lead extraction procedures are those approaches used to apply the sheaths and remove the lead in a safe and efficacious manner. GOALS AND OUTCOMES The clinical outcomes targeted with lead extraction are elimination of infection, elimination of risk associated with a lead (e.g., perforation, arrhythmia), and creation of venous access. Other clinical outcomes include removal of all functional leads and attempting to resolve pocket-related symptoms such as pain.

Outcome definitions depend on the indication of the procedure. If the indication is systemic infection, complete removal of all targeted leads and material without any complication, defined as “complete procedural success,” is required to achieve clinical success. However, in non-infection-related cases, “partial procedural success,” with only a small part or the tip of the lead retained, may be associated with clinical success and the desired clinical outcome, such as resolution of a pocket infection or creation of a conduit. In case of partial procedural success, clinical success is conditional and based on achievement of clinical goals and the absence of untoward effects such as perforation, embolism, or persistent infection caused by the retained part of the lead. The HRS consensus document, in an effort to unify nomenclature, suggested the following definitions1: Procedural success rate is the number of clinically successful procedures divided by number of procedures performed. Lead clinical success rate is the number of leads removed with clinical success divided by the total number of leads attempted. Although there are no published benchmarks, operators should strive for clinical success in 100% of patients with the least possible number of complications. Table 26-1 summarizes current rates of success and complications based on collective studies. Intraprocedural complications are any complication that occurs during the procedure, as recorded from the time the patient enters the operating or procedure room to the time the patient leaves. This includes all preparation, from administering anesthesia to groin access to closing the incision and reversal of anesthesia. Postprocedural complications are any events that become evident within 30 days after the intraprocedural period. Major complications are any life-threatening complications, those that result in death, or any complication that results in persistent or significant disability or significant surgical intervention. A minor complication is any undesired event related to the procedure that requires medical intervention or “minor procedural intervention” and does not limit, persistently or significantly, the patient’s function or threaten life or cause death (Box 26-1).

Indications for Extraction Considerable divergence of opinion surrounds the indications for lead extraction. However, the 2009 HRS consensus document has unified opinions to a large extent.1 Indications are divided into three major categories: infection, venous access, and broken or nonfunctional leads. Also, emerging indications include implant patients who require magnetic resonance imaging (MRI) scanning for diagnosis (Box 26-2). INFECTION Infection remains the most common indication for extraction. Complete extraction is indicated in cases of definite CIED infection when there is erosion, pocket infection, lead vegetations, or sepsis (see Chapter 25). Extraction is also recommended in patients with a device and endocarditis or occult gram-positive bacteremia. Extraction is also reasonable in patients with a device and persistent occult gramnegative bacteremia. Antibiotic therapy should be considered adjunctive therapy, and pocket debridement with local relocation is only palliative.

747

748

SECTION 3  Implantation Techniques

A

B

C

Figure 26-1  Canine model of fibrosis with lead extraction. A, Acute thrombus formation 1 week after lead implantation in a dog. Thrombus has formed at each site where the lead touches the wall and in some regions of stasis or eddying blood flow. Most of this early thrombus lyses. It persists and organizes at sites of continued pressure on the wall and in areas with stagnant blood flow. Inset, Close-up of thrombus. B, Organized fibrous tissue encapsulating the lead forms chronically at sites of pressure. It progresses from fibrous tissue to cartilaginous tissue and finally to bone. C, Magnified view of chronic encapsulation shows the magnitude of the fibrous tissue to be ablated in extracting the lead.

A

B

Figure 26-2  Encapsulation in leads implanted 12 weeks. A, Polyurethane lead has minimal encapsulation. B, Silicone rubber lead is completely encapsulated. Surface thrombogenicity phenomenon is not related to the mechanical properties of the silicone lead. The magnitude of the surface encapsulation contributes to the greater difficulty extracting silicone leads 2 to 3 years after implantation, compared with polyurethane leads. TABLE

26-1 

Summary of Clinical Outcomes of Lead Extraction

Study (No. of Patients) Laser U.S. experience, 1999 (2338)27 PLEXES, 1999 (153)15 European experience, 2007 (292)28 LExICon, 2010 (1449)12 Nonlaser Electrosurgical RF extraction, 2007 (60)29 Evolution mechanical dilator sheath (20)21

Clinical Success

Complete Procedural Success

Partial Procedural Success

Major Complications

— 94.8% — 97.7%

93% 94% 90.9% 96.5%

5% 2.5% 3.4% 2.3%

1.4% 1.2% 3.4% 1.4%

100% 100%

PLEXES, Pacing Lead Extraction with the Excimer Sheath; RF, radiofrequency.

93% 77%

7% 24%

3.3% 0%



26  Techniques and Devices for Lead Extraction

749

Box 26-1 

CLASSIFICATION OF IMPLANT/LEAD COMPLICATIONS Major 1. Death 2. Cardiac avulsion or tear requiring thoracotomy, pericardiocentesis, chest tube, or surgical repair 3. Vascular avulsion or tear requiring thoracotomy, pericardiocentesis, chest tube, or surgical repair 4. Pulmonary embolism requiring surgical intervention 5. Respiratory arrest or anesthesia-related complication leading to prolongation of hospitalization 6. Cerebrovascular accident (stroke) 7. Pacing system–related infection of previously noninfected site

Figure 26-3  Fibrosis. Encapsulating fibrous tissue on extracted lead.

To prevent further serious and potentially lethal complications, all device components, including leads, must be removed to cure the infection. Also, the morbidity associated with a local pocket infection, the lethal sequelae of septicemia, and the potential risk of infected thrombus formation in the heart are well known. Because leaving an infected lead in the body is potentially lethal, the risk of the procedure is clearly less than the risk of lead extraction; that is, the risk of not extracting far exceeds the risk of extracting. The risk of Staphylococcus aureus device infection without extraction was supported by a series of 33 patients from the Duke Medical Center; 10 of 21 patients (47.6%) died without lead extraction, and 2 of 12 (16.7%) died despite lead extraction, and none from lead extraction.5 The safety and efficacy of complete lead extraction, with debridement and delayed reimplantation at a remote anatomic site, were demonstrated in 123 patients at the Cleveland Clinic with device infection. Despite infections with a wide range of bacterial organisms, mostly coagulase-negative staphylococci and S. aureus, extraction was associated with no major complications. Infection recurred only in those four patients who had incomplete extraction or reimplantation concurrent with the extraction.6

Figure 26-4  Fibrosis. Fibrous tissue peeled from encapsulated lead.

Minor 1. Pericardial effusion not requiring pericardiocentesis or surgical intervention 2. Hemothorax not requiring a chest tube 3. Hematoma at surgical site requiring reoperation for drainage 4. Arm swelling or thrombosis of implant veins resulting in medical intervention 5. Vascular repair near the implant site or venous entry site 6. Hemodynamically significant air embolism 7. Migrated lead fragment without sequelae 8. Blood transfusion related to blood loss during surgery 9. Pneumothorax requiring a chest tube 10. Pulmonary embolism not requiring surgical intervention Data from Heart Rhythm Society Expert Consensus on Facilities, Training, Indications, and Patient Management. Heart Rhythm 6:1085-1104, 2009.

Chronic pain at the site of the device or lead insertion should be considered as a subclinical infection, and extraction in such patients is indicated. After extraction, the patient should be treated as having a pocket infection, with adjunctive antibiotics and reimplantation on the contralateral side. NONINFECTED SYSTEMS When functional or nonfunctional leads pose immediate risk, such as in a patient with life-threatening arrhythmias from a retained lead or fragment, or when the lead design poses a risk of perforation (e.g., Accufix with protrusion of J stylet outside lead), the decision to extract is straightforward (Fig. 26-5). Extraction of functional or nonfunctional leads becomes controversial when there is no immediate threat to the patient, because it is possible to abandon a failed or a nonrequired lead and implant ipsilaterally if the vein is patent, or contralaterally or even transiliac if the ipsilateral vein is occluded. The controversy persists because it is difficult to calculate the risk/benefit ratio of lead extraction versus abandoning such leads. Thus, when considering extraction of noninfected leads, it is important to balance the risk of extraction with the patient’s situation and to factor in the operator’s experience and not just literature data. Some operators may choose to extract only when there is infection; others who are more experienced may elect to extract all leads that are not required, whether functional or not, when the opportunity arises. Regarding the patient’s situation, two examples help clarify the approach. A 60-year-old patient with a pacemaker implanted for compete heart block and a failing 20-year-old right ventricular (RV) lead may have either (1) extraction of the RV lead and reimplantation of a new lead or (2) abandonment of the failing RV lead and addition of a new RV lead using the ipsilateral patent vein. The decision on which approach to adopt will depend on the operator’s skill and comfort. On the other hand, with a 95-year-old patient in the same situation, only the second approach seems reasonable, because the abandoned lead will likely never become a clinical issue. The following sections address extraction indications for noninfected leads.

750

SECTION 3  Implantation Techniques

Box 26-2 

INDICATIONS FOR TRANSVENOUS LEAD EXTRACTION* Infection Class I 1. Complete device and lead removal is recommended in all patients with definite CIED system infection, as evidenced by valvular endocarditis, lead endocarditis or sepsis. (Level of evidence: B) 2. Complete device and lead removal is recommended in all patients with CIED pocket infection, as evidenced by pocket abscess, device erosion, skin adherence, or chronic draining sinus without clinically evident involvement of the transvenous portion of the lead system. (Level of evidence: B) 3. Complete device and lead removal is recommended in all patients with valvular endocarditis without definite involvement of the lead(s) and/or device. (Level of evidence: B) 4. Complete device and lead removal is recommended in patients with occult gram-positive bacteremia (not contaminant). (Level of evidence: B) Class IIa 1. Complete device and lead removal is reasonable in patients with persistent occult gram-negative bacteremia. (Level of evidence: B) Class III 1. CIED removal is not indicated for a superficial or incisional infection without involvement of the device and/or leads. (Level of evidence: C) 2. CIED removal is not indicated to treat chronic bacteremia from a source other than the CIED, when long-term suppressive antibiotics are required. (Level of evidence: C) Chronic Pain Class IIa 1. Device and/or lead removal is reasonable in patients with severe chronic pain, at the device or lead insertion site, that causes significant discomfort for the patient, is not manageable by medical or surgical techniques, and for which there is no acceptable alternative. (Level of evidence: C) Thrombosis or Venous Stenosis Class I 1. Lead removal is recommended in patients with clinically significant thromboembolic events associated with thrombus on a lead or a lead fragment. (Level of evidence: C) 2. Lead removal is recommended in patients with bilateral subclavian vein or superior vena cava occlusion precluding implantation of a needed transvenous lead. (Level of evidence: C) 3. Lead removal is recommended in patients with planned stent deployment in a vein already containing a transvenous lead, to avoid entrapment of the lead. (Level of evidence: C) 4. Lead removal is recommended in patients with superior vena cava stenosis or occlusion with limiting symptoms. (Level of evidence: C) 5. Lead removal is recommended in patients with ipsilateral venous occlusion preventing access to the venous circulation for required placement of an additional lead, when there is a contraindication for using the contralateral side (e.g., contralateral arteriovenous fistula, shunt or vascular access port, mastectomy). (Level of evidence: C) Class IIa 1. Lead removal is reasonable in patients with ipsilateral venous occlusion preventing access to the venous circulation for required placement of an additional lead, when there is no contraindication for using the contralateral side. (Level of evidence: C)

Leads Affecting Patient: Functional or Nonfunctional Leads Class I 1. Lead removal is recommended in patients with life-threatening arrhythmias secondary to retained leads or lead fragments. (Level of evidence: B) 2. Lead removal is recommended in patients with leads that, because of design or failure, may pose an immediate threat to the patients if left in place (e.g., Telectronics Accufix J wire fracture with protrusion). (Level of evidence: B) 3. Lead removal is recommended in patients with leads that interfere with the operation of implanted cardiac devices. (Level of evidence: B) Class IIa (nonfunctional leads only) 1. Nonfunctional lead removal is reasonable in patients with leads that, because of design or failure, pose a threat to the patient, which is not immediate or imminent, if left in place (e.g., Accufix without protrusion). (Level of evidence: C) 2. Nonfunctional lead removal is reasonable in patients if CIED implantation would require more than four leads on one side or more than five leads through the superior vena cava. (Level of evidence: C) Class IIb 1. Lead removal may be considered in patients with an abandoned functional lead that poses a risk of interference with the operation of the active CIED system. (Level of evidence: C) 2. Lead removal may be considered in patients with functioning leads that, because of design or failure, pose a potential future threat to the patient if left in place (e.g., Accufix without protrusion). (Level of evidence: C) 3. Lead removal may be considered in patients with leads that are functional but not being used. (e.g., right ventricular pacing lead after upgrade to ICD). (Level of evidence: C) 4. Nonfunctional lead removal may be considered at an indicated CIED procedure, in patients with nonfunctional leads, if no contraindications exist. (Level of evidence: C) Class III 1. Lead removal is not indicated in patients with functional or nonfunctional leads if patient life expectancy is less than 1 year. (Level of evidence C) 2. Lead removal is not indicated in patients with known anomalous placement of leads through structures other than normal venous and cardiac structures (e.g., subclavian artery, aorta, pleura, atrial or ventricular wall, mediastinum) or through a systemic venous atrium or systemic ventricle. Additional techniques, including surgical backup, may be used if the clinical scenario is compelling. (Level of evidence: C) Magnetic Resonance Imaging–Related Indications Class IIa 1. Nonfunctional lead removal is reasonable in patients who require specific imaging techniques (e.g., MRI) but who cannot be imaged because of the presence of the CIED system, and for whom no other imaging alternative is available for the diagnosis. (Level of evidence: C) Class IIb 1. Functional lead removal may be considered in patients who require specific imaging techniques (e.g., MRI) but who cannot be imaged because of the presence of the CIED system, and for whom there is no other available imaging alternative for the diagnosis. (Level of evidence: C) 2. Functional/nonfunctional lead removal may be considered in patients to allow the implantation of an MRI-conditional CIED system. (Level of evidence: C)

Data from Heart Rhythm Society Expert Consensus on Facilities, Training, Indications, and Patient Management. Heart Rhythm 6:1085-1104, 2009. *Recommendations for lead extraction apply only to those patients in whom the benefits of lead removal outweigh the risks, when assessed based on individualized patient factors and operator-specific experience and outcomes. CIED, Cardiac implantable electronic device; ICD, implantable cardioverter-defibrillator.



26  Techniques and Devices for Lead Extraction

A

751

B

Figure 26-5  Extracted lead. A, Chest radiograph of Accufix lead. Note below the lead the J wire is outside the main lead body, exposing the patient to risk of perforation. B, Extracted Accufix lead outside of the body. Note the broken J wire exposed and outside the insulation.

LEADS ASSOCIATED WITH RISK TO PATIENT

Creation of a Conduit

Functional or nonfunctional leads should be extracted when these leads or lead fragments are causing life-threatening arrhythmias or pose immediate risk to the patient because of their design. A common example is a broken J-wire protrusion in an Accufix lead. Also, it is recommended to extract both functional and nonfunctional leads that interfere with the operation of a CIED, as in a nonfunctional RV pacing lead causing “chatter” on a functional implantable cardioverterdefibrillator (ICD) lead, causing repeated inappropriate oversensing or shocks. Further, extraction of functional or nonfunctional leads is recommended if these leads interfere with the treatment of malignancy, both for diagnostic tests (e.g., MRI) and for ionizing radiation. It is also reasonable to extract nonfunctional leads that may pose a risk if left in place, such as the Accufix lead without a J-wire protrusion but that may break in the future and become an immediate risk. In the case of functioning leads, the HRS document specifies that extraction of these leads may be considered when the lead design poses a potential risk in the future, as with the Accufix lead before J-wire fracture or protrusion. Abandoned functional leads that may pose interference risk or those no longer required can be considered for extraction, particularly in the absence of contraindications (see Box 26-2).

The rationale for creating a conduit is applicable to component failures. Consider a patient with a dual-chamber pacemaker and an atrial lead conductor coil fracture. This patient has a normal ventricular lead, an occlusion of the brachiocephalic vein, and the need to implant a new atrial lead. Although venoplasty through the total occlusion is possible, a more reasonable approach to maintaining access through the same vein entry site is to extract the failed atrial lead and to insert the new lead through the extraction conduit, or to remove both existing leads and start over with new leads. This same logic would apply to other situations, such as an upgrade requiring the addition of a new lead. For example, a patient with a dual-chamber ICD requires a cardiac vein implant for biventricular pacing. The alternatives are doing nothing, implanting the new lead through a contralateral vein or a transfemoral vein, or using a cardiac surgical approach. Venoplasty is also reasonable if the existing leads are all functional. Sometimes, when there is severe stenosis with or without symptoms from the obstruction of flow, physicians have initiated balloon venoplasty and stenting without extraction of the leads. This is particularly difficult if either infection or reocclusion occurs, because extraction now becomes impossible without extensive open-heart surgery (Fig. 26-7). A more appropriate approach includes extraction, venoplasty, stenting, and reimplantation through the stent, as reported by Chan et al.7 in a subclavian occlusion that progressed to an SVC occlusion. Implantation through a contralateral vein seems logical, especially if it is the implanter’s only skill-level option. The simplest alternative is to abandon the two original leads on the ipsilateral side and implant the new leads on the contralateral side. In the example of a conductor coil fracture, the patient has the risk of having two functioning and two nonactive leads in the heart and the risk of instrumentation of the superior veins on the opposite side. In the example of adding a left ventricular lead for biventricular stimulation, the patient has the risk of having three functioning leads and two nonactive leads in the heart and the risk of instrumentation of the superior veins on the opposite side. These risks are weighed against the risk of extracting the one atrial lead. The resultant risk of having a complication is the sum of the individual risk factors. For these two examples, another approach would be to implant the new atrial lead or biventricular lead on the contralateral side and tunnel it across to the pulse generator and ventricular lead. In addition to the risk of instrumentation of the superior veins and tunneling, the patient with conductor coil fracture will have two functioning leads and one nonactive lead in the heart, and the patient with the biventricular lead will have three functioning leads in the heart. Total bilateral occlusion of the superior veins further complicates the problem. The transfemoral approach is then the only approach available to the nonsurgeon implanter. The surgical implanter has the options of a transatrial or epicardial approach. The risks associated with these choices make the decision to extract the atrial lead easier.

THROMBOSIS OR VENOUS STENOSIS Lead extraction is indicated for patients with clinically significant thromboembolic events with evidence of clot on the lead, as well as in patients with superior vena cava (SVC) or subclavian vein stenosis or occlusion with symptoms. Lead extraction is also recommended in cases of bilateral occlusion for the creation of a conduit or for planned stent deployment (Fig. 26-6). When there is a contraindication to implantation on the contralateral side (e.g., arteriovenous fistula), extraction for creation of a conduit is recommended; otherwise, extraction is considered reasonable.

Left Figure 26-6  Bilateral occlusion. Lead extraction is recommended.

752

SECTION 3  Implantation Techniques

ventricular lead should be uneventful. However, the addition of a new ICD lead and abandonment of the original ventricular pacemaker lead creates an inactive, abandoned lead. The disposition of inactive leads is controversial, confusing, and at times emotional. Many questions need to be answered. Why should a lead be removed if it is not causing a problem (e.g., penetration, perforation, arrhythmia), is not dislodged, and is not broken?8 (See Box 26-2.)

Risks and Outcomes

Figure 26-7  Severe stenosis. Leads are stented to the superior vena cava (SVC), making extraction in case of infection impossible. The patient required surgery and an SVC graft.

However, without extraction skills, the medical and surgical implanter may choose these alternatives. The risk/benefit ratio is crucial to the rationale for extracting these leads. For example, the life-threatening risk associated with infection in effect forces an implanter to extract the lead and abandon the pocket. The risk of not creating a conduit to insert new leads is a potential risk for a future complication related to bilateral implants, nonactive leads, multiple implanted leads, and tunneling. This risk is obviously less than the life-threatening risk of infection. In the situation of lead failure, the alternatives presented provide an acceptable short-term solution and can be performed by implanters without lead extraction skills. Potential risks are not as compelling a reason for action as the immediate risks associated with lead extraction. However, physicians with experience in lead extraction may not be comfortable with abandoning two leads, creating two inactive leads, and leaving a total of four or five leads implanted. Tunneling of a lead from the opposite side, crossing over the sternum, is a potential source of infection and increased risk of lead fracture. Again, the risk of not extracting must be compared with the risk of extracting to help resolve these issues. To limit the risk of subclavian vein or SVC occlusion, it is considered reasonable to extract nonfunctional leads if a planned CIED implantation would require more than four leads on one side or more than five leads through the SVC.

The risks associated with lead extraction are tamponade caused by intrapericardial vascular disruption of the SVC or heart; hemothorax from extrapericardial vascular tear outside the pericardial sac and into the thorax; arteriovenous fistula or dissecting hematoma (e.g., aortic arch); and failure to complete the lead extraction (Fig. 26-8). The latter is usually not considered a risk; however, a failed lead extraction may lead to additional procedures or may be a precursor for dangerous situations in the future. There are two situations in which the risk of tearing the SVC and heart is reduced but other risks could be increased. The first situation involves patients who have undergone an open-heart procedure; the pericardial space has been obliterated, and fibrous tissue reinforces the SVC and heart wall. In this situation, if an intrathoracic bleed occurs, quick surgical chest entry is difficult. The second situation involves an implant of short duration: less than 2 years for pacemaker leads and less than 1 year for ICD leads. The forces involved in freeing these leads usually are not sufficient to tear the SVC or heart. Extraction centers from the continental United States and Hawaii voluntarily submitted data for a national registry between December 1988 and December 1999.9-11 The most recent published report, from 1996, included data from 226 centers, 2338 patients, and 3540 leads and demonstrated major complications in 1.4% of the cases (<1% for centers with >300 extraction procedures).10,11 The total U.S. data included 7823 extraction procedures and 12,833 leads (presented in 2000). Multivariate analysis of the data from 1994 through 1999 demonstrated four predictors of major complications (1.6%): (1) implant duration of oldest lead, (2) female gender, (3) Tears into the thoracic cavity

C

Arterial-venous fistula and/or dissecting hematoma

B

A

MAGNETIC RESONANCE IMAGING–RELATED INDICATIONS With increased frequency and reliance on MRI for diagnosis and treatment (“gamma knife”) in conjunction with the introduction of an MRI-conditional pacemaker, the requirement for extraction of MRIincompatible systems is becoming increasingly common. Lead extraction is reasonable for nonfunctional leads and may be considered for functional leads that preclude the use of MRI when it is the only diagnostic option, or to permit implantation of an MRI-conditional pacemaker and in future ICDs. INACTIVE LEADS: FUNCTIONAL AND NONFUNCTIONAL BUT NOT IN USE A rationale for extraction of inactive leads is not as straightforward as for active leads. This situation differs from creation of a conduit. For example, if the ipsilateral vein is patent, insertion of a new left

Tears of the SVC and/or heart wall Figure 26-8  Potentially lethal complications from vascular tissue disruption during lead extraction. Disruptions are caused by tears, cutting, perforations, or avulsions of a vascular wall. Tearing or cutting of the superior vena cava (SVC) or atrial wall (A) is the most common complication resulting in cardiac tamponade. Leads that are contiguous with or embedded in the subclavian artery, innominate artery, or aorta can tear these vessels during lead extraction (B). Acutely, a dissecting hematoma develops, with potential rupture into the thorax or, chronically, development of an arteriovenous fistula. Disruption of the right brachiocephalic vein into the right thoracic cavity (C) is insidious; tearing occurs during a difficult lead extraction when the vein and pleura are adherent or when a dissecting hematoma ruptures the pleura.



26  Techniques and Devices for Lead Extraction

ICD lead removal, and (4) use of laser extraction technique. Major complications were (1) death, 0.3%; (2) nonfatal hemopericardium or tamponade, 0.7%; (3) nonfatal hemothorax, 0.2%; (4) transfusion for bleeding/hypotension, 0.1%; (5) pneumothorax requiring a chest tube, 0.1%; and (6) other nonfatal events, 0.2% (including 4 arteriovenous fistulae, 2 pulmonary embolisms, 2 thoracotomies for defibrillator leads trapped in sheaths, 2 respiratory arrests, 2 strokes, 2 cases of renal failure, 1 anoxic encephalopathy, and 1 open-heart retrieval of a device fragment). In the more recent LExICon study of data from 13 centers in the United States and Canada, procedural success was 96.5%, with 97.7% clinical success.12 In LExICon, 1449 patients underwent laser-assisted lead extraction of 2405 leads. Failure to achieve clinical success was associated with body mass index (BMI) of 25  kg/m2 or less and low-extractionvolume centers. Procedural failure was higher in leads implanted for more than 10 years and when performed in low-volume centers. Major adverse events in 20 patients were directly related to the procedure (1.4%), including four deaths (0.28%). Major adverse effects were associated with patients with BMI less than 25  kg/m2. Overall, all-cause in-hospital mortality was 1.86%. Risk of lead extraction depends on the extractor’s experience, duration of implant, and the patient’s age and condition. There is no ongoing national database or registry, and the risks depend on the individual, the assembled team, and the institution. The most reliable indicator of risk is the individual extractor’s personal statistics. It is important that each institution and individual keep track of complications and effectiveness. Risks are caused by maturation of the encapsulating fibrous tissue, which is related to the duration of the implant and the patient’s age. With time, the tensile strength of the encapsulating fibrous tissue increases; it may calcify in 3 to 4 years in children and in 8 to 10 years in older adults. Sedentary patients increase their tensile strength more slowly, and the tissue takes longer to mineralize. In sedentary elderly patients, the tensile strength seems to decrease with time. The influences of duration and age are apparent in the extremes. Also, patients with calcium metabolism abnormalities can calcify at any age in a short duration. Although the properties of encapsulated fibrous tissue are known, it is difficult to apply general principles to a specific patient and assign a risk. Potentially lethal complications requiring extensive surgical procedures include tear of the vein and heart wall causing tamponade, arterial tears causing arteriovenous fistula or dissecting hematoma; and tears into the thoracic cavity causing a hemothorax (see Fig. 26-8). The procedure-related complications are discussed in detail later. Time and surgeon experience are the two factors related to survival. Low blood pressure and poor tissue perfusion are time-dependent events. Being prepared for a cardiovascular emergency is the only way to meet time constraints. This includes having a cardiovascular surgeon immediately available, along with the proper instrumentation and experienced support personnel. A cardiovascular surgeon has the technical skill to manage these complications but may need direction from the extractor on the proper approach. Once a complication resulting in poor or no perfusion is recognized, the repair should begin immediately. The concern of needlessly subjecting the patient to extensive surgery and morbidity pales in comparison to that of applying the therapy late because of confusion or procrastination. Failure to recognize the complication in a timely fashion or the lack of access to qualified personnel may cause a lethal outcome.

Clinical Considerations PATIENT INFORMATION AND PREPARATION All patients presenting for an extraction procedure must have a standard history and physical examination with a detailed description and understanding of the indication for extraction. The initial indication for implantation should be known. Comorbidities that can affect outcome, such as kidney failure, should be noted. The procedure notes

753

Figure 26-9  Transaortic ICD implant. Extraction in the EP laboratory is contraindicated. The patient was referred for extraction in the OR for vascular access control.

should be carefully reviewed for any problems observed during the implantation, such as difficult access. Also, if infection is present, detailed information on the time line, organism, susceptibilities, and antibiotic therapy is needed. Basic laboratory work is usually indicated and includes white blood cell count, hematocrit, hemoglobin, platelet count, blood urea nitrogen, creatinine, potassium, sodium, liver profile, and prothrombin time. The patient’s blood should be typed and crossmatched for a possible blood transfusion. A current chest radiograph and electrocardiogram (ECG) are mandatory (Fig. 26-9). An echocardiogram is mandatory for two groups of patients before the procedure, even if transesophageal echocardiography (TEE) is routinely available in the procedure room: those with infection, to rule out vegetation in the right atrium; and those with heart failure, to define cardiac function. A plan for antibiotics before and after the procedure should be formulated. Also, the need for temporary pacing while waiting for clearance to reimplant a new, permanent CIED should be established. The timing of reimplantation should also be determined before extraction. The operator must know all devices and leads present, including those abandoned. A preprocedural chest radiograph must be obtained and examined for any abandoned leads and unusual locations of lead placement. A lead thought to be in the left ventricle should be extracted in the operating room (OR) with surgical techniques. If there is any question as to the location of a lead, additional imaging using TEE or computed tomography (CT) may be required. It is imperative to know the initial implantation date because the age of the leads may dictate different preparations and approaches to extraction. The need for pacing during and after the procedure should be established. Dependent patients will need temporary pacing during the procedure using an electrophysiology catheter. After extraction is complete, a temporary active-fixation wire can be used until reimplantation of a CIED is possible. The device to be extracted should be interrogated before the procedure and all parameters recorded, to serve as baseline characteristics of leads that will not be extracted. Therefore, these leads should be retested after extraction to ensure they have sustained no damage. In noninfected patients, preprocedural antibiotics should be administered. Antibiotic therapy before the procedure can be given for infected patients when the infective organism and susceptibilities are established. The patient should be continuously monitored by ECG, arterial pressure line, oxygen saturation, and at times a Foley catheter.

754

SECTION 3  Implantation Techniques

A reliable intravenous (IV) line should be placed. In addition, an arterial line should be used for patients needing continuous vasopressor support and for those sent to an intensive care unit. Patients are prepared from chin to midthigh for all transvenous and cardiac surgical approaches, including an emergency procedure, if needed. Transthoracic or TEE should be immediately available to assess for pericardial effusion or thrombus or vegetation dislocation. Because of the potential risks, extraction should be performed only in a facility with accredited cardiac surgery programs. A cardiothoracic surgeon must be physically present on site and be able to initiate emergency surgery. To facilitate the surgeon’s rescue efforts, the procedure room must be equipped with the necessary tools to perform cardiac surgery, such as thoracotomy or sternotomy instrument sets in addition to a sternal saw. Informed Consent Written informed consent should be discussed with the patient, preferably in the presence of a family member. The patient and family must be made aware that lead extraction is a potentially life-threatening procedure, and this must be placed into local context by informing the patient about the hospital’s extraction volume and outcomes as well as the operator’s personal level of experience and outcomes. It is particularly important to discuss all alternatives when considering extraction versus abandonment during an upgrade procedure. ANESTHESIA The types of anesthesia available include local anesthesia, conscious sedation, managed anesthesia care (MAC), laryngeal mask anesthesia (LMA), and general endotracheal anesthesia. The rationale for using a specific form of anesthesia is based on type of procedure, physician comfort level with general anesthesia, perceived risk of a given type of anesthesia, and availability of general anesthesia. General endotracheal anesthesia is the only type of anesthesia that is suitable for all procedures, and essential for some. General anesthesia consists of an “anesthesia package:” anesthesiologist, compliance with preoperative anesthesia protocols, anesthesia and monitoring machines, and general anesthetic agents and gases. It requires procedure room space, scheduling, and an anesthesia recovery room. In addition, the electrophysiologist and anesthesiologist must work as a team to manage the patient. The merits of placing a patient at any desired level of anesthesia and providing a satisfactory environment to perform any type of surgical procedure are universally accepted when presented in this abstract fashion. However, the practical demands of the anesthesia package and the fundamental questions relating to the safety of general anesthesia limit its use. Many of the maneuvers performed during a lead extraction can reduce filling pressure. Traction on an atrial lead may block the SVC and reduce blood flow to the heart. Traction on a ventricular lead reduces the compliance of the chamber wall during diastole or, if strong enough, can pull the wall to the tricuspid valve, reducing blood flow. Immediate injections of a short-term α-adrenergic stimulant such as phenylephrine (Neo-Synephrine) or norepinephrine (Levophed) constrict the cardiovascular system, causing an increase in both filling pressure and systemic blood pressure. This may frequently be required throughout the case to compensate for these transient iatrogenic insults. Use of these agents does not reflect on the safety and efficacy of general anesthesia. In conclusion, the risk of anesthesia is mostly related to the procedure and not the general anesthesia. PROCEDURE ROOM Electrophysiology (EP) procedures are currently performed in general OR suites, device implantation procedure rooms, EP procedure rooms, catheterization laboratories, and fully equipped cardiovascular ORs. The room must be large enough to support the procedure. Small procedure rooms are sufficient for a device

implantation but not large enough for a complicated lead extraction procedure. There should also be space to accommodate emergency procedures and/or a more extensive surgical EP procedure. Procedures should not be performed in smaller rooms without a contingency plan for an emergency. The ideal procedure room should meet most of the requirements for an OR, especially those related to room cleaning, patient draping, gown and gloving, and instrument sterility. It should have the full “anesthesia package” including continuous monitoring of ECG, arterial pressures, and oxygen saturation. Essential specialty equipment includes high-quality fluoroscopy, echocardiography, pacemaker system analyzer (PSA), and other external EP devices to ensure pacing and defibrillation, as well as an excimer laser or dedicated electrosurgical unit for lead extraction. In addition, for minimally invasive cardiac procedures, lighted retractors, access to thoracoscopy equipment, and an emergency tray to open the chest should be available. Additional safety devices to help protect physicians and nurses include lead drapes for radiation protection, smoke evacuators, and chairs for sitting when appropriate during the procedure. POCKET MANAGEMENT Tissue debridement is the surgical removal of all inflammatory and damaged native tissues, leaving only normal native tissue behind. The need for tissue debridement in normal pockets seen on routine reimplantation is minimal. On opening an old pocket, the debridement goal is to remove any exuberant inflammatory tissue (fibrous tissue), leaving only thin, healthy fibrous tissue (biophysical interface) or normal native tissue behind. The fibrous tissue present is involved in the chronic remodeling inflammatory reaction; rarely is an acute inflammatory reaction present. This is important, because exuberant fibrous tissue masses, which are the result of an inflammatory reaction, can injure adjacent tissue, continuing the inflammatory reaction (recursive reaction). Also, if this tissue is contaminated by bacteria, it becomes a nidus for infection; bacteria adhere to the smooth surface of the exuberant encapsulating tissue, and the body’s immunodefense mechanisms cannot reach the bacteria. Leads entrapped in the encapsulating fibrous tissue may be under undue stress if the pulse generator is not placed back in the same position. Tissue debridement and freeing of the leads rectify this situation. Tissue debridement is best performed with an electrosurgical cautery tool. Tissue debridement, even in infected cases, is rarely extensive and can be treated as described earlier. Occasionally, however, the pocket must be extensively debrided and then abandoned; this situation usually involves infection. If an acute inflammatory reaction is extensive, debridement is tedious because of the presence of acute and chronic inflammatory material and proximity of large blood vessels and important nerves. Knowledge of local anatomy is mandatory in this situation. In some cases, the inflammatory tissue can be more than 2.5 cm thick, extending above and below the pectoralis major muscle with fingers to the clavicle, and damaging a large amount of skin. In these cases, skin loss is significant, and reapproximation of skin edges is challenging. Once the debridement is complete, hemostasis is difficult to achieve, especially on the muscles. Wherever possible, muscle fascia should be reapproximated. Tissue Closure Healing by primary intention is the closing of an open wound by reapproximating tissue (muscle, subcutaneous tissue, and skin) using suture material. Suture holds the tissue in place until the tensile strength of the bonding fibrous tissue is sufficient to keep the tissue together. All initial and reimplanted pockets are closed in a conventional manner, reapproximating the tissue with suture material, and allowed to heal by primary intention. Chronic pockets are debrided of all exuberant inflammatory material before closure. These pockets are debrided and closed using a closed-drainage system (Jackson-Pratt) placed in the debrided pocket, if necessary, applying suction to prevent the development of effusions or clot, and



keeping normal tissue contiguous with normal tissue. A large defect resulting from loss of tissue during debridement may be challenging to close. In extreme cases, a major defect requires an experienced surgeon or a plastic surgeon, especially if a flap is needed. Alternatively, the pocket may be allowed to heal by secondary intention. Another philosophy holds that pockets with debridement defects and infected pockets should be left open. Once the device (foreign body) is removed, the infection will heal, so allow it to heal by secondary intention. This rationale shortens the procedure and is an accepted method of healing. Infection is not an issue, and it avoids the need for acquiring surgical debridement and closure skills. Concerns such as morbidity, extensive healing time, long-term antibiotic therapy, constant professional care of the wound, and possible surgical intervention, including skin grafting, are considered the natural cost of healing the wound. Healing by primary intention, on the other hand, does not have these issues. Healing by secondary intention was previously used as the only way to heal an open wound. The healing stages were well documented: suppuration, granulation, closure of defect, and skin closure. This was the recommended method of treating contaminated wounds by surgeons until the 1980s. Since the 1970s, however, primary closure of debrided infected pockets has been successfully and almost exclusively used to manage device-related infections. TRAINING AND SKILLS Lead extraction is a fundamental skill that is required to manage device-related complications. Lead extraction, as with lead implantation, is a requisite skill with predictable and expected results. This was not always the case. From its inception in the early 1980s, the procedures evolved rapidly. The management of a device-related complication centered on the lead extraction procedure, overshadowing all other aspects of management. This was because unexpected tears in the SVC and heart wall sometimes occurred without warning, despite the rigid protocols followed. The technology and those rigid protocols have evolved into current procedures. The procedures are less stressful and have predictable results. Predictability allows an extractor to recognize an approach that has a potential for a poor result and change to an approach with a predictably good outcome. The 2009 HRS Expert Consensus document clearly indicates the minimum training needed for competency. Physicians in training should extract a minimum of 40 leads as the primary operator under supervision. To maintain skills a minimum of 20 leads annually should be performed. Supervising physicians should have extracted 75 leads with efficacy and safety consistent with accepted literature.1 Extraction techniques are much simpler now and are explained in detail. Unfortunately, some of the old, more complicated techniques are also needed to manage an occasional rare situation. Consequently, some of these techniques are also presented. Presentation of the extraction techniques and approaches from the medical and surgical electrophysiologist’s point of view has been challenging. The common ground is that most of the extractions involve transvenous leads. These are extracted using the techniques and approaches common to both groups. The alternative approaches are sometimes different for surgical and medical electrophysiologists. For example, in addition to the transvenous approaches, EP surgeons have the option of a transatrial or epicardial approach. Although not mainstream, these surgical approaches are essential to the management of certain complications. Although medical electrophysiologists cannot perform these procedures, they must be able to direct a non-EP surgeon enlisted to perform the procedure. The new HRS Expert Consensus document was published after 1-year preparation.1 In the past, meaningful consensus was impossible because of the small number of practitioners and limited data. Now, however, the substantial growth and investment of the international HRS community in transvenous lead extraction permits significant consistency in tools, techniques, procedures, and expected benefits and risks.

26  Techniques and Devices for Lead Extraction

755

Lead Extraction Techniques As discussed, segments of chronically implanted leads are encased in encapsulating fibrous tissue and bound to the vein and/or heart wall, bound to another lead, or both. Lead extraction is the removal of chronically implanted leads from these binding sites. Because the tensile strength of encapsulating fibrous tissue is greater than that of the surrounding tissue, leads cannot easily be removed without risking a tear or avulsion of the vein or heart wall. The word ablation best describes the removal, separation, and freeing of leads from encapsulating fibrous tissue. Ablation techniques include traction, countertraction, counterpressure, and tissue disruption, cutting locally with an instrument, laser, or electrosurgery unit. Lead extraction techniques are designed to free the lead from the encapsulating fibrous tissue (countertraction) or to free the encapsulating fibrous tissue (counterpressure) from the vein or heart wall.2 Telescoping sheaths are used remotely to apply countertraction and counterpressure at the selected binding sites. Lead extraction procedures are used to apply the sheaths and remove the lead in a safe and efficacious manner. TRACTION, COUNTERTRACTION, AND COUNTERPRESSURE In the 1960s and early 1970s, transvenous leads were large, bipolar, and without fixation devices. These leads were usually isodiametric, implanted for 1 to 2 years, and removed by traction. With the introduction of tines and pulse generators lasting 4 to 6 years, leads were entrapped in encapsulating fibrous tissue with significant tensile strength. These leads could not be safely removed by traction alone. Traction is the force exerted on the lead by pulling. Applying traction to the lead pulls directly on the binding site. Once the encapsulating tissue has a greater tensile strength than the venous or cardiac tissue, the tissue will tear or avulse. Disruption of the vein or heart wall can be lethal. Because the relative tensile strengths are not known, traction should be used with caution. However, traction is an acceptable extraction technique if applied judiciously. The force applied when pulling on a lead is related to lead size, lead tensile strength, how the lead is grasped, use of locking stylets, and most importantly the extracting physician’s catecholamine level. The catecholamine level is important in determining the actual traction force. When the extractor is relaxed and calm, the perceived force may be realistic; when upset, agitated, or mad, however, the force is much greater than perceived. Consequently, “giving it a little tug” is not wise. Direct Traction All current lead extraction procedures use some form of traction, or pulling force13 (Fig. 26-10). Pulling on leads was a successful method of extracting leads during the early years of pacing, when leads lacked efficient fixation devices and were implanted for short periods. Traction was applied manually for minutes or applied using various weights or elastic bands for days. Traction proved unsafe and had a high incidence of failure when applied to leads with efficient fixation devices and leads implanted for longer periods. The amount of traction required increases and becomes more dangerous as the duration of the implant and the tensile strength of the fibrous tissue increase. Leads with efficient passive-fixation devices may be difficult to remove 4 to 6 months after implantation. A failed previous attempt to extract a lead frequently damaged the lead, making future extraction attempts more difficult. Again, traction must be applied judiciously to minimize the risk to the patient. The pulling force applied to the proximal portion of the lead is distributed to sites where fibrous tissue binds the lead or electrode and makes contact with the vein or heart wall. Multiple leads may be bound to the vein or heart wall and to each other. Because the pulling force is not focused, the distribution of force to the binding sites is unknown. The extractor may inadvertently tear a vein or the heart wall.

756

SECTION 3  Implantation Techniques

hemodynamic compromise persists, such as decreased blood flow through the right ventricle, creating a cardiovascular emergency. If the lead body cannot be released by manipulation, including use of a stiff stylet to help push it through the binding site, an emergency median sternotomy is required to restore manually the heart’s function. Once a lead is freed from a distal binding site, the lead and associated fibrous material can then become wedged in a more proximal binding site. For example, a lead removed from the right ventricle can become wedged at a binding site in the atrium, SVC, or axillary-subclavianbrachiocephalic veins. With direct traction, the lead is freed from the binding sites, distal to proximal. The strongest binding site determines the outcome of an extraction attempt, regardless of its proximal or distal location. Indirect Traction

Tape support

Rubber bands

Figure 26-10  Direct traction. Direct traction is being applied by pulling on the proximal portion of the lead. Rubber bands are used in this case. Variations include using free weights and applying weights with an orthopedic traction apparatus. If a locking stylet is inserted,  the traction point is moved distal to the locking site, usually near the electrode.

Traction, in some form, is integral to lead extraction. The physician must consciously limit the pulling force and apply a continuous, steady traction. Never jerk the lead, because impulse forces tear. Accidents are not predictable and frequently occur without warning, partly because it is impossible to judge accurately the level of force applied to the lead. To gauge the applied force, most direct-traction techniques apply sufficient force to feel the rhythmic tugging of the heart without producing arrhythmias, hypotension, or chest pain. These are crude and unreliable endpoints and do not reflect the tensile strength of the lead or the tissue. Breaking the lead, tearing a vein, or avulsing or tearing the heart wall are all potential complications. As stated, “just a little tug to see if the lead will come out” is not a consistently safe approach, and following the basic principles and guidelines acquired from practical experience minimizes the risk. It is important to understand the difference between pulling from above and pulling from below. The mediastinal structures are not bound from below. If you pull upward on the heart, it will move, along with the lungs, diaphragm, and rest of the mediastinal contents, in that direction. If you pull downward, the superior veins and surrounding structures are bound to the musculoskeletal system and do not move downward. Assume that traction is applied from above to a lead implanted in the right ventricle. With continuous traction, the right ventricle starts to evaginate, decreasing the compliance of the wall and finally obstructing the flow of blood through the tricuspid valve. At the same time, the heart is pulled into the superior portion of the mediastinum. This maneuver is safe as long as the hemodynamic status is monitored and the process is reversible. Reversibility means that traction-induced deterioration in hemodynamic function is corrected on cessation of the traction, and the right ventricle, along with remainder of the mediastinal structures, returns to its normal position. Usually, the structures do return to normal. The danger is slippage of the lead body through a binding site. On release of the traction, the mediastinal forces pulling downward are insufficient to pull the lead back through the binding site. The forces required to elevate the mediastinum to this position are still applied to the heart. Any

Elevation of the mediastinum with traction is the main reason why traction from above is not as effective at pulling a lead through a binding site as is pulling from below. When traction is applied from below, the mediastinum is not pulled down (inferior) because the superior veins and surrounding tissues are bound to the musculoskeletal system. Traction forces applied to the binding sites are directed at freeing the lead, not at moving structures. The limit to the force applied to the axillary-subclavian-brachiocephalic veins is determined by the tensile strength of the lead. If the lead binding in these veins is extensive enough to require that type of force, the veins are probably occluded, atretic, or encapsulating sheaths. Disruption of these veins by tearing or avulsion is of no consequence. Binding sites in the SVC, however, must be treated in the same manner as in the heart. Disruption of the wall of the SVC has the same consequences as disruption of the heart wall. The safety and efficacy (higher success rate) of applying indirect traction from below should now be apparent. Indirect traction is traction applied by an instrument, such as a snare passed into the heart, usually through a femoral vein. The lead is entrapped in the snare, and traction is applied by pulling or pushing. The difficulty is in grasping the lead in a way that allows sufficient traction to be applied. Only a few snares, such as the Dotter basket snare and Needle’s Eye-Snare (both Cook Vascular, Vandergrift, Pa.), or the Amplatz Gooseneck Snare (eV3/Vasocare, Seoul) have sufficient strength to support significant extraction forces. The lead must first be freed from the superior veins and then from the heart. The lead is pulled out of the superior veins and into the atrium or inferior vena cava (IVC). It can be regrasped, if necessary, and traction can be applied to the heart. The techniques for applying indirect traction are the same as for grasping and manipulating the leads in other approaches, such as applying countertraction sheaths, as described later. The risks eliminated by indirect traction are tearing of superior veins, wedging of the lead in the atrium or in a superior vein, and creating a low cardiac output caused by failure of the lead to return to its original position after traction. Indirect traction has the same potential for breaking the lead or tearing the heart wall as direct traction, if their tensile strength is exceeded. Countertraction Countertraction is the technique used to free the lead from compliant, encapsulated fibrous tissue. Countertraction was first used to remove a lead from an implantation site in the right ventricle or atrium. Although the technique for extracting leads from the heart wall is discussed first, this is the last step in a normal lead extraction procedure, using any type of sheath. Extraction sheaths free leads from binding sites, proximal to distal. Once the sheath is passed over the lead and down to the implantation site, traction on the lead pulls the site to the sheath (Fig. 26-11). The traction force is countered by the circumference of the sheath. The countertraction sheath focuses the traction force at the tip of the sheath, limiting the excursion of the heart wall. This prevents compliance changes and blockage of the tricuspid valve, with possible perforation, tearing, and avulsion of the heart wall. The countertraction forces are limited by the tensile



26  Techniques and Devices for Lead Extraction COUNTERTRACTION Countertraction sheath

Lead body traction

Figure 26-11  Countertraction. Countertraction is a safe method extirpating a lead or electrode from a vein or heart wall. Left, Traction on the lead body with evagination of the right ventricular wall decreases the compliance on the wall and pulls it toward the tricuspid valve. Complications include decreased flow through the right ventricle and disruption of the ventricular wall instead of the scar tissue, with tearing of the wall and/or avulsion of tissue. Right, Placing a sheath near the heart wall applying traction causes the traction force to be countered by the sheath. The limit on the traction force applied is the tensile strength of the lead. The lead is extirpated from the scar tissue, and the heart returns to its normal position.

strength of the lead. At some point, the electrode is freed from the encapsulating fibrous tissue, allowing the heart wall to fall away and the electrode to be pulled out of the sheath. The way countertraction actually frees the lead is postulated but not known. It is thought that the traction force wedges the lead against the countertraction sheath. The pulling force on the electrode tries to evaginate the encapsulating fibrous tissue. The electrode is then freed either by (1) a plastic deformation of the tissue that allows it to slide out of the encapsulating tissue as the countertraction sheath peels the

Sheaths

Lead Encapsulating fibrous tissue

Vein

757

tissue off the electrode or (2) an actual disruption or bursting of the encapsulating tissue that frees the electrode, or both. For a passivefixation electrode, the tines are removed intact with the electrode; for an active-fixation electrode, the fixation mechanism is ideally retracted or unscrewed before countertraction is applied. In some cases, continued “unscrewing” of an active-fixation lead results in complete lead removal without the need for countertraction, because of the absence of significant binding at other sites along the lead.14 If the helix will not retract, the electrode and fixation mechanism are removed together. The same scenario likely applies to removal of electrodes from the atrial wall. Countertraction is also used to free the lead from the encapsulating fibrous tissue at binding sites along the vein and heart wall (see Fig. 26-11). This is possible only if the encapsulating fibrous tissue still has plastic qualities (compliant). The tissue at the binding site is pulled against or into the sheath and is removed by evagination, peeling, or tissue rupture. Countertraction can be performed with either the inner or the outer sheath. Counterpressure Counterpressure was the term given to the removal technique used for noncompliant, encapsulating fibrous tissue (mineralized tissue). A sheath larger than the solid encapsulating tissue is used, and the tissue is pulled into the sheath. The encapsulating fibrous tissue is usually attached to the vein, tricuspid valve, or heart wall. The sheath counters the traction force applied to the tissue mass by converting this force into a pressure concentrated locally between the edge of the sheath and the vein wall (counterpressure sheath). This local action peels the calcified mass off the vein or heart wall. The encapsulating tissue is included with the lead inside the sheath (inclusion). The force applied is limited by the tensile strength of the lead and the wall. Because the magnitude of the counterpressure force actually focused on the wall is unknown, application of force is subjective. Counterpressure is potentially dangerous and should be approached with caution. Some believe that mineralization of tissue may lead to a higher risk associated with lead extraction. The inability to pass a binding site safely using counterpressure is the primary reason for abandoning this approach and changing to a transfemoral or transatrial approach. These approaches allow the lead to be pulled out of the superior veins from below, through the binding site. It is unknown whether the lead is being removed by countertraction or counterpressure (Fig. 26-12). In the past, counterpressure was used to describe the removal of tissue from all sites other than the electrode implantation site. In most cases, removal is still credited to counterpressure; compliant tissue is removed primarily by countertraction, and noncompliant tissue by counterpressure. Not discussed are leads bound to one another by the calcified encapsulating tissue. Separation of the two leads is safe, and the traction force is limited only by the tensile strength of the lead. EXTRACTION INSTRUMENTS Lead extraction instruments are separated into mechanical sheaths, powered mechanical sheaths, and snares.

Dilation

Rupture

Inclusion

Countertraction/counterpressure

Ablation Laser/EDS

Figure 26-12  Mechanical and powered sheaths. Telescoping sheaths are inserted transvenously and passed to the first binding site. Countertraction, counterpressure, and/or power ablation is applied to extirpate the lead. Countertraction dilates and/or ruptures the binding site, liberating the lead. The laser and electrosurgical dissection sheath (EDS) is a powered sheath that vaporizes the tissue. Counterpressure is used to pass the sheath over the entire calcified encapsulating fibrous tissue mass (inclusion). Counterpressure is the actual manipulation of the telescoping sheaths to peel the encapsulating tissue off the vein or heart wall.

Mechanical Sheaths Mechanical sheaths are telescoping sheaths made of Teflon, polypropylene, or stainless steel (Fig. 26-13). These telescoping sheaths are designed to pass over the lead, which acts as a rail guiding the sheaths through the veins and down to the heart wall. Countertraction and counterpressure are applied as the sheaths move down the lead from one binding site to another. The outer sheath also acts as a workstation, facilitating the free movement of the inner sheath and lead by eliminating binding, and it protects the surrounding vascular structures. The leading edges of the sheaths are beveled. The rotation of the beveled tips facilitates maneuvering past obstructions and through the narrow channels along the tortuous paths surrounding the lead body. This is

758

SECTION 3  Implantation Techniques

A

B

C

Figure 26-13  Mechanical sheaths. Telescoping sheaths have a beveled tip and come in various sizes. A, The original Teflon sheaths are softer and suppler. B, Polypropylene sheaths are stiffer and allow more force to be applied at the binding site. C, Stainless steel sheaths are rigid and are used to bore through bone or calcified tissue at the vein entry site. The stainless steal sheaths should not be passed into the brachiocephalic vein.

especially true in the superior veins. For the sheaths to pass down the lead in a true course, the lead must be stiff enough to act as a guide rail. The lead is stiffened by pulling it taut. The lead must be stiff enough to resist bending or kinking as the sheaths are passed over it (lead stiffness > sheath stiffness). The telescoping action of the sheaths allows the suppler inner sheath to track over the lead. The larger outer sheath is then advanced using the combination of taut lead and inner sheath as the guide rail. The lead is made taut by traction (pulling on it). A locking stylet is inserted, and a suture is usually tied to the lead, acting as both an extender and a traction handle. As described earlier, experience and judgment are required to avoid tearing and avulsing vein and heart wall tissues. Also, if the traction force exceeds the lead’s tensile strength, it can cause lead disruption and breakage. Insertion of a locking stylet adds some stiffness to the lead and focuses the traction force to a locking site near the electrode. Except for simple cases, in which leads have been implanted for a short duration, a locking stylet should be inserted. Despite these provisions, when there is poor tensile strength of the lead, it is more difficult and more time-consuming to free the lead from its binding site. The forces involved frequently exceed the tensile strength of the lead, unless there is a good locking stylet and suture, resulting in lead disruption and breakage. Powered Mechanical Sheaths.  Powered cutting tips positioned at the leading edge of the mechanical sheath have changed the nature of lead extraction. The ability to free the leads by cutting tissue significantly decreases the countertraction forces. Reduction in the applied force has made lead breakage and separation of the lead body from the distal electrode rare events. The expectation is that any lead should be completely extracted regardless of its tensile strength. Before the advent of powered sheaths, a lead breakage rate of 15% to 20% was common for leads with satisfactory tensile strengths. The first powered sheath was the excimer laser sheath (Spectranetics, Colorado Springs) developed in the mid-1990s. The second was the electrosurgical dissection sheath (EDS; Cook Vascular) in the early 2000s. Both these sheaths are used successfully at present.

excessive forces applied during a lead extraction. At the time, optic fibers were bundled circumferentially inside a cylindrical metal housing, which protected the optic fibers from the applied forces generated while maneuvering the tip through the encapsulating tissue. Initially, the only sheath meeting all the clinical requirements was a 12-French (12F) sheath that was interchangeable with the 12F/16F mechanical Teflon sheaths. In time, larger 14F and 16F sheaths were perfected. These sizes were sufficient to manage all sizes of pacing leads up to the largest ICD leads. The last iteration of the laser sheath was to place a 15-degree bevel at the tip. It is the largest angle permitted by the circular configuration of the optic fibers at the electrode. The laser is controlled by a foot switch. By design, the laser is on for 10 seconds and off for 5 seconds. The sound caused by the rapid pulsing of the laser furnishes a unique sound indicating the laser is on. The laser beam is a light cone that ablates tissue up to a distance of 1 mm. The water vapor generates bubbles that are clearly visible on echocardiography. Although the bubbles and other particulate debris are filtered out in the lungs, there are no apparent clinical sequelae. The cutting action of the laser can disrupt the SVC or the atrial wall if the lead is embedded in the wall. Because there is no way to know when a lead is embedded in the wall, the same emergency precautions apply to the laser as to the mechanical sheaths.

12F laser sheath

EXCIMER LASER SHEATH The development of the excimer laser was a milestone for lead extraction (Fig. 26-14). The excimer laser generated a high-energy 308-nanometer laser beam known to disrupt tissue (both cells and hydrated proteins) by an explosive vaporization of intracellular water. The rapid vaporization helped to cool the site. These were appealing properties for lead extraction. Unfortunately, the laser does not ablate heavily mineralized tissue. If the laser could not be maneuvered through this tissue in a grinding manner, counterpressure techniques were required. The development of the excimer laser sheath was a technical achievement. It required expertise in polymer chemistry and optic fibers to develop a small-diameter, flexible sheath capable of withstanding the

Figure 26-14  Excimer laser sheath. The sheath plugs into the CVX-300 excimer laser system with a black connector at the proximal end. A blue fiberoptic cable conducts the pulsed ultraviolet light to the tubular-shaped working section. Inset shows how the laser sheath is designed to slide over the lead body as it threads its way through the veins to the heart. A micrograph of the tip shows how the 83 fibers are arranged in a single circumferential row at the tip. When the laser light comes out of these fibers, it cuts the fibrotic tissue that binds the lead to the vein walls.



The laser sheath technique was evaluated prospectively in two clinical trials. The Pacing Lead Extraction with the Excimer Sheath (PLEXES) trial included only the initial version of the 12F sheath.15 Although there have been substantial improvements in the 12F sheath, including an outer sheath, better mechanical properties to prevent crushing of the optical fibers, lubrication, a flexible distal and a more still proximal segment, and certainly better understanding of how to use the tool, the PLEXES trial was a dramatic success. This randomized clinical trial compared mechanical extraction tools with laser-assisted lead extraction and was used to support the clinical release of this technology. The complete lead removal rate was 94% in the laser group and 64% in the nonlaser group (P = .001). Failed nonlaser extraction was completed with the laser tools 88% of the time. The mean time to achieve a successful lead extraction was significantly reduced for patients randomized to the laser tools: 10.1 ± 11.5 minutes versus 12.9 ± 19.2 minutes for the nonlaser techniques (P < .04). There was only one death, but it was in the laser group; and there were two other potentially life-threatening bleeding episodes in the laser group. After the trial with the 12F sheaths, a second, nonrandomized cohort trial was done with 14F and 16F sheaths.16 This was particularly important, because implantable defibrillator leads required the 16F sheaths, and many of the bipolar leads (almost all) were better approached with the 14F sheath. In contrast to other, nonlaser sheaths, upsizing of the laser sheath to pass over (include) the fibrosis or calcification is frequently an effective maneuver. In this study, 863 patients underwent extraction of 1285 leads. Expanding the number of research sites from fewer than 10 to 52 gave a broader view of this tool in general practice. The patients treated with the 14F device tended to have older leads than patients in the 12F population; the 16F population, composed mostly of defibrillator patients, was younger, had more recent leads, and was more often male than the 12F population. Clinical success (extraction of entire lead or of lead body minus distal electrode) was observed in 91% to 92% of cases for all device sizes. The overall complication rate was 3.6%, with 0.8% perioperative mortality. The incidence of complications was independent of laser sheath size. Ultimately, a cohort comparison trial of defibrillator and pacemaker leads extracted with laser assistance was done at the Cleveland Clinic.17 ICD extraction results were compared with the results for a matched cohort of patients undergoing extraction of ventricular pacemaker leads from a national registry and with the experience with pacemaker lead extraction at the Cleveland Clinic. Successful complete extraction of ventricular nonthoracotomy implantable defibrillator leads, in the absence of major complications, was achieved in 96.9% of attempts to extract leads from 161 patients. Clinical success was achieved in 98.1% of patients. There were three major complications, including one death. ICD lead extraction was done at an experienced center with equal risk and no significant difference in procedure or fluoroscopy time. The total investigational experience with laser sheaths was also reported (October 1995–December 1999), including 2561 pacing and defibrillator leads in 1684 patients at 89 U.S. sites. Of these leads, 90% were completely removed, 3% partially removed, and 7% failures. Major perioperative complications (tamponade, hemothorax, pulmonary embolism, lead migration, death) were observed in 1.9% of patients, with in-hospital deaths in 13 (0.8%). Minor complications were seen in an additional 1.4% of patients. Multivariate analysis showed that implant duration was the only preoperative independent predictor of failure, and female gender was the only multivariate predictor of complications. Success and complications were not dependent on laser sheath size. At follow-up, various extraction-related complications were observed in 2% of patients. The learning curve showed a trend toward fewer complications with experience.18 A similar experience was observed in Europe.19 The LExICon study was the most recent study evaluating the most recent iteration of the laser-assisted lead extraction system.12 In this study, 2405 leads were extracted in 1449 patients from 13 centers. The procedural success was 96.5% with 97.7% clinical success. Major adverse events in 20 patients were directly related to the procedure

26  Techniques and Devices for Lead Extraction

759

(1.4%) including four deaths (0.28%). Major adverse effects were associated with patients with BMI less than 25 kg/m2. Overall, all-cause in-hospital mortality was 1.86%. Electrosurgical Dissection Sheaths The EDS has two bipolar electrodes positioned at the tip of the bevel (Fig. 26-15). The sheath is connected to an interface plate inserted on a conventional electrosurgery unit (Valley Lab Force V; PEMED, Denver), placed in a bipolar cutting configuration, and activated with a foot switch. The interface plate is attached to the front panel of the electrosurgical unit to ensure that the EDS is connected in a bipolar configuration. The interface also has an attachment to pulse the electrosurgical unit 80 times per minute. A plasma arc is generated between the electrodes. The plasma arc extends out from the electrodes and vaporizes the tissue to a depth of about 1 mm. On continuous discharge, desiccated tissue debris shunts the arc between the electrodes, preventing it from cutting. Also, on continuous discharge, if one of the electrodes touches a conductor coil, a parallel, alternate current (AC) circuit is created consisting of the EDS electrode in contact with the conductor coil, the conductor coil down to an electrode in the heart, and back to the other EDS electrode. An AC current applied to the heart in a unipolar configuration can fibrillate the heart. To ensure cutting and avoid fibrillating the heart, the EDS is operated in a pulsed mode at 80 pulses/min. In the pulsed mode, if a conductor coil is touched, it paces the heart. The EDS is a conventional Teflon mechanical sheath with two tungsten electrodes embedded in the polymer. Placement of the EDS electrodes in a bipolar configuration at the tip of the inner telescoping sheath endows the EDS sheath with properties of mechanical sheaths; it can maneuver through tortuous veins and can apply countertraction and counterpressure. These sheaths are currently available in sizes 7F, 9F, 11F, and 13F (circumference of inner sheath). The electrodes and sheath are radiopaque, allowing visualization during fluoroscopy. The electrodes’ position is continuously adjusted by rotation of the sheath. For example, around a curve, the electrodes are placed on the inner curvature passing down the lead. Also, the electrodes are rotated away from skeletal muscle and nerves to avoid stimulation. Stimulation of skeletal muscle or the phrenic nerve does not harm the patient and is not an issue with general anesthesia. However, skeletal muscle and diaphragmatic contractions can be discomforting and even frightening if the patient is awake. At present, this is the only clinical issue associated with the EDS. The same emergency precautions applicable to mechanical and laser sheaths also apply to the EDS.

Bipolar radiopaque electrodes

Teflon inner sheath with beveled tip

Conventional outer sheath

Figure 26-15  Electrosurgical dissection sheath (EDS). The EDS is a telescoping, beveled Teflon sheath set with two electrodes in a bipolar configuration at the tip of the inner sheath. Encapsulating tissue is ablated with pulsed radiofrequency energy delivered as needed at 80 Hz. The electrodes are radiopaque, allowing precise placement.

760

SECTION 3  Implantation Techniques

Clinical evaluation of the EDS has been formally published only in an observational study from five centers, involving 265 patients with extraction of 459 leads.20 During the investigation, only the 9F and 11F sheaths were used, excluding almost all ICD leads from consideration for extraction. As in all extraction series, some of the leads came out easily and others were more difficult to remove, and the techniques consisted more of an approach than of universal use of one tool to remove all leads. In this case, 542 leads were potentially presented for extraction, but about 15% were removed with direct traction, yielding 459 for which the EDS was employed. The laser tool was used in fewer than 3% of the leads. The average implant duration of the patient’s oldest lead was 8.4 ± 5.0 years; 31% of patients had leads implanted for longer than 10 years. Major complications occurred in 2.6% of patients, including cardiac tamponade in 4 patients (1 surgical repair, 1 after switching to a femoral approach), 1 hemothorax, 1 arteriovenous fistula (surgical repair), and 1 death that was associated with the mechanical removal of an oversized SVC lead for which the EDS was not used. For the 459 leads with attempted removal by the EDS, 99.4% were removed (95.9% completely, 3.5% subtotally with ≤4 cm of lead remaining), and only 0.6% were not removed. Overall, the experience with the EDS has been good. The application of 7F and 13F sheaths with intermittent pulsing of the electrosurgical energy has been useful in removing smaller and larger leads and in making the sheath more powerful in cutting through the fibrosis. Evolution Sheath.  A newer mechanically powered lead extraction sheath set is the Evolution mechanical dilation sheath (Cook Vascular). A rotating inner sheath with a threaded-barrel metal tip is designed to function as a dilating drill (Fig. 26-16). This bores through the encapsulating fibrous tissue as it advances down the lead through the binding sites. The outer sheath is a conventional, beveled plastic sheath. The rotation of the inner sheath is powered by a pistol-grip handle squeezed by the operator (mechanical power). Multiple inner diameter (ID) sizes (7, 9, 11, and 13 French) are available. The initial experience with the Evolution had mixed results.21 There was a high procedural and clinical success rate. The Evolution is particularly useful as a rescue when heavy calcifications are encountered while using the laser sheath. There was a tendency toward wrapping of adjacent leads and also collateral damage to the leads not intended for extraction. The system seems to work best in single-lead systems when collateral damage or wrapping is not an issue. No complications resulted from use of the Evolution. Locking Stylets Locking stylets were developed after the mechanical sheaths. From the beginning, the major pacing companies (Medtronic, Cordis, Pacesetter [St. Jude Medical], and Boston Scientific [Guidant, CPI]) all attempted

Figure 26-16  Evolution mechanical dilator sheath (Cook Vascular).

to make a universal locking stylet (one size stylet to fit all leads). These initial attempts were unsuccessful because of breakage of the locking mechanism. The tensile strength was inadequate to withstand the traction forces. Cook Pacemaker (now Cook Vascular) took another approach, abandoning the concept of a universal stylet. Their firstgeneration locking stylet came in various sizes to fit a variety of conductor coil diameters (Fig. 26-17). The conductor coil had to be measured before selecting the locking stylet. This locking mechanism was a small wire welded to the tip of the stylet and wrapped around the lead. Once the lead was passed down the conductor coil to the electrode, it was rotated counterclockwise, bundling the free wire and causing it to bind against the conductor coil. The greater the traction, the greater was the binding force. The locking stylet bound to the inner conductor coil, ideally at the distal electrode, functioned as a lead

Locking stylet Electrode Countertraction sheath Locking stylet

A

B

C

Figure 26-17  First-generation locking stylet (Cook). A, Ideally, the locking stylet is passed to the electrode and secured. The locking mechanism is a wire that is secured to the tip and wrapped around the stylet. B, When the stylet is turned counterclockwise, the wire bundles together, binding the stylet to the conductor coil. The locking stylet acts primarily as a lead extender to apply traction and secondarily to keep the lead intact during the extraction. When the stylet is positioned at the electrode, the lead has its best chance of remaining intact. If the stylet is positioned near the proximal end, the fragile leads will be pulled apart when traction is applied. C, Clockwise from lower left, Locking stylet, sizing pin, lead cutter, coil expander, soft-grip hemostat, standard stylets, and polypropylene telescoping sheaths.



26  Techniques and Devices for Lead Extraction

extender for applying traction and focused the traction force at the binding site. Focusing the traction force helped maintain the integrity of the lead but did not prevent lead disruption if excessive force was applied or if the lead had poor tensile strength. Also, the locking stylet was conductive, and the heart could be paced during parts of the lead extraction procedure if needed. This was the first effective locking stylet. Cook’s second-generation locking stylet (Wilkoff Locking Stylet) had a different locking mechanism (Fig. 26-18). These stylets had a small flange at the tip designed to stay flat against the stylet until the preloaded thin cylinder was advanced; the cylinder deflected the flange to lock into the conductor coil. This was an efficient locking stylet that was easy to implant and that could be removed by rotating the stylet, breaking the flange. However, it could not be used if the conductor coil diameter was 0.016 inch or less, and it could not be used with extendable/retractable screw-in leads. Spectranetics made the first near-universal locking stylet (Lead Locking Devices 1, 2, 3 and e) to fit all leads. It used a long wire mesh that bundled and bound the stylet to the conductor coil. This type of locking stylet was efficient and functioned well. Ultimately, the Spectranetics LLD-EZ was developed that works for all but a few leads with extremely small IDs to the inner coil. Cook’s most recent, third-generation locking stylet (Liberator Locking Stylet) is a true universal locking stylet (one size fits all). It uses a wire coil that is compressed by a reloaded cylinder, expanding the wire coil and binding it against the conductor coil (Fig. 26-19). Both the Liberator and the LLD-EZ are extremely versatile and provide an advantage over the alternative for either advancement down the conductor coil in locking. As mentioned earlier, the goals for inserting the locking stylet were to provide a lead extender and to focus the traction force at the tip to help maintain lead integrity. Although these goals were met, the insulation still has to be secured with a suture. Without traction to the insulation, it can “snow plow” and tear more easily, making passage of the extraction sheaths difficult, and in some cases preventing their passage. Therefore, traction should be applied to both the suture (insulation) and the locking stylet (conductor coil) to be most effective. A new tool, the Bulldog lead extender, is designed for leads that have no conductor coil, or when the conductor coil is severely damaged. It mechanically locks onto the conductors to the shocking and pacing electrodes and produces an excellent mechanism for improving the

Not engaged

Engaged Figure 26-18  Second-generation locking stylet (Cook). The Wilkoff Locking Stylet employs a different mechanism for applying traction to the lead conductor at the tip of the lead. It also functions as a lead extender to lengthen the lead so that the sheaths can be advanced to the endocardial surface. The locking mechanism does not require precise measurement of the internal diameter of the conductor coil, and each size of the Wilkoff stylet bridges three sizes of the original locking stylet. The mechanism is activated by advancement of the thin cylinder, which nudges the hook to the side, engaging it between the coils of the conductor. This mechanism can be reversed and relocked but does not tolerate rotation. The response to rotation can be an advantage if the stylet needs to be removed.

761

tensile properties of the lead. The Bulldog can also be used to lock onto the cables to the shocking coils in leads with a cylindrical conductor coil, and a locking stylet is still used in the cylindrical coil. Snares Snares are used to grasp leads and to remove tissue in the bloodstream from the vein or transatrial entry site. The vein entry sites typically used are the subclavian, internal jugular, and femoral veins. Only a few snares are safe to maneuver in the cardiovascular system or have the tensile strength to support the forces involved in a lead extraction procedure. The Dotter snare, Needle’s Eye Snare (Cook), and Amplatz Goose Neck Snare are discussed as examples of the types of snares available. The Dotter snare, together with a deflection catheter, is prepackaged in the femoral workstation. Before the availability of powered sheaths, lead breakage and the need to use a femoral approach were common. The only substitute for a snare is a cardiac surgical procedure. Consequently, facility with snares still is a requisite skill. Also, there are still extractors who do not use powered sheaths, relying only on the mechanical sheath extraction, and snares are integral to these procedures. With the Dotter, needle-eye, and gooseneck snares, a reversible loop is created around the lead body to pull the proximal end of the lead out of the superior veins into the IVC, without placing traction on the electrode-myocardial interface (Fig. 26-20). A loop must be created and bound to the lead body. The binding of the loop must be reversible. Irreversibly binding the lead, or inability to remove the loop from around the lead, may result in dangerous traction maneuvers being performed in desperation while trying to extract the lead and snare. Failure to extract the lead subjects the patient to more invasive procedures to remove both lead and snare. Creating a reversible loop using two snares is a complicated maneuver requiring practice to perfect. One technique is to use a Cook deflecting wire guide and a Dotter basket snare. The Cook deflecting wire guide is wrapped more than 360 degrees around the lead body. Next, the tip of the deflection catheter is passed into the Dotter basket snare. When the basket snare is pulled into the workstation, the basket closes, grasping the deflection catheter and completing the loop. The loop is pulled into the workstation, tightly binding the lead body to the workstation, and traction is applied. If needed, the loop is relaxed and repositioned on the lead body. This sequence is repeated until the lead is pulled out of the superior veins, through the right atrium, and into the IVC. The reversible loop is then released, and the deflection catheter is removed. This same process can be done with a gooseneck snare and tip deflecting guidewire or a deflectable EP catheter and gooseneck snare. The Cook Needle’s Eye Snare is a more efficient method of grasping the lead in a reversible manner (Fig. 26-21). This snare has a wire loop that is passed over the lead body. A small, wire-loop tongue is then passed over the opposite side of the lead and into the larger wire-loop tongue. Pulling this apparatus into the workstation binds the lead reversibly for safe, indirect traction. Also, the binding forces are more diffuse, resulting in less lead breakage. The Amplatz Goose Neck Snare is a radiopaque noose that is slipped over the free proximal end of a lead (Fig. 26-22). In situations where the proximal end is floating in the SVC, heart, or a pulmonary vein, the free end can be lassoed and extracted. The gooseneck snare can also be used to grasp the end of a tip-deflecting guidewire or deflectable EP catheter draped over the midportion of the lead. This is an excellent technique to reposition a lead so that the end can be grasped after being pulled down from the subclavian/jugular system, or to grasp the lead reversibly for extraction.

Lead Extraction Approaches Extraction procedure approaches involve transvenous and cardiac surgical extraction techniques. Transvenous approaches are usually performed through the lead implant site, but any other vein suitable for the extraction instruments may be used. Suitable veins include the axillary-subclavian-brachiocephalic, external jugular, internal jugular,

762

SECTION 3  Implantation Techniques

A

B

C

D

Figure 26-19  Third-generation locking stylet (Cook). The universal locking stylet works by binding the locking stylet to the conductor coil. A wire coil is ideally positioned at the tip of the lead, near the distal electrode. The coil is expanded, binding the stylet to the lead’s inner conductor coil. Traction increases the binding force. A stylet now can fit the smallest conductor coil and still have sufficient tensile strength to support a wire coil large enough to bind to the largest-diameter conductor coil. A, Lead conductor without the locking stylet. B, The liberator locket stylet has been advanced to the tip of the lead. C, The cylinder is pushed to crush the wire coil at the tip of the lead, locking to the conductor. D, Comparison of the inner wire with and without the wire coil at the tip of the universal or liberator locking stylet.

A

E

B

C

F

D

G

H

Figure 26-20  Femoral workstation (Cook). The Byrd WorkStation has two snares (Dotter basket and Cook deflection), the first that we found to have the versatility and tensile strength suitable for lead extraction. A, Telescoping Teflon sheaths and Dotter snare advanced to the right atrium with lead body entangled in the snare. Pulling the lead into the sheaths for lead extraction is possible but not recommended because it is not reversible. B, Dotter snare and deflection catheter in atrium. C, Looping the lead body with the deflection catheter. D, Entangling the tip of the deflection catheter in the Dotter snare. E to G, Tightening the loop and pulling it into the Teflon sheaths. H, Sliding the telescoping sheaths to the electrode for removal using countertraction. At any time, the process can be reversed, freeing the lead.



26  Techniques and Devices for Lead Extraction

A

763

B

Figure 26-21  Cook Needle’s Eye Snare. This is the only reversible snare designed specifically for removing leads. A, The lead body is hooked, usually in the atrium, and the tongue is extended, forming a reversible loop. B, The lead body is pulled into the telescoping sheaths for lead removal.

and femoral-iliac. Cardiac surgical approaches to intravascular leads are transatrial, right ventriculotomy, and open-heart surgery (OHS). All epicardial lead extractions are cardiac surgical procedures. In the past, procedure approaches were separated into superior (SVC) and inferior (IVC) vena cava approaches. An SVC approach is defined as the passage of lead extraction instruments through the vein entry site and down the SVC to the heart. The IVC approach was defined as a transfemoral approach using remote extraction instruments inserted in a femoral vein and passed through the IVC into the heart. This classification was based on the two types of extraction tools available at that time. Currently, a more descriptive classification is to

separate the approaches into transvenous and cardiac surgical procedures. Transvenous procedures are further divided into procedures through the vein entry site and those through a remote vein, usually the femoral or internal jugular veins. Cardiac surgical procedures are separated into the individual cardiac surgical approaches: transatrial, ventriculotomy, and OHS. The approach selected depends on the experience, extraction skills, and extraction instruments available to the physician; the reason for the lead extraction; and situations that arise during lead extraction. For example, a transvenous lead implanted in the right ventricle with a conductor coil fracture is ideally extracted from the vein entry site,

A

B

C

D

Figure 26-22  Amplatz Goose Neck snare. A to D, The gooseneck snare places a noose around the end of a lead and is pulled taut. The gooseneck assembly is then pulled into telescoping sheaths for lead removal. This snare is reversible unless the assembly binds in the telescoping sheaths. In our experience, this snare is most effective for removal of small lead segments (e.g., electrodes, lead body segment) from small vessels such as hepatic veins, pulmonary arteries, azygos veins, and pelvic veins.

764

SECTION 3  Implantation Techniques

using a powered sheath. A change in approach must be considered if this same lead is found to be attached to the lateral wall in the distal half of the SVC by a calcified mass of encapsulating tissue. A determination to continue the approach or a decision to choose a new one depends on experience and extraction skills. Two safe approaches are through the femoral vein using snares and a transatrial cardiac surgical approach. If this same lead is found to have large, solid thrombi measuring 4 × 8 cm, it is best extracted through a transatrial approach or OHS. Extracting leads is dangerous if it is not properly performed. Procedures with these inherent dangers can be made safe only by knowledge of the pathology, pathophysiology, extraction skills, and available approaches. Using a nonmedical comparison, flying an airplane has inherent, potentially life-threatening risks, but with proper training, experience, and “flying by the numbers,” it is safe. A lead extraction performed in an organized, step-by-step manner, following known principles and proven guidelines, is similar. The antithesis is “flying by the seat of your pants” or extracting a lead in a reckless, cavalier fashion, hoping for the best. While reading this section, remember that life-threatening complications are rare. During the evolution of lead extraction, the EP community and surgeons helped define the procedures, techniques, and approaches to minimize and ultimately eliminate complications of all types. The material presented represents more than 25 years of experiences that form the basis for current lead extraction procedures. TRANSVENOUS APPROACHES Lead Vein Entry Site A transvenous approach through the lead vein entry site is a natural approach. After the pocket debridement procedure, which includes freeing the leads to near the vein entry site, it is natural to continue and remove the lead from this site. In some situations, the lead is broken or cut and retracted into the axillary-subclavian-brachiocephalic veins. If this lead can be grasped by an instrument passed into the vein and exteriorized, it is then considered to be a lead passing through the vein entry site, for purposes of this discussion. The lead can be extracted by direct traction, if applicable, or by a mechanical or powered telescopic sheath. Most extractors currently use this natural approach. Working through the vein entry site is efficient and subjects the patient and physician to the least amount of radiation, with the fewest maneuvers and least time required. Radiation exposure is related to the amount of fluoroscopy time. Also, once the lead is removed, a new lead may be readily inserted through the conduit created during the extraction. As previously discussed, direct traction is applied by pulling directly on the lead manually, with a suture or locking stylet or both. Indirect traction refers to grasping the lead with a snare and applying traction by the snare. Some leads are easily removed by direct traction. The vein entry site is not always easily accessed. In some situations, the lead is entrapped in calcified encapsulating tissue and cannot be entered using the nonmetal extraction sheaths, with or without power. The cause of the calcified encapsulating tissue at the vein site is usually related to introducer technique. If the introducer needle scores the clavicle or first rib, elevating the periosteum, the periosteum will re-form about the lead, entrapping it in a bone sheath. If the introducer needle passes through the costoclavicular ligament, this damaged tissue will mineralize and entrap the lead. Natural maturation of a thrombus into fibrous tissue, which mineralizes with time, also may create this problem. Usually, however, the problem is associated with the periosteum and costoclavicular ligament, and metal sheaths are used. Telescoping stainless steel sheaths look dangerous but are safe and effective if properly used (see Fig. 26-13, C). The principle is simple: keep the sheaths “tracking true” over the lead, and apply the force needed to destroy this tissue. A combination of pushing and rotation of the beveled tip is most effective. Once the metal sheaths break into the vein, they are removed and replaced by plastic extraction sheaths. “Tracking true” is a principle used for all sheath maneuvers. All sheath

maneuvering must be performed under fluoroscopy, to ensure that the sheaths are tracking over the lead. Any kinking or other deviation of the vein course is dangerous. It creates a false passage that may be extravascular and may damage nearby structures. Complications.  Telescoping sheaths use a combination of countertraction, counterpressure, and tissue ablation (powered sheaths) to maneuver past the intravenous and intracardiac binding sites to the heart wall. These techniques, used with various types of sheaths, have already been described in detail. The maneuvering of these sheaths over the lead and down to the heart is separated into the three anatomic regions: axillary-subclavian-brachiocephalic veins, SVC, and intracardiac. This is the most dangerous portion of the procedure, and a detailed understanding of the issues unique to these three regions is essential for a safe and successful lead extraction. Complications associated with lead extraction involving loss of vein or heart wall integrity are tearing (including bone spicules), avulsion, rupturing, penetration, embedding of lead into the wall, and exclusion of the lead from the vascular space. The sequelae of these events are related to the anatomy of the region. The presence of fibrous tissue must be included when considering the anatomy of the region. Inflammatory reaction and the resultant fibrous tissue formation increase the tensile strength of the tissue. For example, a dissecting arterial hematoma or pericardial effusion is rarely seen in patients with previous OHS, because scar tissue has the positive effect of reinforcing the tensile strength of the surrounding tissue. The forces required to tear aorta, subclavian, or innominate arteries or heart wall reinforced with scar tissue exceed those normally applied during lead extraction. The axillary veins are surrounded by soft tissue on both sides, and the loss of vein wall integrity causes a low-pressure extravasation of blood, which is usually of no consequence. The subclavian-brachiocephalic veins are surrounded by structures that, if damaged, could lead to lifethreatening consequences. On the left side, the vein is contiguous with the subclavian artery and aorta. During an inflammatory reaction, if the lead becomes embedded in the vein wall and involves the wall of the subclavian artery, innominate artery, or aorta, passage of extraction sheaths over the lead could tear these contiguous vessels, causing an arteriovenous fistula or a dissecting hematoma or both. The arteriovenous fistula could cause high-output heart failure, and the dissecting hematoma could cause major blood loss. If the hematoma ruptures into the left thoracic cavity, the resultant hemorrhage could be lethal. Immediate surgical intervention is required for a dissecting hematoma. An emergency median sternotomy provides satisfactory surgical exposure. If time permits, a minimally invasive approach may be preferable, especially for correction of a small arteriovenous fistula. Also on the left side, it is common to maneuver in and out of the subclavian-brachiocephalic veins, causing low-pressure extravasation. After vein occlusion and organization, frequently all that is left is an atretic, encapsulating fibrous tissue sheath (sometimes mineralized). For a single lead, the telescoping sheaths may be larger than the circumference of this fibrous tissue sheath, and the entire capsule may be included, along with the lead in the telescoping sheaths. If two or more leads are present, the circumference of the telescoping sheaths will remove at least one wall of the encapsulating sheath entirely or in segments. The resulting extravasation is not clinically significant with reasonable venous pressures. In exception cases in which the venous pressure reaches a systemic level of 70 to 90 mm Hg, a dissecting hematoma would ensue, causing the same clinical scenario as described earlier. The right-sided vein is contiguous with the right pleura. If the encapsulating fibrous tissue and embedded lead constitute the inferior vein wall, a tear in the pleura will result in hemorrhage into the right thoracic cavity. This can be lethal without immediate surgical intervention. The area is difficult to reach through a median sternotomy or an anterior thoracotomy. Because of the time constraints, a median sternotomy with elevation of the clavicle and right anterior chest wall is radical but provides adequate exposure. In less urgent situations, the patient may be repositioned for a less extensive approach. Venous



bleeding into the right chest, if not massive, can be insidious, and may not be recognized until the onset of cardiovascular collapse. It is not painful, and the signs and symptoms associated with blood volume depletion can be masked by anesthesia or by increased catecholamines compensating for the low filling pressures. With sufficient blood loss, compensation is no longer possible, blood pressure falls, metabolic acidosis develops, and cardiovascular collapse ensues. The SVC passes from the brachiocephalic veins to the right atrium. Along the upper half of the SVC, the lateral surface is contiguous with the right pleura, and the lower half is within the pericardium. Loss of integrity of the upper half results in blood loss into the right thoracic cavity; in the lower half, it causes cardiac tamponade. The sequelae of blood loss into the right chest are identical to those described for the right subclavian-brachiocephalic veins. In an emergency, a median sternotomy provides adequate exposure to either the upper or the lower half of the SVC. Cardiac Tamponade.  Bleeding into the pericardial space causes a cardiac tamponade (pathologic cardiac compression). Small amounts of blood (~200 mL), accumulating rapidly in the pericardium, will cause symptoms. Rapid accumulation increases ventricular wall compliance, decreasing filling of the ventricles and the resultant stroke volume. Rapidly accumulating blood in the pericardial space clots, whereas a slow accumulation does not. Clot formation can localize the compression, and some parts of the heart are more sensitive to compression than others. A 1-cm tear causes immediate tamponade with instantaneous decrease in systolic pressure. A precipitous drop of systolic blood pressure with failure to recover within 2 to 3 minutes is an emergency requiring immediate surgical intervention. The patient and operating field are then prepared for a median sternotomy. The TEE is usually definite, but if it is not, and no other cause is apparent, a tamponade must be considered the cause. The time constraints force a decision to be made within 2 to 3 minutes to prevent irreversible brain damage. A median sternotomy is used to decompress the pericardium, manually remove the clot, and surgically repair the tear. Needle aspiration and tube drainage are ineffectual for removing clot. A tear in the lower half of the SVC measuring 2 mm is an example of a slow-onset pericardial effusion. A slow onset of tamponade, while maintaining a blood pressure, allows more time to confirm the tamponade and to make the decision of whether to use a less invasive pericardial drainage procedure. Pericardial drainage tubes inserted into a pericardial effusion are therapeutic in relieving the compression, with immediate restoration of blood pressure. It provides a drainage system for monitoring bleeding and in some cases for blood replacement, cell saver, or direct reinfusion, and it buys time to set up for a corrective surgical procedure. A rushed insertion of a percutaneous pericardial tube without an effusion being present can be a disaster. This is especially true in an enlarged heart if the diaphragm is penetrated and torn during insertion of the tube, creating the need for surgical correction. The safest approach is through a small, subxyphoid incision that opens the pericardium under direct vision. Although the incision is slightly larger than for a percutaneous approach, it is safe. Other conditions mimicking a tamponade are mechanical occlusion of the SVC, lead traction applied to the RV wall decreasing compliance and filling, tachyarrhythmia, and metabolic acidosis from poor perfusion. Reflex therapeutic actions for a drop in blood pressure during lead removal include pausing lead extraction maneuvers (including lead traction), immediate IV administration of a vasopressor (phenylephrine or norepinephrine), cardioversion of arrhythmias, and administration of sodium bicarbonate in patients with low cardiac output. These reflex actions are used throughout any procedure, at any time, to compensate for transient decreases in filling pressure from the causes mentioned. They should be considered routine maintenance and not emergency treatment. Loss of Wall Integrity.  The right atrium and right ventricle are also contained within the pericardium, and loss of wall integrity from a

26  Techniques and Devices for Lead Extraction

765

penetration, tear, or tissue avulsion can cause cardiac tamponade as described earlier. The treatment is the same. There are four mechanisms for tearing the wall not previously discussed: bone spicule laceration of the right atrium, chronic penetration of the right ventricle, fibrous tissue between the electrode and the heart wall, and size disparity between the electrode and the sheath. The first mechanism involves a variation of the encapsulating tissue seen only in some extreme cases of mineralization. An example is a large silicone lead (>10F) that was in place for more than 20 years and making contact with the inferolateral atrial wall. The encapsulating tissue was completely mineralized, with “bonelike spicules” embedded within the wall. With any traction on the encapsulating sheath, the spicules act as a knife blade, causing a surgical incision in the wall. This scenario is rare. It has not been seen with any of the silicone leads manufactured since the late 1970s. To be safe, a lead bound to the lateral wall of the atrium should be removed with caution. A second mechanism involves the application of countertraction in removing a lead from the ventricular wall. For example, an ICD lead implanted for 12 years is attached to the thin anterior wall of the right ventricle. The tissue at the electrode removed during the extraction contains epicardial fat, indicating a defect in the ventricular wall and suggesting that the electrode had penetrated the wall, most likely during implantation. Unless the lead has perforated and is positioned within the pericardial space, it is undetectable. Fortunately, this is a rare occurrence. A third mechanism that could tear the heart wall involves a band of tissue attached to the extracted electrode that is still connected to the heart wall. Continued traction on the freed lead could avulse the tissue or tear the heart wall. When this is seen, the sheath (preferably powered) is maneuvered until the band is cut. With mechanical sheaths, care must be taken with the force used to break the band. This mechanism is readily seen on fluoroscopy, and once recognized, care is taken. A fourth mechanism in loss of wall integrity is caused by a large size disparity between the extraction sheath and the lead. Although this mechanism has been reported, it is rare. If an attempt is made to apply countertraction with a sheath larger than the lead, the electrode and the ventricular wall both will be pulled into the sheath, potentially tearing the wall. Once the ventricular wall tissue is pulled into the sheath, it becomes a form of direct traction and not countertraction. For this to occur, the size difference between the lead and the sheath must be sufficient to accommodate the electrode-tissue mass. The cardiac tissue being pulled into the sheath cannot be seen. The only protection is avoiding large size differences between the lead and the sheath. Unfortunately, this is not always possible. For example, the smallest laser sheath is 12F with a 16F outer sheath, so extracting a 4F lead involves a sizable mismatch, and care must be taken. Also, a 9F sheath may need to be changed to an 11F sheath to include calcified encapsulating tissue, resulting in a size mismatch during countertraction. Summary.  Today, the vast majority of leads are successfully removed through the vein entry site. The current procedures and extraction tools provide a safe, reliable, and effective method of removing these leads from most of the pathologic environments created at the biophysical interface. Recognizing the limits of an extraction approach (e.g., a dangerous situation) and changing to a more appropriate, safe approach is the key to eliminating complications. A national lead extraction database no longer exists, and extraction data are now kept by individual practitioners. Individual data are considered anecdotal, and the data from one individual cannot be extrapolated to another. These comments apply to most of the lead extraction discussions. Remote Vein Sites A remote vein site is a vein other than the lead vein entry site. A remote vein site requires a remote instrument, such as some type of snare, to manipulate the lead. The femoral vein was the first remote vein site used. During the early evolution of lead extraction, removing leads with mechanical sheaths from the superior veins through the vein

766

SECTION 3  Implantation Techniques

entry site was frequently a failure and potentially dangerous. A more difficult approach through a femoral or other remote vein site was more effective and safer. The problems were related to maneuvering the long, telescoping mechanical sheaths from the femoral vein to the heart wall and the complexities associated with grasping the lead body. With the advent of powered sheaths, the safety and efficacy of removing leads from the vein entry site improved dramatically. Although most of the leads can be removed from the vein entry site, there are still dangerous situations and lead breakages. In these cases, a remote vein or a transatrial surgical procedure are the only options. In many cases, the femoral vein approach is still the best remote vein approach. However, other remote veins (contralateral external jugular, internal jugular, or axillary-subclavian-brachiocephalic) may be more suitable and easier to use. Some physicians have developed combination approaches, applying mechanical sheaths from both the vein entry site and a remote vein site. This combination constitutes a safe and efficacious approach, as developed by Bongiorni et al.,22 and has become increasingly popular, particularly when the need for reimplantation through the original venous access is no longer required. For cases such as lead breakage, use of a snare to grasp the lead and the subsequent removal of the lead using direct traction or a powered sheath is advantageous. Powered sheaths are not long enough in moderately tall patients for a femoral approach. Consequently, these approaches are confined to the superior veins, via both remote and vein entry sites. The techniques used involve manipulation of snares to grasp the lead body. Although these techniques are simple in principle, they can be difficult to achieve in a timely fashion. Initially, there were no snares designed for lead removal, so a suitable off-the-shelf snare designed for other purposes (“off-label”) had to be found. The criteria for such a snare included the tensile strength to withstand the forces applied during lead extraction, safety of the surrounding tissue when maneuvering the snare, and reversibility of the grasping mechanism. The Dotter snare was the first snare to meet the tensile strength requirements. When the Dotter snare was combined with the Cook deflection snare, the safety and reversibility requirements were met. Later, two snares were manufactured meeting these requirements: Cook Needle’s Eye Snare and Amplatz Goose Neck Snare, which are still in use (see earlier discussion). Angled, pigtailed angiographic catheters, endsnares, bioptomes, and every conceivable catheter has been used to good effect for some patients. Thus the principles of use are more important rather than the precise tool. A classification of remote vein approaches deviates from the historic use of the IVC (femoral vein) approach. A natural classification is to employ the removed vein (e.g., femoral approach, internal jugular approach). Remote vein site use is discussed here based on this natural classification. The goal is the same as for the vein entry discussion: to define the approach, procedure techniques, and expected results in relation to the pathology and pathophysiology associated with the implanted lead. Femoral Approach As discussed earlier, before the advent of powered sheaths, the femoral approach was used extensively. The indications for its use were failure to extract leads from the superior veins by any technique, lead breakage, and avoidance of the application of excessive force with the mechanical sheaths. The techniques used have not evolved significantly over the past 15 years. The transvenous approach through a femoral vein requires a special sheath set (e.g., Byrd WorkStation) that functions as an introducer, as a workstation for manipulation of snares, and as countertraction sheaths (Fig. 26-23). The set consists of an introducer needle, a guidewire, a 16F workstation, an 11F tapered dilator, an 11F telescoping sheath, a Cook deflection snare, and a Dotter basket snare. The workstation serves many functions. Initially, it acts as a protective sheath. The outer sheath prevents the insertion, withdrawal, and manipulation of the inner sheath and snares from damaging the veins or heart. To prevent clot formation, the workstation has a valve (Check-Flo) to continuously irrigate the sheath. The workstation and

Figure 26-23  Byrd Femoral WorkStation (Cook). Telescoping sheaths are passed to the heart. The outer sheath functions as a workstation protecting the vein and heart wall during maneuvering of  the inner sheath. Once the lead is secured by the reversible loop, the sheaths are advanced to the electrode to apply countertraction. The workstation is packaged with telescoping sheaths, guidewire, and dilator to be inserted as an introducer. The dilator is removed and the snares inserted.

snares form a reversible loop to pull the proximal portion of the lead out of the superior veins; the workstation also acts as the outer telescoping countertraction sheath. The safe insertion and removal of the workstation is a prerequisite for an extraction procedure through a femoral vein. The workstation is 16F and must be inserted with care. Fluoroscopic monitoring is mandatory. Once the guidewire is passed into the heart, the workstation with its tapered dilator must be maneuvered through the iliac vein and IVC and into the right atrium. The route can be circuitous, especially from the left side. In rare cases, the curvature may be too sharp for the stiff dilator to follow the guidewire. Forcing the dilator in this situation is unsafe, and the approach should be abandoned. A torn retroperitoneal iliac vein or IVC is a serious complication. Once the workstation is inserted, irrigation fluids are run continuously through the Check-Flo valve to prevent clotting. Pulling leads down and out of the superior veins has been remarkably successful. Many leads freed from the heart cannot be pulled up through these same veins. The lead binding forces caused by the circumferential bands of fibrous tissue are the same in both directions. The hypothesis for this difference is the free upward mobility of the mediastinal structures and the inability to pull the superior veins downward. The mediastinum is easily pulled upward, compressing the veins. This compression of the fibrous tissue bands around the lead as they bunch together is postulated to increase the binding strength. The superior veins cannot be pulled downward, and irreversible lead slippage through the binding sites is not an issue. Cardiac function is not influenced by pulling leads downward out of the superior veins. Failure to extract the proximal lead from the superior veins using this technique is rare and usually caused by other complicating factors, such as thrombosis of the superior veins and excessive fibrosis around the lead caused by a previous extraction attempt that left the conductor coil exposed or pulled the lead taut against the heart and vein wall. Such leads are removed using approaches (e.g., transatrial) reserved for more complicated extractions. To apply countertraction through the workstation, the proximal end of the lead must be entangled in the basket snare. This is accomplished by placing the basket snare close to the lead and rotating it slowly. The lead will flip into the basket. The basket closes when the 11F sheath is advanced over the snare. For most leads, the snare and lead are pulled into the 11F sheath. The workstation and 11F sheaths are then worked in a telescoping fashion to a point near the electrode. At this point,



countertraction is applied to extract the electrode, as previously described. Removal of the workstation must be carefully performed. Once the lead is extracted, clot and debris may be attached to the end of the tubing. If this material dislodges in the femoral vein entry site, it can act as a nidus, forming a thrombus or initiating thrombophlebitis and its sequelae. To prevent this complication, blood is aspirated during the withdrawal of the workstation. If the entry site does not bleed freely after withdrawal of the workstation, a surgical exploration of the vein is recommended. Bleeding is controlled by applying pressure over the vein entry site after withdrawal of the sheath and during Valsalva maneuvers induced by the anesthesiologist. A suture or staple is required to close the skin. A potential complication is thrombophlebitis and pulmonary embolus. Concern about this complication was the incentive for the workstation. Postoperatively, anti-embolic stockings (pneumatic, if possible) and subcutaneous heparin (5000 units twice daily) are the only precautions taken. The technique for grasping the lead in a reversible loop using a Cook deflection catheter and a Dotter snare or with other tools is more complicated. Once mastered, it is an effective method of performing precision extraction. For example, a patient may have six leads in the heart. Two new leads are connected to a pacemaker and are to be saved. Four leads are abandoned and are to be extracted. The abandoned atrial and ventricular leads can be extracted, leaving the newly implanted leads intact. The IVC approach allows this level of precision. Superior Vein Approaches The other transvenous approaches include the external, internal jugular, and axillary-subclavian-brachiocephalic veins, usually on the contralateral side. The telescoping sheaths used with the femoral approach are mechanical (powered sheaths are not available). The creation of a conduit by the powered sheaths from the vein entry site encourages the use of snares passed through these sheaths to remove leads (e.g., broken, free-floating leads). A snare is used to grasp the lead, and if needed, sheaths are passed over the snare to the lead. The difference is in the extraction tools available. For example, the femoral workstation is too long and is not applicable for the superior vein approaches. Using standard introducer techniques, a guidewire is inserted and telescoping mechanical sheaths are passed into the SVC or heart. These sheaths then act as a workstation for passage and manipulation of a snare. The same snares used for the femoral approach are usable with the superior vein approaches. The Needle’s Eye Snare has a shorter, simpler version for the superior veins. Once snared, the lead can be removed using indirect traction, mechanical sheaths, or powered sheaths. The noose snares are also effective from the superior approaches. All the principles and guidelines for lead extraction apply to these approaches. Combined Approaches To some degree, most remote approaches are a combination of a lead vein entry site and a femoral vein approach. An extensive effort may have been used to free the lead from the superior veins; this was always in preparation for the intended use of the remote approach. From its inception, some physicians championed the use of a combined approach. Initially, the vein entry approach and femoral vein approach were combined, sometimes with two teams working, one for each approach. The goal was to free the lead by applying the extraction techniques from both approaches and removing the lead in an opportunistic fashion (the resultant easiest approach). The electrophysiologist might work from the vein entry site and a radiologist from the femoral vein site. Although successful, this approach was overkill for most lead extractions, especially once powered sheaths became available. A combination of the vein entry site approach and a right internal jugular approach is used by some physicians as their primary approach to lead extraction. They use snares and/or a grasping instrument passed through the internal jugular vein into the SVC to pull the lead out of the axillary-subclavian-brachiocephalic veins and, if

26  Techniques and Devices for Lead Extraction

767

necessary, to pull the lead into the atrium. Mechanical sheaths are then applied to complete the extraction (to date, powered sheaths are not used).23 The techniques used with remote approaches can be applied through the vein entry site. A lead may have broken or been cut, retracting into the axillary-subclavian-brachiocephalic veins, floating in the SVC or heart, or migrating into the pulmonary veins. If the lead can be reached and grasped inside the axillary-subclavian-brachiocephalic veins by a surgical instrument, it can be pulled out of the vein entry site and secured with a suture or a locking stylet, or both. The lead can then be extracted using the vein entry approach. If the lead cannot be grasped by an instrument but a snare can be passed into the SVC from the vein entry site or a contralateral vein, the lead is grasped and removed using mechanical and/or powered sheaths. Before powered sheaths became available, the femoral approach was common, but now it is rarely used. Surgical electrophysiologists have the transatrial approach as a viable alternative. Regardless of the frequency of use today, the transfemoral approach is a requisite procedure for managing device-related complications. Retaining Superior Access with Femoral Snares.  Often, the superior access is required for reimplantation, but the subclavian system is occluded. Even so, remarkably, the lead easily slides out without the ability to advance the extraction sheath past the area of occlusion. Reimplantation access is then thwarted. However, the use of a snare, usually an Amplatz Goose Neck, provides traction on the lead during advancement of the extraction sheath to the level of the right atrium, permitting advancement of a guidewire for access through the sheath after the lead removal.24 SURGICAL APPROACHES The surgical approach to lead extraction is a cardiac surgical procedure. The three procedures used for transvenous endocardial implants are the transatrial approach, right ventriculotomy, and an open-heart procedure using cardiopulmonary bypass (CPB). These procedures should be performed only by experienced cardiac surgeons. The technical and patient management skills of an experienced cardiac surgeon negate the normal risk associated with the complexity of the surgical procedure. The transatrial procedure is a general procedure that can be used for both extraction and implantation of leads. It can be used instead of the transvenous remote approach for lead extraction. It has the added advantage of being an implantation site that bypasses the SVC and IVC. The right ventriculotomy is a technique for removing leads from the right ventricle in special situations. Currently, an openheart procedure is reserved for removing thrombotic material (usually infected) from the right atrium and ventricle and for removing leads implanted in the left ventricle. Transatrial Approach The transatrial approach, first described by Byrd in 1985, is a surgical EP procedure suitable for intracardiac implantation, explantation, and ablation procedures.25 The only disadvantages are the morbidity associated with surgical thoracic pain and the need for a medical electrophysiologist to work with a cardiac surgeon. It is a primary approach for noninfected patients who are candidates for a transatrial lead implantation. Younger patients with occlusion of one brachiocephalic vein or with SVC syndrome have the old leads extracted through a transatrial approach, followed by implantation of new leads. The advantage of the transatrial approach is the ability to remove leads that are not accessible or removable by the SVC or IVC approach. Most of the transatrial extractions are failures of the IVC approach. Rarely, failure of an SVC approach will lead directly to a transatrial approach (e.g., when the workstation cannot be passed through the femoral veins into the heart). Infected patients who are candidates for transatrial lead implants will have the leads extracted by an SVC or IVC approach and the transatrial implantation done after the infection is properly treated.

768

SECTION 3  Implantation Techniques

by 1 or 2 days, compared with a transvenous procedure. Patients must be managed in an intensive care setting until the thoracic pain sequelae are controlled. Right Ventriculotomy

Figure 26-24  Transatrial approach. This is a minimally invasive cardiac surgical approach. The third or fourth cartilage is removed, and a purse-string suture is placed in the right atrium. A pituitary rongeur is inserted through the atriotomy incision and used to grasp the lead. The proximal portion of the lead body is removed from the superior veins by direct traction, and the distal lead is removed by mechanical or powered sheaths and countertraction.

A right ventriculotomy is a cardiovascular surgical procedure. This approach is rare. Because this procedure is virtually unknown, a cursory discussion of indications for use is in order. Initially, it was reserved for infected broken leads retained in the right ventricle that were not reachable by the other approaches. These are fragile leads that break near the ventricular wall or within a fibrous tissue tunnel along the ventricular wall and are impossible to grasp using transvenous or transatrial techniques. It is also used with lead penetration requiring lead removal and a repair of the heart wall, and possibly for an emergency tear in the ventricular wall caused by an attempt to remove a lead. In the latter, the defect is turned into a ventriculotomy site for lead extraction. The first ventriculotomy procedures were performed by Byrd in the late 1980s. The heart is exposed through a median sternotomy incision. The heart is then elevated on a pad, exposing the right ventricle. The tip of the electrode is localized by fluoroscopy and by using needles for triangulation of the electrode. A purse-string suture is placed around the electrode, and a ventriculotomy incision is made to the electrode. The electrode is grasped with a clamp and pulled out of the heart. Because the lead segment is being pulled in the direction of the tines, the tines slip out of the embedding scar without resistance. At present, the procedure is performed through a minimally invasive incision on the anterior surface of the left chest through the fifth intercostal space. The purse-string and extraction techniques are the same. This is a stressful procedure for the surgeon, and number of procedures performed to acquire some comfort level is unknown. As long as a need exists for right ventriculotomy, attempts will continue to perfect it. Open-Heart Procedure

The transatrial approach is performed as originally described, through a limited surgical incision on the right anterior chest wall (Fig. 26-24). The right atrium is exposed by removal of the third or fourth right costal cartilage (determined by fluoroscopy). The pericardium is opened and suspended, and a pledgeted purse-string suture is placed in the right atrium. If the pericardium has been obliterated from a previous procedure or disease process, a small region of the lateral wall of the right atrium is dissected free. Using fluoroscopy, a pituitary biopsy instrument is inserted through the purse-string. The lead body is grasped in the atrium and pulled out. The lead is then cut, extracting the proximal and distal segments separately. The proximal portion of the lead can usually be pulled out by direct traction. The only limitation to the force employed is the tensile strength of the lead. In occasional cases where the tensile strength is insufficient, telescoping powered sheaths may be required. The distal segment is extracted by inserting a locking stylet, advancing telescoping powered sheaths to the wall, and removing the electrode from the wall using countertraction. This procedure is repeated for each lead to be extracted. On completion of the lead extraction, the atriotomy site is used to insert new leads, or to perform another EP procedure, or the purse-string suture is tightened, tied, and abandoned. After transatrial extraction, patient management is more involved than for the transvenous extraction techniques. The pericardium must be drained, in most cases by a closed-drainage system such as a chest tube, if the pleural space is free; by a mediastinal tube, if the pleural space is obliterated; or by a Jackson-Pratt closed-drainage system, if both the pleural and pericardial spaces are obliterated. The thoracic cavity is occasionally entered and a chest tube inserted to drain both the pericardium and the pleura. These drainage tubes are removed in 2 to 3 days. The procedure-related morbidity increases the hospital stay

The concept of using CPB to perform an open-heart procedure is intuitively obvious. It is a standard cardiac surgical procedure involving a median sternotomy incision. Right-sided leads were initially removed by direct traction and under direct vision during OHS. Transvenous and transatrial lead extraction techniques evolved to eliminate the need for an OHS procedure. Implantation of leads in the left atrium and ventricle is a notable exception (Fig. 26-25). Leads are implanted into the left ventricle in two ways: through a congenital atrial or ventricular septal defect or retrograde through the aortic valve. All physicians consider the presence of left-sided leads and embolic symptoms an urgent indication for lead removal. Most consider their presence, with the potential for a complication, to be an urgent indication for lead extraction. A few physicians believe that, in the absence of complications (cerebrovascular accident, coronary artery occlusion, infarction of another organ, or sequelae of peripheral embolus), leaving the leads intact is an acceptable option. The rationale is that the extraction procedure is more dangerous than the presence of left-sided leads. The views on lead removal are just as varied. Some believe the leads should be removed; the chambers debrided of vegetation; and congenital defects, if present, repaired with CPB. Others think it is safe to extract the leads using the established right-sided techniques and protecting the brain from emboli by compressing the carotid arteries when necessary. If the second approach has any merit, it would be in removing newly implanted leads. If the newly implanted leads are proved to be free of vegetation and the procedure is monitored using TEE, it is probably safe to extract using direct traction. Specific data are not available on the numbers of physicians using these opinions. Byrd’s experience is based on the management of 10 consecutive patients, most of whom had chronic leads and were symptomatic. Symptoms included transient ischemic attack and/or cerebrovascular accident, and vegetation was apparent in symptomatic patients. All



26  Techniques and Devices for Lead Extraction

769

Atrial septal defect (sinus venosus defect)

Left atrial ventricular lead implantation

Lead extraction, repair ASD, and transatrial implant

Figure 26-25  Left-sided implantation. Transvenous implantation in the left atrium and/or ventricle or a transarterial implantation through the aortic valve into the left ventricle is rare. Left, Transvenous implantation through an atrial septal defect (ASD), such as a sinus venosus defect, is the most common approach. The anatomy guides the leads into the left atrium. Extraction of these leads is dangerous because of the potential for an arterial embolization of debris. Right, We perform these procedures with the use of cardiopulmonary bypass, repairing the congenital defect after lead extraction. After extraction, the left ventricle is monitored by transesophageal echocardiography, and all debris is removed through an incision in the aorta before bypass support is removed. The new pacemaker or ICD is implanted transatrially to avoid passing the lead through the junction of the superior vena cava and atrium.

but one patient had leads passing from right to left through an atrial septal defect. One patient had a lead that was implanted through the subclavian artery and passed retrograde through the aortic valve into the left ventricle. The procedure included establishing CPB, using cardioplegia to stop ventricular contraction, cross-clamping the aorta as needed, extracting the leads using conventional tools, debriding the chambers, repairing the septal defects, continuously observing the left atrium and ventricle by TEE, and carefully restarting the heart with protection from inadvertent ejection of embolic material. A new transatrial right-sided implantation was performed off bypass with the use of fluoroscopy and the conventional approach. With this technique, all leads were removed, the congenital defects repaired, and the new devices implanted without sequelae. Developing a safe technique that does not use an OHS procedure would be difficult.

Special Situations The most challenging development in lead extraction is related to the placement of leads into the coronary sinus (CS) and cardiac veins. Cardiac resynchronization therapy (CRT) has made this a common and evolving issue. The short-term outcomes thus far when extracting these leads have not been noteworthy, partly because of the short implantation durations and the simple, extraction-friendly design of the leads. Smooth, thin, single diameter, and unipolar with good tensile properties are all characteristics that enhance the safe and quick removal of the leads. However, because of concerns with their stability in the cardiac veins, these leads have been developed into more complicated shapes, with multipolar design and fixation mechanisms, and are unlikely to be easily removed.

To evaluate extraction tools and a novel lead design technique for reducing the barriers to extraction of complicated leads, Wilkoff et al.26 used a sheep model with atrial defibrillator leads placed in the CS to the great cardiac vein. The leads, originally designed for atrial defibrillation in the Metrix atrial defibrillator (InControl, Redmond, Wash.), were modified but kept their pigtail configuration for lead stability. Three configurations—one without modification of the defibrillation coil, one with medical adhesive backfill under the defibrillation coil, and one covered with an expanded polytetrafluoroethylene polymer (ePTFE)—were implanted in sheep and were subjected to extraction at either 6 or 14 months. The model proved to be excellent for developing profound fibrosis, and the unmodified leads were almost impossible to remove without hemopericardium. The medical adhesive backfill was much better, and there was almost no trouble removing the ePTFE-covered leads. The study also demonstrated that laser sheaths were dangerous in the CS, because the sheath approximated the size of the vein; a special 7F electrosurgical extraction sheath was relatively much safer to use. During the procedures, the electrosurgical sheath was rotated away from the pericardial and toward the myocardial surface. Although CS lead extraction has not yet become a clinical issue, implanters should make sound decisions now that promote the extraction of these leads. From the sheep experience, implanters should avoid construction that allows for tissue ingrowth. In some cases, significant ingrowth around CS leads clearly makes extraction more difficult. This is particularly true in patients with the new Starfix (Medtronic) leads, which are designed to increase fibrosis to affix the lead to the intended vein position. The ingrowth of the fibrotic tissue into any lead, but especially in this lead, will make the long-term extraction experience much more challenging and potentially life threatening (Fig. 26-26).

770

SECTION 3  Implantation Techniques

A

B

Figure 26-26  Coronary sinus (CS) fibrosis. Even non-Starfix leads may result in intense fibrosis in the CS. A, Non-Starfix pacing lead extracted from the CS. The use of laser was needed proximal to the CS. Note intense fibrosis at the end of the lead and also part of the vein trailing.  B, Extracted Starfix lead. Note intense fibrosis around the anchoring mechanism.

Conclusion Transvenous lead extraction has become part of standard CIED management. Although the procedure is associated with potentially lifethreatening complications, the risk of these complications is low when the procedure is performed according to the standards presented here

and as specified in the HRS consensus document. When complications arise, the outcome for the patient is directly related to the performance of the entire extraction team. A systematic and team approach to transvenous lead extraction is the key to quality outcomes, and monitoring quality measures is the only way to assess the performance of the program and provide continuous improvement.

REFERENCES 1. Wilkoff BL, Love CJ, Byrd CL, et al: Transvenous lead extraction. Heart Rhythm Society Expert Consensus on Facilities, Training, Indications, and Patient Management (endorsed by American Heart Association). Heart Rhythm 6:1085-1104, 2009. 2. Byrd CL, Schwartz SJ, Hedin N: Intravascular techniques for extraction of permanent pacemaker leads. J Thorac Cardiovasc Surg 101:989-997, 1991. 3. Byrd CL: Advances in device lead extraction. Curr Cardiol Rep 3:324, 2001. 4. Byrd CL: Extraction of transvenous pacing leads. Am Heart J 124:1667-1668, 1992. 5. Chamis AL, Peterson GE, Cabell CH, et al: Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation 104:1029-1033, 2001. 6. Chua JD, Wilkoff BL, Lee I, et al: Diagnosis and management of infections involving implantable electrophysiologic cardiac devices. Ann Intern Med 133:604-608, 2000. 7. Chan AW, Bhatt DL, Wilkoff BL, et al: Percutaneous treatment for pacemaker-associated superior vena cava syndrome. Pacing Clin Electrophysiol 25:1628-1633, 2002. 8. Suga C, Hayes DL, Hyberger LK, et al: Is there an adverse outcome from abandoned pacing leads? J Interv Card Electrophysiol 4:493499, 2000. 9. Smith HJ, Fearnot NE, Byrd CL, et al: Five-years experience with intravascular lead extraction. U.S. Lead Extraction Database. Pacing Clin Electrophysiol 17:2016-2020, 1994. 10. Fearnot NE, Smith HJ, Goode LB, et al: Intravascular lead extraction using locking stylets, sheaths, and other techniques. Pacing Clin Electrophysiol 13:1864-1870, 1990. 11. Byrd CL, Schwartz SJ, Hedin NB, et al: Intravascular lead extraction using locking stylets and sheaths. Pacing Clin Electrophysiol 13:1871-1875, 1990.

12. Wazni O, Epstein LM, Carrillo RG, et al: Lead extraction in the contemporary setting: the LExICon study: an observational retrospective study of consecutive laser lead extractions. J Am Coll Cardiol 55:579-586, 2010. 13. Bilgutay AM, Jensen MK, Schmidt WR, et al: Incarceration of transvenous pacemaker electrode: removal by traction. Am Heart J 77:377-379, 1969. 14. Karagoz T, Celiker A, Hallioglu O, Ozme S: Unusual extraction of an active fixation ventricular pacing lead with outer coil fracture in a child. Europace 5:185-187, 2003. 15. Wilkoff BL, Byrd CL, Love CJ, et al: Pacemaker lead extraction with the laser sheath: results of the Pacing Lead Extraction with the Excimer Sheath (PLEXES) trial. J Am Coll Cardiol 33:16711676, 1999. 16. Epstein LM, Byrd CL, Wilkoff BL, et al: Initial experience with larger laser sheaths for the removal of transvenous pacemaker and implantable defibrillator leads. Circulation 100:516-525, 1999. 17. Saad EB, Saliba WI, Schweikert RA, et al: Nonthoracotomy implantable defibrillator lead extraction: results and comparison with extraction of pacemaker leads. Pacing Clin Electrophysiol 26:1944-1950, 2003. 18. Byrd CL, Wilkoff BL, Love CJ, et al: Clinical study of the laser sheath for lead extraction: the total experience in the United States. Pacing Clin Electrophysiol 25:804-808, 2002. 19. Kennergren C: Excimer laser assisted extraction of permanent pacemaker and ICD leads: present experiences of a European multi-centre study. Eur J Cardiothorac Surg 15:856-860, 1999. 20. Love C, Byrd C, Wilkoff BL, et al: Lead extraction using a bipolar electrosurgical dissection sheath: an interim report. Europace 3:223-228, 2001.

21. Hussein AA, Wilkoff BL, Martin DO, et al: Initial experience with the Evolution mechanical dilator sheath for lead extraction: safety and efficacy. Heart Rhythm 7:870-873, 2010. 22. Bongiorni MG, Di Cori A, Zucchelli G, et al: A modified transvenous single mechanical dilatation technique to remove a chronically implanted active-fixation coronary sinus pacing lead. Pacing Clin Electrophysiol 34:e66-e69, 2011. 23. Bongiorni MG, Giannola G, Arena G, et al: Pacing and implantable cardioverter-defibrillator transvenous lead extraction. Ital Heart J 6:261-266, 2005. 24. Fischer A, Love B, Hansalia R, et al: Transfemoral snaring and stabilization of pacemaker and defibrillator leads to maintain vascular access during lead extraction. Pacing Clin Electrophysiol 32:336-339, 2009. 25. Byrd CL, Schwartz SJ: Transatrial implantation of transvenous pacing leads as an alternative to implantation of epicardial leads. Pacing Clin Electrophysiol 13:1856-1859, 1990. 26. Wilkoff BL, Belott PH, Love CJ, et al: Improved extraction of ePTFE and medical adhesive modified defibrillation leads from the coronary sinus and great cardiac vein. Pacing Clin Electrophysiol 28:205-211, 2005. 27. Byrd CL, Wilkoff BL, Love CJ, et al: Intravascular extraction of problematic or infected permanent pacemaker leads: 1994-1996. U.S. Extraction Database, MED Institute. Pacing Clin Electrophysiol 22:1348-1357, 1999. 28. Kennergren C, Bucknall CA, Butter C, et al: Laser-assisted lead extraction: the European experience. Europace 9:651-656, 2007. 29. Neuzil P, Taborsky M, Rezek Z, et al: Pacemaker and ICD lead extraction with electrosurgical dissection sheaths and standard transvenous extraction systems: results of a randomized trial. Europace 9:98-104, 2007.

27  27

Imaging of Implantable Devices BRYAN BARANOWSKI  |  ELIZABETH VICKERS SAAREL  |  MINA K. CHUNG

Thoracic imaging (and occasionally abdominal imaging) plays an

important role in the implantation, maintenance, and removal of pacing and defibrillation systems. Many available contemporary modalities, including radiography, fluoroscopy, venography, echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI), are frequently used in the diagnosis and treatment of patients with pacemaker and implantable cardioverter-defibrillator (ICD) devices. The most common modalities used before, during, and after device implantation are radiography, fluoroscopy, and venography, critical tools for physicians who perform pacemaker and ICD surgery. In addition, echocardiography has widespread applications, ranging from confirmation of the acute procedural complication of cardiac rupture with cardiac tamponade to optimization of pacing in cardiac resynchronization therapy (CRT). CT imaging is primarily used in preoperative and postoperative settings to assess complex cardiac anatomy, especially in patients with corrected and uncorrected congenital heart conditions. In contrast, MRI may be used for preoperative assessment of cardiovascular anatomy but is more often employed for diagnosis of pathologic conditions outside the thoracic cavity. Its potential for electromagnetic interference with implanted pacemaker and ICD devices is discussed here.

Radiography Radiographs provide essential information about the location, type, and integrity of the pulse generators and leads of both pacing and defibrillation systems. X-ray films also provide basic details of patient anatomy. Interpretation of a chest radiograph should be focused and systematic, with examination of the bony structures, cardiac silhouette, lung fields, trachea, and aorta as well as the presence and location of all preexisting hardware, prosthetic valves, and valve rings or calcification (Fig. 27-1). Abdominal radiographs should be obtained when abdominal device implantation is anticipated. PREPROCEDURAL CHEST RADIOGRAPHY Preprocedural posteroanterior (PA) and lateral chest radiographs provide essential information about patient anatomy and help identify the location, type, and integrity of implanted lead and device hardware in patients with preexisting pacing and defibrillation systems. Identification of Patient Anatomy Chest wall deformities, such as scoliosis and kyphosis, can occasionally make the implantation of endovascular leads difficult because of distortion of venous and cardiac anatomy. Identification of massive cardiomegaly may influence the choice of lead length. Anomalies such as a right-sided aortic knob suggest the presence of congenital abnormalities, discussed later. Identification of Pacing and Defibrillation Systems It is important to identify the type and location of preexisting pacing or defibrillation systems, particularly in the significant and growing numbers of patients presenting for generator exchange, lead addition, lead extraction, or device upgrade. With expanding indications and longevity of patients, a patient can have multiple functional and abandoned leads or even separate pacemaker and ICD devices. The type and position of the generators as well as the type, position, and integrity of all leads should be examined. A thorough examination requires

a PA as well as a lateral chest radiograph and, in the patient with an abdominally located device, an abdominal film. PACEMAKER/ICD PULSE GENERATORS AND IMPLANTABLE LOOP RECORDERS For transvenous systems, the pulse generator is typically located in the subcutaneous, prepectoral region caudal to the clavicle, overlying the pectoralis major muscle. In some patients, the device is located in a subpectoral or submammary position (Fig. 27-2). In pediatric patients and patients with older, larger ICD pulse generators or epicardial ICD lead systems, devices may be located in the abdomen, typically in the left upper quadrant and occasionally in the right upper quadrant or epigastrium (Fig. 27-3). Although most pulse generators are implanted in the subcutaneous region in adult patients, many have been implanted below the rectus abdominis muscle in children and younger women. The pulse generator is also generally implanted abdominally in patients in whom a femoral vein approach is required (Fig. 27-4). The generator manufacturer and type can be identified from radiography. Most pacemaker and ICD pulse generators have a radiopaque code or logo identifying the manufacturer and model of the device (Figs. 27-5 and 27-6). If the manufacturer can be determined, the proper programmer can be selected. Most current manufacturer programmers can “auto-identify” the specific devices of that manufacturer. Manufacturer technical support divisions may be able to aid in identification of lead systems and devices and can often access device data, such as leads implanted, pacing or shocking configurations, and implant thresholds. Some patients may have both pacing and ICD systems, as well as leads or devices that originate from different manufacturers. Figure 27-7 shows the appearance of implantable loop recorders. The pacemaker or ICD connector block should be carefully examined radiographically. The connector pins should be advanced beyond the distal pin set-screw blocks (Fig. 27-8). It is usually difficult to determine radiographically whether set screws are in contact with the electrodes. Clues to the polarity of pacing pulse generators include the number and type of connector pins. Determining the type of connector pins (International Standard 1 [IS-1], 3.2-mm Voluntary Standard [VS]-1, 5- or 6-mm, or the new IS-4 connectors) before device replacement avoids an intraoperative discovery that a compatible device is not readily available for the exchange. Radiographically, detection of connector pins that appear longer than the conventional IS-1 pins should prompt checking of lead connector type. Migration of the pulse generator may be seen radiographically in older patients with loosened prepectoral fascia, patients who have lost significant amounts of weight, or with pulse generators implanted within larger areas of subcutaneous prepectoral fatty tissue.1 In patients who have symptoms associated with the current generator location, revision of the pocket or anchoring of the generator may be considered. The migration of the pulse generator may influence the sterile draping area before device replacements. PACING AND DEFIBRILLATION LEADS When planning lead revision and/or extraction, one should assess the types, location, and integrity of all leads radiographically. Higher radiographic penetration may be required to more clearly demonstrate lead components. Dislodgment can be identified and is aided

771

772

SECTION 3  Implantation Techniques

Jugular vein Rt. subclavian vein

Superior vena cava

Lt. subclavian vein Brachiocephalic veins Aortic arch

Pulmonic valve Right atrium appendage Aortic valve prosthesis Right atrium

Tricuspid annulus with ring in place

Apex Figure 27-1  Overlay of diagram on posteroanterior chest radiograph. Typical location for formation of subclavian veins, brachiocephalic veins, superior vena cava, and right atrium along with their associated osseous landmarks; Lt, left; Rt, right. (From Castle LW, Cook S: Pacemaker radiography. In Ellenbogen KA, Kay GN, Wilkoff BL, editors: Clinical cardiac pacing. Philadelphia, 1995, Saunders, p 538.)

by comparison with old films. Leads generally do not have manufacturerspecific, characteristic radiopaque identifiers, but radiography may provide clues to the lead type (active or passive fixation; unipolar or bipolar) and integrity.2 Venous Anatomy for Localization of Lead Positions Most pacemaker and ICD leads are inserted transvenously. The subclavian, axillary, and cephalic veins are most often used for lead insertion, with the internal or external jugular or femoral veins used rarely. The cephalic vein courses lateral to the biceps, continuing in a groove between the deltoid and pectoralis major muscles, then empties into the axillary vein (Fig. 27-9). The axillary vein drains the basilic and

brachial veins, coursing medially over the lateral margin of the first rib to become the subclavian vein under the clavicle. This marks the usual site for insertion of pacemaker or defibrillator leads (see Fig. 27-1). A change in the directionality of the lead can sometimes indicate the location of the venous insertion site or suture tie-down sleeve. A more lateral insertion site suggests a cephalic or lateral axillary insertion site. Medial insertions into the subclavian vein should be inspected for evidence of lead crush injuries. Lateral axillary insertion sites should be examined for excessive angulation. After entering the venous system, leads typically pass through the brachiocephalic veins, which are formed by the joining of the internal jugular and subclavian veins behind the head of the clavicle, to the superior vena cava (SVC), and then to the right atrium or right ventricle. In a small percentage of patients, a persistent left SVC is present and drains into the coronary sinus (see later).3 On preparation for a procedure requiring insertion of a new lead, peripheral subclavian and SVC venography can be helpful in anticipating the need for lead extraction or preparation of a new site for venous access because of venous occlusion or severe stenoses (Fig. 27-10). Chronic venous occlusion is often marked by the presence of venous collaterals. The coronary sinus (CS), which enters the inferior septal region of the right atrium, just anterior and superior to the opening of the inferior vena cava, receives most of the venous drainage of the heart (see Coronary Sinus Lead Positions). The main CS traverses the atrioventricular (AV) groove between the left atrium and left ventricle. Tributaries include the middle cardiac vein; posterior ventricular branch; posterolateral, lateral, and anterolateral marginal branches; and great cardiac vein, which is the extension of the CS beyond the takeoff of the left atrial oblique vein of Marshall. When the vein of Marshall is not present, the valve of Vieussens is used to define the interface of the CS and great cardiac vein. The posterior, posterolateral, and lateral branches of the CS are typical targets for left ventricular or biventricular pacing in CRT devices (see Chapter 22). Chest radiography can be essential in determining whether absence of clinical response to CRT is caused by inadequate lead position (e.g., lead placement in anterior branch) or lead dislodgment. The azygos vein, which enters the posterior wall of the SVC, is sometimes the target vessel for ICD coil-lead implantation in patients with high defibrillation threshold (DFT), as the vessel travels posteriorly behind the heart, providing an additional favorable “shock vector” option4 (Fig. 27-11; see also Fig. 27-4). Text continued on page 780

Figure 27-2  Transvenous pacemaker system in subpectoral position. Posteroanterior and lateral chest radiographs in child with congenital complete heart block and dual-chamber pacemaker.



27  Imaging of Implantable Devices

773

A

B Figure 27-3  Abdominal pacemaker and implantable cardioverter-defibrillator (ICD) systems. A, Posteroanterior and lateral chest radiographs of an abdominal pacemaker system with epicardial leads in a child with congenital heart disease. B, Abdominal ICD system with epicardial leads. Continued

774

SECTION 3  Implantation Techniques

C

D

E

F

Figure 27-3, cont’d  C to E, Abdominal ICD system with transvenous leads. F, Abdominal ICD lead system with an epicardial and a transvenous lead.



27  Imaging of Implantable Devices

775

A

B

C Figure 27-4  Implantable cardioverter-defibrillator with defibrillation leads, including azygos coil lead. The leads are inserted using a right femoral vein approach. A, Posteroanterior chest radiograph shows the coils of the dual-coil defibrillation-pace/sense lead are positioned in the right atrium and right ventricle. The second lead is placed in the azygos vein. B, Lateral chest radiograph demonstrates the posterior positioning of the azygos coil. C, Abdominal radiograph displays the leads tunneled from the right femoral vein access site to the ICD device pocket in located in the left upper quadrant.

776

SECTION 3  Implantation Techniques

MEDTRONIC

ST. JUDE MEDICAL

BIOTRONIK

BOSTON SCIENTIFIC

SORIN GUIDANT

A Figure 27-5  Pacing pulse generators and radiographic appearance. A, Dual-chamber pacemakers.



27  Imaging of Implantable Devices

777

CRT-P PACEMAKERS MEDTRONIC INSYNC III

ST. JUDE MEDICAL ANTHEM RF

B Figure 27-5, cont’d  B, Cardiac resynchronization therapy pacemakers (CRT-P) indicated for biventricular pacing. (Courtesy Medtronic, Minneapolis; St. Jude Medical, St. Paul, Minn; Guidant, Boston Scientific, Natick, Mass; Biotronik, Berlin; and ELA/Sorin, Milan.)

778

SECTION 3  Implantation Techniques

BOSTON SCIENTIFIC TELIGEN

MEDTRONIC VIRTUOSO AND SECURA

GUIDANT VITALITY MEDTRONIC MAXIMO VR

ST. JUDE FORTIFY VR WITH SJ4 LEAD HEADER

BIOTRONIK DR-T

ST. JUDE EPIC + DR

ELA ALTO 2 DR

A Figure 27-6  Implantable cardioverter-defibrillator (ICD) pulse generators and radiographic appearance. A, Single-chamber and dual-chamber ICD pulse generators.



27  Imaging of Implantable Devices BOSTON SCIENTIFIC COGNIS

779

ST. JUDE MEDICAL UNIFY

ST. JUDE EPIC HF GUIDANT RENEWAL 3 HF

MEDTRONIC CONCERTO AND CONSULTA BIOTRONIK LUMAX HF-T

MEDTRONIC INSYNC II MARQUIS SORIN OVATIO

B Figure 27-6, cont’d  B, Cardiac resynchronization therapy ICDs (CRT-D) indicated for biventricular pacing. Arrows denote manufacturer’s identification symbol. (Courtesy Guidant, Boston Scientific, Natick, Mass; St. Jude Medical, St. Paul, Minn; Medtronic, Minneapolis; Biotronik, Berlin; and ELA/Sorin, Milan.)

780

SECTION 3  Implantation Techniques

MEDTRONIC REVEAL XL

ST. JUDE MEDICAL SJM CONFIRM Figure 27-8  Examination of device for lead connector pin insertion into header. Pins can be visualized extending past the distal connector blocks (arrows).

Pacemaker Leads Besides identification of the venous and cardiac insertion sites of pacing leads, chest radiographs can help determine polarity and fixation types. A unipolar lead has a single electrode at the tip of the lead; a bipolar lead has two electrodes separated by a space. Active-fixation leads have screws that extend from the tip of the lead (Fig. 27-12, A). Passive-fixation leads have various types of tines that are radiolucent (cannot be visualized radiographically) (Fig. 27-12, B). Active-fixation leads may be fixed in the extended position or may have an extendable/ retractable screw. Different manufacturers denote extension of the latter with various markers (Fig. 27-13).

Figure 27-7  Implantable loop recorders. The Medtronic Reveal XT and St. Jude Medical SJM Confirm implantable loop recorders and corresponding radiographic appearance. (Courtesy Medtronic, Minneapolis, and St. Jude Medical, St. Paul, Minn.)

A

B

Atrial Lead Positions.  In patients who have not undergone cardiac surgery, most atrial leads are fixed to the right atrial (RA) appendage and will exhibit a J shape with an anteriorly directed curve on the lateral view.5 Patients who have undergone cardiac surgery may not have suitable RA appendage remnants for fixation. Lead placement is

C

Figure 27-9  Right upper-extremity axillary/subclavian venography showing typical venous anatomy. A, Venogram shows axillary vein. B, Digital subtraction image demonstrates axillary vein with entry of cephalic vein and coursing under the clavicle, where the axillary vein transitions to the subclavian vein. C, Bilateral upper-extremity venography shows patency of both subclavian veins and the superior vena cava.



27  Imaging of Implantable Devices

B

A

C

781

Right

Left

Figure 27-10  Peripheral venography demonstrating occlusion of subclavian vein. A, Left panel shows patency of left subclavian/brachiocephalic vein to superior vena cava. Right panel is peripheral right venogram demonstrating location of an occlusion (arrow) of the right subclavian vein with collateralization. B, Peripheral right venography showing occlusion of the right subclavian vein. C, Peripheral left venography in the same patient as in B, demonstrating occlusion of the left subclavian vein with extensive collateralization.

generally guided by optimization of electrical characteristics, such as sensing and pacing thresholds and lead fixation stability. Leads may be implanted laterally, septally, caudally, or cranially in the right atrium, generally requiring active-fixation leads. Although most pacing systems use one atrial lead, pacing for atrial arrhythmia suppression may incorporate alternative-site or dual-site pacing.6,7 Placements targeting Bachmann’s bundle or the RA septum typically display lead tips directed near the high septum of the right atrium.8,9 The CS or septum near the CS may also be targeted; leads placed in the CS generally exhibit a large, open posterior curve. Higher posterior crossings on lateral films may suggest passage of the lead through a patent foramen ovale or atrial septal defect to the left atrium or ventricle.10

Figure 27-11  Azygos vein occlusive venography. A balloon catheter was inserted near the origin of the azygos vein, to delineate its course before addition of a defibrillation coil, which was advanced to a position just above the diaphragm, behind the left ventricle. The atrial lead is in the upper left corner of the image, and the anterior or right ventricular defibrillation coil is in the lower portion. (Courtesy Kalyanam Shivkumar, MD, PhD.)

Ventricular Lead Positions.  Ventricular pacing leads have traditionally been targeted to the right ventricular apex (RVA). The lead should display some slack, particularly as it traverses and is lifted by the tricuspid valve. The RVA is generally located to the left of the spine on the PA view with a slight inferior direction. On the lateral view, the lead is usually directed anteriorly (Fig. 27-14), unless the septal aspect of the apex is targeted. A more posterior course suggests positioning in the CS or middle cardiac vein. A large posterior curve suggests possible passage through a patent foramen ovale or atrial or ventricular septal defect to the left ventricle (Fig. 27-15). Although the RVA has been the traditional site for ventricular pacing lead placement, awareness of the potential for left ventricular (LV) dyssynchrony from RVA pacing has led to more frequent use of right ventricular outflow tract (RVOT) or septal pacing11 (Fig. 27-16). A position away from the RVA may also be sought when there are high pacing thresholds at the apex or if an ICD lead is present at the apex, to avoid device-device interactions (Fig. 27-17). His bundle pacing has been proposed as an alternative to RVA pacing in the absence of infraHisian conduction system disease12 (Fig. 27-18). An extra set of bipolar sensing electrodes at the level of the right atrium on a ventricular lead body identifies a VDD single-lead pacing system, which is designed to sense in the atrium and allow atrial-synchronous ventricular pacing (Fig. 27-19).

782

SECTION 3  Implantation Techniques

A

B

Figure 27-12  Radiographic appearance of transvenous leads. A, Active-fixation, bipolar lead. B, Passive-fixation ICD lead.

Coronary Sinus Lead Positions.  The branches of the CS are common targets for leads placed for LV or biventricular pacing for CRT.13 Placement of the CS lead involves localization and cannulation of the CS, CS venography, and placement of the lead in the target branch. Coronary sinus ostium (CS os) cannulation is accomplished using an angiographic approach or electrophysiologic approach. Angiographic technique involves the use of a variety of guiding sheaths and diagnostic catheters (described in Chapter 22) with boluses of contrast agent for locating the CS os. The EP technique involves the use of guiding sheaths with mapping catheters to help determine the presence of CS recordings on intracardiac electrograms. Typically, in patients with congestive heart failure, CS anatomy is extremely variable because of cardiac dilation as well as to rotation and alteration from prior cardiac procedures, making localization of the ostium difficult. In addition, patients with atrial fibrillation may have a greatly enlarged right atrium, for which larger-curve guiding sheaths or catheters may be helpful in CS os cannulation. A quick fluoroscopic visualization may show the extent of cardiomegaly or cardiac rotation, or anatomic markers, such as right coronary artery calcifications or the radiolucent fat pad in the AV groove. In the anteroposterior (AP) view, the CS os can be on either side of the spine and variable vertically, relative to the floor of the tricuspid valve. A thorough understanding of the RA anatomy with judicious use of contrast material helps the implanting physician assess the position of the catheter tip relative to the CS os. After gaining access to the CS, the outer guide sheath is advanced into the proximal portion of the CS at least 3 to 4 cm over a guidewire or a softer inner catheter to prevent mural dissection. Balloon occlusion with contrast venography can then identify potential target tributaries, strictures, and collateral vessels in selection of an optimal target vessel (Fig. 27-20). Balloon inflation must be performed with caution to avoid overinflation and dissection of the vein. After visualization of the distal vessels, the balloon is deflated to promote proximal runoff, allowing visualization of tributaries proximal to the balloon tip. Continued acquisition of images for a few extra seconds after contrast injection allows flow to tributaries through collaterals, which might highlight the posterior and posterolateral LV veins that could otherwise go unnoticed. Two radiographic planes are helpful for assessing the CS tributaries and ostia for optimal target vessel determination. The most common positions used are left anterior oblique (LAO) 25 to 45 degrees, AP, and right anterior oblique (RAO) 15 to 30 degrees. Coronary sinus anatomy is variable, and no consensus exists regarding the nomenclature of CS branch anatomy; as discussed earlier, however, common terminology is used, as depicted in Figure 27-20.

From the CS ostium, the first branch is the middle cardiac vein (MCV), near which a posterior ventricular branch may enter. The distal CS becomes the great cardiac vein (GCV) after the takeoff of the vein of Marshall/valve of Vieussens. The GCV terminates at the takeoff of the anterior cardiac vein (ACV), which courses down the anterior interventricular groove. Between the MCV and ACV, posterior, posterolateral, lateral, anterolateral, and anteroseptal branches may be present. Using clock face positions as viewed in LAO projection, the CS os generally is located at 7 o’clock, the MCV at about 6 o’clock, the posterolateral veins at 5 o’clock to 2 o’clock, and GCV/ACV at 12 o’clock. If present, a persistent left SVC drains into the CS directly.14 Figure 27-21 illustrates typical lead tip positions. Epicardial Lead Positions.  When placed for potential CRT, unipolar or bipolar leads are placed on the LV posterolateral free-wall epicardium either after failure to place transvenous CS leads or at concomitant valve or coronary bypass surgery (Fig. 27-22). Minimally invasive methods for implantation are available for patients not in need of concomitant cardiac surgery.15-17 Epicardial leads may also be placed in patients with congenital abnormalities or as part of cardiac surgical procedures with risk for or resulting in complete heart block (see Fig. 27-3) and in patients with prosthetic tricuspid valves (Fig. 27-23). In the past, epicardial leads had a higher incidence of malfunction than transvenous pacing leads, but newer lead designs may improve epicardial lead longevity. The leads are tunneled to the pulse generator pocket in either the pectoral or the abdominal area. Evaluation may require chest and abdominal radiographs, depending on the location of the pacemaker or ICD device, to allow examination of integrity of a lead throughout its entire course. Identification of Possible Pacemaker Lead Malfunction.  The presence of abandoned leads usually indicates that the leads were malfunctioning or were no longer needed. Examples of the latter situation are (1) permanent atrial fibrillation with change to a single-chamber from a dual-chamber pacemaker at device replacement and (2) upgrade from a permanent pacemaker to an ICD, abandoning and capping of the ventricular pacing lead and implanting an ICD lead. The proximal portion of the lead is usually capped, unattached to the generator, and free in the generator pocket. Some implanters cut the leads, but doing so risks retraction of a lead into the venous system, greatly increasing the difficulty of future extraction (Fig. 27-24, A). The implanter should determine whether the abandoned lead is present in its entirety or whether its proximal portion has been severed or retracted into the vein (Fig. 27-24, B). Text continued on page 791



27  Imaging of Implantable Devices

783

Medtronic 5076

Extended

Extended

B

Retracted

St. Jude 1580 ICD lead

A

Retracted

Medtronic 6947 ICD lead Extended Extended Retracted Retracted

D Biotronik ICD lead

E C

Extended

F

G

Retracted

Extended

Retracted

Figure 27-13  Active-fixation screw positions. A, Medtronic 5076 bipolar pacing lead with extended and retracted screw positions. The fluoroscopy image shows the screw is extended with appearance of a space between the two distal radiopaque rings (arrow). B, St. Jude 1688T bipolar pacing lead with radiographs of extended and retracted screw positions. In the extended position, two helical turns of the screw are visible.  C, Medtronic 6947 ICD lead with extended and retracted screw positions. The fluoroscopy image shows the screw is extended with disappearance of the space between the two distal radiopaque rings. D, St. Jude 1580 ICD lead with radiographs of extended and retracted screw positions, showing two helical turns of the screw in the extended position. E, Biotronik ICD lead with screw extended. F, Boston Scientific 0186 ICD lead in extended and retracted screw positions. G, Biotronik Setrox lead in extended and retracted screw positions. (Courtesy Medtronic, Minneapolis; St. Jude Medical, St. Paul, Minn; and Biotronik, Berlin.)

784

SECTION 3  Implantation Techniques

A

Figure 27-14  Ventricular pacing lead position in right ventricular apex and atrial lead in right atrial appendage. Posteroanterior (A) and lateral (B) radiographs demonstrate the anterior course of the right atrial appendage lead and the apical anterior course of the right ventricular apex lead.

B

A

C

B

D

Figure 27-15  Abnormal lead placement into left ventricle. A and B, Posteroanterior (PA) and left lateral views show a dual-chamber pacing system. The ventricular wire has an unusually high curve on the PA view; on the lateral view, it can be seen to extend in a posterocranial direction, only then to curve back on itself with the tip of the lead in the wall of the left ventricle (arrow). This is an example of improper ventricular lead placement, with the wire traversing the foramen ovale and extending through the body of the left atrium, through the mitral valve, and into the left ventricle. C and D, PA (C) and lateral (D) views demonstrating a single-chamber ICD system with the defibrillation lead crossing an atrial septal defect (ASD) to the left ventricle. The lead courses posteriorly through the ASD, through the mitral valve to the left ventricle.



27  Imaging of Implantable Devices

E

G

785

F

H

Figure 27-15, cont’d  PA (E) and lateral (F) views during a BiV device implant demonstrating a single-coil ICD lead crossing an ASD to the left ventricle. G and H, Ventricular lead placement into the coronary sinus. Anteroposterior (G) and lateral (H) views demonstrating inferior, posterior course of the ventricular lead placed into the middle cardiac vein of the coronary sinus via a left sided superior vena cava. (A and B from Trohman RG, Wilkoff B, Byrne T, Cook S: Successful percutaneous extraction of a chronic left ventricular pacing lead. Pacing Clin Electrophysiol 14:1448, 1991.)

786

SECTION 3  Implantation Techniques

A

B

Figure 27-16  Ventricular pacing lead position in right ventricular outflow tract. Posteroanterior (A) and lateral (B) chest radiographs with a left-sided single-chamber pacemaker. The lead tip is in the anterior RVOT, and the abdominal transvenous ICD lead tip is placed in the right ventricular apex. (Courtesy Walid Saliba, MD.)

A

B

Figure 27-17  Posteroanterior (A) and lateral (B) chest radiographs of dual-chamber pacing system on the left, with ventricular pacing lead placed higher on the right ventricular wall, and a dual-chamber ICD system implanted on the right, with the ventricular ICD lead at the apex. The ventricular pacing lead is implanted higher and away from the high-voltage ICD lead.



27  Imaging of Implantable Devices

A

787

B

Figure 27-18  His bundle pacing. Posteroanterior (A) and lateral (B) views of a pacemaker system with right atrial, right ventricular apical, and lead placed at the His bundle (arrows).

A

B

C

D

Figure 27-19  Posteroanterior (A) and lateral (B) views of the single-lead VDD pacing system with a bipolar atrial sensing electrode (arrow) and bipolar ventricular pace/sense electrodes. The system was subsequently upgraded with the addition of a new atrial bipolar lead, as shown on PA (C) and lateral (D) views, because of inadequate atrial sensing.

788

SECTION 3  Implantation Techniques

AL

ACV CS

L

PL CS ostium

PV MCV

A LAO 25 CRAN 0

B

LAO 11 CAUD 1

C

Figure 27-20  A, Coronary sinus balloon (CS) venography demonstrating branch anatomy in the left anterior oblique view; ACV, anterior cardiac vein; AL, anterolateral marginal vein; L, lateral marginal vein; MCV, middle cardiac vein; PL, posterolateral marginal vein; PV, posterior ventricular branch. B, CS venography demonstrating dissection of the CS from sheath insertion. Extravasation of contrast is limited within the epicardium. C, Contrast visualized layering in the pericardial space, indicating perforation.



27  Imaging of Implantable Devices

A

B

Figure 27-21  Coronary sinus (CS) lead positions in cardiac resynchronization therapy systems. A, Left anterior oblique (LAO; left) and posteroanterior (PA; right) projections demonstrating positioning of a unipolar pacing lead in an anterolateral marginal branch of the coronary sinus. Arrows highlight the course of the CS leads. B, CS venography in the LAO projection (left) demonstrating a large lateral branch of the CS. LAO (middle) and right anterior oblique (RAO; right) projections after placement of a bipolar CS pacing lead show the tip to be in the middle to distal segment of the superior division of the lateral branch. C, LAO (top) and RAO (bottom) CS venograms (left) and projections demonstrating the CS lead tip positioned in the distal middle cardiac vein (right). Positioning of the lead in the lateral branch resulted in unacceptable diaphragmatic stimulation. D, LAO (left) and RAO (right) projections showing the CS lead tip (arrows) in an anterior CS branch location.

LAO

LAO

RAO

RAO

C

D

789

790

SECTION 3  Implantation Techniques

Figure 27-22  LV leads in CRT-D. Left ventricular epicardial leads connected to a cardiac resynchronization therapy implantable cardioverterdefibrillator. Posteroanterior (left) and lateral (right) chest radiographs show epicardial screw-tip leads placed on the LV epicardium (arrows).

A

C

B

D

Figure 27-23  Epicardial RA and RV pacing leads. A and B, Posteroanterior (PA) and lateral chest radiographs showing epicardial right atrial and right ventricular pacing leads in a woman with a tricuspid valve prosthesis. C and D, PA and lateral chest radiographs in a patient with prosthetic mechanical aortic and mitral valves and nonresponse to CRT delivered from a coronary sinus lead positioned in an anteroseptal CS branch (great cardiac vein). She underwent surgical placement of epicardial pacing leads, but chest radiographs show ventricular leads were placed on the right ventricle.



27  Imaging of Implantable Devices

A

791

B

Figure 27-24  Abandoned leads. A, Posteroanterior chest radiograph. Two of the pacing leads are connected to a left prepectoral dual-chamber pacemaker. Two leads have been cut and abandoned in the pocket. B, PA chest radiograph showing a right pacemaker system and abandoned leads, including a cut lead from the left that has retracted into the left subclavian vein.

Active-fixation leads have a radiopaque screw that may be fixed (extended) or retractable-extendable. The chest radiograph should be examined to determine whether the screw is extended properly, recognizing that there may be alternative markers to screw extension besides apparent extension past the tip electrode. Screw extension is marked by removal or creation of a space between radiopaque rings and by visualized extension of the screw past the tip (see Fig. 27-13, A). Particularly when troubleshooting device or lead malfunction before surgical exploration of a device system, the clinician must scrutinize the chest radiograph for lead integrity and connection to the device header, examining the header for any obvious disconnections. Often, the pin can be seen extending past the distal connector block (see Fig. 27-8). The lead coil should also be scrutinized for obvious discontinuity, abnormal angulation, and kinking, particularly between the pulse generator and the venous insertion site (Fig. 27-25). Medial venous insertion sites appear to be more prone to the subclavian clavicle-first-rib crush syndrome, or subclavian crush syndrome18,19 (Fig. 27-26). In addition, acute angulation of leads may lead to inner conductor fracture (Fig. 27-27). This situation may occur with insertions into the lateral axillary vein or with acute angulation out of the subclavian vein. Crimping of the lead insulation by tight ligatures around suture sleeves may cause the radiographic appearance of

pseudofracture20,21 (Fig. 27-28). Pacing characteristics may be unaffected by such crimping, but over time, lead insulation damage or coil fracture may result and should be monitored. Another type of pseudofracture describes a transition from a coaxial to a linear configuration, such as in ICD leads at the transition from the coil to the cable, or where coils come together from a bifurcated (now obsolete) connector configuration. Excessive unintentional or intentional coiling and knotting of the leads may occur because of a large generator pocket or loose, fatty subcutaneous tissue, allowing rotation or repeated flipping of the pulse generator with physical activity or from patient manipulation, called twiddler’s syndrome or “reel syndrome”22,23 (Fig. 27-29). Chest radiography leads to diagnosis, and early identification of the problem with follow-up chest radiographs may help prevent its perpetuation. Such excessive coiling and knotting of the leads can lead to lead fracture, insulation breaks, or inappropriate defibrillator shocks. A special situation in which radiographic imaging has been important has been for examination of the Telectronics Pacing Systems (Englewood, Colo.; now part of St. Jude Medical, Sylmar, Calif.) Accufix active-fixation and Encor passive-fixation atrial leads.24,25 Designed to maintain a J shape, these leads have retention wires located within the insulation in the Accufix lead and inside the coil in

Figure 27-25  Pacemaker lead conductor fracture. The right-sided dual-chamber pacemaker is connected to leads inserted via the right internal jugular vein (left). The expanded view (right) demonstrates that these leads contain conductor fractures (arrows). There is also an abandoned and cut right ventricular lead that has retracted into the right subclavian vein.

792

SECTION 3  Implantation Techniques

A

B

C

Figure 27-26  Subclavian clavicle–first rib crush syndrome. A, There is a fracture with frank lead discontinuity at the clavicle–first rib. The venogram shows that the insertion of the leads into the subclavian vein was at a very medial site. B and C, Posteroanterior chest radiograph and magnified view show insulation breaks in two leads at the clavicle–first rib junction with intact third lead.

Figure 27-27  Conductor fracture. Two examples of inner conductor fractures (arrows) caused by acute angulation of pacing leads. (Courtesy Ludwig Binner, MD, University of Ulm, Germany.)



27  Imaging of Implantable Devices

Figure 27-28  ICD lead “pseudofracture.” Two suture tie-down sleeves were positioned to produce a strain-relief loop on this ICD lead. The slight separation in the outer coil spacing (arrows) represents not disruption of the wire but merely too tight a placement of the ligature.

the Encor lead. The retention wire may fracture, protrude, and migrate, leading to cardiovascular perforation. Open J shapes appear more prone to fracture than more closed shapes. Coned-in views with higher penetration and digital fluoroscopy have been used to assess the retention wire (Fig. 27-30). The Encor lead appears less prone to fracture complications, but fracture is more difficult to detect. It has been associated with angulation in the interelectrode space. Chest radiographs and digital fluoroscopy with high magnification and multiple views should be used to optimize visualization of these retention wires.26 Implantable Cardioverter-Defibrillator Leads The cornerstone of current ICD systems is a transvenous pace/sensedefibrillation lead placed into the right ventricle and typically connected to an “active-can” ICD pulse generator located in the prepectoral region, usually on the left side.27 These leads may have a single, high-voltage defibrillation coil, which should be situated in the right ventricle, or two high-voltage coils, the distal coil being positioned in the right ventricle, and the proximal coil positioned in the SVC–high RA area. The ventricular ICD lead tip is

typically placed at the RVA with enough lead slack to allow a lift at the tricuspid valve. ICD leads may also be placed in the RVOT (Fig. 27-31). In patients with high DFT, a separate SVC coil lead may also be placed in the SVC-brachiocephalic region; alternately, a subcutaneous patch, coil, or array may be placed (Fig. 27-32). Subcutaneous electrodes are usually placed inferior and posterior to the axilla but may be placed in the left prepectoral region if the ICD is not an active-can device or if the ICD is located elsewhere (e.g., abdominal or right prepectoral region). Epicardial patch defibrillation leads (see Fig. 27-3, B and F) were placed using sternotomy or lateral thoracotomy in early ICD systems but rarely may still be required in patients who are not candidates for transvenous lead systems—because of absence of any venous vascular access, repeated infection with endocarditis, or tricuspid valve replacement, with some forms of congenital heart disease, and in small children. Coronary sinus defibrillation leads were used in an early atrial defibrillator device but are not in current standard ICD systems. The atrial defibrillator device Metrix (InControl, Redmond, Wash.) used an S-shaped lead to maintain stability in the CS (Fig. 27-33). However, this lead is not currently being marketed, and other straight leads may be at a higher risk for dislodgment. Moreover, placement of defibrillation coil leads in the main CS may preclude future access of this venous system for CRT leads. The azygos vein may be cannulated for placement of ICD defibrillation leads (Fig. 27-34; see also Fig. 27-11). The azygos enters the SVC posteriorly, just below the confluence of the brachiocephalic veins, and can provide access to a position posterior to the heart for optimization of the defibrillation vector. Similarly, an additional defibrillation lead/ array can be placed in the subcutaneous tissue along the posterolateral wall to change the defibrillation vector in patients who cannot achieve a safe DFT through traditional dual-coil ICD leads.28 Identification of Lead Malfunction.  Although defibrillation lead diameters have become smaller, with some as small as pacing leads, most ICD leads have a larger diameter relative to pacing leads and thus may be more susceptible to subclavian crush syndrome. Chest radiographs should be inspected closely in the region near the venous insertion and suture sleeve tie-down sites. Leads, patches, coils, and arrays should be inspected for fracture and excessive bending or kinking. This inspection may require abdominal films and customized views. “Phantom fracture” and pseudofracture are used to describe a pseudodiscontinuity of one manufacturer’s ICD lead just distal to the proximal high-voltage coil29 (Fig. 27-35). This appearance is a normal feature of

Figure 27-29  Twiddler’s syndrome. A, Magnified view of a radiograph of a patient with twiddler’s syndrome.  B, During surgical exploration, the pacer had to be twisted 18 revolutions to uncoil the leads. Note the wormlike characteristic of the multiple loops of the intercoiling electrode wires. (From Castle LW, Cook S: Pacemaker radiography. In Ellenbogen KA, Kay GN, Wilkoff BL, editors: Clinical cardiac pacing. Philadelphia, 1995, Saunders, p 560.)

A

793

B

794

SECTION 3  Implantation Techniques

Figure 27-30  Lead wire protrusion. Accufix atrial lead with fracture and protrusion of the J retention wire (arrow) with migration into the right atrium. Detection of such protrusions is enhanced by the use of higher-penetration, coned-in views. (Telectronics, Englewood, Colo., now part of St. Jude Medical, Sylmar, Calif.)

this particular lead. A discontinuity of radiopaque markers on the perimeter of some epicardial patches is likewise no cause for concern, because these markers are not a part of the defibrillation electrode and do not indicate lead fracture (see Fig. 27-32, E).

important to note cardiac position and mediastinal anatomy on a chest radiograph before all device procedures, to screen for previously undiagnosed congenital cardiovascular anomalies.

SPECIAL CONSIDERATIONS IN CONGENITAL HEART DISEASE

Occasionally, implantation of leads from the left subclavian or axillary vein results in unexpected inferior passage of the lead on the left side of the chest, before it crosses the midline. This situation typically indicates the presence of a persistent left-sided SVC. From this access, leads placed from the left subclavian vein pass via the left SVC through the CS to the right atrium or ventricle (Fig. 27-37). The ventricular lead usually enters the atria posteriorly and loops in the right atrium before entering the right ventricle (Fig. 27-38). Preoperatively, a persistent left SVC may be suspected from CS dilation detected on echocardiography, CT, or MRI. In patients with persistent left SVC, placement of transvenous leads from the right axillary/ subclavian venous system proceeds normally through the SVC and right atrium.32

Congenital cardiovascular anomalies may result in unusual locations of pacing or ICD lead systems. An understanding of the native and corrected anatomy is essential for correct interpretation of radiographic imaging in patients with implanted devices. Epicardial pacing indications include residual intracardiac shunts, prosthetic pulmonary ventricular AV valves (usually tricuspid), severe right ventricular endocardial fibroelastosis, lack of viable access to the heart through systemic veins, and prohibitively small stature (Fig. 27-36). Thus, abdominal and chest radiographs should be obtained in patients with these diagnoses before and after pacemaker or ICD placement.30,31 It is also

Persistent Left-Sided Superior Vena Cava

Figure 27-31  Placement of ICD lead on anteroseptal wall of right ventricular outflow tract.



27  Imaging of Implantable Devices

795

A

B

C Figure 27-32  Transvenous ICD systems in patients with high defibrillation thresholds. A, Posteroanterior chest radiograph of a transvenous abdominal ICD system with separate right ventricular (RV) and superior vena cava (SVC) leads. B, PA and lateral chest radiographs of a patient with an abdominal ICD system with separate RV and SVC coils and an axillary patch electrode. The atrial lead has been retracted to the brachiocephalic vein. C, PA and lateral chest radiographs of a left pectoral ICD system with SVC and RV defibrillation coil electrode and a subcutaneous axillary coil electrode. Continued

796

SECTION 3  Implantation Techniques

D

E Figure 27-32, cont’d  D, PA and lateral chest radiographs of a left pectoral ICD system with an SVC-RV defibrillation coil lead requiring an extra SVC defibrillation lead and a subcutaneous coil implanted along the low lateral posterior chest wall. E, PA and lateral radiographs of a right pectoral ICD lead system with RV defibrillation coil, epicardial patch electrode, and coronary sinus defibrillation coil.

A

B

C

Figure 27-33  Atrial defibrillation lead system. Posteroanterior (A), overpenetrated PA (B), and lateral (C) chest radiographs demonstrate the InControl Metrix atrial defibrillator with S-shaped coronary sinus (white arrows) and atrial (black arrows) defibrillation leads.



27  Imaging of Implantable Devices

A

797

B

Figure 27-34  Azygos vein defibrillation lead. Posteroanterior (A) and lateral (B) chest radiographs of patient in Figure 27-17 in whom high defibrillation thresholds required the addition of an azygos vein defibrillation coil (arrows). Note the posterior course from the superior vena cava.

Dextrocardia Dextrocardia should be recognized on the preprocedural chest radiograph (Fig. 27-39), particularly because its presence may affect on which side an ICD system may be placed. It is important to note the position of the stomach bubble on the chest radiograph in patients with dextrocardia. In those with situs inversus totalis, in whom the normal right-versus-left position of all organs is completely reversed, the stomach bubble is also right-sided (Fig. 27-39, D). In those with discordance of cardiac position and abdominal organ position (e.g., dextrocardia with a left-sided stomach bubble), situs inversus totalis is

ruled out, and some form of heterotaxy syndrome is present. Patients with heterotaxy syndrome have a high incidence of abnormal systemic venous return and other cardiac anomalies (Fig. 27-40). Fontan Procedure A majority of patients with congenital heart disease and functional single-ventricle anatomy undergo staged palliative surgery culminating in a modified Fontan procedure. Epicardial systems should be used in such patients because of the high risk for thrombotic complications from endocardial leads. Senning and Mustard Procedures Palliative surgery for some congenital heart disease includes creation of intra-atrial baffles that direct systemic venous blood return to the pulmonary ventricle and pulmonary venous return to the systemic ventricle, using either the Senning or Mustard procedure. A majority of patients undergoing palliation with a Senning or Mustard pro­ cedure have D- (“uncorrected”) or L- (“corrected”) transposition of the great arteries. In D-transposition of the great arteries, leads for permanent pacemakers or ICDs are typically placed via the SVC to the morphologic left atrium and left ventricle (Figs. 27-41 to 27-43). In L-transposition of the great arteries, after the “doubleswitch” procedure (Senning or Mustard and great arterial switch), the leads are placed via the SVC through the intra-atrial baffle to the left-sided atrium and left-sided morphologic right ventricle (Fig. 27-44). Tetralogy of Fallot Patients with tetralogy of Fallot have normal AV and ventriculoarterial (VA) connections, so the intravenous course of pacing and defibrillation leads is similar to that in patients with normal cardiac anatomy. Patients with this disorder have a higher incidence of persistent leftsided SVC than the general population (Fig. 27-45). Corrected L-Transposition of Great Arteries

Figure 27-35  Pseudofracture of a Guidant (Boston Scientific) Endotak ICD lead just distal to the proximal high-voltage coil. This pseudodiscontinuity (inset) is the normal appearance of this lead.

Patients with unoperated L-transposition of the great arteries have ventricular inversion. Ventricular transvenous pacing leads pass through the SVC to the right atrium and then to the morphologic, posterior, left ventricle. If advanced through the left ventricle, transvenous leads enter the pulmonary artery. Affected patients have a high likelihood of other associated congenital cardiac anomalies.

798

SECTION 3  Implantation Techniques

A

B

C

E

D

F

Figure 27-36  Device systems in infants and children. A and B, Anteroposterior (left) and lateral (right) chest and abdominal radiographs of an infant with an epicardial dual-chamber pacemaker system for postoperative complete heart block. The pulse generator in the left upper quadrant of the abdomen is connected to bipolar atrial and ventricular leads. C and D, AP and lateral chest radiographs in a 4-kg infant with an ICD system, composed of a right anterior subcutaneous coil, posterior epicardial coil, and right atrial and right ventricular epicardial pacing leads. E and F, Cardiac resynchronization ICD (CRT-D) device in a 30-kg patient with coronary sinus (CS) venography (E) and final device system positioning with the CS lead positioned in the great cardiac vein (F).



27  Imaging of Implantable Devices

799

Persistent Left Superior Vena Cava

ate

Innomin

PV Rt.

Lt. SVC

PV

SVC

CS Rt. IVC

Hepatic veins

Lt. SVC

Figure 27-37  Persistent left superior vena cava (SVC). Schematic representation of the three different types of persistent left SVC with various insertions of the left SVC into the right heart system; CS, coronary sinus; IVC, inferior vena cava; Lt, left; PV, pulmonary vein; Rt, right. (From Castle LW, Cook S: Pacemaker radiography. In Ellenbogen KA, Kay GN, Wilkoff BL, editors: Clinical cardiac pacing. Philadelphia, 1995, Saunders, p 588.)

Figure 27-38  Persistent left superior vena cava (SVC). Posteroanterior (left) and lateral (right) chest radiographs show ICD lead tunneled from the abdomen to the left subclavian vein insertion site, then traversing the left-sided SVC to the distal coronary sinus to the right atrium, and then looping to the right ventricle. A pacemaker from the right pectoral region is also present with atrial and ventricular leads entering via the right subclavian vein.

800

SECTION 3  Implantation Techniques

A

C

B

D

Figure 27-39  Dextrocardia. A, Posteroanterior chest radiograph obtained in August 1985 shows dextrocardia with a prosthetic mitral valve in place. Remnant stab electrodes can be identified overlying the right precordium (small curved and straight black arrows). The single-chamber pacing system has two screw-in epicardial leads present (open arrows). B, Lateral view of same patient. C, PA chest radiograph dated July 1989 demonstrates abandonment of the previously placed epicardial system. A single-chamber bipolar system is now present, with the new transvenous lead near the right ventricular apex (arrow). D, PA chest radiograph of patient with dextrocardia with situs inversus, pacing system from the left with right atrial, His bundle, and right ventricular pacing leads connected to a cardiac resynchronization pacemaker pulse generator. (A to C from Castle LW, Cook S: Pacemaker radiography. In Ellenbogen KA, Kay GN, Wilkoff BL, editors: Clinical cardiac pacing. Philadelphia, 1995, Saunders, p 549.)



27  Imaging of Implantable Devices

801

Figure 27-40  Dextrocardia. Anteroposterior (left) and lateral (right) chest radiographs in a child with dextrocardia, heterotaxy syndrome, and a single-chamber, transvenous pacing system. The bipolar atrial pacing lead is positioned in the left-sided atrial appendage; the stomach bubble is on the left.

Implantation Fluoroscopy and Venography Direct fluoroscopy during the procedure guides the entire lead implantation process. Different radiographic projections can aid delivery of the lead to the most desired sites in the right atrium, right ventricle, and CS. TRANSVENOUS ACCESS VENOGRAPHY The first and second ribs and clavicle serve as the standard landmarks in accessing the axillary/subclavian vein on either the left or the right side. The part of the vein inferolateral to the clavicle and at the lateral border of the first rib is typically considered the axillary vein, and the portion medial to this region, coursing under the clavicle, the subclavian vein (see Fig. 27-9). Cephalic vein access is usually achieved through venous cutdown under direct visualization, whereas axillary/ subclavian access is through a percutaneous puncture using bony landmarks or fluoroscopy to help avoid pneumothorax. Access through the axillary vein is advantageous to subclavian access, in that leads can be inserted more laterally, usually lateral to the subclavius muscle or ligament, potentially reducing the risk of subclavian crush syndrome, as well as the risk of pneumothorax, because access occurs in the extrathoracic portion of the vein. The subclavian/ axillary artery lies posterior and cranial to the subclavian/axillary vein. During axillary vein access under PA fluoroscopic guidance, the needle is directed toward the anterolateral first rib with a superficial course until the needle tip is seen to overlie the first rib. The needle is then directed with higher vertical angulation (with more posterior direction) toward the first rib, with care taken to avoid penetration of the needle intrathoracically, medial to the medial border of the rib. In patients with morbid obesity, bony deformities, previous subclavian venous central line access, prior upper-extremity deep vein thrombosis, congenital heart disease, or preexisting leads, venous access can be difficult because of stenosis or altered relationships among the venous system, ribs, and clavicle. In these cases, ipsilateral upper-extremity venography can be very helpful in defining the course and patency of the axillary/subclavian system. Preoperative upperextremity venograms to assess the patency in patients with previously implanted leads (see Fig. 27-9) are also often helpful, although intraoperative fluoroscopic or cineangiographic venography can be performed with simultaneous venous access.33 A left-sided SVC may also be confirmed with venography.

TRADITIONAL PACING SITES The right atrial lead follows the contour of the vascular system without excess redundancy, except in cases of venous tortuosity, but with a J-shaped lead, slack is generally left at the distal portion of the lead. Right ventricular leads are generally placed with enough lead slack to allow for lift and closure of the tricuspid valve. Lack of this lifting motion during fluoroscopy may signify a diseased tricuspid valve or tethering of the tricuspid leaflets or chordae by the pacing or ICD lead. In the latter case, repositioning of the lead requires withdrawal of the lead tip back to the right atrium and fresh entry to the right ventricle between leaflets. Radiographically, a lead positioned at the RVA displays the tip of the lead pointing slightly downward in the AP view and anteriorly on the lateral view; posterior angulation of the lead suggests positioning in the CS. A lead placed onto the RVOT or septum is located more cranially (see Fig. 27-31). An LAO or a left lateral view may help to determine septal rather than anterior wall location. Undue tension on leads may result in dislodgment or poor pacing thresholds (Fig. 27-46). In children, greater lead redundancy is desirable to allow for future growth, without causing excessive tension on the pacing or ICD lead.34 ALTERNATIVE-SITE PACING Pacing strategies to suppress atrial arrhythmias have involved selective alternate–atrial site or dual–atrial site pacing. Pacing the high septum of the right atrium, near Bachmann’s bundle or the CS os, may shorten intra-atrial conduction and minimize dispersion of refractoriness, perhaps improving atrial fibrillation.8,9 Fluoroscopically, the right atrial (RA) lead is directed in the LAO view toward the interatrial septum and then withdrawn until the tip begins to straighten, indicating proximity to the RA roof, where it is then fixed to the high septum. The position appears anteriorly directed on the RAO view.9 The LAO projection is helpful in guiding leads to the low RA septum. The target is the low septum just superior to the CS os and below the foramen ovale. Traditional RVA pacing may cause a dyssynchronous left ventricular electrical activation pattern, resulting in dyssynchronous contraction and relaxation that can contribute to heart failure and reduce long-term survival.35-37 Therefore, alternative–ventricular site pacing has become more conventional. The RVOT or septum has been targeted for right ventricular (RV) leads (see Figs. 27-16 and 27-31). These sites may also be used when pacing thresholds are high at the apex or if an ICD lead is present

802

SECTION 3  Implantation Techniques

A

C

B

D

E End/2

F

UNABLE TO RAISE ARM

G

Figure 27-41  Device systems in D-transposition (uncorrected) of great arteries (DTGA) after Mustard procedure. A, Anteroposterior (left) and lateral (right) chest radiographs show a right-sided pacemaker pulse generator, a left-sided atrial bipolar lead advanced through the Mustard baffle, a ventricular bipolar lead in the left ventricle, and an abandoned unipolar ventricular lead in the left ventricle. B, Dual-chamber ICD system in a patient with DTGA after Mustard procedure. C to G, Patient with DTGA after Mustard palliation had atrial single-chamber pacemaker for sinus node dysfunction (C) but developed superior vena cava–right atrial baffle obstruction (D). The atrial lead was explanted and baffle stented (E) with replacement of the atrial single chamber pacemaker system (F, AP chest radiograph; G, lateral radiograph).



27  Imaging of Implantable Devices

803

Figure 27-42  Pacemaker system in D-transposition of the great arteries after Senning procedure. Anteroposterior (AP; left) and lateral (middle) chest radiographs show the left-sided pulse generator, a bipolar atrial lead advanced through the baffle to the left atrium, and the ventricular bipolar lead tip in the left ventricle. The AP fluoroscopic image (right) shows lead placement into the left atrial appendage in a different patient with DTGA after a Senning procedure.

at the apex and separation is required to prevent device-device interactions (see Fig. 27-17).38 The lead may be placed with use of the AP or RAO view, with a gently curved stylet to help advance the lead through the tricuspid valve to the RVOT or pulmonary artery. The lead is then slowly withdrawn with counterclockwise torque to aim the tip toward the RVOT septum, where it can be actively fixed. The LAO view can be used to help determine whether the lead tip is septally or anteriorly directed. His bundle pacing has also been targeted on the RV septum with the goal of maintaining synchronous ventricular activation during ventricular pacing.

LEADS AND COMPLICATIONS Coronary Sinus Venography and Lead Placement Coronary sinus venography and lead placement are described previously in this chapter and in detail in Chapter 22. Azygos Venography and Lead Placement The azygos vein may be a target for ICD defibrillation leads in patients with high DFT (see Figs. 27-11 and 27-34). The azygos vein may be cannulated in the LAO projection and enters the SVC posteriorly just at or below its origin at the confluence of the right and left brachiocephalic veins. The vein often is acutely angled cranially and may require special guiding catheters (e.g., an internal mammary artery [IMA] catheter) to aid in introduction of a guidewire. Venography is often helpful in determining the ostium of the azygos vein and to define its course and branches. Subcutaneous Patch, Coil, or Array Defibrillation leads intended for subcutaneous implantation in patients with high DFT have been designed to contain a single coil, a multicoil array, or a patch electrode that can increase the surface area of the defibrillation vector (see Fig. 27-32). These subcutaneous electrodes may be placed across the posterolateral wall of the chest to provide a more posterior vector, or to the left pectoral region in the absence of a left pectoral active-can ICD. The lead system may be best visualized on the lateral chest radiograph or an RAO or LAO fluoroscopic view.28 Lead Extraction The tip of the telescoping sheath used for lead extraction is radiopaque and is continuously monitored by means of fluoroscopy while being advanced along the course of the lead (Fig. 27-47). Often, the leads are fibrosed and calcified and are clearly visible with fluoroscopy. Also, the dimensions and configuration of the cardiac silhouette and obliteration of the left hemidiaphragm should be followed closely to enable prompt recognition of cardiac tamponade. (See Chapter 26.)

Figure 27-43  Transvenous ICD system implanted in pediatric patient after Senning procedure for D-transposition of great arteries. Anteroposterior chest radiograph shows a bipolar pacing lead advanced through the atrial baffle, with the tip in the left atrial appendage, and a dual-coil ICD lead advanced through the atrial baffle, with the tip in the left ventricle. Two epicardial temporary pacing wires are present on the surface of the right ventricle.

Detection of Acute Complications Fluoroscopy may detect development of acute pneumothorax, usually from difficult venous insertion attempts, and may allow immediate follow-up of the stability of the pneumothorax. Enlarging pneumothoraces or hemodynamic compromise usually requires insertion of a chest tube.

804

SECTION 3  Implantation Techniques

Figure 27-44  Pacemaker system in a patient with L-transposition (corrected) of great arteries after Senning and great arterial switch (“double switch”) procedures. Anteroposterior (left) and lateral (right) chest radiographs show the left subpectoral pulse generator, the atrial bipolar lead advanced through the atrial baffle into the left atrium, and the ventricular bipolar lead tip in the apex of the left-sided morphologic right ventricle.

Right

Left

Ant.

Post.

Figure 27-45  ICD lead positioning in tetralogy of Fallot with persistent left superior vena cava. Fluoroscopic views show that the ICD proximal defibrillation coil is positioned in the coronary sinus, and the distal coil in the right ventricle; Ant., anterior; Post., posterior. (Courtesy Gerald Serwer, MD, University of Michigan, Ann Arbor.)



27  Imaging of Implantable Devices

A

C

805

B

D

Figure 27-46  Lead slack. A and B, Chest posteroanterior and lateral radiographs of a transvenous dual-chamber pacing system in a child with congenital complete heart block. The atrial and ventricular leads had adequate redundancy after initial system implantation, when the patient was 8 years old. C and D, Six years later, however, both the atrial and ventricular leads have inadequate redundancy. Tension on the ventricular lead caused poor pacing and sensing thresholds with intermittent complete loss of capture.

806

SECTION 3  Implantation Techniques

Figure 27-47  Extraction sheath, inserted over the lead targeted for extraction, is guided by means of fluoroscopy.

In cases of pericardial effusion caused by lead perforation, the diagnosis of cardiac tamponade is usually made clinically from a constellation of findings, including hypotension, pulsus paradoxus, and electrical alternans. Cardiac or vascular lacerations or tears are more frequently seen with lead extraction than with traditional lead insertion, but subclinical lead perforations may be more common than suspected. On fluoroscopy, development of a “double shadow” on the cardiac silhouette, with visualization of an inner, contracting cardiac border surrounded by a noncontractile pericardial shadow, suggests perforation or laceration with pericardial effusion. Rarely, electromechanical dissociation can occur after defibrillation testing in patients with severe heart failure and severe RA dysfunction. Particularly if prompted by pulse oximetry or blood pressure alarms, a quick fluoroscopic check can help determine the return of mechanical cardiac contractions.

Postimplantation Radiography

Figure 27-48  Pneumothorax. Anteroposterior chest radiograph shows dual-chamber pacing system in place with fixed electrodes in both the right atrial appendage and the right midventricular septum. There is a large pneumothorax on the left.

Pericardial Effusion, Cardiac Perforation, and Cardiac Tamponade Although the cardiac silhouette may be seen to enlarge on chest radiography, particularly compared with the preimplantation chest radiographs, one should not rely on the chest radiograph for a diagnosis of pericardial effusion. If there is clinical suspicion of a pericardial effusion, an echocardiogram should be obtained. Effacement of the left hemidiaphragm with enlarged cardiac silhouette compared with the preprocedural chest radiographs usually indicates pericardial effusion. An extracardiac location of the tip of the pacing lead suggests cardiac perforation with migration of the lead outside the heart (Fig. 27-50). Unless there is significant migration of the lead tip past the cardiac

A chest radiograph should be obtained after implantation of a pacemaker or ICD system. Postprocedural PA and lateral chest radiographs can confirm the correct and stable position of the generator and leads and assess for complications, such as ipsilateral or contralateral pneumothorax, pleural effusion or hemothorax, and even retained surgical sponges.39 COMPLICATIONS Pneumothorax Pneumothorax is best demonstrated on an upright PA view in full expiration. Pneumothorax is characterized by absence of lung markings over the lung fields (Fig. 27-48). The border of the lung apex, surrounded by clear air space inside the thoracic cavity, may be visualized. In rare cases the leads have punctured the SVC, causing a contralateral pneumothorax and usually associated with contralateral hemothorax. Hemothorax Hemothorax is an unusual complication during routine lead placement. Venous tears during lead extraction, however, can be associated with clinically significant hemothorax, which is usually evident during the procedure. Rarely, delayed ooze into the pleural space caused by subclavian vein or SVC laceration can result in significant pleural leak (Fig. 27-49). A hemothorax or pleural effusion is best recognized on upright PA or lateral chest radiograph.

Figure 27-49  Hemothorax. Anteroposterior portable chest radiograph obtained immediately after pacemaker insertion demonstrates a large hemothorax on the left secondary to perforation of the left subclavian artery. There is almost complete opacification of the left hemithorax. (A from Castle LW, Cook S: Pacemaker radiography. In Ellenbogen KA, Kay GN, Wilkoff BL, editors: Clinical cardiac pacing. Philadelphia, 1995, Saunders, p 551.)



27  Imaging of Implantable Devices

807

Figure 27-50  Lead dislodgment and perforation. Upper panels, Posteroanterior and lateral chest radiographs after atrial and ventricular pacemaker placement. Perforation of the atrial lead past the cardiac border is suspected. Lower panels, On follow-up PA and lateral chest radiographs, the atrial lead clearly has perforated the cardiac border and become dislodged caudally. (Case reported in Khan MN, Joseph G, Khaykin Y, Ziada KM, Wilkoff BL: Delayed lead perforation: a disturbing trend. Pacing Clin Electrophysiol 28:251, 2005.)

shadow, the chest radiograph may be insensitive to detection of cardiac perforation, and other imaging modalities, such as echocardiography and cardiac CT, may help determine whether a lead is indeed extracardiac in location.40 Lead Dislodgment Postimplantation chest radiography helps confirm the position of the lead. Incomplete fixation of the lead screw and insufficient slack caused by inadvertent pulls on the lead during suturing of the sleeve can be causes of lead dislodgment. Atrial lead dislodgment may be suspected if the atrial lead hangs straight vertically, if a J shape was seen during implantation (see Fig. 27-50). Dislodgment of the atrial lead into the right ventricle may result in inappropriate ventricular pacing. Ventricular lead dislodgement may be recognized from proximal dislodgments of apically positioned leads or falling of the lead from a higher septal or RVOT location. Similarly, CS lead dislodgment can also be recognized on AP and lateral chest radiographs. Lead Conductor Fracture and Insulation Breaks The lead should be inspected in its entirety. There should be no discontinuity of the coil and no sharp angulation or kinking. Such findings suggest lead fracture or the potential for fracture. Pseudofracture caused by crimping of insulation from excessive suture ligatures warrants close attention to pacing impedance, noise, sensing, and

pacing measurements at postimplantation and follow-up device interrogations.

Echocardiography Echocardiography can play an integral role in diagnostic and therapeutic aspects of pacemaker and defibrillation systems. Using echocardiograms, physicians can assess left ventricular function, detect and enable guided treatment of pericardial effusion and cardiac tamponade, and detect or follow native or lead vegetations. Echocardiography also helps optimize timing of programming (e.g., AV delay optimization) and assessment of RA dyssynchrony in patients receiving or being considered for CRT. COMPLICATIONS Pericardial Effusion Echocardiography is the “gold standard” for assessing pericardial effusion after implantation or explantation of pacing or defibrillation systems. A quick bedside echocardiographic assessment to detect pericardial effusion can be performed if clinical suspicion is high. Echocardiography may enable quantification of pericardial effusion as well as help determine whether cardiac tamponade physiology exists.

808

SECTION 3  Implantation Techniques

Native/Lead Vegetations Vegetations may be detected on transthoracic echocardiography but are more often defined by transesophageal echocardiography (Fig. 27-51). Distinction between fibrous stranding and infected vegetations may be needed from clinical history and blood culture results.

Computed Tomography

Figure 27-51  Vegetation on a pacing lead demonstrated on transesophageal echocardiography (TEE).

Echocardiography can also be used to monitor effusions, determine the timing of and need for pericardiocentesis, and guide percutaneous pericardiocentesis.

In certain patients before and after implantation, CT may clarify the anatomy of congenital or repaired anomalies, greatly aiding in the planning of appropriate approaches to lead implantation. Cardiac CT has also been used in the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD).41 Postprocedural applications include the assessment of lead tip migration, cardiac perforation, and pericardial effusion. Cardiac CT has been used in the past to assess epicardial ICD patch location and the extent of myocardial coverage, as well as relationships to the underlying myocardium. Most often, CT may be used as a substitute for MRI in patients with pacemakers and ICDs. Multislice CT is being investigated for assessment of CS anatomy, which may help determine candidacy for transvenous versus epicardial approaches to CRT42 (Figs. 27-52 and 27-53). Integration of CT with real-time lead positioning is also being explored.

Magnetic Resonance Imaging

Cardiac Perforation Echocardiography may detect the presence of a lead artifact in the pericardial space or close to the epicardial surface. This finding may be useful in conjunction with confirmation of the presence of a pericardial effusion and other clinical indicators, such as presence of a pericardial rub, pain, and evidence of cardiac tamponade.

As with CT, cardiac MRI may identify important cardiac structural details before device implantation. MRI has been used in the diagnosis of ARVD and restrictive or hypertrophic cardiomyopathies, as well as in the detection of hibernating myocardium. Cardiac MRI has generally been contraindicated in patients with implanted pacemakers or ICDs. However, several investigators have studied the safety of noncardiac MRI in patients with implanted

H R

LV epicardial lead

RES/SHADE/SURF LAO/RAO 178 CRAN/CAUD –29 LV endocardial lead

A

H

P

10.00 mm/div F

F

10.00mm/div

Figure 27-52  Computed tomography scan in patient presenting as “nonresponder” to biventricular pacing. Left ventricular endocardial lead in a posterolateral branch of the coronary sinus was previously abandoned because of intermittent diaphragm stimulation. A new LV lead was placed epicardially. The posteroanterior and lateral chest radiographs (not shown) suggest the lead may be anterior. A CT scan demonstrated that the LV epicardial lead was actually positioned on the right ventricular outflow tract (RVOT), explaining his nonresponse. The patient noted that despite the intermittent diaphragm stimulation, he felt much better when the endocardial lead was being used.

L

B O

100 95

W C

1534 740

Figure 27-53  Three-dimensional CT reconstruction used to assess target branches off the coronary sinus for LV lead repositioning in patient with diaphragm stimulation. Apart from the posterolateral branch, in which the lead was positioned, few alternative targets were seen along the lateral wall of the left ventricle. The existing lead was extracted, and a smaller, 4-French bipolar LV lead was advanced more distally within the posterolateral branch, with good capture threshold found and no diaphragm stimulation.



27  Imaging of Implantable Devices

809

Figure 27-54  MRI-compatible pacemaker and lead. System is identified by coil markers on the proximal lead and by device markings.

pacemakers. Potential risks include heating of leads, rapid or asynchronous pacing, reed switch inhibition, and induction of ventricular fibrillation.43 Use of noncardiac MRI of varying static magnetic field strengths has been reported in more than 300 patients with implanted pacemakers.44 Pacing threshold changes have been reported, but no adverse patient events. Studies have generally avoided pacemakerdependent subjects. Thus, data so far suggest that patients who are not pacemaker dependent may safely undergo noncardiac MRI at specific absorption rates (SARs) of less than 2 W/kg.44-46 The pacemaker should be interrogated before the procedure to assess pacemaker dependence and inactivate minute ventilation or other rate-response features. Outputs may be programmed to subthreshold levels, but this step may not be necessary. The patient should be continuously monitored and personnel familiar with pacemakers present in case emergency programming is required. After the procedure, the pacemaker should again be interrogated and a full check performed, including threshold testing. Currently, MRI is contraindicated in patients with ICDs. Although future generations of ICDs may become MRI safe, there may be a higher risk of current induction through the defibrillation coils, and MRI in patients with these devices has not been well studied.

Nevertheless, cardiac implantable electronic devices (CIEDs), including leads and pacemakers, which are MRI compatible have been under development. These devices may be identified by proprietary markings (Fig. 27-54).

Conclusion Radiography can provide important data about pacing and ICD systems. Preoperative radiographs can yield important anatomic information for the implanting physician. Intraoperative fluoroscopy and venography are invaluable tools, guiding optimal lead placement. Lateral and posteroanterior chest radiographs should be obtained after implantation to confirm correct lead placement and to detect potential complications of the implantation procedure. The chest radiograph is an important component of system troubleshooting. During such evaluation, the position and type of generator, the positions and types of all functional and abandoned leads, and the radiographic integrity of components of the system should be determined. Abdominal films may be required if any portion of the pacing or ICD system is in the abdomen. A systematic evaluation of the anatomy and system components is essential.

REFERENCES 1. Hill P: Complications of permanent transvenous cardiac pacing: a 14-year review of all transvenous pacemakers inserted at one community hospital. Pacing Clin Electrophysiol 10:564, 1987. 2. Filice R: Cardiac pacemaker leads: a radiographic perspective. Can Assoc Radiol J 35:20, 1984. 3. Lappegard K: Pacemaker implantation in patients with persistent left superior vena cava. Heart Vessels 19:153, 2004. 4. Cesario D, Bhargava M, Valderrabano M, et al: Azygos vein lead implantation: a novel adjunctive technique for implantable cardioverter defibrillator placement. J Cardiovasc Electrophysiol 15:780, 2004.

5. Bongiorni MG, Moracchini PV, Nava A, et al: Radiographic assessment of atrial dipole position in single pass lead VDD and DDD pacing. The Multicenter Study Group. Pacing Clin Electrophysiol 21:2240, 1998. 6. Hertzberg BS, Chiles C, Ravin CE: Right atrial appendage pacing: radiographic considerations. AJR Am J Roentgenol 145:31, 1985. 7. Daubert C, Gras D, Berder V, et al: [Permanent atrial resynchronization by synchronous biatrial pacing in the preventive treatment of atrial flutter associated with high-degree interatrial block]. Arch Mal Coeur Vaiss 87(suppl):1535, 1994.

8. Padeletti L, Michelucci A, Pieragnoli P, et al: Atrial septal pacing: a new approach to prevent atrial fibrillation. Pacing Clin Electrophysiol 27:850, 2004. 9. Bailin SJ, Adler S, Giudici M: Prevention of chronic atrial fibrillation by pacing in the region of Bachmann’s bundle: results of a multicenter randomized trial. J Cardiovasc Electrophysiol 12:912, 2001. 10. Van Gelder BM, Bracke FA, Oto A, et al: Diagnosis and management of inadvertently placed pacing and ICD leads in the left ventricle: a multicenter experience and review of the literature. Pacing Clin Electrophysiol 23:877, 2000.

810

SECTION 3  Implantation Techniques

11. Lieberman R, Grenz D, Mond HG, Gammage MD: Selective site pacing: defining and reaching the selected site. Pacing Clin Electrophysiol 27:883, 2004. 12. Deshmukh PM, Romanyshyn M: Direct His-bundle pacing: present and future. Pacing Clin Electrophysiol 27:862, 2004. 13. Kautzner J, Riedlbauchova L, Cihak R, et al: Technical aspects of implantation of LV lead for cardiac resynchronization therapy in chronic heart failure. Pacing Clin Electrophysiol 27:783, 2004. 14. Von Ludinghausen M: The venous drainage of the human myocardium. Adv Anat Embryol Cell Biol 168:I, 2003. 15. Fernandez AL, Garcia-Bengochea JR, Ledo R, et al: Minimally invasive surgical implantation of left ventricular epicardial leads for ventricular resynchronization using video-assisted thoracoscopy. Rev Esp Cardiol 57:313, 2004. 16. Zenati MA, Bonanomi G, Chin AK, Schwartzman D: Left heart pacing lead implantation using subxiphoid videopericardioscopy. J Cardiovasc Electrophysiol 14:949, 2003. 17. Derose JJ, Jr, Belsley S, Swistel DG, et al: Robotically assisted left ventricular epicardial lead implantation for biventricular pacing: the posterior approach. Ann Thorac Surg 77:1472, 2004. 18. Roelke M, O’Nunain SS, Osswald S, et al: Subclavian crush syndrome complicating transvenous cardioverter defibrillator systems. Pacing Clin Electrophysiol 18:973, 1995. 19. Weiner S, Patel J, Jadonath RL: Lead failure due to the subclavian crush syndrome in a patient implanted with both standard and thin bipolar spiral wound leads. Pacing Clin Electrophysiol 22:975, 1999. 20. Hecht S, Berdoff R, Van Tosh A, Goldberg E: Radiographic pseudofracture of bipolar pacemaker wire. Chest 88:302, 1985. 21. Weissman JL, Kanel KT: Ligature causing pseudofracture of a cardiac pacemaker lead. AJR Am J Roentgenol 166:464, 1996. 22. Fahraeus T, Hoijer CJ: Early pacemaker twiddler syndrome. Europace 5:279, 2003. 23. Carnero-Varo A, Perez-Paredes M, Ruiz-Ros JA, et al: “Reel syndrome”: a new form of twiddler’s syndrome? Circulation 100:e45, 1999.

24. Lloyd MA, Hayes DL, Holmes DR, Jr: Atrial “J” pacing lead retention wire fracture: radiographic assessment, incidence of fracture, and clinical management. Pacing Clin Electrophysiol 18:958, 1995. 25. Daoud EG, Kou W, Davidson T, et al: Evaluation and extraction of the Accufix atrial J lead. Am Heart J 131:266, 1996. 26. Byrd CL, Wilkoff BL, Love CJ, et al: Intravascular extraction of problematic or infected permanent pacemaker leads: 1994-1996. U.S. Extraction Database, MED Institute. Pacing Clin Electrophysiol 22:1348, 1999. 27. Stanton MS, Hayes DL, Munger TM, et al: Consistent subcutaneous prepectoral implantation of a new implantable cardioverter defibrillator. Mayo Clin Proc 69:309, 1994. 28. Avitall B, Oza SR, Gonzalez R, Avery R: Subcutaneous array to transvenous proximal coil defibrillation as a solution to high defibrillation thresholds with implantable cardioverter defibrillator distal coil failure. J Cardiovasc Electrophysiol 14:314, 2003. 29. Kratz JM, Schabel S, Leman RM: Pseudofracture of a defibrillating lead. Pacing Clin Electrophysiol 18:2225, 1995. 30. Taliercio CP, Vliestra RE, McGon MD, et al: Permanent cardiac pacing after the Fontan procedure. J Thorac Cardiovasc Surg 90:414, 1985. 31. Alexander ME, Cecchin F, Walsh EP, et al: Implications of implantable cardioverter defibrillator therapy in congenital heart disease and pediatrics. J Cardiovasc Electrophysiol 15:72, 2004. 32. Biffi M, Boriani G, Frabetti L, et al: Left superior vena cava persistence in patients undergoing pacemaker or cardioverterdefibrillator implantation: a 10-year experience. Chest 120:139, 2001. 33. Higano ST, Hayes DL, Spittell PC: Facilitation of the subclavianintroducer technique with contrast venography. Pacing Clin Electrophysiol 13:681, 1990. 34. Gheissari A, Hordof AJ, Spotnitz HM: Transvenous pacemakers in children: relation of lead length to anticipated growth. Ann Thorac Surg 52:118, 1991.

35. Bedotto JB, Grayburn PA, Black WH, et al: Alterations in left ventricular relaxation during atrioventricular pacing in humans. J Am Coll Cardiol 15:658, 1990. 36. Stojnic BB, Stojanov PL, Angelkov L, et al: Evaluation of asynchronous left ventricular relaxation by Doppler echocardiography during ventricular pacing with AV synchrony (VDD): comparison with atrial pacing (AAI). Pacing Clin Electrophysiol 19:940, 1996. 37. Tse HF, Lau CP: Long-term effect of right ventricular pacing on myocardial perfusion and function. J Am Coll Cardiol 29:744, 1997. 38. Epstein AE, Kay GN, Plumb VJ, et al: Combined automatic implantable cardioverter-defibrillator and pacemaker systems: implantation techniques and follow-up. J Am Coll Cardiol 13:121, 1989. 39. Grier D, Cook PG, Hartnell GG: Chest radiographs after permanent pacing: are they really necessary? Clin Radiol 42:244, 1990. 40. Sussman SK, Chiles C, Cooper C, Lowe JE: CT demonstration of myocardial perforation by a pacemaker lead. J Comput Assist Tomogr 10:670, 1986. 41. Tandri H, Bomma C, Calkins H, Bluemke DA: Magnetic resonance and computed tomography imaging of arrhythmogenic right ventricular dysplasia. J Magn Reson Imaging 19:848, 2004. 42. Jongbloed MR, Lamb HJ, Box JJ, et al: Noninvasive visualization of the cardiac venous system using multislice computed tomography. J Am Coll Cardiol 45:749, 2005. 43. Sakakibara Y, Mitsui T: Concerns about sources of electromagnetic interference in patients with pacemakers. Jpn Heart J 40:737, 1999. 44. Martin ET: Can cardiac pacemakers and magnetic resonance imaging systems co-exist? Eur Heart J 26:325, 2005. 45. Martin ET, Coman JA, Shelloch FG, et al: Magnetic resonance imaging and cardiac pacemaker safety at 1.5-Tesla. J Am Coll Cardiol 43:1315, 2004. 46. Roguin A, Zviman MM, Meininger GR, et al: Modern pacemaker and implantable cardioverter/defibrillator systems can be magnetic resonance imaging safe: In vitro and in vivo assessment of safety and function at 1.5 T. Circulation 110:475, 2004.

28  28

Timing Cycles of Implantable Devices PAUL J. WANG  |  AMIN AL-AHMAD  |  HENRY H. HSIA  |  PAUL C. ZEI  |  MINTU P. TURAKHIA  |  MARCO V. PEREZ

To better understand device behaviors and to optimize management

of patients with implantable pacemakers, physicians must be familiar with the timing cycles and their constant interactions with the patient’s intrinsic rhythm.1 Timing cycles refer to the beat-by-beat behavior of implantable cardiac electronic devices (CIEDs) in response to changes in intrinsic and paced behavior. Some parameters involved in timing cycles are programmable, whereas others are unalterable within the device itself. Each type of device uses timing cycles in a somewhat different way. This chapter provides a detailed discussion of the various parameters that affect timing cycles in pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy devices.

Revised Pacing System Code It is necessary to have a basic understanding of the operational modes of the pacemakers. The pacing systems are single chamber, limited to either atrium or ventricle, or systems may be dual chamber. Systems may sense in one chamber and pace the other, sense one and pace both, or sense and pace both chambers. Their functionality can vary from beat to beat, depending on the programmed mode and the underlying rhythm. As a result of a joint approach of the North American Society of Pacing and Electrophysiology (NASPE) and British Pacing and Electrophysiology Group (BPEG), an NBG (NASPE and BPEG Generic) Code was developed (Table 28-1). The latest revision in 2002 incorporates multisite pacing.2 This three- to five-position code designates the programmed mode of the device. The first (position I) letter designates the chamber(s) paced; A stands for atrium, V for ventricle, D for pacing capability in both atrium and ventricle, and O if the unit is deactivated without pacing. Position II letter designates the chamber(s) sensed; O stands for asynchronous operation without sensing. The third (position III) letter describes the unit’s response to a sensed signal; I indicates that the pacing is inhibited by a sensed event; T indicates a pacing stimulus triggered by a sensed event; and D represents an operating mode that a stimulus may be triggered by a sensed event in one chamber and inhibited by a sensed event in the other. For example, a DDD pacemaker senses an atrial signal that triggers a ventricular pacing output; however, a sensed ventricular signal will inhibit the pacing stimulus in the ventricle. The fourth (position IV) letter describes the rate-modulation capability. Position V of the revised NASPE/BPEG code is used to denote multisite pacing; O indicates no more than one site in each chamber paced; A indicates that more than one pacing is present in the atrium; V indicates that more than one pacing site is present in the ventricle; and D indicates that more than one pacing site is present in the atrium and ventricle. In the DDDRO mode, there is sensing and pacing at single sites within the atrium and the ventricle, atrial tracking, ventricular inhibition, and rate-adaptive pacing. In DDDRV mode, all the same features are available as DDDRO, but in addition, there is pacing at two sites in the ventricles, such as in the right ventricle and the left ventricle. Dual-site atrial pacing for atrial fibrillation prevention would be represented as the DDDRA mode.

Single-Chamber Pacing Modes and Timing Cycles As just described, the pacing mode describes the set of basic pacemaker functions. Associated with each pacing mode is a set of rules that

govern the timing of events. The beat-to-beat intervals that define when paced events occur in that mode are called timing cycles. The physicians must be familiar with the nomenclature and definition of the timing cycles, as well as the basic rules that govern their behaviors. SSI MODE The AAI and VVI modes act in a comparable manner, with pacing and sensing in the same chamber (atrium or ventricle) and the pacing output is inhibited by a sensed event in that chamber. For practical purposes, AAI and VVI modes may be considered to be a common SSI mode. In each mode, a pacing output is delivered at the end of the escape interval that corresponds to the programmed lower rate limit of the device. If a sensed event (S) occurs, the pacing output is inhibited, and the escape interval is reset. VVI MODE In the VVI mode, the ventricular inhibited pacing mode, the pacemaker senses and paces in the ventricle. This mode is most appropriate for patients in chronic atrial fibrillation (AF) in whom atrial sensing or pacing is not needed. Patients who require infrequent pacing may sometimes be programmed to the VVI mode. In the VVI mode, following a sensed intrinsic ventricular activation (R wave) or a paced event (V), the pacemaker waits for the next intrinsic beat. However, if the escape interval elapses before a ventricular signal is sensed, the pacemaker delivers a ventricular pacing stimulus. Any sensed or paced ventricular event initiates the ventricular escape interval. Intrinsic events may occur at intervals shorter than the escape interval, but the longest time between any two ventricular events is the ventricular escape interval (Figs. 28-1 and 28-2). The escape interval defines the lower rate limit (usually expressed in pulses per minute), which may also be called the minimum or basic (or base) pacing rate. The timing of ventricular sensed events is initiated when the intrinsic signal reaches the necessary sensing threshold after passing through specific amplifiers and filters. The point in the intrinsic signal that is sensed may be delayed compared to the onset of the ventricular activation of the surface electrocardiogram (ECG). The largest amount of delay in sensing of the intrinsic signal from a right ventricular apical lead occurs in the setting of right bundle branch block. Ventricular Blanking and Refractory Periods To sense and pace within the same chamber, “same chamber” refractory periods must be included to avoid inappropriate oversensing of the intrinsic event or pacing3,4 (Fig. 28-3). Immediately following a ventricular paced event, during a ventricular blanking period (VBP) or time interval (ranges from 50-100 msec), all ventricular sensed events are “blanked” or not sensed. The VBP is designed to prevent oversensing of the afterpotentials from pacing stimuli. After this period of absolute lack of sensing, there is a ventricular refractory period (VRP), a programmable time window (usually expressed in milliseconds) during which the pacemaker sensing amplifier is active but does not use the ventricular sensed event to reset the timing cycle. Noise sampling may occur during the VRP, which is used to prevent oversensing caused by the paced evoked potentials, the intrinsic ventricular electrogram (VEGM), or repolarization signals (T wave).

813

814

SECTION 4  Follow-up and Programming

TABLE

Revised NASPE/BPEG Generic Code for Antibradycardia Pacing*

28-1  Position Category

I Chamber paced O = None A = Atrium V = Ventricle D = Dual (A + V) S = Single (A or V)

Manufacturer’s designation only

II Chamber sensed O = None A = Atrium V = Ventricle D = Dual (A + V) S = Single (A or V)

III Response to sensing O = None T = Triggered I = Inhibited D = Dual (T + I)

IV Rate modulation O = None R = Rate adaptive

V Multisite pacing O = None A = Atrium V = Ventricle D = Dual (A + V)

*Code was modified in 2002 and includes multisite pacing.

Ventricular Oversensing and Undersensing

V-V 1000 ms

V-R 760 ms

R-V 1000 ms

Figure 28-1  VVI mode. Ventricular paced events are noted by V and ventricular sensed events are noted by R. The ventricular rate in VVI mode in this example is 1000 milliseconds (msec, ms) and is indicated by the V-V interval. The intrinsic R wave comes 760 msec after the second ventricular paced event. The next ventricular paced event occurs 1000 msec after the intrinsic ventricular event.

1

2

3

Ventricular sensing may result in abnormalities in the ventricular timing cycles. The pacemaker senses an event that does not represent ventricular depolarization. Parts of the QRS complex, the T wave,5 afterdepolarizations,6 atrial activity,7,8 noise from lead abnormalities,9 myopotentials, and electromagnetic interference (EMI) are possible causes of ventricular oversensing.10,11 In ventricular oversensing the additional sensed event will reset the ventricular escape interval, resulting in longer intervals than the programmed pacing cycle length (Fig. 28-4). In ventricular undersensing the pacemaker does not sense an intrinsic ventricular depolarization (R wave). The ventricular escape interval is not reset by this R wave, but instead is created by the previous sensed or paced event. The pacing interval will be shorter than the pacing cycle length (Fig. 28-5). 4

5

6

7

ECG

Lower rate counter 0

Ventricular sense Ventricular pace Ventricular refractory

300 ms

Figure 28-2  Diagrammatic representation of VVI mode of pacing (rate = 80 pulses per minute). The QRS complex marked 1 is sensed. Beats 2 and 3 are paced complexes. A ventricular extrasystole (beat 4) and a normal conducted QRS (beat 5) are sensed. Beats 6 and 7 are paced. The pacemaker ventricular refractory period (300 msec) is shown by a rectangle. Complexes 4 and 5 reset and start the lower rate counter before the zero level has been reached, that is, before completion of the escape or automatic interval. The pacemaker emits its stimulus only from the zero level. (From Lendermans FW: Diagrammatic representation of pacemaker function. In Barold SS, editor: Modern cardiac pacing, Mt Kisco, NY, 1985, Futura, pp 323-353.)

*

V-V 1000 ms

V-R 760 ms

R-V 1000 ms

Figure 28-3  VVI ventricular refractory periods. The solid blue squares in the open bar indicate the ventricular blanking periods, during which events are not sensed. The shaded blue rectangles in the bar indicate the ventricular refractory periods, during which ventricular sensed events are not used to reset timing cycles.

1000 ms

R-V 1200 ms

V-V 1000 ms

Figure 28-4  VVI ventricular oversensing. The T wave of the first beat (indicated by asterisk) is sensed outside the ventricular refractory period. The ventricular escape interval is 1000 msec. Because of the T wave of the first beat is sensed, the R-V interval is 1200 msec instead of 1000 msec. The following V-V interval is the expected 1000 msec.



28  Timing Cycles of Implantable Devices

800 ms

*

*

1000 ms

V-V 1000 ms

V-V 1000 ms

V-V 1000 ms

Figure 28-5  VVI ventricular undersensing. The second R wave (indicated by asterisk) is not sensed. The next event is a ventricular paced event after a ventricular escape interval of 1000 msec. The subsequent V-V interval is also 1000 msec.

Hysteresis Rate Hysteresis provides for a longer ventricular escape interval from the last ventricular sensed event to the first ventricular paced event (R-V, hysteresis interval) but no change in the time from the last ventricular paced event12 (Fig. 28-6). Hysteresis allows the intrinsic heart rate to be lower before pacing occurs, but when pacing occurs, it will occur at a faster rate. For example, if the hysteresis pacing rate is 50 beats per minute (bpm) and the base pacing rate is 60 bpm, pacing will not occur if the patient continues to maintain rates above 50 bpm. When the heart rate falls below 50 bpm, however, pacing will occur at 60 bpm. This feature favors intrinsic activation and facilitates conduction in the patient with AF or atrioventricular (AV) synchrony in the patient in sinus rhythm. When hysteresis is programmed on, the maximum V-to-V interval (defined by the lower rate interval) is shorter than the maximum R-to-V interval (defined by the hysteresis interval). Hysteresis is often expressed as an absolute rate (beats per minute) or interval (milliseconds) from the intrinsic R wave to the first ventricular paced event (V). Hysteresis may also be expressed as the difference between the hysteresis rate and the pacing rate, or the difference between the hysteresis escape interval (R-V) and the pacing escape interval (V-V). The hysteresis rate is sometimes expressed as a percentage subtracted from the lower rate. The hysteresis often results in a decreased frequency of pacing by allowing more time to expire after an intrinsic event. Typically, the lower rate interval is set to the slowest rate that is desirable hemodynamically. Once pacing occurs, however, it will continue until the intrinsic ventricular rate exceeds the pacing rate.

V-V 1000 ms

815

*

V-V 1000 ms

Figure 28-7  VVO mode. In the VOO mode, there are ventricular paced events and no sensing. The first two ventricular events are paced at a V-V interval of 1000 msec. The third event is an intrinsic ventricular event but it is not sensed in the VOO mode. The next V event (indicated by asterisk) occurs during the physiological refractory period of the preceding ventricular event. The final V event (also indicated by asterisk) is also in the physiologic refractory period.

programmed on to prevent EMI from resulting in ventricular inhibition in the pacemaker-dependent patient. AAI MODE In the AAI mode, the atrial inhibited pacing mode, the pacemaker will deliver an atrial pacing stimulus at the end of the atrial lower rate limit, measured from the previous paced or sensed atrial event. If the atrial channel does not sense an intrinsic atrial event, and the programmed lower rate limit has expired, the pacemaker will deliver an atrial impulse (Fig. 28-8). Timing is based on intrinsic atrial sensed events (P) or atrial paced events (A). The intervals used in timing can be described as P-P, P-A, A-A, and A-P. Conceptually, the timing intervals in the AAI pacing mode are similar to those of the VVI pacing mode. However, it is important to note that in the AAI mode, only atrial events, and not ventricular events, will result in reset of the timing cycle (Fig. 28-9). Individual physician and regional practice variations exist, but generally the best-suited candidates for the AAI mode are patients who are in sinus rhythm and have intact AV conduction. Because this mode does not pace the ventricle, it is not appropriate for patients who are suspected to have compromised A-V conduction.13 The ability to maintain 1 : 1 AV conduction during atrial pacing at rates of 120 or 130 bpm or faster during the pacemaker implant procedure is frequently used to determine the absence of significant AV conduction abnormalities. Recent concern about the possibly deleterious impact of ventricular pacing has increased the interest in atrial pacing.14

VOO MODE

Atrial Periods and Hysteresis

In the VOO mode, ventricular pacing without ventricular sensing is present (Fig. 28-7). No intrinsic events are sensed, and therefore ventricular pacing occurs independent of the intrinsic rhythm. VOO is

The atrial refractory period (ARP) is similar to the VRP and constitutes a time interval after a paced or sensed atrial event in which the pacemaker is refractory to spontaneous atrial signals (Fig. 28-10). It is also divided into an atrial blanking period (ABP), often programmable, followed by a refractory period during which noise sampling occurs

*

V-V 1000 ms

V-R 760 ms

R-V 1200 ms

Figure 28-6  VVI ventricular hysteresis. The first and second ventricular events are paced with a V-V interval of 1000 msec. The third event is a ventricular sensed event. The fourth event is a ventricular paced event (indicated by asterisk) after an R-V interval of 1200 msec. The hysteresis interval is 1200 msec and the pacing interval is 1000 msec.

P-A 1000 ms

A-P 800 ms

P-A 1000 ms

A-P 800 ms

Figure 28-8  AAI mode. Atrial paced events are noted by A and atrial sensed events by P. The atrial pacing rate in the AAI mode in this example is 1000 msec and represents the time from either an atrial paced or sensed event to the next atrial paced event. Each of the P-A intervals occurs at 1000 msec, whereas the ventricular sensed events may occur earlier than the atrial pacing rate.

816

SECTION 4  Follow-up and Programming

Figure 28-9  AAI pacing. Pacemaker rate = 70 pulses per minute (ppm) (interval = 857 msec), and refractory period = 250 msec. There is intermittent prolongation of the interstimulus interval because the atrial lead senses the far-field QRS complex just beyond the 250-msec pacemaker refractory period. When the refractory period was programmed to 400 msec, the irregularity disappeared, with restoration of regular atrial pacing at a rate of 70 ppm. Stars indicate intervals with oversensing. (From Barold S, Zipes D: Cardiac pacemakers and antiarrhythmia devices. In Braunwald E, editor: Heart disease: a textbook of cardiovascular medicine, ed 4, Philadelphia, 1992, Saunders, pp 726-755.)

(Fig. 28-11). The ABP is used primarily to prevent sensing of afterpotential of the pacing stimulus. The ARP (ranges from 150-500 msec) is used to prevent the atrial lead from oversensing the afterpotential of a paced stimulus, the local evoked potential produced by atrial pacing stimulus, or “far-field” sensing of the ventricular depolarization. Atrial hysteresis may also be used in the AAI mode. The P-A interval, the atrial escape interval, is longer than the A-A interval, the atrial pacing interval. Atrial hysteresis, similar to ventricular hysteresis, may be used to minimize atrial pacing (Fig. 28-12).

P-A 1000 ms

A-P 800 ms

P-A 1000 ms

Bradycardia Timing Cycles DUAL-CHAMBER TIMING CYCLES Dual-chamber devices in the DDD mode provide a mechanism to combine pacing and sensing in either or both chambers.15-17 These functions include pacing in both the atrium and the ventricle, inhibition of pacing by sensed events in the respective chamber, and AV coordinated pacing (Fig. 28-13). A sensed intrinsic atrial event inhibits atrial pacing, and a sensed intrinsic ventricular event inhibits ventricular pacing. An atrial sensed event that occurs before the atrial escape interval has “timed out” is “tracked,” or followed by a ventricular paced output. Timing is based on atrial sensed events (P), atrial paced events (A), ventricular sensed events (R), and ventricular paced events (V). Intervals between atrial and ventricular events can be described as A-R, A-V, P-R, and P-V (Fig. 28-14).

A-P 800 ms

Figure 28-10  AAI mode atrial refractory periods. Atrial paced events are noted by A and atrial sensed events by P. The solid blue part of bar indicates the atrial blanking period, during which events are not sensed. The shaded blue part of bar indicates the atrial refractory period, during which atrial sensed events are not used to reset timing cycles. The atrial pacing rate in the AAI mode in this example is 1000 msec and represents the time from either an atrial paced or an atrial sensed event to the next atrial paced event. Each of the P-A intervals occurs at 1000 msec while the ventricular sensed events may occur earlier than the atrial pacing rate.

A-A 1000 ms

R-A

Atrial refractory

Figure 28-11  AAI mode blanking period. The blue area of bar indicates the atrial blanking period, during which events are not sensed. The purple bar indicates the atrial refractory period.

P-A 1200 ms

Figure 28-12  AAI atrial hysteresis. The atrial pacing interval in this example is 1000 msec. The atrial hysteresis interval is 1200 msec. The first event is an atrial paced event (A), followed by the second event, which is also an atrial paced event 1000 msec later. The third event is an intrinsic atrial event (P) at an 800-msec interval. The fourth atrial event is a paced event at a hysteresis interval of 1200 msec. The hysteresis interval begins with an intrinsic atrial event and ends with an atrial paced event.

P-R 160 ms

Atrial blanking

A-P 800 ms

800 ms

A-R 160 ms

P-V 200 ms

R-P

700 ms

A-V 200 ms

V-A

800 ms

P-R 160 ms

V-P

700 ms

Figure 28-13  DDD mode. The lower rate is 60 beats per minute or 1000 msec in this example of ventricular-based timing. The atrial escape interval, the time from the R-A or V-A, is 800 msec, equal to 1000 msec minus the A-V interval of 200 msec. A, Paced atrial event; P, sensed atrial event; R, sensed ventricular event; V, paced ventricular event.



28  Timing Cycles of Implantable Devices

Ap

Ap

Ap

As

VPC

817

Unsensed APC

Ap

Vs Vs

1 AV

Vp VA

AV

2

Vp

3

AV

AV

Vp

4 VA Reset

LRI TARP = AV + PVARP

PVARP

PVARP

PVARP

VRP URI

AV

Abbreviated Onset of VA interval Reset PVARP

VA Reset PVARP

5

Vp

AV

PVARP

Reset

Figure 28-14  Diagrammatic representation of the function of a DDD pacemaker. Lower rate timing is ventricular based and controlled by ventricular events (paced or sensed). Hatching indicates refractory periods; Ap, atrial paced beat; As, atrial sensed beat; Vp, ventricular paced beat; Vs, ventricular sensed beat. The four fundamental intervals are as follows: LRL, lower rate interval; VRP, ventricular refractory period; AV, atrioventricular delay; PVARP, postventricular atrial refractory period. The two derived intervals are atrial escape (pacemaker VA) interval = LRL − AV; total atrial refractory period (TARP) = AV + PVARP. Reset refers to the termination and reinitiation of a timing cycle before it has timed out to its completion according to its programmed duration. Premature termination of the programmed AV delay by Vs is indicated by its abbreviation. The upper rate interval (URI) is equal to TARP. As (third beat) initiates an AV interval terminating with Vp; As also aborts the atrial escape interval initiated by the second Vp. The third Vp resets the LRI and starts the PVARP, VRP, and URI. The fourth beat consists of Ap, which terminates the atrial escape interval (AEI) initiated by the third Vp, followed by a sensed conducted QRS (Vs). The AV interval is therefore abbreviated. Vs initiates the AEI, LRI, PVARP, VRP, and URI. The fifth beat is a ventricular extrasystole (ventricular premature contraction) that initiates AIE, PVARP, and VRP and resets the LRI and URI. The last beat is followed by an unsensed atrial extrasystole because it occurs within the PVARP. (From Barold S, Zipes D: Cardiac pacemakers and antiarrhythmia devices. In Braunwald E, editor: Heart disease: a textbook of cardiovascular medicine, ed 4, Philadelphia, 1992, Saunders, pp 726-755.)

Atrioventricular Interval The atrioventricular interval (A-V interval, AVI) is a programmable parameter that determines the maximum time after an atrial event during which an intrinsic ventricular event can occur before delivery of a ventricular pacing stimulus (see Fig. 28-13). It is initiated after a sensed or a paced atrial event. AVI is similar to the native P-R interval and thus is programmed to optimize the hemodynamic benefit of AV coordination. AVI permits atrial contraction resulting in ventricular filling in end-diastole. AVI is programmed at rest to maintain coordinated timing of atrial and ventricular contractions, allowing intrinsic AV conduction when possible, and conserve generator energy. Patients who do not have coordinated AV contractions from PR prolongation may have impaired left ventricular filling, because atrial contraction occurs much earlier than the ventricular contraction. Recent trials involving patients with both preserved and depressed ventricular function suggest maintaining intrinsic AV conduction and minimizing right ventricular pacing is also desirable hemodynamically, because improved ventricular contraction and cardiac output are seen with normal ventricular activation. Therefore the clinician balances permitting a short enough A-V interval to optimize coordination of AV contraction with permitting sufficient time for conduction to result in intrinsic ventricular activation. The programmed A-V interval that results in optimal hemodynamics may vary considerably and may be difficult to predict accurately. Many clinicians select the programmed A-V interval that allows a P-R interval of up to 280 to 300 msec. Assessment of interatrial conduction delay may have a role in setting the optimal A-V interval, but data are still limited.18 There may be a time differential with atrial activation depending on whether the atrium is paced or is activated intrinsically. Usually, the time for a paced electrical impulse to result in atrial activation is longer than the time required for intrinsic atrial activation. A differential A-V interval may be programmed, as discussed later. Also, to conserve battery energy, the clinician may extend the AVI in patients without AV block to reduce pacing. Crosstalk and Ventricular Safety Pacing.  Crosstalk is the inappropriate sensing of far-field signals from the opposite cardiac chamber, causing pacing inhibition or oversensing. One of the most serious

manifestations of crosstalk in a dual-chamber pacing system is oversensing of far-field atrial stimuli, resulting in ventricular inhibition and asystole in the “pacemaker-dependent” patient. The AVI thus encompasses multiple refractory and blanking intervals on each atrial/ ventricular channel, as well as on the “opposite” channel to prevent crosstalk (Figs. 28-14 and 28-15). An atrial pacing output also initiates multiple timing windows on the ventricular channel. Atrial pacing output triggers a VBP at the beginning of the A-V interval in an attempt to avoid oversensing the atrial stimulus artifact on the ventricular lead (Fig. 28-16). This absolute VBP is usually short, ranging from 20 to 44 msec, and may be programmable in certain pacemaker models. Immediately after the VBP, the ventricular sensing amplifier becomes active during the ventricular safety pacing (VSP, or crosstalk sensing) window in the second portion of the AVI (up to 80-120 msec). Signals sensed during the “crosstalk sensing window” (<120 msec from the atrial pacing output) are considered “nonphysiologic” because of the close coupling interval and may be caused by oversensing of atrial pacing afterpotentials, spontaneous premature ventricular depolarizations, or noise (see Fig. 28-16). VSP is designed to prevent inappropriate inhibition of the ventricular pacing caused by crosstalk (Figs. 28-17 and 28-18). After an atrial paced depolarization, if there is a sensed event occurring during the VSP window, instead of inhibiting ventricular pacing, the pacemaker will deliver a ventricular pacing stimulus at a shortened A-V interval, typically 80 to 130 msec. The shortened A-V interval makes the identification of VSP apparent and decreases the likelihood of a ventricular paced event occurring during ventricular repolarization, particularly if the baseline A-V interval is relatively long, minimizing the risk of ventricular proarrhythmia. Crosstalk in this situation is most likely to occur in the presence of high atrial pacing output (e.g., 6 V at 1 msec) along with high ventricular sensitivity (e.g., 2 mV). VSP may also be seen when atrial undersensing occurs and the conducted intrinsic ventricular beat is sensed in the crosstalk safety pacing window (Fig. 28-19). On the atrial channel, a paced event may result in an absolute ABP, preventing sensing of afterpotential of the pacing stimulus (Fig. 28-20). In some devices, a sensed atrial event also initiates an ABP. After the APB, atrial sensed events may be used for detection of pathologic atrial tachyarrhythmia for mode switching, overdrive suppression algorithm,

818

SECTION 4  Follow-up and Programming

P-R 160 ms

A-R 160 ms

P-V 200 ms

A-V 200 ms

P-R 160 ms

Atrial sensing Ventricular sensing Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period Figure 28-15  DDD refractory periods. The lower rate is 60 beats per minute or 1000 ms in this example of ventricular-based timing. The atrial escape interval, the time from the R-A or V-A, is 800 msec, equal to 1000 msec minus the A-V interval of 200 msec. A, Paced atrial event; P, sensed atrial event; R, sensed ventricular event; V, paced ventricular event. The refractory periods and sensing windows are given on the atrial and ventricular sensing channels. On the atrial channel, the atrial blanking period is after an atrial paced or sensed (usually) event. After a sensed or paced ventricular event, on the atrial channel, there may be a postventricular atrial blanking period followed by a postventricular atrial refractory period. On the ventricular channel, the ventricular sensed or paced event creates a ventricular refractory period. On the ventricular channel after an atrial paced event, there is a cross-channel ventricular blanking period, usually followed by a crosstalk safety pacing window and an alert period.

or noise reversion. After a ventricular sensed or paced event, there may be a postventricular atrial blanking period, to prevent the sensing of ventricular paced events or far-field ventricular sensed events on the atrial channel. After a ventricular paced or sensed event, a postventricular atrial refractory period (PVARP) is created (see Fig. 28-20). During PVARP, atrial events are refractory sensed events and do not affect timing of events (see later).

A-V 200 ms

Ventricular blanking period (same channel) Crosstalk sensing window Sensing window Ventricular refractory period Figure 28-16  DDD safety pacing windows. On the ventricular channel after an atrial paced event, there is a cross-channel ventricular blanking period followed by a crosstalk safety pacing window and an alert period. During the cross-channel ventricular blanking period, no sensing occurs on the ventricular channel. This blanking period prevents the atrial stimulus from inhibiting ventricular output. During the crosstalk safety pacing window, a ventricular sensed event will result in a ventricular paced event at a shorter-than-usual atrioventricular (A-V) interval, usually 80 to 130 msec. During the sensing window, a sensed ventricular event will result in inhibition of the next ventricular paced event. After the ventricular paced or sensed event, there will be a ventricular refractory period.

Differential AVI.  In some devices, the AVI initiated after a sensed atrial event (SAV) can be different from the AVI initiated after a paced atrial event (PAV). This difference in the SAV and PAV is called a differential AVI. The optimal A-V interval achieves coordination of the atria and ventricles, particularly left atrium and left ventricle. Usually, impulse formation starts in the sinus node and travels to the right atrial lead on its way to the AV node. Thus, by the time the event is sensed on the atrial channel, contraction of the atria has already begun, necessitating only relatively short delay to the time that ventricular excitation occurs. Time elapses between the initiation of an intrinsic atrial depolarization and the point that most of the atria are depolarized. This delay is determined by the distance from initiation to the location of the lead, as well as conductive properties of the atrial tissue. By the time the atrial lead has sensed the intrinsic depolarization, it has already gotten a “head start” to the AV node compared to an atrial paced event. By programming the AVI of a sensed atrial depolarization (PV) to be shorter than that after an atrial paced event (AV), the time to ventricular pacing after a paced atrial beat will be similar to that after a sensed atrial event (Fig. 28-21). This is an attempt to provide a more physiologic AV synchrony. The SAV may be expressed as a percentage of the PAV, or as an absolute difference (up to 100 msec) between the two differential A-V intervals. Rate-Adaptive or Dynamic Atrioventricular Delay.  The shortening of AVI with exercise provides optimal AV synchrony and is designed to mimic the normal physiologic shortening of the P-R interval. The programmable parameter called rate-adaptive or dynamic A-V interval permits the modulation of sensed or paced AVI based on the ventricular rate, either intrinsic or sensor driven. In addition to the hemodynamic benefit of shortening the AVI, rate-related shortening of AVI decreases the total atrial refractory period (see Upper Rate Behavior), allowing a correspondingly higher, 2 : 1 atrial tracking rate. The changes in dynamic AVI may be linear or nonlinear based on the sensed atrial rate or the sensor-driven rate and are programmed from a baseline AVI to a “minimum AVI.” Atrioventricular Interval Hysteresis.  The AVI can also be modulated based on the presence or absence of AV conduction, with a sensed ventricular event during AVI, a feature called “positive” or “negative” AV/PV hysteresis. The term “AV hysteresis” is generally used to describe adaptations of either paced or sensed AVI relative to patient’s intrinsic P-R interval. Similar to heart rate hysteresis, AVI hysteresis is a



28  Timing Cycles of Implantable Devices A-V 200 ms

819

A-V (safety pacing) 110 ms

Atrial sensing Figure 28-17  Ventricular safety pacing. Left side, An atrial paced event and a ventricular paced event are separated by the A-V interval of 200 msec. Right side, An atrial paced event is followed by a ventricular paced event after 110 msec. This represents safety pacing resulting from a ventricular sensed event in the crosstalk safety pacing window.

A P

V P

A P

A P

V S

V S

A P

V P

Ventricular sensing Atrial and ventricular blanking period (same channel) Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular refractory period

A P

A P

V S

V S

A P

V S

Figure 28-18  Ventricular safety pacing. Top channel is the surface electrocardiogram (ECG). Lower marker channel has the atrial channel on top and the ventricular channel on bottom. In the absence of crosstalk, the first, fourth, and last atrioventricular (A-V) intervals are equal to the programmed value of 200 msec. Intermittent crosstalk (solid blue circles) leads to activation of the ventricular safety pacing mechanism so that the A-V interval of the second, third, fifth, and seventh beats (black circles) is abbreviated to 110 msec. The marker channel confirms the presence of crosstalk with ventricular sensing (Vs) of the atrial stimulus (Ap) within the ventricular safety pacing period but beyond the short ventricular blanking period initiated by Ap. The arrows point to ventricular pacing (Vp) triggered at the end of the ventricular safety pacing period (110 msec after the release of Ap). In a DDD pulse generator with ventricular-based lower rate timing, activation of the ventricular safety pacing mechanism from continual crosstalk leads to an increase in the pacing rate, although the atrial escape interval remains constant. (From Barold S, Zipes D: Cardiac pacemakers and antiarrhythmia devices. In Braunwald E, editor: Heart disease: a textbook of cardiovascular medicine, ed 5, Philadelphia, 1997, Saunders, pp 705-741.)

A-V 200 ms

prolongation of AVI in response to a ventricular sensed event (R), called “positive AV/PV hysteresis.” The longer-than-programmed A-V interval permits intrinsic AV conduction and minimizes unnecessary ventricular pacing. Positive AV/PV hysteresis is most beneficial to patients who have variable AV conduction. However, if the intrinsic AV conduction exceeds the AVI hysteresis and no spontaneous R wave was sensed at the end of the AVI (as in AV block), A-V interval is shortened to the original programmed value. A search function extends the A-V interval periodically from the programmed baseline value to the longer AVI hysteresis interval to promote intrinsic AV conduction and ventricular activation (Figs. 28-22 and 28-23). This function may be called “search positive AV hysteresis”; alternatively, “negative AV/PV hysteresis” is programmed to promote and maintain ventricular pacing and avoid fusion. After an atrial event, if native ventricular conduction is sensed (R wave), the next AVI will be shortened to promote ventricular pacing and capture (Fig. 28-24). This function may be used to promote ventricular capture, when this is hemodynamically desirable. Such conditions might include pacing for hypertrophic cardiomyopathy or biventricular pacing.

A-V 200 ms

A-V (safety pacing) 110 ms

Atrial sensing

Figure 28-19  Ventricular safety pacing resulting from atrial undersensing. Left side, An atrial paced event and a ventricular paced event are separated by the A-V interval of 200 msec. Right side, An undersensed intrinsic atrial event is followed by an atrial pacing stimulus that does not capture because of physiologic refractoriness. The atrial event conducts to the ventricle. The sensed intrinsic ventricular event falls exactly within the crosstalk safety pacing window, resulting in a ventricular safety pacing.

Atrial blanking period (same channel) Postventricular atrial blanking Postventricular atrial refractory period Figure 28-20  DDD atrial blanking period. After an atrial paced or sensed event, there is a blanking period on the atrial channel. After a sensed or paced ventricular event, a postventricular atrial blanking period may be followed by a postventricular atrial refractory period. During the latter, an atrial sensed event will not be tracked or used to inhibit atrial pacing at the atrial escape interval.

820

SECTION 4  Follow-up and Programming

P-R 160 ms

Sensed P-V 160 ms

A-R 160 ms

S

A V

Paced A-V 200 ms

P-R 160 ms

P P

P

Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period

pacemaker-mediated tachycardia (PMT), which may continue without intervention (Figs. 28-26 and 28-27). PMT may occur at or below the maximum tracking rate and is often induced by spontaneous premature ventricular beats or loss of atrial capture. The rate of PMT depends on the retrograde conduction time, the programmed A-V interval, and the maximum tracking rate. PMT usually occurs at the maximum tracking rate. However, the retrograde conduction time may be long enough to permit tracking of the atrial event with the programmed A-V interval so that the PMT rate may be less than the maximum tracking rate. To avoid PMT, the PVARP is usually programmed longer

Postventricular Atrial Refractory Period After a sensed or paced ventricular event, atrial sensed events do not result in a corresponding A-V interval for a programmable period of time. The PVARP is used to prevent sensing of retrograde P waves following a paced or sensed ventricular event usually not preceded by an atrial or paced event (Fig. 28-25). The atrial channel may sense a retrograde atrial signal as an intrinsic event and trigger ventricular pacing, resulting in another ventricular paced event, which also conducts retrograde. This repetitive sequence is known as P-V 160 ms

A V

S

P-V 160 ms

S P

S P

P-R 200 ms

P-R 200 ms

Figure 28-21  Differential atrioventricular (A-V) interval. A differential A-V interval (AVI) permits a shorter AVI for a sensed atrial event compared to the interval for a paced atrial event. In the first complex here, the sensed atrial event initiates an AVI of 160 msec, but AV conduction occurs within 140 msec. Similarly, in the second complex, the paced atrial event initiates an AVI of 200 msec, but AV conduction is faster. In the third complex, the P wave is sensed and initiates a shorter AVI of 160 msec compared to the AVI of 200 msec. In the last complex, the sensed P wave also starts an AVI of 160 msec, but AV conduction occurs.

Figure 28-22  Positive atrioventricular (A-V) interval hysteresis. In positive AVI hysteresis, the A-V interval is increased to permit intrinsic AV conduction. If conduction is present, the extended A-V interval persists. If AV conduction is absent, the A-V interval will be shortened to its previous length.

S S

S

Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period

Figure 28-23  Positive AVI hysteresis. After a period of pacing, a search mechanism is initiated, and the system automatically extends the paced or sensed AV delay. If a native R wave occurs within the extended AV delay, the longer AV delay is maintained, restoring intact AV conduction and allowing for a normal ventricular activation sequence. Although the P-R interval is longer than the P-V interval, there is intact AV conduction. When the AV delay is extended on the 256th cycle, a sensed R wave is seen by the pacemaker, thus inhibiting the ventricular output and reestablishing the longer AV/PV delay engendered by adding the positive hysteresis interval to the programmed intervals. This results in functional AAI pacing or inhibited pacing, except in the presence of AV block. Although this could be accomplished with a fixed, long AV or PV delay, when and if AV block develops, the pacing system will be functioning in a hemodynamically deleterious, long AV/PV delay until intact conduction resumes. P, Atrial sensed; R, ventricular sensed; V, ventricular paced event. (Courtesy St. Jude Cardiac Rhythm Management Division, Sylmar, Calif).



28  Timing Cycles of Implantable Devices

821

Figure 28-24  Negative AV/PV hysteresis. Stable PV pacing is interrupted by one cycle (110 msec) at a shorter A-Vs interval than the P-V interval (150 msec). This causes shortening of the As-Vp (P-V) interval by the programmed value restoring PV pacing with full ventricular capture. After a period of pacing, the system extends the AV/PV interval to determine whether intact conduction is still present or will allow the longer interval to remain in effect. P, Atrial sensed; R, ventricular sensed; V, ventricular paced event. (Courtesy St. Jude Cardiac Rhythm Management Division, Sylmar, Calif.)

PVC A-R 160 ms

P-R 160 ms

PVARP

A-R 160 ms

A-R 160 ms

P *

S

P A

P

S S

V

P

P S

S

S

S

Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period

Figure 28-25  Postventricular atrial refractory period (PVARP). A premature ventricular contraction (complex) (PVC) results in retrograde conduction indicated by the asterisk. Because the P wave occurs within the PVARP, the P wave is not tracked and does not initiate a ventricular paced event. Instead, the next atrial paced event occurs after the atrial escape interval has been completed.

P-R 160 ms

A-R 160 ms

PVC 160 ms

P-V 200 ms

P-V 160 ms

P

A V

P

S S

S S

S

S P

S P

Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period

Figure 28-26  Pacemaker-mediated tachycardia. A premature ventricular complex (contraction) (PVC) results in retrograde conduction. Since the retrograde P wave occurs after the postventricular atrial refractory period, the P wave is tracked and initiates a ventricular paced event. This ventricular paced event results in another retrograde P wave that is tracked, resulting in pacemaker-mediated tachycardia.

822

SECTION 4  Follow-up and Programming

Figure 28-27  Pacemaker-mediated tachycardia terminated and initiated by ventricular extrasystole. The three ECG leads were recorded simultaneously. Upper rate interval (URI) = 500 msec (120 ppm); lower rate interval (LRI) = 857 msec (70 ppm); AV delay = 150 msec. The cycle length of the tachycardia is longer than the URI. (From Barold SS, Falkoff MD, Ong LS, Heinle RA: Basic concepts, upper rate response, retrograde ventriculoatrial conduction, and differential diagnosis of pacemaker tachycardias. In Saksena S, Goldschlager N, editors: Electrical therapy for cardiac arrhythmias: pacing, antitachycardia devices, catheter ablation, Philadelphia, 1990, Saunders, pp 225-264.)

Lower rate = 70 ppm (857 ms) Upper rate interval = 135 ppm A-V interval = 150 ms PVARP = 400 ms VRP = 250 ms

PVARP = 400 ms

than the retrograde conduction time; however, if it is programmed excessively long, the sum of the PVARP and the A-V interval, the total atrial refractory period will determine the rate at which one ventricular paced event occurs for two atrial sensed events, the 2 : 1 atrial tracking rate (see next). Extension of PVARP in response to a premature ventricular complex (PVC), called the “PVC PVARP extension” (or response), is available in many devices. This algorithm is designed to lengthen the PVARP and to avoid sensing of a retrograde P wave following a premature ventricular beat, which may cause initiation of PMT. Of note, a “PVC” is usually defined by the pacemaker as a “spontaneous ventricular depolarization” without a preceding atrial paced or sensed event. In some cases, a long PVARP may lead to absence of atrial tracking (Fig. 28-28). Similarly, oversensing of a T wave and programming on the PVC PVARP extension may cause perpetuation of absence of atrial tracking at rates below the lower rate limit (Fig. 28-29). Repetitive functional atrial undersensing may occur in the absence of PVC PVARP extension, particularly when the AV conduction is prolonged and the intrinsic A-V interval plus PVARP is longer than the sinus cycle length.19 Features such as “autointrinsic search” that cause prolongation of AV conduction may result in PMT by permitting retrograde conduction.20

PVARP = 375 ms

Figure 28-28  Lack of P-wave tracking caused by long PVARP (400 msec). Top tracing, Sinus rate is about 85 beats per minute, and there is a first-degree AV block. The P waves fall within the postventricular atrial refractory period (PVARP) initiated by the preceding sensed QRS complex. VRP, Ventricular refractory period. Bottom tracing, Shortening the PVARP to 375 msec restores 1 : 1 atrial tracking with the programmed A-V interval (150 msec). (From Barold SS, Falkoff MD, Ong LS, Heinle RA: Timing cycles of DDD pacemakers. In Barold S, Mugica J, editors: New perspectives in cardiac pacing, Mt Kisco, NY, 1988, Futura.)

P-V 160 ms

P-V 160 ms

PVC 160 ms

PVC 200 ms

Upper Rate Behavior In patients in the DDD, DDDR, VDD, or VDDR modes, one-to-one (1 : 1) ventricular tracking of the intrinsic atrial activity is

PVC 160 ms

* PVARP extension A S V

S P

PVARP extension (R)

P

S

PVARP extension (R)

S

S

Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period

Figure 28-29  Perpetuation of failure to track caused by PVARP extension. T-wave oversensing is classified as a premature ventricular complex (PVC). The PVC postventricular atrial refractory period (PVARP) extension feature results in PVARP being extended, placing the subsequent sinus P wave within PVARP. Because AV conduction is present, the next QRS complex is considered a PVC, which again causes PVARP extension.



28  Timing Cycles of Implantable Devices

CM5

ML5

A

CM5

ML5

B Figure 28-30  Upper rate behavior. A, Apparent loss of atrial tracking related to upper rate limitation. Lower rate interval (LRI) = 1000 msec; upper rate interval (URI) = 500 msec; atrioventricular (A-V) interval (AVI) = 75 msec. The ECG was recorded during a treadmill stress test. The P waves on the right were sensed (documented later by markers during repeated exercise, not shown), but the pacemaker does not emit a ventricular paced beat because a QRS complex occurs before the termination of the 75-msec AVI, thereby producing a sensed, repetitive, preempted Wenckebach upper rate response. B, Same patient as in A. During recovery of the stress test, as the sinus rate slows, the AVI gradually shortens in a few cycles until it reaches 75 msec. This produces a “reverse Wenckebach” response with gradually more ventricular capture (fusion beats) until full ventricular capture is reestablished, preceded by an atrial sensed–ventricular paced interval of 75 msec. (From Douard H, Barold SS, Broustet JP: Too much protection may be a nuisance. Stimucoeur 25:183-187, 1997).

hemodynamically desirable. However, tracking of atrial arrhythmias may result in rapid ventricular pacing and result in unfavorable hemodynamics. Therefore, these tracking modes have a parameter to limit the fastest rate that the atrium can be tracked. The fastest rate at which atrial activity can be tracked 1 : 1 to the ventricle is known as the upper rate, also called the maximum tracking rate (MTR), with a corresponding upper rate interval or maximum tracking interval (Fig. 28-30). In DDD mode, whether atrial or ventricular based, when the intrinsic atrial activity is faster than the programmed upper rate limit, “upper rate behavior” will be seen. Atrial rates above the MTR can still be sensed and tracked. However, delays in subsequent ventricular paced beats occur so that the ventricular rate does not exceed the programmed MTR (Fig. 28-31). This effectively prolongs the AVI. The A-V interval is further extended on repeated cycles, and the subsequent atrial depolarization eventually falls within the PVARP. Because the atrial event occurs within the PVARP, it is not sensed by the atrial channel and thus does not lead to ventricular pacing. The next atrial event, however, can be tracked and can cause ventricular pacing. The pattern that emerges is increasing duration between intrinsic atrial sensed events and ventricular paced events until an atrial event is not followed by a ventricular paced beat. Such behavior is similar to a Wenckebach period during AV conduction and is called “pseudo-AV Wenckebach.” The A-V interval extension is greatest when the P wave occurs just after the completion of the preceding PVARP (Fig. 28-32). A-V interval extension may be seen at constant atrial rates during atrial or sinus tachycardias as well as during atrial premature beats (Fig. 28-33).

823

If the intrinsic atrial rate continues to increase above the MTR, it will eventually reach the 2 : 1 AV tracking rate, defined by the total atrial refractory period (TARP), which is the sum of the PVARP and the AVI (Fig. 28-34). The TARP defines the period during which sensing may occur and limits the MTR. TARP determines the rate at which atrial tracking occurs in a 2 : 1 ratio. At this atrial rate, every other P wave falls into the PVARP and is not sensed. If the intrinsic atrial rate is fast enough, one P wave can fall within the TARP while the next P wave falls outside the TARP and is tracked. If the atrial rate is slightly faster, the first P wave will be tracked and the second P wave fall just within the PVARP and is not tracked. As a result, for every two intrinsic atrial events, there is one ventricular paced beat. Such a phenomenon occurs when the intrinsic atrial rate is faster than the 2 : 1 AV block rate. The 2 : 1 AV block rate can be calculated as 60,000 (in msec) divided by TARP (in msec). For example, for an AVI of 150 msec and PVARP of 250 msec, ventricular pacing may follow atrial sensing at a 1 : 1 rate up to 149 bpm. At a sinus rate of 150 bpm, 2 : 1 atrial tracking occurs and the ventricular rate abruptly drops to 75 bpm. When patients have intrinsic A-V conduction, the upper rate limit (URL) is not needed to permit tracking of rapid sinus rates during exertion. Therefore, when intrinsic A-V conduction is present, the URL may be programmed at a relatively low rate. When patients have complete AV conduction block, however, it is important to permit tracking as the atrial rate rises during exertion. The URL (MTR) should be programmed high enough to allow 1 : 1 tracking through maximum physiologic atrial rates. However, having the 2 : 1 atrial tracking rate faster than the atrial MTR permits a zone of pseudo-Wenckebach behavior before development of 2 : 1 block. To accomplish this effect, the TARP (PVARP + AVI) is programmed shorter than the URL interval. There may be limitations to minimizing TARP because of retrograde conduction necessitating a PVARP to be programmed longer than the retrograde conduction time. To avoid precipitous falls in heart rate, it is preferable to have the 2 : 1 AV block rate set above the MTR to accommodate high intrinsic sinus rates without sudden AV block. This is achieved by minimizing TARP, with several common ways to reduce TARP and raise the 2 : 1 block rate. The PVARP can be shortened (with increased risk of PMT), and the AVI can be programmed to be rate adaptive and to shorten with faster ventricular rates. Rate-adaptive or dynamic PVARP is also available in some models, which shortens PVARP at a faster rate and thus reduces TARP and increases the 2 : 1 AV block rate. Caution should be used with rate-adaptive PVARP to confirm that retrograde conduction will not occur at rapid ventricular rate, so that the conduction time does not exceed the PVARP, resulting in PMT. Alternatively, the pacemaker can be programmed to DDDR mode and can rely on the sensor to drive pacing during exertion. If sensor-driven ventricular pacing occurs close to the sinus rate, the ventricular pacing rate will closely follow the sinus rates, even though the ventricular pacing rate exceeds the atrial MTR. This phenomenon has been termed sensor-driven rate smoothing and resembles tracking above the MTR (Fig. 28-35). Upper rate behavior may also result in triggering an apparent failure to sense P waves because the P wave falls within PVARP, and the subsequent QRS complexes are categorized as premature ventricular beats. An algorithm to increase the PVARP following a PVC may result in prolonged absence of atrial tracking (Figs. 28-36 and 28-37). Upper rate behavior may also be characterized by intrinsically conducted beats that may preempt the ventricular paced beats at the upper rate. Barold et al.21 describe a relatively short programmed A-V interval, a sinus rate faster than the programmed upper rate, a relatively slow programmed upper rate, and relatively normal AV conduction as most likely to be associated with this phenomenon. Lower Rate Behavior: Atrial- versus Ventricular-Based Timing The use of atrial-based versus ventricular-based timing cycles determines when atrial paced events occur. In ventricular-based timing in the DDD mode, an atrial escape interval (AEI) is initiated after a sensed

824

SECTION 4  Follow-up and Programming

As

Vp

As

Vp

As

Vp

As

Vp

As

Vp

As

Vp

Unsensed P W

1. AV delay

W

W

W

2. Ventricular triggering period 3. Ventricular blanking period 4. Lower rate interval 5. Atrial escape interval 6. Atrial refractory period

Reset

Reset

Reset

Reset

Reset

Reset

Reset

Reset

As PVARP

As PVARP

As PVARP

As PVARP

Reset

As Atrial escape interval PVARP

PVARP

7. Ventricular refractory period 8. Upper rate interval

Pace event time line

Sense event time line

LRI AEI

AV

Figure 28-31  DDD mode upper rate response with Wenckebach pacemaker AV block. The upper rate interval (URI) is longer than the programmed total atrial refractory period (TARP); AEI, atrial escape interval. The P-P interval (As-As) is shorter than the URI but longer than the programmed TARP. The As-Vp interval lengthens by a varying period (W) to conform to the URI. During Wenckebach response, the pacemaker synchronizes Vp to As, and because the pacemaker cannot violate its (ventricular) URI, Vp can be released only at the completion of the URI. The AV delay (As-Vp) becomes progressively longer as the ventricular channel waits to deliver its Vp until the URI has timed out. The maximum prolongation of the A-V interval represents the difference between the URI and the TARP. The As-Vp interval lengthens as long as the As-As interval (PP) is longer than the TARP. The sixth P wave falls within the postventricular atrial refractory period (PVARP) and is unsensed and not followed by Vp. A pause occurs, and the cycle restarts. In the first four pacing cycles, the intervals between ventricular stimuli (Vp-Vp) are constant and equal to the URI. When the PP interval becomes shorter than the programmed TARP, Wenckebach pacemaker AV block cannot occur, and fixed-ratio pacemaker AV block (e.g., 2 : 1) supervenes. (From Barold SS, Falkoff MD, Ong LS, Heinle RA: All dual-chamber pacemakers function in the DDD mode. Am Heart J 115:1353-1362, 1988.)

or paced ventricular event (R-A or V-A). In ventricular-based timing, AEI is “fixed.” The lower rate limit (LRL) is the maximum time allowed between a ventricular event (either sensed or paced) and the subsequent ventricular pacing stimulus (V-V or R-V). The LRL is thus the AEI plus the AVI to the subsequent ventricular pacing (R-A-V or V-A-V). The length of the AEI can be determined by subtracting the AVI from the cycle length of LRL (in msec). If another ventricular sensed event occurs during the AEI, it will reset and initiate a new AEI. If an atrial sensed event occurs during the AEI (after the PVARP), it will initiate the AVI with a subsequent ventricular sensed or paced event within URL constraints. However, if the AEI expires before sensing any atrial or ventricular event, the pacemaker will provide an atrial paced beat. In ventricular-based timing, the effective ventricular rate can be faster than the programmed LRL. This occurs in patients with intact AV conduction and is mainly caused by the difference between the paced AVI and the shorter, intrinsic AV conduction. For example, in a pacemaker programmed to an LRL of 60 bpm (1000 msec) that has a programmed AVI of 200 msec, the AEI is 800 msec (LRL − AVI = AEI). If AV conduction is present at 150 msec, the sensed R wave will reset the timing cycle, whereas the AEI is “fixed” at 800 msec. The effective interval between consecutive atrial pacing is thus 950 msec (AEI + A-R), which is approximately 63 bpm (Figs. 28-38 and 28-39). In patients with intact AV conduction, the effective ventricular rate can

be faster than the programmed LRL in a ventricular-based timing system. Compared to a ventricular-based timing in which the AEI is fixed, the atrial interval (A-A) is fixed in atrial-based timing. A sensed R wave occurring during AVI inhibits ventricular output but does not reset the basic A-A interval, and thus LRL is not altered. When an R wave is sensed during AEI, the A-A interval is reset, but not the AEI. This results in a longer atrial-to-atrial interval, which simulates a physiologic “compensatory” pause. Some pacemaker models deploy a “modified” atrial-based algorithm, such that routine atrial sensed or paced events reset the A-A timing cycle, whereas premature ventricular beats reset the AEI or the V-A interval (Fig. 28-40). Early sensing of the ventricular complex on the atrial channel (crosstalk) in a pacemaker with atrial-based timing may result in prolonged AEIs22 (Figs. 28-41 and 28-42). In Figure 28-41, A, at greater ventricular sensitivity there is no evidence of a prolonged AEI, while at less ventricular sensitivity (B), AIE is significantly prolonged. Figure 28-42 reveals that the first PVC may be sensed first on the atrial channel, resulting in prolongation of the AEI. In this device, when PVCs are sensed first on the ventricular channel, ventricular-based timing is used to set AEI. The second PVC in the figure is sensed as a PVC and thus does not result in AEI prolongation. The response to a PVC varies based on the individual manufacturer’s timing cycles. A PVC may result in initiation of the entire lower rate



28  Timing Cycles of Implantable Devices

825

TARP PVARP Ap

Ap

Vp

Vp

Vp

P1 P2 P3 P4

URI

AEI

AV

PVARP W period

LRI

W period = URI–(AV + PVARP) = URI–TARP Figure 28-32  Diagrammatic representation of the mechanism of A-V interval prolongation. The pulse generator has a separately programmable total atrial refractory period (TARP) and upper rate interval (URI); lower rate timing is ventricular based. The maximum A-V interval (AV) extension, or waiting period (W), = URI − (AV + postventricular atrial refractory period [PVARP]) = URI − TARP. A P wave (P1) occurring immediately after termination of the PVARP exhibits the longest A-V interval, that is, AV + W. A P wave just beyond the W period (P4) initiates an A-V interval equal to the programmed value. P waves occurring during the W period (P2 and P3) exhibit varying degrees of AV prolongation to conform to the URI, depicted as the shortest interval between two consecutive ventricular paced beats. If the pacemaker is programmed with As-Vp shorter than Ap-Vp, W becomes URI − (As-Vp) − PVARP; that is, AV extension becomes longer if basic As-Vp is shorter than Ap-Vp. However, the maximum As-Vp duration is URI − PVARP, regardless of programmed A-V interval. AEI, Atrial escape interval; LRI, lower rate interval; Ap, atrial paced beat; Vp, ventricular paced beat. (In Barold SS, Falkoff MD, Ong LS, Heinle RA: Basic concepts, upper rate response, retrograde ventriculoatrial conduction, and differential diagnosis of pacemaker tachycardias. In Saksena S, Goldschlager N, editors: Electrical therapy for cardiac arrhythmias: pacing, antitachycardia devices, catheter ablation. Philadelphia, 1990, Saunders, pp 225-264.)

interval in milliseconds (60,000 divided by lower rate in beats per minute) before initiating an atrial paced event, resulting in an R-R interval that is longer than the lower rate interval (Biotronik). On the other hand, the interval from the PVC to the atrial paced event is equal to PVARP plus 330 msec in another timing cycle schema (St. Jude). If an atrial event is sensed within the PVARP, the interval to the atrial paced event is 330 msec (St. Jude). In remaining cases, AEI is equal to the lower rate interval minus the programmed A-V interval (Medtronic, Boston Scientific, ELA/Sorin).23 SENSOR-DRIVEN OR ADAPTIVE-RATE PACING Hemodynamics of Exercise and Rate Since the development of pacemakers in the early 1960s, the goals of pacing therapy have evolved from basic pacing for life support to

Figure 28-33  Two-lead electrocardiogram showing DDD pacing. Ventricular-based lower rate timing with sensed atrial premature contractions (APC). Lower rate interval (LRI) = 1000 msec; AV = 200 msec; upper rate interval (URI) = 600 msec; postventricular atrial refractory period (PVARP) = 155 msec. Note the extended A-V interval generated by the APCs to conform to the URI. This response with single beats should not be called a “Wenckebach” upper rate response; rather, it is best called an AV extension upper rate response.

optimizing physiologic function. The pacemakers have developed from VOO to DDDR systems. In response to enhanced sympathetic drive during exercise, the heart rate and stroke volume increase, leading to greater cardiac output (CO = HR × SV). Unlike people who can raise their heart rate considerably during exercise, patients with sinus node or conduction system dysfunction are unable to so adequately. Heart rate is the predominant determinant of cardiac output compared with stroke volume, so the pacemaker must provide rate-adaptive pacing to optimize physiologic response. Impaired heart rate response to increased metabolic demand is known as “chronotropic incompetence.” Its definition varies, sometimes described as inability to achieve 75% of the maximum predicted heart rate for age. Individuals with chronotropic incompetence include patients who are in sinus bradycardia with sinus node dysfunction or those in AF with a slow ventricular rate response. Both populations may exhibit blunted heart rate

APC

APC

URI = 600 ms

826

SECTION 4  Follow-up and Programming

TARP = PVARP + AVI AV 200 ms

PVARP 360 ms

S

A

S P

P V

Atrial blanking period Crosstalk sensing window Sensing window Postventricular atrial blanking Postventricular atrial refractory period Ventricular blanking Ventricular refractory period Figure 28-34  Total atrial refractory period (TARP). TARP represents the sum of the postventricular atrial refractory period (PVARP) and the A-V interval (AVI, AV). In this case, TARP = 360 msec + 200 msec = 560 msec. Therefore, 2 : 1 atrial tracking would occur at an atrial cycle length of 560 msec.

ARP ASW AVI 420

420

420 ms

MTR 440 ms

440 ms

440 ms

AP AS

VP

AS

VP

VP

VP

Figure 28-35  Sensor-driven appearance of atrial tracking. Diagram shows that a P wave may inhibit the sensor-driven atrial stimulus and can resemble P –wave tracking above the maximum tracking rate (MTR) of 100 bpm or 600 msec. The second and third ventricular complexes are preceded by intrinsic P waves that appear within the atrial sensing window (ASW). Sensing of atrial activity in this window results in inhibition of the atrial stimulus or P-wave tracking above the MTR. The fourth ventricular complex was preceded by an atrial paced event because the intrinsic P wave was within the atrial refractory period ARP. AP, Atrial paced; AS, atrial sensed; AVI, atrioventricular interval; VP, ventricular paced event. (From Higano ST, Hayes DL: P wave tracking above the maximum tracking rate in a DDDR pacemaker. Pacing Clin Electrophysiol 12:1044-1048, 1989.)



28  Timing Cycles of Implantable Devices

827

response to stress. Algorithms have been developed to estimate an individual’s expected maximum heart rate, as during vigorous exercise. One of the most common estimations is based on patient age (220 − age = maximum heart rate). Rate-Adaptive Pacing To provide a greater heart rate response with exertion in efforts to support the metabolic demands during exercise, rate-adaptive pacing is essential for patients with chronotropic incompetence. For example, patients in sinus bradycardia with sinus node dysfunction could benefit from either an atrial or a dual-chamber rate-responsive pacemaker to achieve a higher heart rate response during exertion than their sinus node can provide. Similarly, patients who have chronic AF and slow ventricular rate may benefit from a VVIR pacemaker, which increases rate of ventricular pacing with exertion.

A

Timing Cycles of Sensor-Driven Pacing The timing cycles in sensor-driven pacing preserve the timing cycles of the basic non-rate-adaptive mode. In the VVIR mode, there is a sensor-indicated rate that serves as the LRL. The ventricular escape interval will vary based on the sensor-indicated rate. Similarly, in the DDDR mode, the sensor-indicated rate serves as the LRL. The timing cycles in DDDR are based on the sensor-indicated interval serving as the lower rate interval. The escape interval in a ventricular-based timing device is calculated by subtracting the paced A-V interval from the sensor-indicated interval. Rate-Adaptive Algorithms

B

C Figure 28-36  Apparent P-wave undersensing. Lower rate = 60 pulses per minute (ppm); upper rate (UR) = 140 ppm; AV delay after P-wave sensing = 135 msec (adaptive AV delay with minimum AV delay of 75 msec); postventricular atrial refractory period (PVARP) = 320 msec; automatic PVARP extension = 100 msec. A, At rest, the atrial rate is 112 beats per minute (bpm), causing atrial sensing and ventricular pacing with AV interval of about 100 msec. B, After 1 minute of exercise, Wenckebach upper rate response occurs, and the pacemaker does not sense a P wave (arrow) in the PVARP. The P wave in the PVARP allows spontaneous AV conduction with a P-R interval of about 260 msec. The pacemaker interprets the spontaneous QRS complex as a premature ventricular contraction (complex) and therefore automatically lengthens the PVARP to 320 + 100 = 420 msec. Subsequent events all are spontaneous, that is, P wave and conducted QRS complex with P-R interval longer than the programmed As-Vp interval at that particular atrial rate (apparent lack of atrial tracking). The spontaneous QRS complex continually activates the PVARP extension as the P waves continually fall within the extended PVARP. C, In the recovery phase, ECG shows sinus rhythm (P-R = 200 msec) and conversion to an atrial synchronous ventricular paced rhythm with an A-V interval of 100 msec. The P-R interval preceding ventricular pacing shows an abrupt shortening of about 40 msec without a change in P-P interval. This results in earlier detection of the conducted QRS complex and subsequently the next P wave falls outside the extended PVARP of 420 msec. (From van Gelder BM, van Mechelen R, den Dulk K, el Gamal M: Apparent P wave undersensing in a DDD pacemaker after exercise. Pacing Clin Electrophysiol 15:1651, 1992.)

Special algorithms attempt to permit more physiologic response to exertion by modulating programmable intervals as rate changes. For example, in some systems the AVI can be shortened when an increased atrial rate is sensed or when the sensor-driven rate increases (rateadaptive AV delay). This feature attempts to simulate the physiologic narrowing of the AV conduction time (P-R interval) that occurs with exercise. When responding to increased intrinsic atrial rates, it also permits a higher MTR. Since the AVI is shortened, the TARP (PVARP + AVI) also shortens, allowing for a higher 2 : 1 atrial tracking rate (60,000/TARP in beats per minute). A high 2 : 1 AV block rate affords a higher MTR that maintains 1 : 1 AV synchrony. For individuals who cannot tolerate a shortened PVARP because of persistent retrograde conduction, who have impaired AV conduction, rate-modulation of the AVI can be particularly useful. The A-V interval also may shorten as the sensor-driven rate increases. This permits the hemodynamic effects of sensor-driven pacing to be optimized with an A-V interval that shortens with exertion. The PVARP may also be rate modulated. The rate adaptation is based on the physiologic observation of decreased retrograde conduction with increased activity seen in normal subjects. When rate-adaptive PVARP is programmed, as the sensor-determined rate increases, the PVARP shortens, which also shortens TARP (similar to rate-adaptive AVI) and allows for a higher 2 : 1 tracking rate. However, shortening the PVARP rests on the assumption that retrograde conduction will shorten with exertion. Individuals who have retrograde conduction that is slower than that assumed by the algorithms may be at risk for development of PMT. NOISE RESPONSE To minimize EMI from lead problems, myopotentials, and environmental noise, noise response algorithms have been developed. Positioned after the VRP, the noise-sampling period (usually 60-200 msec) will interpret any sensed events as nonphysiologic noise. This detection results in extension of VRP or sampling period. If the noise is intermittent, inappropriate sensing may inhibit pacing. With more continuous noise, the pacing can become asynchronous. Depending on the nature of the extrinsic electromagnetic source, the device may “revert” to one of several nominal settings, such as a reset mode, an emergency VVI mode, or the elective replacement indicator settings.

828

SECTION 4  Follow-up and Programming

Lower rate = 70 ppm (857 ms) Upper rate interval = 135 ppm A-V interval = 150 ms PVARP = 400 ms VRP = 250 ms

PVARP = 400 ms

PVARP = 375 ms

Figure 28-37  Loss of P-wave tracking caused by long PVARP (400 msec). The sinus rate is about 85 ppm, and there is first-degree AV block. The P waves fall within the PVARP initiated by the preceding sensed QRS complex. Shortening the PVARP to 373 msec (bottom) restores 1 : 1 atrial tracking with the programmed A-V interval (150 msec). VRP, Ventricular refractory period. (From Barold SS, Falkoff MD, Ong LS, Heinle RA: Timing cycles of DDD pacemakers. In Barold S, Mugica J, editors: New perspectives in cardiac pacing, Mt Kisco, NY, 1988, Futura.)

As

Vp

As

DDD mode As Vp

Vp

As

Vs

Vp

As

Vp

Abbreviated 1. AV delay 2. Ventricular triggering period 3. Ventricular blanking period

Reset

Reset

4. Lower rate interval

Reset

5. Atrial escape interval 6. Atrial refractory period

Reset

As PVARP

PVARP

7. Ventricular refractory period

As PVARP

Reset

PVARP

PVARP

Reset

8. Upper rate interval Pace event time line

Atrial ref. extension

Sense event time line

Figure 28-38  DDD mode with ventricular-based lower rate timing. Diagrammatic representation of timing cycles; REF, refractory; ventricular triggering period, ventricular ventricular safety period. The second ventricular sensed event (Vs) is a sensed ventricular extrasystole. The fourth A-V interval initiated by an atrial sensed event (As) is abbreviated because Vs occurs before the A-V interval has timed out. The PVARP generated by the ventricular extrasystole is automatically extended by the atrial refractory period extension. This design is based on the concept that most episodes of endless-loop tachycardia (pacemaker macro-reentrant tachycardia caused by repetitive sensing of retrograde atrial depolarization) are initiated by ventricular extrasystoles with retrograde ventriculoatrial (VA) conduction. Whenever possible, the A-V interval and atrial escape (pacemaker VA) interval (AEI) are depicted in their entirety for the sake of clarity. The arrow pointing down within the AEI indicates that As has taken place. The As inhibits the release of the atrial stimulus expected at the completion of AEI. (From Barold SS, Falkoff MD, Ong LS, et al: All dual-chamber pacemakers function in the DDD mode. Am Heart J 115:1353, 1988.)



28  Timing Cycles of Implantable Devices

A-R 160 ms

A-R 160 ms

R-A

R-R

A-V 200 ms

R-P

1000 ms

A-R 160 ms

V-A

1000 ms

A-R 160 ms

800

800

V-P

960 ms

Figure 28-39  Ventricular-based timing cycles. The lower rate limit is 1000 msec, and the AV delay is 200 msec. The atrial escape interval is 800 msec. The R-R intervals are given; note that the R-R interval is 1000 msec between the first and second beats. Between the second and third beats, the R-R interval is also 1000 msec; between the third and fourth beats, it is 960 msec because the AV conduction time is less than 200 msec. A, Atrial paced event; P, atrial sensed event; R, ventricular sensed event; V, ventricular paced event.

A-R 160 ms

660

829

A-V 200 ms

A-R 160 ms

A

B

Figure 28-41  Prolongation of atrial escape interval in atrial-based timing pacemaker. A, In the left panels, atrial sensitivity was programmed to 0.5 millivolt (mV) and the ventricular sensitivity was 1 mV. The premature ventricular complex (PVC) resulted in an atrial escape interval (AEI) of 660 msec, corresponding to the programmed AEI of 600 msec. B, In the right panels, atrial sensitivity was still programmed at 0.5 mV, but the ventricular sensitivity was decreased to 4 mV. The PVC (arrow) resulted in prolongation of the AEI of 800 msec, which corresponds to the programmed lower rate interval of 750 msec. (From Barold SS: Far-field R-wave sensing causing prolongation of the atrial escape interval of DDD pacemakers with atrial-based lower rate timing. Pacing Clin Electrophysiol 26:2188-2191, 2003.)

PACEMAKER-MEDIATED TACHYCARDIA ALGORITHMS

R-R

1000 ms

1040 ms

960 ms

Figure 28-40  Atrial-based timing cycles. The lower rate limit is 1000 msec, and the AV delay is 200 msec. The atrial escape interval  is 800 msec. The R-R intervals are given; note that the R-R interval is 1000 msec between first and second beats. Between the second and third beats, the R-R interval is 1040 msec; between the third and the fourth beats, it is 960 msec because the AV conduction time is less than 200 msec. A, Atrial paced event; P, atrial sensed event; R, ventricular sensed event; V, ventricular paced event.

Figure 28-42  Prolongation of atrial escape interval in atrial-based timing pacemaker. AEI prolongation is caused by far-field R-wave sensing on the atrial channel. Lower rate limit is 800 msec in an atrial-based timing system, except for after premature ventricular complexes (PVCs), when ventricular-based timing is present. After the first PVC, the As marker precedes the Vs marker, suggesting early sensing of the R wave on the atrial channel. Early atrial sensing results in AEI prolongation because it is an atrial-based timing system. The second PVC is not sensed first on the atrial channel and therefore is considered to be a PVC, resulting in ventricular-based timing and no AEI prolongation. (From Barold SS: Far-field R-wave sensing causing prolongation of the atrial escape interval of DDD pacemakers with atrial-based lower rate timing. Pacing Clin Electrophysiol 26:2188-2191, 2003.)

Algorithms also prevent or terminate the PMT phenomenon in dualchamber pacemakers. PMT, or “endless loop tachycardia” (ELT), results from retrograde conduction to the atrium after a ventricular depolarization, which can be sensed and “tracked” by the atrial lead and trigger another ventricular pacing event. The retrograde limb of the PMT is the native conduction system, and the anterograde limb is atrial tracking in the dual-chamber model. Each ventricular paced beat results in retrograde conduction and perpetuation of PMT. As discussed earlier, PMT is often triggered by a PVC. The uncoupling of AV synchrony, such as in failure of atrial capture or excessively long programmed AVI, may result in PMT. The most common PMT prevention algorithm is PVC PVARP extension. Without a preceding atrial activation, patients are especially vulnerable to PMT after PVC because retrograde ventriculoatrial (VA) conduction occurs relatively easily because the native conduction system is not yet refractory. When the pacemaker senses a ventricular event without a preceding atrial event, it identifies it as a PVC and automatically lengthens the PVARP to protect against potential retrograde conduction. Such a parameter does not require that the

830

SECTION 4  Follow-up and Programming

1

2

3

8

9

PVARP

PVARP

PVARP

PVARP

PVARP = 400 ms

Parameter: PVARP = 280 ms

200 ms

Figure 28-43  Pacemaker-mediated tachycardia (PMT) intervention using extension of PVARP. PMT is initiated with a premature ventricular beat at the left side of the panel. After eight Vp-As intervals occur in less than 400 msec, the PMT intervention is initiated. The ninth Vp event extends the PVARP to 400 msec for one cycle. Because the next atrial event is not tracked, PMT terminates.

PVARP is extended at all times, resulting in an increase in the TARP and a decrease in the 2 : 1 atrial tracking rate. Algorithms also may detect retrograde conduction when it is present in a sensing window (e.g., WARAD). Some algorithms may classify an atrial sensed and ventricular paced rhythm as PMT if atrial tracking occurs at a specific rate. The PMT detection rate may be the upper tracking rate or a rate above the upper tracking rate. Other algorithms detect PMT if repetitive atrial sensing follows ventricular pacing with a consistent V-A interval of less than 400 msec (compatible with retrograde VA conduction). When PMT is detected, different responses can occur. Some devices will extend the PVARP, whereas others will suspend atrial tracking for one cycle, causing PMT to terminate (Fig. 28-43). In some generators, sensor activity is used in combination with the atrial sensed rate to determine if PMT is present. For example, with eight consecutive intervals with a VA time of less than 400 msec, and if the atrial rate is less than the sensor-determined rate of activities of daily living, PMT is diagnosed and a PMT termination algorithm initiated (Medtronic). In another algorithm, the PMT detect rate may be programmed from 90 bpm to the MTR. In one strategy, if 10 beats occur at a rate greater than the PMT rate, the PVARP is extended to 480 msec (St. Jude).24 MODE SWITCHING Automatic mode switch (AMS) refers to the ability of the pacemaker to switch automatically from one mode of operation to another in response to a sensed atrial tachyarrhythmia25-28 (Fig. 28-44). When atrial tachyarrhythmias occur, atrial tracking modes such as DDD(R) or VDD(R) can result in rapid ventricular pacing with resultant hemodynamic compromise. Mode-switching algorithms detect the presence of atrial tachyarrhythmias and convert the pacemaker to a nonatrial tracking mode such as VVI(R) or DDI(R). In some cases, mode switching in DDD may result in either DDI or DDIR. An alternative mode switch is VDI or VDIR. Before mode switching, there may be a period of atrial tracking resulting in short paced intervals. Once mode switching is confirmed, the mode changes to the nonatrial tracking mode and the rate gradually decreases to the LRL. Mode-switching functions are often programmable. The algorithms vary but may be triggered by a specific atrial rate threshold, either absolute or averaged (in beats per minute). There is usually a requirement for sustained high rate duration (a number of beats or a time duration) before mode switching occurs. Other devices deploy a “running counter” that increases when the atrial rate is faster and decreases when the atrial rate is slower than a specified rate limit. The pacemaker will switch modes only when the counter has reached a predetermined number. This prevents inappropriate mode switch caused by frequent isolated atrial ectopic beats. Some algorithms permit detection of premature atrial beats on a beat-to-beat basis. Lau et al.25 describe the “perfect” mode-switching system as having (1) rapid onset to avoid rapid ventricular pacing during initial detection of atrial tachyarrhythmias, (2) absence of fluctuation in rate or inappropriate response, (3) ability to restore AV synchrony rapidly after

termination of atrial tachyarrhythmia, (4) ability to sense atrial tachyarrhythmias at a variety of rates and signal amplitudes, and (5) ability to avoid response to crosstalk, sinus tachycardia, and extraneous noise. Nonetheless, detection of atrial arrhythmias remains the greatest challenge for mode switching algorithms.29-31 Undersensing is possible because the amplitude of the atrial electrogram (AEGM) may decrease significantly during atrial tachyarrhythmia compared with sinus rhythm. As the atrial channel becomes more sensitive, undersensed events will decrease, but oversensing of noise or extraneous signals may increase (Fig. 28-45). ABP does not usually play a significant role in atrial undersensing during AF.32 Oversensing can also be problematic, such as far-field signals (crosstalk) from ventricular depolarizations, T waves, myopotentials, or environmental noise. In the case of undersensing, mode switching may fail to occur, whereas in oversensing, mode switching may occur inappropriately. Symptoms are usually minimized during mode switching because of the relatively rapid onset of mode switching. Even when mode switching occurs rapidly, however, some patients may remain symptomatic because of the abrupt change in rate. A comparison of three different mode-switching algorithms downloaded into an implanted pacemaker was made (Fig. 28-46). The mean atrial interval (MAI) was compared to 4 of 7 intervals and 1 of 1 interval as criteria for mode switching; the shorter the criteria, the greater the number of episodes observed. The duration of mode switching decreased with shorter criteria, as expected. The symptoms did not vary significantly. ATRIAL FLUTTER RESPONSE Because atrial flutter may be associated with every other AEGM falling into a blanking period, mode switching during atrial flutter may not reliably occur. A special response may occur when atrial flutter is detected to result in mode switching and to prevent pacing during the atrial vulnerable period.33 If an atrial event is detected within PVARP, a programmable interval is created. Subsequent atrial events sensed within this programmable interval will also not be tracked, and each such event will create another programmable interval. This algorithm permits atrial tracking to be withheld even before mode switching occurs. In addition, atrial pacing does not occur until the programmable interval or PVARP expires. Once the PVARP or the programmable interval expires, atrial pacing may occur if there is at least

ECG MC

EGM

ECG MC

AEGM Figure 28-44  Activation of mode-switching function from DDDR to DDIR. Activation of the mode-switching function results in conversion to the DDIR mode at 60 beats per minute; AEGM, atrial electrogram; ECG, surface electrocardiogram; MC, marker channel. (From Lau CP, Leung SK, Tse HF, Barold SS: Automatic mode switching of implantable pacemakers. I. Principles of instrumentation, clinical, and hemodynamic considerations. Pacing Clin Electrophysiol 25:967-983, 2002.)

831

28  Timing Cycles of Implantable Devices

Undersensing (% of time)



Thera DR

Marathon DDDR

60

60

60

40

40

40

20

0

1

2

3

0

Episodes 120

1

2

0

3

1

2

80

80

60

60

60

40

40

40

20

20

20

0

1

2

3

0

1

2

3

60

1.5

0

Meta DDDR

0

1

2

Minutes 3 2.5 2.5 2

40

3

Duration of MS

80

20

Marathon DDDR

80

103

100

Programmed AS (mV) Thera DR

Oversensing (% of tests)

No. of MS

20

20

A

B

Meta DDDR

35 20 MAI 4/7 1/1

Score 25 23 20

0

18.2

20.4

15

1.4

10

1 0.5

Symptoms

0.4 MAI 4/7 1/1

5 0

MAI 4/7 1/1

Figure 28-46  Effect of mode-switching (MS) criterion on frequency, duration, and symptoms. Three different MS algorithms were downloaded into an implanted pacemaker. The mean atrial interval (MAI) was compared to 4 of 7 intervals and 1 of 1 interval as a criterion for mode switching. The shorter the criteria, the greater the number of episodes observed. The MS duration decreased with shorter criteria as expected. The symptoms did not vary significantly. (From Marshall HJ, Kay GN, Hess M, et al: Mode switching in dual-chamber pacemakers: effect of onset criteria on arrhythmia-related symptoms. Europace 1: 49-54, 1999.)

3

Programmed AS (mV)

Figure 28-45  Ability to mode-switch depends on atrial sensitivity. Atrial undersensing increases as the device is made less sensitive. A, At atrial sensitivities (AS) greater than 1 mV, atrial undersensing becomes apparent. B, As the atrial sensitivity approaches 2 mV, the degree of oversensing noise becomes minimal. (From Lau CP, Leung SK, Tse HF, Barold SS: Automatic mode switching of implantable pacemakers. I. Principles of instrumentation, clinical, and hemodynamic considerations. Pacing Clin Electrophysiol 25:967-983, 2002.)

Figure 28-47  Atrial flutter algorithm to trigger mode switching. If atrial cycles are sensed at an interval shorter than twice the AV delay plus the postventricular atrial blanking period for eight consecutive cycles (asterisk), the algorithm extends the PVARP to 400 msec for one cycle; AEGM, atrial electrogram; MD, marker diagram. (From Israel CW, Barold SS: Failure of atrial flutter detection by a pacemaker with a dedicated atrial flutter detection algorithm. Pacing Clin Electrophysiol 25:1274-1277, 2002.)

50 msec and no more than the AV delay before the next ventricular paced beat. A related algorithm permits atrial flutter to trigger mode switching. If atrial cycles are sensed at an interval shorter than twice the AV delay plus the postventricular atrial blanking period (PVABP) for eight consecutive cycles, the algorithm extends the PVARP to 400 msec for one cycle (Fig. 28-47). The atrial signal that had been tracked is now refractory and may activate mode switching. Figure 28-48 shows an example of an atrial flutter with an atrial cycle that places an atrial signal within the PVABP so that the atrial flutter response never occurs.

II AEGM MD

II AEGM MD

Figure 28-48  Failure of atrial flutter detection algorithm. Atrial flutter has an atrial cycle that places an atrial signal within the postventricular atrial blanking period (PVAB) so that the atrial flutter response never occurs; AEGM, atrial electrogram; MC, marker channel. (From Israel CW, Barold SS: Failure of atrial flutter detection by a pacemaker with a dedicated atrial flutter detection algorithm. Pacing Clin Electrophysiol 25:1274-1277, 2002.)

832

SECTION 4  Follow-up and Programming

Atrial smoothing window Atrial event

AV delay (150 ms)

Atrial event

578 ms

650 ms

698 ms

R–R interval (800 ms) Right ventricular event

Right ventricular event

728 ms

800 ms

848 ms

Right ventricular smoothing window

Figure 28-49  Rate-smoothing algorithm. Adjusts the intervals of the successive atrial and ventricular events based on the previous cycle length rather than just the programmed atrial escape interval or upper rate tracking interval. When rates are decreasing, the rate of slowing is constrained by rate smoothing “down.” In contrast, with increases in rate, such as with rapid atrial tracking rate, smoothing “up” constrains the rate. In the example, the atrial and ventricular events must occur within the atrial and ventricular smoothing windows.

RATE SMOOTHING Rate-smoothing algorithms are designed to “smooth” and prevent sudden changes in heart rates accompanied by hemodynamic compromise or symptoms. Sinus arrest may result in an abrupt decrease in heart to the escape rate (e.g., from 80 to 50 bpm). Rate smoothing “down” results in a more gradual decrease in heart rate. The rate of decrease in rate is constrained by the programmed rate-smoothing percentage, usually from 3% to 24%. A rate-smoothing atrial or ventricular window is created that determines when the next atrial paced or ventricular paced event will occur. The ventricular window is created by calculating the previous V-V interval and multiplying by the rate-smoothing percentage. For example, if the previous cycle length was 1000 msec and rate smoothing up was 12% and down was 8%, the width of the rate-smoothing up window would be 120 msec and the down window would be 80 msec. The atrial rate-smoothing window is calculated by subtracting the AV delay from the boundaries of the ventricular rate-smoothing window (Fig. 28-49). Sudden changes in ventricular rate can also occur in patients with intermittent atrial arrhythmias or AF.34 Tracking of an atrial arrhythmia that may be too transient or too slow to trigger mode switching may result in palpitations or other symptoms because of the abrupt increase in heart rate. Rate smoothing “up” may limit the ventricular rate to avoid the suddenness of the heart rate increase. Mode switching may interact with a variety of other programmed parameters. Ventricular tachycardia prevention algorithms may become inactivated by mode switching.35 FALLBACK Fallback response provides a response very similar to rate smoothing by limiting the rate of the heart rate change.36 Fallback may occur when the rate decreases from URL tracking to the LRL during mode switching or other rate-drop response. RATE-DROP RESPONSE Patients who experience neurocardiogenic or vasovagal syncope become symptomatic when the heart rate falls precipitously. The ratedrop response (RDR) algorithm is designed to recognize a rapid decline in heart rate using a heart rate duration detection window. The degree of rate drop (in beats per minute) within the specified duration (in number of beats) is programmable. The newer algorithm uses an averaged ventricular baseline rate as the reference. Once the RDR is triggered, dual-chamber pacing is then initiated at a relatively fast rate, either an absolute rate (100-120 bpm) or a relative rate (70% or 80% of maximum heart rate) (Fig. 28-50). The sudden bradycardia response

(SBR) is another example of this type of rate algorithm. This response is initiated by a decline in the atrial rate by more than 10 bpm for a programmed number of beats (1 to 8) based on a weighted average serving as the baseline rate. The SBR consists of pacing at a rate that is 5 to 40 bpm faster than the previous rate. PREVENTION OF ATRIAL FIBRILLATION There has been considerable interest in using atrial pacing for prevention of AF.37-41 The Pacemaker Selection Trial for the Elderly (PASE) study and the Canadian Trial of Physiological Pacing (CTOPP) showed that atrial pacing or dual-chamber pacing is associated with a lower occurrence of AF compared with ventricular pacing alone.42-44 Pacing from sites other than the right atrium, such as the atrial septum or Bachmann’s bundle, has been shown to decrease the incidence of AF. Atrial pacing at two sites, such as the right atrium and coronary sinus ostium (CS os), has also been examined for its effect on AF. Multisite atrial pacing has shown varying efficacy in AF prevention. Specific atrial pacing algorithms have been studied as possible methods of decreasing AF. Prospective randomized trials, such as the Atrial Dynamic Overdrive Pacing Trial (ADOPT) and Overdrive Atrial Septum Stimulation (OASIS) trial, demonstrated significant reductions in AF burden using the AF suppression algorithm (St. Jude Medical). Continuous atrial overdrive pacing is maintained by setting the atrial lower rate higher than the intrinsic sinus rate. The atrial pacing rate is adjusted in response to either the mean atrial rate or the occurrence of premature atrial beats. AF pacing parameters may be set to stimulate the atrium at rates faster than the intrinsic atrial rate to suppress the triggers of AF (Fig. 28-51). When two P waves are detected within a 16-cycle window, the atrial pacing algorithm is initiated. The pacing occurs for a programmable number of pacing cycles, a programmable number of intervals, and then the interval is gradually decreased. Atrial pacing preference (APP) paces in response to the atrial rate but not to premature atrial beats. In contrast, atrial pacing may specifically respond to atrial pacing in a specific interval. The atrial overdrive in a DDD(R) mode is triggered whenever two spontaneous P waves are sensed in a 16-beat window. The extent of atrial overdrive is a nonprogrammable parameter, determined by the instantaneous atrial rate. The continuous atrial pacing algorithm also increases atrial pacing and paces at 30 msec shorter than the intrinsic atrial cycle length. A double-algorithm approach alters pacing in response to atrial premature beats (used by the Medtronic AT 500). However, such high rate overdrive pacing may result in undersensing because of a short atrial sensing window. Rare cases of proarrhythmia have been reported. There is a need for greater understanding of the efficacy, technique, and physiology of atrial pacing compared to dual-chamber pacing. In addition to AF prevention, some evidence indicates that atrial



28  Timing Cycles of Implantable Devices

833

Intervention rate at 100 ppm Intervention duration

Lower rate at 40 ppm Time = Sensed atrial beats = Paced atrial beats (detection beats) = Paced atrial beats Figure 28-50  Rate-drop response. The rate-drop response results in pacing at a faster rate (intervention rate) when an abrupt drop in the ventricular rate occurs, defined as a minimum drop in heart rate over a range of detection intervals. A minimum rate for a specific number of intervals alone may be used to trigger this response. The intervention rate is the pacing rate for the programmed period of time.

overdrive pacing may terminate some atrial arrhythmias leading to atrial fibrillation. NONCOMPETITIVE ATRIAL PACING To prevent atrial pacing after an intrinsic atrial event has occurred during an atrial refractory period (competitive atrial pacing), a noncompetitive atrial pacing feature may be programmed on. This programmable parameter delays the time at which the atrial pacing stimulus occurs. Atrial sensed events may occur in PVARP during upper rate behavior and competitive pacing is most likely to occur when there is sensor-driven atrial pacing (Fig. 28-52). Shortening PVARP is another method of preventing competitive pacing but retrograde conduction may limit this option (Fig. 28-53).

Figure 28-51  Atrial fibrillation (AF) pacing suppression algorithm. AF pacing parameters may be set to stimulate the atrium at rates faster than the intrinsic atrial rate to suppress the triggers of AF. When two P waves are detected within a 16-cycle window, the atrial pacing algorithm is initiated. The pacing occurs for a programmable number of pacing cycles. In this example, atrial pacing is already at 84 beats per minute. Since two sinus beats occur the pacing rate increases. The pacing occurs for a programmable number of intervals, and then the interval is gradually decreased.

MANAGED VENTRICULAR PACING Growing evidence in literature suggest right ventricular pacing is detrimental to hemodynamics in a number of patient populations, with many studies indicating an increased incidence of atrial fibrillation with ventricular pacing.45 A managed ventricular pacing (MVP) algorithm is designed to minimize unnecessary RV pacing. The MVP algorithm operates in an AAI(R) mode to minimize ventricular pacing; however, ventricular backup pacing is available if heart block occurs. Thus, some clinicians have described MVP as ADIR with mode switching to DDDR.46 Backup ventricular pacing occurs after any A-A interval occurs without a sensed ventricular event and is delivered at an interval equal to the A-A interval plus 80 msec. MVP automatically “mode switches” from AAI(R) to DDD(R) when no ventricular sensed

834

SECTION 4  Follow-up and Programming

1

3

2

ECG Marker channel Relative refractory period, Pace atrium safely, atrial pace may induce atrial Pace atrium no capture tachycardia safely, capture Figure 28-52  Noncompetitive atrial pacing algorithm. Pacing after a premature atrial beat occurring during PVARP may cause atrial arrhythmias. Algorithms have been developed to prevent so-called competitive pacing. If an atrial event occurs within PVARP, an additional window called the noncompetitive atrial pacing period is created. Atrial pacing will be delayed until the end of this period, allowing the atrium additional time to repolarize. (Redrawn from Medtronic Enpulse device manual.)

event occurs in 2 of 4 preceding A-A intervals (multiple heart blocks occur in 4-beat window) (Fig. 28-54). MVP will maintain the dualchamber DDD(R) mode for 1 minute and then performs an “AV conduction check.” The device monitors AV conduction by temporarily switching back to AAI(R) timing during one A-A cycle. The AV conduction check is scheduled at 2, 4, 8, . . . minutes, up to 16 hours after a transition to DDD(R) has occurred. If spontaneous R waves are sensed, the device will revert back to the AAI(R) operation (Fig. 28-55). Because cross-chamber blanking during AAIR pacing may affect sensing of ventricular arrhythmias, atrial pacing is inhibited during ventricular arrhythmia.46 Significant reduction of ventricular pacing has been demonstrated with the MVP algorithm. A dynamic ARP has been developed to avoid inappropriate switch to DDD(R) mode caused by nonconducted premature atrial ectopy or far-field R-wave

Sensor-indicated interval

Sensor-indicated interval

NCAP 300 ms

Sensor P DDDR A

R

NCAP P

30 ms

V-V intervals Figure 28-54  AAIR-to-DDDR mode switching. The managed ventricular pacing algorithm permits the pacemaker to switch automatically from AAIR to DDDR mode and from DDDR to AAIR mode. When transient loss of conduction occurs in the AAIR mode, after an A-A interval without a ventricular sensed event, a ventricular paced event will occur 80 msec after the escape interval. If two of the four most recent A-A intervals are missing a ventricular event, the device will switch from AAIR to DDDR or from AAI to DDD. 1, AAIR mode; 2, AV block results in ventricular backup paced beat; 3, switch to DDDR mode. (Redrawn from Medtronic Intrinsic reference manual.)

oversensing. The net result of MVP is reduced frequency of ventricular pacing.45,47 In the MVP mode there may be undesirable lengthening of AV conduction with negative hemodynamic consequences.46 In one study, about 14% of patient had more than 40% AVIs longer than 300 msec. The hemodynamic significance of the A-V intervals in these patients is unknown.48 MVP may result in long V-V intervals and thus may lead to pause-dependent and pacing-facilitated ventricular proarrhythmia. Studies indicate, however, that this occurs no more than in other modes (e.g., DDDR).46 In the MVP mode the ARP in AAI(R) is set to 600 msec or 75% of the prior R-R interval, whichever is shorter. The ARP length may lead to functional undersensing of atrial activity and competitive atrial pacing. During the onset of relatively slow atrial arrhythmias, for example, an atrial tachycardia just faster than 100 bpm starting after sinus bradycardia at 50 bpm, the first atrial event will fall into the ARP. The second beat of the atrial tachycardia may be sensed, but the third will fall into the ARP, and so on. Thus, using MVP mode may not be desirable in the presence of slow atrial arrhythmias. The AAIsafeR algorithm functions in the AAI mode with a conversion to DDD in the event of high-grade AV block.49,50 This algorithm uses a number of criteria to switch from atrial pacing to DDDR: (1) consecutive intrinsic A-V intervals greater than 350 to 450 msec, (2) “x out of y” A-A intervals without ventricular sensed event, (3) consecutive A-A intervals without ventricular sensed events, (4) pauses

Sensor P

V P P Parameters: Sensor-indicated rate = 120 ppm (500 ms) 200 ms PAV interval = 150 ms PVARP interval = 230 ms Postventricular atrial blanking (PVAB) = 180 ms Ventricular refractory period = 230 ms Figure 28-53  Noncompetitive atrial pacing (NCAP) algorithm and ventricular timing. If an atrial event is sensed during PVARP, the atrial pacing impulse will be delayed. To stabilize the ventricular rate, the A-V interval may be shortened to a minimum of 30 msec. (Redrawn from Medtronic Enpulse device manual.)

1

2

3

ECG Marker channel

V-V intervals Figure 28-55  DDDR-to-AAIR mode switching. The managed ventricular pacing algorithm permits the pacemaker to switch automatically from AAIR to DDDR mode and from DDDR to AAIR mode. In the DDDR mode (1), the device periodically checks for AV conduction. If AV conduction is present (2), the device switches to the AAIR mode (3). (Redrawn from Medtronic Intrinsic reference manual.)



835

28  Timing Cycles of Implantable Devices

VENTRICULAR RATE REGULARIZATION Because irregularity of ventricular rates during AF may be responsible for many AF symptoms, algorithms may attempt to pace in an effort to regularize the rhythm. These algorithms adjust the presence of pacing in response to the presence of ventricular sensed beats. Ventricular response pacing (VRP) and ventricular rate regulation (VRR) respond to sensed ventricular events (Fig. 28-56). If a ventricular sensed event occurs, the ventricular pacing rate is increased, and if a ventricular paced event occurs, the rate is decreased. Clinical studies show that variability in ventricular intervals in AF is greatly decreased (Fig. 28-57). DUAL-CHAMBER HYSTERESIS AND SEARCH HYSTERESIS Dual-chamber devices are capable of exhibiting hysteresis analogous to ventricular or atrial hysteresis. In dual-chamber hysteresis, the escape interval timed from an intrinsic ventricular event is longer than the escape interval following a paced ventricular event. In search hysteresis, periodically the LRL is lowered to promote intrinsic activity. At a programmed number of intervals, the device looks for intrinsic activity. During this period, if there is no intrinsic activity, pacing will occur at a rate that is a programmed amount (hysteresis offset) less than the LRL for a specified duration (e.g., 8 cycles). If no intrinsic atrial activity is sensed, pacing will resume at the LRL or sensor-indicated rate. Search hysteresis helps to promote intrinsic impulse formation. REPETITIVE VENTRICULOATRIAL SYNCHRONY Competitive atrial pacing may also occur after a premature ventricular complex that conducts retrograde. Unlike in PMT, the P wave falls within PVARP. However, the next atrial pacing stimulus comes soon after the P wave and therefore is not captured due to tissue refractoriness. The next ventricular event is paced and conducts retrograde.

↑ rate 1–2 bpm

Ventricular event

Compare 160

Pace Sensor

ODO

140 120 100 80 60

VVIR 0

10

VRR 20

VVR walk 30

40

VVIR walk 50

60

70

Time (min) Figure 28-57  Ventricular response pacing (VRP). At rest and during exercise, during VRR (VVIR mode with VRP on), there is lower proportion of patients with fast ventricular rates compared with VVIR only (with VRP off). (From Tse HF, Newman D, Ellenbogen KA, et al: Effects of ventricular rate regularization pacing on quality of life and symptoms in patients with atrial fibrillation. Atrial Fibrillation Symptoms Mediated by Pacing to Mean Rates (AF SYMPTOMS) study. Am J Cardiol 94:938-941, 2004.)

As a result, the pattern of V-A conduction and competitive atrial pacing perpetuates itself. This phenomenon has been called “repetitive non-reentrant V-A synchrony” and may result in impaired hemodynamics. TIMING CYCLES IN OTHER DUAL-CHAMBER MODES VDD Mode The VDD mode offers both atrial and ventricular sensing with only ventricular pacing (Fig. 28-58). Tracking of atrial activity occurs similar to the DDD mode. When an atrial event is sensed, the AVI is initiated, and if a ventricular intrinsic event is not sensed by the end of the interval, a ventricular paced event is triggered. Sensing also occurs in the ventricle, which inhibits ventricular pacing. The VDD mode is not appropriate for individuals who have impaired sinus node function because there is no atrial pacing. This mode is mostly employed in pacemaker systems with a single lead that paces and senses the ventricle and that senses the atrium using a specially designed “floating” atrial electrode. DDI Mode

VRP initiated

Sense

VVIR vs. VVIR with VRP

Ventricular rate (bpm)

programmed at 2, 3, and 4 seconds, (5) ventricular sensed events within the ventricular safety pacing window after two consecutive atrial sensed events, and (6) 12 consecutive ventricular sensed events. After 100 DDDR cycles, the algorithm switches to AAI to assess for AV conduction. If more than three AAI-to-DDD switches occur on 3 consecutive days, or 15 or more in 1 day, the algorithm is disabled until reprogramming.46

Pace

↓ rate 0–1 bpm

Rate ≥ sensor (up to VRP limit) Figure 28-56  Ventricular response pacing (VRP). In response to a ventricular sensed event, the ventricular pacing rate is increased 0 to 1 beats per minute. In response to a ventricular paced event, the ventricular pacing rate is decreased. (From Tse HF, Newman D, Ellenbogen KA, et al: Effects of ventricular rate regularization pacing on quality of life and symptoms in patients with atrial fibrillation. Atrial Fibrillation Symptoms Mediated by Pacing to Mean Rates (AF SYMPTOMS) study. Am J Cardiol 94:938-941, 2004.)

Atrioventricular sequential pacing with dual-chamber sensing, non-Psynchronous, DDI mode provides sensing and pacing in the atrium and ventricle but does not track. When atrial events are sensed, atrial pacing is inhibited, but unlike the DDD mode, the AVI is not initiated (Fig. 28-59). Ventricular paced events following atrial sensed events will occur at the LRL rather than after the AV delay. Ventricular sensed events result in inhibition of ventricular pacing and reset the AEI. Absence of intrinsic atrial events or ventricular events by the end of the LRL results in pacing in the atrium and the ventricle, respectively. This mode is best suited for patients at risk for atrial tachyarrhythmias because there is no atrial tracking resulting in rapid ventricular pacing during atrial tachyarrhythmia. This mode can be useful when the mode-switching feature is unavailable or does not accurately function. In DDI mode the absence of tracking results in the inability of faster intrinsic sinus rates to be followed by ventricular paced beats as the sinus rates increase in response to greater metabolic demands with exertion and exercise. In addition, AV synchrony is lost when the intrinsic sinus rate exceeds the LRL, and AV conduction is absent or

836

SECTION 4  Follow-up and Programming

1 P-R

2 R-R

R-R 800 ms A-V 160 ms

4 V-V

3 P-V

5 P-R

160 ms

Figure 28-58  VDD mode. In the VDD mode, atrial sensed events are tracked, initiating an AV delay. If the AV delay is not followed by a sensed ventricular event within the programmed AV delay, a ventricular paced event will occur unless the upper rate limit has been reached. In this example, the lower rate is 60 bpm, and the upper rate limit is 120 bpm, with an AV delay of 200 msec. A, Atrial paced event; P, atrial sensed event; R, ventricular sensed event; V, ventricular paced event. In beat 1, the P wave starts an AV delay, but AV conduction occurs, so that the timing cycle is reset by the ventricular sensed event, the ventricular complex of beat 2. Before the lower rate limit can time out from beat 2 to beat 3, an intrinsic P wave again occurs. In this case, in beat 3, there is no ventricular sensed event by the time the A-V interval expires, so another ventricular paced event occurs in beat 3. The ventricular paced event in beat 3 resets the timing cycle, and a new V-V interval is created. From beat 3 to beat 4, there is no intrinsic P wave or R wave. Therefore, a ventricular paced event at the lower rate limit of 60 bpm (1000 msec) occurs. A new ventricular escape interval is created. Between beat 4 and beat 5, a P wave occurs, which is again tracked, creating a new AV delay. As in beat 1, intrinsic conduction occurs before the new AV delay is completed.

impaired. The use of DDIR pacing programmed so that sensor-driven pacing predominates will result in maintenance of AV synchrony. Other Modes Many other modes are used less frequently as permanent settings and are used only in particular circumstances. As discussed, the asynchronous modes AOO, VOO, and DOO pace constantly in the atrium, ventricle, or both chambers, respectively. These modes are generally used

1

2

3

4

P-R

A-R

P-V

A-V

R-A 800 ms

V-V 1000 ms

2

3

4

P-R

A-R

P-A-V

A-V

R-A 800 ms

V-V 1000 ms 200 ms

1

V-V 1000 ms

V-A 800 ms

Figure 28-60  DVI mode. In the DVI mode, the atrium and the ventricle are paced, but only the ventricle is sensed. As a result, atrial pacing may occur after an intrinsic atrial event. In beat 1, the R wave is sensed and creates a new atrial escape interval of 800 msec. In beat 2, atrial pacing occurs since a ventricular event has not occurred since the last ventricular event. Because there is conduction of the R wave, a ventricular paced event does not occur. In beat 3, a spontaneous P wave occurs, followed by atrial and ventricular pacing. The atrial pacing after a spontaneous P wave could result in atrial arrhythmias. In beat 4, atrial and ventricular pacing occurs because no ventricular sense event has occurred.

to prevent potential oversensing, such as EMI from electrocautery during surgery. Other sources of possible interference include transcutaneous electrical stimulation (TENS), diathermy, and lithotripsy in pacemaker-dependent patients. The triggered modes VVT and AAT deliver an impulse immediately when an event in the respective chamber is sensed. These modes historically were used diagnostically to mark sensed events (in evaluating undersensing or oversensing) before the availability of intracardiac electrograms and marker channels. However, triggered modes are infrequently used in current practice. The VDI mode is used similar to the VVI mode, in which pacing in the ventricle will occur unless an intrinsic ventricular depolarization is sensed within the LRL. However, atrial sensed events are also sensed, but do not result in ventricular tracking, and instead are recorded for later evaluation, such as evaluation of atrial arrhythmias. In some devices, mode-switching algorithms will initiate the VDI mode when atrial tachyarrhythmia is sensed. In the DVI (AV sequential, ventricular inhibited) mode, which is the least used, the pacemaker will provide pacing in both atrium and ventricle (D), but only events in the ventricle (V) inhibit pacing. An atrial escape interval will be reset after a sensed or paced ventricular event, followed by an asynchronous atrial pacing output. However, a sensed spontaneous ventricular event within the AEI will inhibit and reset both atrial and ventricular pacing stimuli. The atrial pacing stimulus is followed by the A-V interval, and a spontaneous R wave will inhibit the ventricular output. The difference between DVI and DDI is that no atrial sensing is incorporated in the DVI mode, in which constant, competitive atrial pacing may occur (Fig. 28-60). The absence of atrial sensing may result in a paced atrial impulse immediately after an intrinsic atrial event, potentially triggering atrial tachyarrhythmia.

V-A 800 ms

Figure 28-59  DDI mode. In the DDI mode, atrial sensed events are not tracked, but they inhibit atrial pacing. If the AV delay is not followed by a sensed ventricular event within the programmed AV delay, a ventricular paced event will occur unless the upper rate limit has been reached. In this example, the lower rate is 60 bpm, with an AV delay of 200 msec. A, Atrial paced event; P, atrial sensed event; R, ventricular sensed event; V, ventricular paced event. In beat 1, the P wave inhibits atrial pacing, and the R wave occurs before the lower rate limit times out. In beat 2, atrial pacing occurs at the end of the atrial escape interval since no spontaneous P wave occurs. The R wave occurs before the lower rate interval of 1000 msec expires. In beat 3, a P wave occurs and results in inhibition of atrial pacing. Atrial pacing occurs at the end of atrial escape interval of 800 msec since no atrial sensed event has occurred. Because no sensed ventricular event occurs, a ventricular paced event also occurs.

Timing Cycles in Biventricular Pacing GOALS OF BIVENTRICULAR PACING The primary goal of bradycardia pacing is to achieve adequate heart rates to prevent symptoms and meet metabolic demands.51,52 To achieve this goal, bradycardia pacing timing cycles are designed to keep the heart rates from being too slow and to maintain appropriate AV synchrony. Heart failure may be associated with abnormal electrical delay and mechanical dyssynchrony. Such depressed and uncoordinated interventricular and intraventricular contraction delays are responsible for the reduced pumping effectiveness. Cardiac resynchronization therapy (CRT) improves the functional capacity of patients with wide QRS complexes, left ventricular (LV) dysfunction, LV dilation, and heart



28  Timing Cycles of Implantable Devices

failure. Indices such as quality of life, 6-minute walk distance, and New York Heart Association functional class have also been shown to improve with biventricular (BiV) pacing CRT. In addition, randomized studies show decreased mortality and improved LV dimensions and function. However, the benefits of CRT are based on improved hemodynamics, achieved by stimulating the heart in a more coordinated manner and minimizing inter/intraventricular dyssynchrony (resynchronization). Thus, resynchronization requires that consistent pacing be maintained despite the absence of bradycardia. These distinct goals demand a new set of timing cycle rules for BiV devices. TIMING CYCLES: DIFFERENCES FROM DUAL CHAMBER Pacing Modes Pacing modes for CRT pacemakers and general criteria for mode selection are similar to standard pacing. In patients with chronic atrial fibrillation, VVIR pacing is the most common mode, to achieve rate responsiveness and to maintain as close as possible to 100% ventricular pacing. In patients without AF, the most common mode is VDI, DDD, or DDDR. VDI is appropriate for patients with normal sinus node function and intact AV conduction. DDDR should be selected in patients with chronotropic incompetence from relative sinus bradycardia. VDI, DDD, or DDDR mode allows atrial tracking with AV coordination. The optimal hemodynamics of CRT requires maintenance of AV synchrony with maximum BiV pacing and capture. There is no role, therefore, for AAI or other algorithms that promote intrinsic AV conduction. The basic timing cycle during CRT relies on an A-V interval that maintains ventricular capture. The timing cycles for BiV pacemakers are potentially complex, depending on which chamber(s) is sensed, which ventricle(s) is paced, the inter-ventricular delay, and the chamber(s) that resets the escape intervals.52-56 For most commercially available BiV devices, the sensing chamber(s) is usually the right ventricle and occasionally both ventricles (for older devices with Y connection). BiV pacing activates both ventricular chambers either simultaneously or sequentially (Fig. 28-61). Atrioventricular Interval For biventricular pacing to result in the desired hemodynamic effect, it is necessary for appropriately timed BiV paced beats to occur after paced or sensed atrial events.57 Therefore, AVI must be sufficiently short to ensure BiV capture and minimize fusion, yet long enough to allow adequate diastolic filling during the atrial contraction. Because the degree of native PR shortening during exercise may be significant, this may be a particularly challenging task. Similarly, programming an extremely short, fixed AV delay that applies to all rates and physiologic conditions is unlikely to be optimal, with ventricular depolarization and contraction occurring too early. In almost all cases, therefore, a form of rate-adaptive AV delay is used in CRT devices. AS

VAI

AP

LVP RVP

VAI

LVP RVP

RV-RV

AP

RVS

RV-RV

AP

RVS LVP

837

AP

RVP LVP

Figure 28-62  Biventricular pacing with RV sensed event before LV paced event. An atrial paced event (Ap) starts the AV delay. The right ventricular sensed event (RVS) occurs before the left ventricular paced event (LVP) (positive RV-LV interval) in the first cycle. On the subsequent cycle, the AV delay has been shortened so that the right ventricular paced event (RVP) may preempt the RVS. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

Several algorithms have been designed to maintain BiV pacing and activation. When a ventricular event is sensed on one pacing cycle, the A-V interval is shortened on the next timing cycle (AV hysteresis). If an atrial event is followed by a sensed right ventricular (RV) event, which is then followed by an LV paced event, on the next cycle, an RV paced event and an LV paced event may occur by shortening the time from the atrial sensed event to the RV paced event (Fig. 28-62). In addition, if the LV paced event occurs before the RV sensed event, it is possible to shorten the LV-RV timing on subsequent cycles (Fig. 28-63). However, such “negative” AV hysteresis function is often ineffective; permitting even one cycle with intrinsic conduction may have deleterious consequences. Perpetuation of native AV conduction and the absence of BiV pacing can result, as discussed later. If an intrinsic ventricular event is sensed within the A-V interval, one option might be to trigger a ventricular paced stimulus from the opposite ventricle, so-called ventricular sensed response. For example, if a sensed event is detected by the RV lead, an LV pacing output is delivered immediately to maximize LV capture and BiV activation (Fig. 28-64). However, it is unclear if the benefit of this strategy has limits, particularly with closely timed ventricular premature beats. Interventricular Timing Delay Analogous to the A-V interval in atrioventricular delay, there may be delay between pacing in the right and left ventricles (interventricular delay). Several permutations of the relationship exist between the RV and LV timing based on the role of BiV or unipolar sensing. With RV sensing alone, which is predominantly the case in most current devices, the RV-LV interval may be positive, negative, or zero (Fig. 28-65) Several studies have demonstrated clinical or hemodynamic benefits of adjusting interventricular delay in patients who were classified as “nonresponders” to conventional CRT. Various echocardiographic Doppler parameters and timing intervals have been used to assess interventricular dyssynchrony, and tissue Doppler imaging (TDI) has been used to determine intraventricular dyssynchrony for V-V AP

AP

LVP RVP

RV-RV

Figure 28-61  Biventricular pacing with right ventricular (RV)–based timing may occur after atrial event. A premature ventricular beat PVS creates a new VAI. AP, Atrial paced event; AS, atrial sensed event; LVP, left ventricular paced event; RVP, RV paced event; RVS, RV sensed event; VAI, ventriculoatrial interval; RV-RV, interval between RV events. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

LVP RVS

LVP RVP

Figure 28-63  Biventricular pacing with LV paced event before RV sensed event. In the first cycle, there is a left ventricular paced event (LVP) before the right ventricular sensed event (RVS). In the subsequent cycle, an LVP is followed by a right ventricular paced event (RVP), which may be achieved by shortening the LV-RV interval in response to the RVS. AP is an atrial paced event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

838

SECTION 4  Follow-up and Programming

AS

AP

AP

AP

VAI (LVS) RVP LVP RVP LVP

RVS LVP

Figure 28-64  Biventricular sense response. If a right ventricular sensed event (RVS) occurs, one option is for a left ventricular event to occur almost immediately to promote biventricular pacing; AS, atrial sensed event; AP, atrial paced event; LVP, left ventricular paced event; RVP, right ventricular paced event; VAI, ventriculoatrial interval. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.) AS

AS

LVP RVP

AS

RVS LVP

LVS RVP

AS

LVS RVS

Figure 28-65  Biventricular RV-LV interval. The RV-LV interval may be positive, negative, or zero; AS, atrial sensed event; LVP, paced left ventricular event; LVS, left ventricular sensed event; RVP, right ventricular paced event; RVS, right ventricular sensed event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

optimization. The introduction of delay raises several theoretical issues. As discussed further in the context of univentricular sensing and biventricular pacing, an interventricular delay may increase the risk of ventricular tachycardia from an unsensed, improperly timed ventricular depolarization. Lower Rate Behavior As in dual-chamber pacing, a lower rate limit is established. Atrial pacing will occur if an intrinsic atrial event does not occur at the LRL. A combination of events may initiate ventricular events. In current devices, both ventricles may be paced, but timing is based on the right ventricle only. One can theorize that more combinations are possible, such as pacing both ventricles but using the right ventricle, left ventricle, or both ventricles for ventricular timing. Univentricular Sensing and Biventricular Pacing Sensing may occur in one ventricle as it does in dual-chamber pacing. Usually, ventricular tachycardia is not a risk from competitive pacing. For example, if LV activation occurs before LV pacing, the LV pacing stimulus would unlikely be captured (Fig. 28-66). However, a set AP

AP

(LVS)

RVP

LVP

Figure 28-67  Right ventricular sensing only with premature left ventricular extrasystoles. The right ventricle may be the only ventricular chamber sensed. A spontaneous premature ventricular complex (PVC) originating in the left ventricle will not be sensed if there is a significantly prolonged and negative RV-LV interval. Therefore the left ventricular pacing combined with the spontaneous LV sensed event may result in ventricular proarrhythmia. AS, Atrial sensed event; LVP, left ventricular paced event; LVS, left ventricular sensed event; RVP, right ventricular paced event; RVS, right ventricular sensed event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

of circumstances may increase the risk of competitive pacing. For example, if the intrinsic LV-RV conduction time is long and a long RV-LV delay is programmed, several scenarios may result in a greater risk of competitive pacing. In one situation an LV sensed event occurs before RV and LV pacing occurs. Because there may be a considerable interval between the intrinsic LV event and the LV pacing stimulus, the left ventricle may no longer be refractory, resulting in LV stimulation at a short coupling interval (Fig. 28-67). In another example, an unsensed premature beat that originates in the left ventricle may be followed by an RV paced event and then an LV paced event. In such a case, the RV paced event occurred before conduction from the spontaneous LV PVC to the right ventricle. BIVENTRICULAR SENSING AND BIVENTRICULAR PACING Various rules could be created to determine, for example, how both ventricles might be used for timing. These rules might depend on when the ventricular sensed event occurred. If the sensed event occurred in the A-V interval, as previously described, a new V-A interval and timing cycle might be created with no pacing (Fig. 28-68). A variation on this function might be to permit a ventricular paced event from the opposite ventricle to occur (Fig. 28-69). This could be immediately after the sensed ventricular event within the A-V interval (Fig. 28-70) or after the programmed RV-LV delay (Fig. 28-71). The V-A interval might be reset at the point of the RV sensed event within the A-V (see Fig. 28-69, A) interval or at the end of the programmed A-V interval (see Fig. 28-69, B). An RV sensed event will be followed by an LV paced event, probably after a modified interval. Also, after a ventricular sensed event in the A-V interval, it might be possible not to trigger a ventricular paced beat from the opposite chamber, and instead have an A-V interval “time-out” and the ventricular paced event occur at AS

AVI

AP

RV-LV VAI

RVP LVP (LVS)

RVS LVP (LVS)

Figure 28-66  Right ventricular sensing only with positive RV-LV interval. The right ventricle may be the only ventricular chamber sensed. There may be an intrinsic LV event that follows the RV paced event. Since the LV event is not sensed, the LV pacing stimulus will still be delivered. Because the LV stimulus occurs after the intrinsic LV events, the LV stimuli are unlikely to capture. AP, Atrial paced event; LVP, left ventricular paced event; LVS, left ventricular sensed event; RVP, right ventricular paced event; RVS, right ventricular sensed event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

RVS (RVP) (LVP)

RVP

LVP

Figure 28-68  Right ventricular sensing only with inhibition of pacing. The right ventricle may be the only ventricular chamber sensed. When a right ventricular event is sensed, this sensed event may reset the timing cycles and result in inhibition of pacing. AP, atrial paced event; AS, Atrial sensed event; AVI, atrioventricular interval; LVP, left ventricular paced event; RVP, right ventricular paced event; RVS, right ventricular sensed event; VAI, ventriculoatrial interval. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)



28  Timing Cycles of Implantable Devices AS

AP AVI

AVI RV-LV VAI

RVS (RVP) LVP*

A

AS

AVI

RVS (RVP) LVP*

LVS AP

RV-LV VAI

RVS (RVP) (LVP) LVS**

Figure 28-69  Biventricular sensing and pacing. A, Right ventricular sensed event (RVS) is used to start the ventriculoatrial interval (VAI). B, Right ventricular pacing interval that would have occurred at the end of the atrioventricular interval (AVI) is used to start the VAI. Parentheses indicate the timing of the paced events that would have occurred if the intrinsic sensed event had not occurred. AS, Atrial sensed event; LVS**, left ventricular sensed event; LVP*, left ventricular paced event; RVP, right ventricular paced event; RVS, right ventricular sensed event. In future devices, sensing and pacing will likely occur in both the right and the left ventricle. Sensing in the right ventricle will result in inhibition in the in right ventricle, but pacing in the left ventricle may still occur. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

AS

AP

RVS LVP

RVP

LVP

Figure 28-70  Biventricular sensing and pacing. Triggering may be present in devices that sense and pace in both the right ventricle and the left ventricle. If a left ventricular event is sensed, a right ventricular stimulus will be delivered immediately. If a right ventricular event is sensed, a left ventricular stimulus will be delivered immediately. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

VAI

RVP (LVP)

LVP

AVI

AP

RV-LV VAI

LVS (RVP) (LVP) RVS

Figure 28-72  Biventricular sensing and pacing. Triggering may be present in devices that sense and pace in both the right ventricle and the left ventricle. If a left ventricular event is sensed, RV and LV pacing are not inhibited. However, right ventricular stimulus will be delivered immediately. If a right ventricular event is sensed, the timing cycles are reset. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

the end of the A-V interval. In BiV sensing and pacing, an LV sensed event in the AVI might result in an RV paced event at the end of the programmed AVI (Fig. 28-72). Alternatively, the LV sensed event in the AVI might trigger an RV paced event that would be used to reset the VA timing cycle (Fig. 28-73). Safety pacing with BiV pacing might be performed using either both ventricles or only one as backup pacing. For sensed events outside the A-V interval and after the ventricular refractory period, there are also a variety of responses. A sensed event in the left ventricle or right ventricle might be used interchangeably or might result in a specific pacing response. For example, sensing in either chamber first might be used to trigger a ventricular paced event in the opposite chamber. Alternately, a sensed event in the left or right ventricle might inhibit pacing in either channel to prevent pacing within the vulnerable period. For example, an LV sensed event might inhibit LV pacing, but an RV paced event would occur unless an RV sensed event occurred within the programmed LV-RV delay. If a negative RV-LV delay were programmed, the RV sensed event could result in resetting the timing cycles or an immediate LV paced event.

AP

It is possible for a device to be programmed to have BiV sensing but only to pace from one ventricle, such as the left ventricle. In this case a sensed LV event might result in inhibition of LV pacing and resetting of the VA timing cycle (Fig. 28-74). If an RV sensed event occurred first, the LV paced event might be inhibited, resetting the timing cycle (Fig. 28-75), or might result in an LV paced event immediately, to minimize the delay after the RV sensed event (Fig. 28-76). Upper Rate Behavior The primary purpose of upper rate behavior in traditional dualchamber pacing is to prevent rapid atrial tracking during atrial tachycardia. The maximum tracking rate is a programmable parameter, whereas the 2 : 1 AV block rate is determined by the TARP (60,000/

AS

RV-LV

RVS

AP

RV-LV

Biventricular Sensing with Univentricular Pacing

VAI

AS

AVI

VAI

RVS (RVP) (LVP) LVS**

VAI

B

AS

VAI

AP AVI

RV-LV

AP

RV-LV

839

AP VAI

RVP

LVP

Figure 28-71  Biventricular sensing and pacing. Triggering may be present in devices that sense and pace in both the right ventricle and the left ventricle. If a left ventricular event is sensed, a right ventricular stimulus will be delivered immediately. If a right ventricular event is sensed, a left ventricular stimulus will be delivered immediately. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

LVS RVP

RVP

LVP

Figure 28-73  Biventricular sensing and pacing. Triggering may be present in devices that sense and pace in both the right ventricle and the left ventricle. If a left ventricular event is sensed, a right ventricular stimulus will be delivered immediately. If a right ventricular event is sensed, a left ventricular stimulus will be delivered immediately. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

840

SECTION 4  Follow-up and Programming

AS

AP AVI

AVI

(AP) VAI

VAI

LVP

AP

VAI

LVS (LVP)

AS

AP AVI

AVI

LVS

(AP)

VAI

LVP

VAI

AP

VAI

RVS LVP

RVS LVP

Figure 28-74  Biventricular sensing and unipolar pacing. Sensed events in the left ventricle result in inhibition and reset the timing cycle. AS, atrial sensed event. AP, atrial paced event; AVI, atrioventricular interval; LVP, left ventricular paced event; LVS, left ventricular sensed event; VAI, escape interval. Parentheses indicate that pacing is not delivered because of refractoriness. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

Figure 28-76  Biventricular sensing and unipolar pacing. Left ventricular paced events reset the timing cycles. Right ventricular sensed events result in triggering a left ventricular paced event. AS, atrial sensed event; AVI, atrioventricular interval; LVP, left ventricular paced event; RVP, right ventricular paced event; RVS, right ventricular sensed event; VAI, escape interval. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

TARP). When the MTR is slower than the 2 : 1 AV block rate, pseudoWenckebach behavior occurs as the atrial rate increases and exceeds the MTR before 2 : 1 AV block develops. When the 2 : 1 AV block rate is slower than the MTR, a sudden 50% drop in heart rate occurs as the atrial rate exceeds the 2 : 1 AV block limit. For biventricular pacemakers, a thorough understanding of the upper rate behavior is crucial in maintaining BiV pacing. Most patients who need CRT have intact AV conduction, so pacemaker-Wenckebach behavior should be avoided because extension of AVI allows sensing inhibition and prevents BiV pacing. Episodes of high atrial rate are frequently observed in this population, during heart failure exacerbation, exercise with deconditioning, or recurrent atrial arrhythmias. To maintain 100% BiV pacing, TARP should be sufficiently short and the MTR should be sufficiently high.

“asynchronously” shortly after the delayed, nonsensed LV activation. Such improperly timed pacing stimulus may induce ventricular arrhythmia. A cross-chamber trigger mode on PVC would require an upper rate limit to avoid tightly coupled stimulation that may induce ventricular arrhythmia.

Premature Beats and Biventricular Timing Cycles A premature ventricular beat is defined as a ventricular sensed event without a preceding paced or sensed atrial event. In dual-chamber timing cycles, a premature ventricular beat (complex, contraction, PVC) occurring in the V-A interval (VAI) would reset the atrial escape interval (AEI) in ventricular-based timing devices. The presence of PVC provides special challenges in a BiV system. The PVC PVARP extension algorithm automatically lengthens PVARP to protect against potential PMT. However, such PVARP extension can cause subsequent functional atrial undersensing and loss of BiV pacing. Thus, the PVC PVARP extension function should be deactivated in a BiV system. In addition, because of the interventricular (RV-LV) conduction delay, which could be considerable in patients with dyssynchrony, a PVC creates ambiguity for the timing cycles. Approaches include a system that uses single-chamber sensing only, a cross-chamber (RV-LV) refractory period after the first ventricular sense, or a ventricular triggering mode in the opposite chamber. In a RV sense, LV refractory system, a PVC could have RV sensing in the VAI that resets the AEI; the subsequent ventricular pacing (AEI + AVI) can occur AS

AP AVI

AVI

LVP

VAI

(AP) VAI

AP

VAI

RVS(LVP)

Refractory Periods and Biventricular Pacing Refractory periods are present after sensed or paced events. In early BiV devices with RV and LV leads in parallel via a Y-connection, a single ventricular depolarization may be sensed by both RV and LV leads. With BiV sensing, the PVARP could be reset by the second component of the ventricular sensed (usually LV) signal. In such cases of late LV sensing, the PVARP and TARP are effectively extended by an interval that equals the interventricular sensing delay (RV-LV). Such prolonged TARP could greatly reduce the atrial sensing window for atrial tracking. The newer BiV devices use dedicated RV sensing only, with pacing from both right and left ventricles. After RV or LV pacing, a crosschamber refractory period may be created. If there is a delay in the LV-RV interval, the total sensed refractory period may be prolonged. If the device is programmed to a positive LV-RV delay and a new refractory period is created after the RV pacing stimulus, the total ventricular refractory period may be quite long. This prolonged sensing refractoriness can compromise detection of ventricular tachyarrhythmias. Loss of Biventricular Pacing Because the hemodynamic consequences may be significant, it is important to identify possible causes of loss of BiV pacing.58 BiV pacing may be lost when A-V conduction becomes more rapid and the RV sensed event occurs within the A-V interval (Fig. 28-77). BiV pacing may be lost when the atrial rate increases so that the P wave falls within the PVARP of the preceding ventricular beat. This occurs when the atrial cycle length is equal to the sum of the PVARP and sensed A-V delay (TARP = AVI + PVARP) or above the maximum atrial AS

AP AVI

AVI

RVS

Figure 28-75  Biventricular sensing and unipolar pacing. Left ventricular paced events reset the timing cycles. Right ventricular sensed events also reset the cycle, inhibiting left ventricular pacing. AS, atrial sensed event; AVI, atrioventricular interval; RVP, right ventricular paced event; RVS, right ventricular sensed event; VAI, escape interval. Parentheses indicate that pacing is not delivered because of refractoriness. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

LVP

VAI

AP VAI

RVS

LVS

Figure 28-77  Biventricular pacing and sensing. More rapid AV conduction results in a right ventricular sensed event. AS, Atrial sensed event; AP, atrial paced event; AVI, atrioventricular interval; LVP, left ventricular paced event; LVS, left ventricular sensed event; RVP, right ventricular paced event; RVS, right ventricular sensed event, VAI, escape interval. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)



28  Timing Cycles of Implantable Devices AP

AP 150 ms

500 ms

100 ms 150 ms

50 ms

TARP rate or MTR ITARP rate

RVS

LVS

LVP RVP 250 ms

No therapy Figure 28-78  Relationship between atrial rate and presence of biventricular pacing. As the atrial rate reaches the total atrial refractory period (TARP) (PVARP + PV), BiV pacing will stop. When the atrial rate falls to intrinsic TARP (ITARP = PVARP + P-R interval), BiV pacing resumes. LRL, Lower rate limit, x-axis, atrial rate; y-axis, biventricular rate; MTR, Maximum tracking rate. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

tracking interval. The P wave will not be tracked, so conduction will occur. Because the resultant QRS complex will initiate a PVARP, the next P wave will fall within the PVARP. In this situation the programmed A-V interval is less than the intrinsic P-R interval, and thus the onset of loss of BiV pacing requires a faster atrial rate than the rate at which BiV pacing will be restored. BiV pacing will not be restored until the atrial cycle length is greater than the sum of the PVARP and the PR interval, called the intrinsic total atrial refractory period (ITARP). In patients with prolonged P-R interval, ITARP may be significantly longer than TARP. Once atrial undersensing in PVARP occurs during atrial tachycardia, loss of BiV pacing is perpetuated and may be restored only at much slower atrial rates. Restoration of BiV pacing will occur when the P wave following the last conducted QRS complex falls outside the PVARP. The relationship between atrial rate and loss of BiV pacing is shown diagrammatically in Figure 28-78. The ability to shorten the PVARP (indicated by PVARP’) may restore tracking of atrial sensed events and may restore BiV pacing (Fig. 28-79). Atrial premature beats with conduction may cause a similar phenomenon by causing atrial undersensing and loss of BiV pacing.59 COMPETITIVE VENTRICULAR PACING Biventricular pacing as just described has introduced a new cause of competitive ventricular pacing. In this case, an LV stimulus follows LV activation, because LV sensed events are not used to inhibit ventricular pacing. For example, a conducted ventricular beat with a positive RV sense–LV sense interval caused by left bundle branch block may occur, followed by LV pacing before RV pacing because the left ventricle is no AS

100 ms LV vulnerable

LRL

AS

841

AS

AS

AS

Figure 28-80  Biventricular pacing with RV-based timing and competitive pacing. The left ventricular paced event (LVP) may occur when the left ventricle is no longer refractory; AP, atrial paced event; RVP, right ventricular paced event; RVS, right ventricular sensed event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

longer refractory, potentially inducing a ventricular arrhythmia (Fig. 28-80). A feature called left ventricular pacing protection (LVPP) has been introduced to prevent LV competitive pacing. After an LV paced or sensed event has occurred, an LV paced event will not occur for the programmed LVPP (Fig. 28-81). Another circumstance for competitive ventricular pacing is the occurrence of an LV premature event before conduction can occur to the right ventricle. Particularly if the RV-LV interval is positive, the LV stimulus may find the left ventricle. CONCLUSIONS As CRT has become an important part of the therapy of patients with left ventricular failure and ventricular dyssynchrony, there has been increasing recognition of the importance of pacing timing cycles in biventricular pacing. Because BiV pacing is effective only with constant pacing, the implications of timing cycles for maintenance of BiV pacing are particularly important. There are unique implications for lower rate and upper rate behavior.

Timing Cycles: Pacing Algorithms in Implantable Cardioverter-Defibrillators One of the most serious issue involving timing cycles is the interaction between pacing and arrhythmia detection. The basic timing cycles in most ICDs are similar to those of comparable pacemaker devices. AP

AP

500 ms

140 ms 160 ms

150 ms 150 ms

AS RVS

LVS

(LVP) RVP LVPP

RVP LVP

RVP LVP

RVP RVP LVS LVP

RVP RVP LVS LVP

PVARP PVARP PVARP′ PVARP PVARP′ PVARP Figure 28-79  Biventricular pacing is lost when sinus rates exceed the maximum tracking rate and is restored when the PVARP is shortened. AS, atrial sensed event; LVP, left ventricular paced event; LVS, left ventricular sensed event; PVARP, postventricular atrial refractory period; PVARP’, PVARP shortened in response to loss of biventricular pacing; RVP, right ventricular paced event; RVS, right ventricular sensed event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

200 ms

150 ms LV vulnerable

Figure 28-81  Biventricular pacing with RV-based timing and LV refractory extension. To prevent the possibility of a left ventricular pacing event (LVP) when the left ventricle is no longer refractory, LV pacing may be inhibited when it occurs too soon after an intrinsic LV event (LVS). AP, Atrial paced event; LVPP, left ventricular protection period; RVP, right ventricular paced event; RVS, right ventricular sensed event. (From Wang P, Kramer A, Estes NA 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002.)

842

SECTION 4  Follow-up and Programming

Many devices have many of the following refractory or blanking periods: atrial blanking after ventricular sensed and paced events, ventricular sensed refractory period, ventricular refractory period, postventricular atrial sensed refractory period, atrial blanking after atrial pacing, and ventricular blanking after atrial paced events. Circumstances in which the maximum tracking rates and the sensor-driven rates are close to the ventricular tachycardia (VT) detection rate are most likely to result in abnormalities in arrhythmia detection. Examples of cases in which the pacing rates are likely to be particularly fast include sensor-driven pacing, tracking at or near the upper rate limit, rate smoothing, rate drop or sudden bradycardia response, ventricular rate regularization, and atrial pacing prevention algorithms. Abnormalities such as atrial oversensing with tracking in the DDD mode may lead to failure to detect VT. Cases of prolonged undersensing of VT have been reported during rate smoothing. Cooper

Atrial EGM Vent EGM

↓ 5 VSJ

A

VP↓ 373

V↑ 305

Guidant

V↑ 338

260 ms (VA)

AP↓ 1768 VP↓ 545

AP

AP↓ 595 VP↓ 595 EVSJ

~280 ms

(VF)

VP↓ 545

300 ms (AV delay)

135 ms 65 ms Sensed VRP VxAP VF 560 ms (mtr*drs = 500*1.12)

B

V↑ 385

AP↓ V↑ 1768 338

~280 ms

240 ms Paced VRP VP

(VF)

VF

~280 ms

Figure 28-82  Rate smoothing leading to AV pacing during ventricular tachycardia and resultant underdetection. Top channel, surface ECG; middle channel, atrial electrogram; bottom channel; ventricular ECG. B, Diagrammatic representation of the sensing windows. VT at 280-msec cycle length falls in an alternating manner into the blanking periods for the atrial and ventricular paced events. AV delay = 360 msec; rate smoothing “down” = 12%; maximum tracking rate (mtr) = 120 bpm. AP, Atrial paced event; VP, ventricular paced event; VRP, ventricular refractory period; VxAP, postatrial pace blanking. (From Glikson M, Beeman AL, Luria DM, et al: Impaired detection of ventricular tachyarrhythmias by a rate-smoothing algorithm in dual-chamber implantable defibrillators: intradevice interactions. J Cardiovasc Electrophysiol 13:312-318, 2002.)

Figure 28-83  Ventricular rate stabilization leading to pacing during ventricular tachycardia and resulting in underdetection. Surface ECG (top); marker channel (middle), and ventricular electrogram (bottom). Sustained monomorphic ventricular tachycardia (VT) occurs. The shorter VS in the marker channel indicates safety pacing caused by VT sensing after the atrial pacing (AP) in the crosstalk safety pacing window. (From Barold SS: Ventricular rate stabilization algorithm of ICD causing dual-chamber pacing during ventricular tachycardia. J Interv Card Electrophysiol 9:397-400, 2003.)

et al.60 observed that VT remained undetected because the VT beats occurred within the ventricular blanking period after atrial paced events. Atrial pacing occurred because rate smoothing had been turned on. Such an interaction is promoted by a slow VT and rate-smoothing algorithm. Shivkumar et al.61 reported a similar case of failure to detect an episode of ventricular tachycardia. In a prospective study, Glikson et al.62 examined the role of rate smoothing in preventing VT detection. During ICD testing in 54 episodes of induced ventricular fibrillation/polymorphic VT, three episodes (5%) of minimal delay in detection were observed. However, in the 10 monomorphic VT episodes, four cases had absent detection and two had delayed detection. Based on these observations and simulator-based modifications of programmable parameters, the authors observed that long AV delay, high upper rate, and more aggressive rate smoothing increases the risk of VT underdetection. Figure 28-82 illustrates an example of VT that is underdetected because of rate-smoothing algorithm. A similar case has been described for the ventricular rate stabilization algorithm (Fig. 28-83). Rate smoothing has also been proposed as a mechanism for the prevention of VT by minimizing abrupt variations in cycle lengths in a short-long-short pattern. Wietholt et al.63 conducted the PREVENT study by randomizing patients in a 3-month crossover design to periods of rate smoothing versus no rate smoothing; 57 of the 153 patients (38%) had 358 VT episodes with rate smoothing off versus 145 episodes with rate smoothing on. Ventricular sensed events, even at a tachyarrhythmic cycle length, are considered “sensed” for the purpose of bradycardia timing cycles. Thus, such events result in inhibition of ventricular pacing. Once ventricular tachyarrhythmia detection has occurred, the pacing mode may stay the same or may be altered. In the ventricular tachycardia response (VTR), once VT detection has occurred, the mode switches to VDI at the ATR/VTR fallback lower rate limit. In some older generators, there is suspension of bradycardia pacing immediately before shock delivery to prevent underdetection of VT from pacing-related refractory periods. In other generators, the mode may switch from DDD(R) to VVI after charging has ended and during defibrillation therapies. During shock therapy, specific changes to sensing may occur. After shock therapy and in some devices after charging, there may be a refractory period. After VT detection and before shock delivery, a number of ICDs nominally suspend pacing for at least 1 to 2 seconds after the shock. Changes in the bradycardia parameters typically occur following a shock. Frequently, the outputs and lower rate limit may be increased for a programmable period.



28  Timing Cycles of Implantable Devices

843

REFERENCES 1. Barold SS: Modern concepts of cardiac pacing. Heart Lung 2:238252, 1973. 2. Bernstein A, Daubert J, Fletcher R, et al: The revised NASPE/ BPEG generic code for antibradycardia, adaptive-rate, and multisite pacing. Pacing Clin Electrophysiol 23:260-264, 2002. 3. Barold SS: Clinical significance of pacemaker refractory periods. Am J Cardiol 28:237-239, 1971. 4. Barold SS, Gaidula JJ: Pacemaker refractory periods. N Engl J Med 284:220-221, 1971. 5. Yokoyama M, Wada J, Barold SS: Transient early T wave sensing by implanted programmable demand pulse generator. Pacing Clin Electrophysiol 4:68-74, 1981. 6. Okreglicki A, Akiyama T, Ocampo C, Flynn D: Polarization potentials causing pacemaker oversensing. Jpn Circ J 62:868-870, 1998. 7. Paraskevaidis S, Mochlas S, Hadjimiltiadis S, Louridas G: Intermittent P wave sensing in a patient with DDD pacemaker. Pacing Clin Electrophysiol 22:689-690, 1999. 8. Frohlig G, Helwani Z, Kusch O, et al: Bipolar ventricular far-field signals in the atrium. Pacing Clin Electrophysiol 22:1604-1613, 1999. 9. Rosenheck S, Sharon Z, Leibowitz D: Artifacts recorded through failing bipolar polyurethane insulated permanent pacing leads. Europace 2:60-65, 2000. 10. Barold SS, Falkoff MD, Ong LS, Heinle RA: Oversensing by singlechamber pacemakers: mechanisms, diagnosis, and treatment. Cardiol Clin 3:565-585, 1985. 11. Tse HF, Lau CP: The current status of single-lead dual-chamber sensing and pacing. J Interv Card Electrophysiol 2:255-267, 1998. 12. Friedberg HD, Barold SS: On hysteresis in pacing. J Electrocardiol 6:1-2, 1973. 13. Barold SS: Prolonged atrioventricular block during AAI pacing for sick sinus syndrome. J Cardiovasc Electrophysiol 11:14-22, 2000. 14. Tripp IG, Armstrong GP, Stewart JT, et al: Atrial pacing should be used more frequently in sinus node disease. Pacing Clin Electrophysiol 28:291-294, 2005. 15. Barold SS, Falkoff MD, Ong LS, Heinle RA: Programmability in DDD pacing. Pacing Clin Electrophysiol 7:1159-1164, 1984. 16. Barold SS, Belott PH: Behavior of the ventricular triggering period of DDD pacemakers. Pacing Clin Electrophysiol 10:12371252, 1987. 17. Barold SS, Falkoff MD, Ong LS, Heinle RA: All dual-chamber pacemakers function in the DDD mode. Am Heart J 115:13531362, 1988. 18. Parravicini U, Mezzani A, Bielli M, et al: DDD pacing and interatrial conduction block: importance of optimal AV interval setting. Pacing Clin Electrophysiol 23:1448-1450, 2000. 19. Bode F, Wiegand U, Katus HA, Potratz J: Inhibition of ventricular stimulation in patients with dual chamber pacemakers and prolonged AV conduction [see comment]. Pacing Clin Electrophysiol 22:1425-1431, 1999. 20. Dennis MJ, Sparks PB: Pacemaker mediated tachycardia as a complication of the autointrinsic conduction search function [see comment]. Pacing Clin Electrophysiol 27:824-826, 2004. 21. Barold SS, Gallardo I, Sayad D: Wenckebach upper rate response of pacemakers implanted for nontraditional indications: the other side of the coin. Pacing Clin Electrophysiol 25:1283-1284, 2002. 22. Barold SS: Far-field R-wave sensing causing prolongation of the atrial escape interval of DDD pacemakers with atrial-based lower rate timing. Pacing Clin Electrophysiol 26:2188-2191, 2003. 23. Kusomoto F: Pacemaker timing cycles: ventricular based and atrial based. In Al-Ahmad A, Ellenbogen K, Natale A, Wang PJ, editors: Pacemakers and implantable defibrillators: an expert’s manual, Minneapolis, 2010, Cardiotext. 24. Crossley GH, Pickett A: Miscellaneous pacing algorithms. In Al-Ahmad A, Ellenbogen K, Natale A, Wang PJ, editors:

Pacemakers and implantable defibrillators: an expert’s manual, Minneapolis, 2010, Cardiotext, p 158. 25. Lau CP, Leung SK, Tse HF, Barold SS: Automatic mode switching of implantable pacemakers. I. Principles of instrumentation, clinical, and hemodynamic considerations. Pacing Clin Electrophysiol 25:967-983, 2002. 26. Estes NA, 3rd: Atrial tachyarrhythmias detected by automatic mode switching: quo vadis? [comment]. J Cardiovasc Electrophysiol 15:778-779, 2004. 27. Israel CW: Analysis of mode switching algorithms in dual chamber pacemakers. Pacing Clin Electrophysiol 25:380-393, 2002. 28. Leung SK, Lau CP, Lam CT, et al: Is automatic mode switching effective for atrial arrhythmias occurring at different rates? A study of the efficacy of automatic mode and rate switching to simulated atrial arrhythmias by chest wall stimulation. Pacing Clin Electrophysiol 23:824-831, 2000. 29. Passman RS, Weinberg KM, Freher M, et al: Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias [see comment]. J Cardiovasc Electrophysiol 15:773-777, 2004. 30. Wood MA, Ellenbogen KA, Dinsmoor D, et al: Influence of autothreshold sensing and sinus rate on mode switching algorithm behavior [see comment]. Pacing Clin Electrophysiol 23:1473-1478, 2000. 31. Walfridsson H, Aunes M, Capocci M, Edvardsson N: Sensing of atrial fibrillation by a dual chamber pacemaker: how should atrial sensing be programmed to ensure adequate mode shifting? Pacing Clin Electrophysiol 23:1089-1093, 2000. 32. Nowak B, Kracker S, Rippin G, et al: Effect of the atrial blanking time on the detection of atrial fibrillation in dual chamber pacing. Pacing Clin Electrophysiol 24:496-499, 2001. 33. Goethals M, Timmermans W, Geelen P, et al: Mode switching failure during atrial flutter: the “2:1 lock-in” phenomenon. Europace 5:95-102, 2003. 34. Simpson CS, Yee R, Lee JK, et al: Safety and feasibility of a novel rate-smoothed ventricular pacing algorithm for atrial fibrillation. Am Heart J 142:294-300, 2001. 35. Eguia LE, Pinski SL: Inactivation of a ventricular tachycardia preventive algorithm during automatic mode switching for atrial tachyarrhythmia. Pacing Clin Electrophysiol 24:252-253, 2001. 36. Barold SS, Mond HG: Fallback responses of dual chamber (DDD and DDDR) pacemakers: a proposed classification. Pacing Clin Electrophysiol 17:1160-1165, 1994. 37. Ward KJ, Willett JE, Bucknall C, et al: Atrial arrhythmia suppression by atrial overdrive pacing: pacemaker Holter assessment. Europace 3:108-114, 2001. 38. Blommaert D, Gonzalez M, Mucumbitsi J, et al: Effective prevention of atrial fibrillation by continuous atrial overdrive pacing after coronary artery bypass surgery [see comment]. J Am Coll Cardiol 35:1411-1415, 2000. 39. Levy T, Walker S, Rex S, Paul V: Does atrial overdrive pacing prevent paroxysmal atrial fibrillation in paced patients? Int J Cardiol 75:91-97, 2000. 40. Lam CT, Lau CP, Leung SK, et al: Efficacy and tolerability of continuous overdrive atrial pacing in atrial fibrillation. Europace 2:286-291, 2000. 41. Attuel P, Danilovic D, Konz KH, et al: Relationship between selected overdrive parameters and the therapeutic outcome and tolerance of atrial overdrive pacing. Pacing Clin Electrophysiol 26:257-263, 2003. 42. Israel CW, Gronefeld G, Ehrlich JR, et al: Prevention of immediate reinitiation of atrial tachyarrhythmias by high-rate overdrive pacing: results from a prospective randomized trial. J Cardiovasc Electrophysiol 14:954-959, 2003. 43. Hakala T, Valtola AJ, Turpeinen AK, et al: Right atrial overdrive pacing does not prevent atrial fibrillation after coronary artery bypass surgery. Europace 7:170-174, 2005. 44. Connolly SJ, Kerr CR, Gent M, et al: Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to

cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 342:1385-1391, 2002. 45. Sweeney MO, Bank AJ, Nsah E: Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 357:1000-1008, 2007. 46. Sweeney MO: Algorithms for minimizing right ventricular pacing. In Al-Ahmad A, Ellenbogen K, Natale A, Wang PJ, editors: Pacemakers and implantable defibrillators: an expert’s manual, Minneapolis, 2010, Cardiotext, pp 79-115. 47. Sweeney M, Ellenbogen K, Casavant D, et al: Multicenter, prospective, randomized safety and efficacy study of a new atrial-based managed ventricular pacing mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol 16:811-817, 2005. 48. Sweeney MO, Ellenbogen K, Tsang ASL, et al: Severe atrioventricular decoupling, uncoupling, and ventriculoatrial coupling during enhanced atrial pacing: Incidence, mechanisms and implications for minimizing right ventricular pacing in ICD patients. J Cardiovasc Electrophysiol 19:1175-1180, 2008. 49. Savoure A, Frohlig G, Galley D, et al: A new dual-chamber pacing mode to minimize ventricular pacing. Pacing Clin Electrophysiol 28(suppl 1):43-46, 2005. 50. Pioger G, Leny G, Nitzsche R, Ripart A: AAIsafeR limits ventricular pacing in unselected patients. Pacing Clin Electrophysiol 30:S66-S70, 2007. 51. Abraham WT: Cardiac resynchronization therapy for the management of chronic heart failure. Am Heart Hosp J 1:55-61, 2003. 52. Barold SS, Herweg B, Giudici M: Electrocardiographic follow-up of biventricular pacemakers. Ann Noninvas Electrocardiol 10:231255, 2005. 53. Barold SS, Herweg B: Upper rate response of biventricular pacing devices. J Interv Card Electrophysiol 12:129-136, 2005. 54. Chang KC, Chen JY, Lin JJ, Hung JS: Unexpected loss of atrial tracking caused by interaction between temporary and permanent right ventricular leads during implantation of a biventricular pacemaker. Pacing Clin Electrophysiol 27:998-1001, 2004. 55. Akiyama M, Kaneko Y, Taniguchi Y, Kurabayashi M: Pacemaker syndrome associated with a biventricular pacing system. J Cardiovasc Electrophysiol 13:1061-1062, 2002. 56. Wang P, Kramer A, Estes NA, 3rd, Hayes DL: Timing cycles for biventricular pacing. Pacing Clin Electrophysiol 25:62-75, 2002. 57. Riedlbauchova L, Kautzner J, Fridl P: Influence of different atrioventricular and interventricular delays on cardiac output during cardiac resynchronization therapy. Pacing Clin Electrophysiol 28(suppl 1):19-23, 2005. 58. Taieb J, Benchaa T, Foltzer E, et al: Atrioventricular cross-talk in biventricular pacing: a potential cause of ventricular standstill. Pacing Clin Electrophysiol 25:929-935, 2002. 59. Lipchenca I, Garrigue S, Glikson M, et al: Inhibition of biventricular pacemakers by oversensing of far-field atrial depolarization. Pacing Clin Electrophysiol 25:365-367, 2002. 60. Cooper JM, Sauer WH, Verdino RJ: Absent ventricular tachycardia detection in a biventricular implantable cardioverterdefibrillator due to intradevice interaction with a rate smoothing pacing algorithm. Heart Rhythm 1:728-731, 2004. 61. Shivkumar K, Feliciano Z, Boyle NG, Wiener I: Intradevice interaction in a dual-chamber implantable cardioverter-defibrillator preventing ventricular tachyarrhythmia detection [see comment]. J Cardiovasc Electrophysiol 11:1285-1288, 2000. 62. Glikson M, Beeman AL, Luria DM, et al: Impaired detection of ventricular tachyarrhythmias by a rate-smoothing algorithm in dual-chamber implantable defibrillators: intradevice interactions. J Cardiovasc Electrophysiol 13:312-318, 2002. 63. Wietholt D, Kuehlkamp V, Meisel E, et al: Prevention of sustained ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators: the PREVENT study. J Interv Card Electrophysiol 9:383-389, 2003.

844

SECTION 4  Follow-up and Programming

29  29

Pacemaker Troubleshooting and Follow-up CHARLES J. LOVE

P

acemakers have advanced from nonprogrammable, single-chamber, asynchronous devices (VOO) to multichamber systems with extensive programmability. They now include not only the ability to adjust the pacing rate automatically on the basis of signals that are independent of the intrinsic heart rhythm (e.g., VVIR, DDDR), but also the capability of automatically regulating the stimulation power and sensitivity settings. In the near future, automaticity will extend to optimization of the atrioventricular (AV) and dual-ventricular site (VV) intervals as well. The analysis of a pacing system was comparatively easy during the early days of pacing, whereas the challenge in evaluating the modern pacemaker has increased to a degree concordant with the sophistication of the current devices. To facilitate these evaluations, manufacturers have incorporated a multitude of diagnostic tools in the pacemaker. These tools have become essential to determine what the pacemaker is doing and why it is doing it. The various diagnostic capabilities typically either eliminate the need for ancillary testing or provide the direction for additional testing. Occasionally, a given feature provides absolutely unique information that is not readily available by any other technique. These tools, which are integral to the implanted device, can be accessed by the programmer and are the subject of the first part of this chapter. To take advantage of these diagnostic features and to determine the appropriate function of a pacing system, the clinician must have an in-depth knowledge of the system’s components, including the pulse generator, leads, programmed parameters, automatic algorithms, sensors, connectors, and other implanted devices, as well as the patient’s physiology. It is crucial that the clinician understand the importance of evaluating the entire system rather than focusing on isolated individual components. The evaluation of malfunctioning pacemaker systems is the subject of the second part of this chapter.

Bidirectional Telemetry Telemetry is the ability to transmit information or data from one device to another, a capability that was essential to the introduction of pacemaker programmability. This is the ability to noninvasively change the functional and diagnostic parameters of the pacing system by coded commands transmitted to the pacemaker from a programmer.1-4 The first generation of programmable pacemakers used unidirectional telemetry from the programmer to the pacemaker but was not able to transmit data from the pacemaker to the programmer. This limited the confirmation of a programming change that was electrocardiographically silent (e.g., sensitivity, refractory period) when a parameter was programmed. Bidirectional telemetry is communication in two directions. With respect to pacing systems, this means that the pacemaker and programmer can communicate with each other, an essential capability for the development of the multiple diagnostic capabilities that are the subject of this chapter.5,6 First implemented in rechargeable pacemakers, bidirectional telemetry was developed to confirm the proper alignment of the recharging head with the implanted pacemaker. When the recharging wand was not aligned properly with the pacemaker, there was an audible beep from the charging unit to notify the patient and whoever was in attendance of this condition. When the two devices were properly aligned, the system was silent.

844

Bidirectional capability was next applied to confirmation of programming. This was particularly valuable for those parameters that did not result in an overt change in pacing system performance and could not be independently identified on an electrocardiographic recording. This ability is essential for the DDDR pacemaker and modern implantable cardioverter-defibrillators (ICDs), because these devices can have dozens of independently programmable parameters, most of which are not readily identifiable on the electrocardiogram (Fig. 29-1, A). Bidirectional telemetry allows interrogation of programmed parameters and measured data when the patient is seen during follow-up for routine evaluation, during remote follow-up interrogation, or for a suspected pacing system malfunction. Without this feature, there would be no way to determine the current settings of a device for features other than rate and pulse width. It also makes the retrieval of detailed data collected by the pacemaker in its various event counters feasible. Presently, interrogation of pacemaker settings and data can be accomplished remotely. This technique uses a device located in the patient’s home, a physician’s office, or anywhere an Internet connection or telephone service (wired or cellular) connection is available. Data are retrieved from the device and sent to a central receiving station. The data are made into a report and then can be faxed to the appropriate individual or made available through an Internet website portal. Although the technology exists to allow programming remotely, this is not currently available because of regulatory issues. MEASURED DATA Complementing the interrogation of programmed data is the provision of measured data, including data obtained from the pacemaker detailing information on lead and battery function at evaluation. Information regarding demand and asynchronous rates may also be measured (Fig. 29-1, B). Telemetry allows this information to be transferred from the pacemaker to the programmer for evaluation by the clinician. Battery Status Although not all systems provide the information in the same manner (some are graphic and others are numeric), data concerning battery function often include a measure of battery voltage, impedance, and current drain.7-11 All three parameters are interrelated. The battery current drain is a measure of the average current being drawn from the battery, assuming 100% pacing at the programmed rate and output settings. Inhibition or pacing at higher rates, as might occur with intrinsic rhythm or sensor drive, respectively, directly affects the functional battery current drain, as do changes in lead or stimulation impedance. The reported current drain is only an estimate of the actual battery current drain. Newer devices are able to estimate remaining longevity based on true current drain measurements, giving a much more accurate assessment (see Fig. 29-1, C). The measured current drain of the battery at a known set of parameters can be used to qualitatively assess the effect of programming changes on the longevity of the system. After the rate or output (or both) has been changed, the measured data can be reassessed and the effect of the programming change on longevity estimated. A simple calculation may be used to obtain an estimate of battery longevity when the pacemaker is relatively new. Most



845

29  Pacemaker Troubleshooting and Follow-up

EXTENDED PARAMETERS

BASIC PARAMETERS Initial Mode ........................................... DDDR Base rate ........................................... 70 Hysteresis rate ................................... Off Rest rate ............................................ Off Max track rate ................................... 130 2:1 Block rate ...................................164 AV delay ........................................... 200 PV delay ........................................... 170 RR AV/PV delay ........................ Medium Shortest AV/PV delay ....................... 70 Ventricular refractory ........................ 250 Atrial refractory (PVARP) ................. 275 Ventricular: V. AutoCapture .................................. On Automatic pulse amplitude ........ 0.875 Backup pulse configuration ..... Bipolar E/R sensitivity ................................ 2.3 V Pulse width .................................. 0.4 V Sensitivity .................................... 2.0 V Pulse configuration .............. Unipolar V Sense configuration ............... Bipolar Atrial: A Pulse amplitude .......................... 2.50 A Pulse width ................................... 0.6 A Sensitivity ..................................... 0.3 A Pulse configuration ................ Bipolar A Sense configuration ............... Bipolar Magnet response ................. Battery test

=> => =>

=> =>

Present DDDR 60 Off Off 120 145 200 170 Medium 70 275 300 On 0.875 Bipolar 2.3 0.4 2.0 Unipolar Bipolar

=>

Initial Autointrinsic conduction search ...........100 Negative AV/PV hysteresis/search ...... Off Auto mode switch .............................DDIR Atrial tachycardia detection rate .........150 AMS base rate .................................... 70 => AF Suppression™................................. Off Post vent. atrial blanking (PVAB) .........140 Vent. safety standby ..............................On Vent. blanking .........................................12 PVC options ......................................... Off PMT options ......................................... Off

ppm ppm ppm ppm ppm ms ms ms ms ms

Present 100 Off DDIR 150 60 Off 140 On 12 Off Off

ms ms ppm ppm ms ms

SENSOR PARAMETERS V

Initial Sensor .................................................. On Max sensor rate .................................. 120 Threshold ................................ Auto (+0.0) Meas. average sensor .........................2.0 Slope .......................................... Auto (+3) Measured auto slope ...........................13 Reaction time .............................. Very fast Recovery time .............................. Medium

mV ms mV

2.50 V 0.4 ms 0.3 mV Bipolar Bipolar Battery test

Present On 120 ppm Auto (+0.0) 2.0 Auto (+3) 13 Very fast Medium

* Not applicable => Initial value differs from present value T=> Temporary programmed value ... Unknown/invalid values

A MEASURED DATA

MEASURED DATA Date last programmed ................................ Oct 11. 2010 10:09 am Magnet rate ................................................................. 98.5 ppm Ventricular: Pulse amplitude ........................................................... 0.8 V Pulse current ............................................................... 1.8 ma Pulse energy ............................................................... 0.4 µj Pulse charge ................................................................... 1 µC Lead impedance ........................................................ 455 Ω Atrial: Pulse amplitude ........................................................... 2.2 V Pulse current ............................................................... 4.7 ma Pulse energy ............................................................... 3.4 µj Pulse charge ................................................................... 2 µC Lead impedance ..........................................................512 Ω Battery data ..................... (W.G. 9438 - nom. 0.95 Ah) Voltage ....................................................................... 2.74 V Current .......................................................................... 10 µA Impedance .................................................................. 2.1 kΩ

B

Magnet rate ........................................................... 98.5 ppm Estimated remaining longevity .................................. 4 years

ERI

Battery data .......................... (W.G. 9438 - nominal 0.95 Ah) Voltage .......................................................... 2.75 V Current ............................................................. 16 µA Impedance ....................................................... <1 kΩ R Vent.

L. Vent.

Pulse amplitude .................................... 2.2 V Pulse current ........................................ 5.1 mA

5.2 V 4.5 mA

C

Figure 29-1  Example of pacemaker parameters and measured data. A, Final interrogation of a St. Jude Medical pacemaker showing the programmed parameters and the changes identified since the initial evaluation. B, Measured data telemetry, showing the condition of the battery and lead systems. C, Measured data telemetry showing the condition of the battery and lead systems with projected longevity based on current setttings and historical battery drain.

manufacturers provide the usable battery capacity reported in ampere-hours (A-hr). For this calculation, the battery’s capacity is converted to microampere-hours (µA-hr) and then divided by the measured battery current drain. The result is the anticipated number of hours of normal function at the programmed rate and output. This number, divided by 8760 (the number of hours in 1 year),

yields an estimate of the longevity of the system in years. This calculation is best performed with a new system, before there has been significant battery depletion. Many newer pacemakers perform these calculations and display the remaining longevity in years or months, providing a relatively good estimate of remaining longevity.

846

SECTION 4  Follow-up and Programming

Virtually every pacemaker incorporates a change in either the magnet or the demand rate (and sometimes in mode or other functions) to signal a level of battery depletion that warrants pulse generator replacement. Most of these changes occur when the battery voltage reaches a predefined level, which is specific for each manufacturer and even for each model of pacemaker. These changes are termed elective replacement time (ERT), recommended replacement time (RRT), or elective replacement indicator (ERI), with further changes in rate or function associated with continued battery depletion labeled either end of life (EOL) or end of service (EOS). Although these changes may occur abruptly, usually a 3- to 6-month period exists between activation of the ERT indicator and erratic behavior or device nonfunction caused by continued battery depletion. A marker to determine when to increase the frequency of pacing system surveillance (either transtelephonically or in the office) is included in some systems and is typically a magnet rate intermediate between a fully functional battery and the ERT indicator. Alternatively, this indication may be given to the clinician during interrogation of the device by a message on the programmer screen or on the programmer report. This is termed an intensified follow-up indicator and provides an indication of changing battery status before the ERT is reached. Given the degree of programmability of most current pacemakers, a dual-chamber pacemaker programmed to pace all the time at maximal output on each channel may last only 2 years. An identical model programmed to outputs of 2.5 V or lower on each channel that are inhibited a significant portion of the time may be anticipated to function properly for 10 years or longer. It would be inappropriate to follow the second unit on a monthly basis beginning 1 year after implantation, whereas it would be equally inappropriate to plan only annual checks on a pacing system programmed with high outputs and 100% pacing. By following some measure of the status of the battery, either directly or indirectly, the clinician can achieve a qualitative assessment about when to increase the frequency of pacing system follow-up.12 There are two primary indicators of battery status: battery voltage and battery impedance. Battery voltage progressively decreases over time. The lithium/iodine (Li/I2) power cell is the most common power source in pacemakers, whereas the power source in an ICD is lithium/silver vanadium oxide (Li/VSO). Some of the newer pacemakers are now using Li/VSO–polycarbon monofluoride (LVSO/P). The nominal unloaded output voltage of the Li/I2 cell is 2.8 V, with each manufacturer triggering the RRT indicator at a specified battery voltage based on circuit design considerations. LSVO/P in pacemaker application has an initial voltage of 3.20, with an early drop to 2.90 V, where it plateaus, then drops to an elective replacement voltage of 2.60 V. The battery voltage and programmed output voltage are not identical. The “programmed output voltage” is achieved by modifying the 2.8-V battery output with either voltage multipliers or charge pumps to provide a higher voltage. The battery voltage can also be divided to deliver a voltage lower than 2.8 V. As energy is consumed, the battery voltage progressively decreases because of increased internal impedance. Even with decreasing battery voltage, the device circuitry is designed to maintain the stability of the programmed voltage delivered to the patient. The ability to track the progressive decrease in battery voltage and increase in battery impedance provides an effective guide to the clinician regarding the frequency with which the pacing system should be routinely checked for signs of battery depletion (Fig. 29-2). In addition, the measured battery voltage is affected by the battery current drain: the higher the current drain, the lower the battery voltage. Battery impedance is inversely related to battery voltage. In the Li/I2 power cell, the release of electrons is generated by the combination of the lithium ion with two iodine atoms. The result of this chemical reaction is the release of two electrons and the formation of lithium iodide. As it accumulates, the lithium iodide forms a resistive barrier between the anode and the cathode. With progressive cell depletion, the increasing amount of lithium iodide results in a rise in the internal

ppm 105

Magnet rate

100 95 90 V 2.9

Battery voltage

2.8 2.7 2.6 Battery Impedance

kOhm 32.0 24.0 16.0 8.0 0

12

24

36

48

60

72

84

M Figure 29-2  Pacemaker magnet rate, battery voltage, and battery impedance. Graph over time demonstrates the inverse relationship between battery voltage and battery impedance. For this particular St. Jude Medical pacemaker, the magnet rate drops proportionally to the battery voltage. kOhm, killiohms; M, months; ppm, Pulses per minute; V, volts;

impedance of the battery, which some pacemakers can measure and report in the telemetry data. The higher the battery impedance, the lower is the cell voltage. Battery voltage and impedance may be tracked together or individually. If these measurements are provided to the manufacturer’s technical service engineers, along with the programmed parameters and an estimate of the percentage of pacing versus inhibition, the remaining longevity of that pacing system can be estimated with reasonable accuracy, assuming that the various parameters remain stable. These calculations have more recently been incorporated into the programmer interface to provide an online estimate of longevity in years or months. These estimates are sometimes shown as a range based on the tolerances of the battery measurements (i.e., giving minimum and maximum ranges of longevity), as well as an estimate based on present current drain and actual device use based on data acquired from the event counter diagnostics (see Fig. 29-1, B). Lead Status Although many systems provide data on lead function, including pulse voltage, current, charge, and energy, the most common measurement is lead impedance (stimulation resistance). Changes in lead impedance directly affect the other measures of lead function. The terms resistance and impedance, although technically different, are often used interchangeably by the clinical community. Impedance is a complex concept that reflects a changing environment involving a variety of factors. This results in fluctuations in the moment-tomoment resistance. The resistance to electron flow in a pacing system progressively rises during delivery of the stimulation pulse as a result of polarization at the electrode-myocardium interface and, as a continuously changing variable, it is appropriately termed impedance. Many pulse generators and pacing system analyzers make this measurement at a specific point within the pacing stimulus; this is a resistance. Other devices report the resistance as an average of the impedance throughout the pulse. The actual resistance to current flow imparted by the conductor coil is fixed and represents a small portion of the total stimulation resistance. The polarization at the electrode-myocardium interface, partly related to the surface area and geometry of the electrode, and the impedance associated with



conduction of the pulse through the body’s tissues play a larger role in the overall resistance of the system. All these factors are incorporated in the single measurement termed lead impedance or, more accurately, stimulation impedance. Stimulation impedance is affected by many factors, but primarily by the design of the electrode, including size, configuration, and materials. Manufacturers have designed some electrodes with high impedance values. For any given output, a high-impedance system reduces the overall current drain of the battery and effectively increases the longevity of the device. Other leads have been designed specifically for low polarization to allow for detection of capture with each pace stimulus. Polarization and impedance are not the same phenomenon, although one affects the other. For any given lead model, there may be a broad range of normal impedance values; for a specific lead within that model series, however, the impedance should fall within a relatively narrow range. The clinician can use knowledge of lead impedance to monitor and identify a developing mechanical problem with the lead. This requires baseline and historical data to recognize subtle changes that may reflect conductor fracture or an insulation breach. It is essential to know what device is being used to make these measurements. As noted previously, different devices may obtain these data at different points of the pacing stimulus. Because of these differences, the impedance measurement obtained with a pacing system analyzer at implantation may be significantly different from that obtained by telemetry from the implanted pacemaker moments, if not years, later. This difference does not necessarily imply a problem. Furthermore, impedance may naturally evolve over time, with a fall in impedance occurring during the days to weeks after implantation, followed by a gradual rise toward the initial measurements. Multiple factors may affect impedance, particularly in a unipolar system. For example, measurements obtained during deep inspiration may significantly differ from those obtained during maximal exhalation. In the same patient, impedance measurements based on a single-output pulse have been reported to vary by 100 ohms (Ω), or even more, during the same follow-up evaluation, while remaining consistent with normal function. If a marked change in lead impedance from previous measurements (e.g., >200 Ω) is encountered during a routine follow-up evaluation, the pacing system should be further eva­luated.13,14 If the patient has no clinical symptoms and has stable capture and sensing thresholds, surgical intervention would be premature, although more frequent follow-up in the office or by remote interrogation would be prudent. However, a dramatic change in telemetered lead impedance in the presence of a clinical problem directs the physician toward the likely source of the difficulty (Fig. 29-3). A dramatic fall in impedance usually reflects a break in the insulation.15-17 In a unipolar system, an insulation problem provides an alternative pathway for current flow starting closer to the pulse generator, resulting in less energy reaching the heart. An outer insulation break in a bipolar lead tends to result in “unipolarization” of the lead. The amplitude of the stimulus artifact as recorded by an analog electrocardiogram (ECG) is determined by the distance the current travels in the tissues from the cathode (tip electrode) to the anode (ring electrode or housing of the pulse generator). A normally functioning bipolar pacing system in which both active electrodes are inside the heart, separated only 1 to 2 cm, results in a small stimulus artifact. In a unipolar system, the current travels from the tip electrode to the housing of the pulse generator, and therefore the stimulus artifact is large despite equivalent output settings. Some of the newer digital ECG designs result in a marked signal-to-signal variation in amplitude as a result of the digital sampling rate of the recording system. Other recording systems create an artificial uniform amplitude artifact with any high-frequency electrical transient, thereby precluding differentiation of a bipolar from a unipolar pacing system based on the analysis of the ECG recording. In a previously stable system, a mechanical problem developing with the lead—either a breach in the insulation or a conductor

29  Pacemaker Troubleshooting and Follow-up

847

Measured data-Lead impedance Atrial Ventricular Previous Present Previous Present 27-JUL-2009 27-JUL-2009 Date of last test Impedance 200 220 530 460 Amplitude 2.5 2.5 2.5 2.5 V Pulse width 0.40 0.40 0.60 0.60 ms Current 13 11 5 5 mA Lead config. (paced) Unipolar Unipolar Bipolar Bipolar Energy 12.5 11.4 7.1 8.2 µJ Measured data-Intrinsic amplitude Date of last test Chamber tested Measured amplitude Lead configuration (sensed)

Previous Present 27-JUL-2009 Atrium 4.1 Unipolar

3.6 mV Unipolar

Measured data-Intrinsic amplitude Date of last test Chamber tested Measured amplitude Lead configuration (sensed)

Previous Present 27-JUL-2009 Ventricle >12.0 Bipolar

9.9 mV Bipolar

Figure 29-3  Measured data telemetry. Rate-modulated dualchamber pacemaker data report a low impedance on the atrial lead of 200 to 220 ohms (Ω) (Boston Scientific 1297). Although a unipolar lead, this impedance is very low and may be the result of an insulation failure. This also produces an increase in the battery or cell current, caused by a higher-output current, charge, and energy being delivered by the pacemaker (compare energy to that of the ventricular lead), whether or not it reaches the heart.

fracture—results in a change in the stimulation impedance, which may be reflected by a change in the ECG-recorded stimulus artifact (Fig. 29-4). In a bipolar pacing system, an insulation defect between the proximal conductor and the tissues of the body is not likely to affect capture thresholds, but it results in a larger stimulus artifact, making it appear unipolar. Depending on the actual location of the insulation failure in either the bipolar or the unipolar lead, stimulation of the extracardiac muscle contiguous to the insulation defect may occur. Insulation failures may also attenuate the elect­ rical signal reaching the pacemaker, possibly resulting in sensing failure. In a bipolar lead, an insulation defect developing between the proximal and distal conductors can present as a variety of clinical manifestations. Intermittent contact between the two conductors generates a voltage “transient” that the pacemaker can sense, resulting in inhibition or triggering, depending on the programmed sensing mode and the channel on which the problem has occurred. This small electrical signal is not seen on the surface ECG and is appropriately termed oversensing. If the two conductors remain in contact, current flowing down the distal conductor is short-circuited to the proximal conductor and never reaches the electrodes. This may result in a loss of capture and a further reduction in amplitude of the normally diminutive bipolar stimulus artifact on the ECG. In addition, loss of appropriate sensing may occur. Programming of the output configuration to unipolar (most pacing systems, but not ICDs, now have this capability) may prevent the loss of capture and possibly undersensing from an internal short circuit. This does not prevent the oversensing behavior associated with makebreak electrical transients generated by intermittent contact between the two conductors, as is caused by failed inner insulation. Typically, a bipolar lead with failed internal insulation exhibits a higher impedance

848

SECTION 4  Follow-up and Programming

V S

V VV S RR

V P

V S

V P

V V V P R R

VV PR

V P

V S

V VV S SR

Figure 29-4  Simultaneous electrocardiogram (ECG) rhythm strip and event markers. Single-chamber, bipolar, rate-modulated pacemaker with an internal insulation failure of the lead. There are both oversensing (VS and VR) and functional undersensing when the true native complex coincides with the refractory period initiated by the oversensing. During the intervention for lead replacement, the measured lead impedance was 125 Ω. The event markers are both labeled (VP, ventricular pacing; VR, sensed event occurring during the refractory period; VS, ventricular sensing) and identified by different amplitudes of the marker artifacts. The surface ECG should also be examined. This recording system generates a largeamplitude “artifact” to simulate the paced output, with any high-frequency transient that is detected independent of the output configuration of the pulse. If no stimulus is detected, no artifact is generated. There are paced QRS complexes identified by the event markers that have no “pacing stimulus” on the ECG, whereas others have a large “unipolar” pacing stimulus visible. The identification of the pacing system malfunction was facilitated by the simultaneous event markers.

when pacing is programmed to the unipolar rather than the bipolar output configuration.18,19 This is opposite to the expected higher impedance of a bipolar system. Although programming to a unipolar configuration may result in an apparent resolution of a malfunction, it is not a cure and should be considered only as a temporary measure, one that allows the observed problem to be managed on an elective rather than emergent basis. The malfunctioning lead should be replaced expeditiously. An increase in lead impedance may be the result of a conductor fracture or a connector problem.20 When this occurs, the lead impedance often rises to high levels. It is inappropriate, however, to assume that a normal lead impedance is 500 Ω. Leads are available that are designed to have high impedance, with values ranging from 1500 to 2500 Ω. Other leads, at implantation, may have an impedance in the range of 250 to 300 Ω. Therefore, it is essential to look for a trend in serial lead impedance measurements rather than a single measurement. Impedance, taken in conjunction with the stability or changes in capture and sensing thresholds, is the best way to determine the condition of a pacing lead. A mechanical problem with the lead— either a conductor fracture resulting in high impedance or an insulation failure resulting in low impedance—eventually results in an overt clinical problem that can be identified by telemetric measurement of the stimulation impedance. If the impedance is sufficiently high, there is no current flow and no effective output. It must be understood that, although the telemetered event markers indicate a pace output, there may be loss of capture. The reduced current flow also results in a fall in the measured current drain of the battery. Note that any problem may be intermittent. This typically occurs when the two broken ends make contact at times but are separated at other times, or in the case of an insulation failure, when lead movement either opens the compromised area or pushes the edges of the break together, resulting in intermittent normal function. Before the availability of telemetry for lead impedance measurements, physicians could obtain similar information by oscilloscopic analysis of the pacemaker stimulus. In the 1970s, some manufacturers included a photograph of the pulse wave contour at a variety of

different impedance values with the technical manual accompanying each pacemaker. Some computer-based pacemaker ECG follow-up systems are able to record and display the pacemaker pulse at an expanded scale. This allows the pace waveform to be recorded and tracked as a routine part of the periodic pacing system evaluation. Although this feature is available, it is not routinely used, given the ready access to lead impedance measurements provided by the implanted pacing system. Lead impedance measurements have an indeterminate incidence of false-negative results when the lead problem is only intermittently manifested. The system forces the pacemaker to function asynchronously in an effort to obtain the measurements. The measurements, however, are made over a few cycles. If there is a true lead problem, but it is intermittent and was not present when the measurements were being made, the telemetered lead impedance may be normal. Therefore, if a problem is suspected, repeated measurements should be performed. Use of provocative maneuvers, such as placing manual pressure along the subcutaneous course of the lead, or having the patient raise or in other ways manipulate the ipsilateral arm, may be required to unmask a problem. Some pacemakers are able to report lead impedance measurements on a beat-by-beat basis, allowing the clinician to observe the digital readout of lead impedance on the programmer screen over many cycles. As with the oscilloscopic monitoring of the pulse wave morphology, this technique reduces but does not eliminate the incidence of false-negative results. A further enhancement is the “automatic periodic monitoring” of lead impedance, which results in a graphic display reporting the history of lead impedance performance. Measurements can be obtained continuously or daily. This increases the frequency of measurement, increasing the likelihood of diagnosing an intermittent lead problem and possibly intervening on an automatic basis (Fig. 29-5). Some devices respond by automatically programming the pacemaker from bipolar polarity to unipolar in the presence of either a marked rise in impedance, reflecting a conductor fracture,21 or a marked drop in impedance, consistent with an insulation failure.



29  Pacemaker Troubleshooting and Follow-up

849

Lead Impedance >2500 1250 <100 SEP NOV JAN MAR MAY JUL THR SAT MON WED OCT DEC FEB APR JUN AUG FRI SUN TUE Intrinsic Amplitude >20.0 10.0 0.1 Atrium

Ventricle

Daily Measurement-Data Table Date Figure 29-5  Pacemaker lead impedance and intrinsic signal amplitude. Graphic display (top) and tabular summary (bottom) of serial automatic atrial and ventricular lead impedance measurements as well as intrinsic signal amplitude from an implanted Boston Scientific pacemaker. This event counter reports measurements made on a daily basis for the past 7 days and the mean weekly measurements before that time, with the potential for extending back a full year. These data were retrieved at a follow-up evaluation.

02-SEP-98 01-SEP-98 31-AUG-98 30-AUG-98 29-AUG-98 28-AUG-98 27-AUG-98 21-AUG-98 14-AUG-98 07-AUG-98

EVENT MARKER TELEMETRY The challenges associated with interpreting the paced ECG have greatly increased with the expanded use of multichamber, multisensor, ratemodulated systems. Even with the simplest pacing systems, multiple assumptions had to be made. Most clinicians are comfortable evaluating a surface ECG composed of P waves representing native atrial depolarizations and QRS complexes (or R waves) representing native ventricular depolarizations. The pacemaker does not respond to the P or R wave, but to the intrinsic deflection of the electrical potential inside the heart that occurs as the wave of depolarization passes by the pacing electrode. Although the events inside the heart frequently correspond to events recorded by the ECG, there may be events inside the heart that are not visible on the ECG. In addition, the pacemaker senses and responds to events occurring outside the heart if they are detected by the sense amplifier. Standard ECG recordings may not depict these internal and external electrical events, yet they can affect the behavior of the pacing system. Similarly, standard ECG recordings do not detect the usual sensor signals that may also drive the pacemaker to a variety of different rates and timing settings. The introduction of dual-chamber pacing significantly increased the level of complexity of the paced rhythm. The interaction between the two channels of the pacing system, with the spontaneous rhythms occurring in either the atria or the ventricles, added to the potential for confusion. The addition of rate-modulated pacing (i.e., allowing pacemaker to respond to one or more sensor signals invisible on ECG) contributed to the challenge of interpreting the paced ECG. Further complexity was added to the pacemaker timing cycles with various atrial-ventricular (A-V) interval modulation schemes designed to enhance conduction down the patient’s atrioventricular (AV) node, to

Amplitude (mV) >3.5 >3.5 PACED >3.5 >3.5 >3.5 >3.5 >3.5 >3.5 >3.5

Atrium

Impedance (Ω) 480 500 500 480 500 470 470 480 480 480

Amplitude (mV) PACED PACED PACED PACED PACED PACED PACED PACED PACED PACED

Ventricle Impedance (Ω) 680 710 710 710 680 670 710 710 720 680

prevent conduction down the AV node, or simply to enhance the ability to achieve higher pacing rates while maintaining AV synchrony. Various functions (e.g., rate hysteresis, therapeutic pacing rates) in response to sudden decreases in native heart rates complicate these systems even further. Most recently, the widespread use of multichamber pacing for cardiac resynchronization and atrial fibrillation suppression has created an even greater degree of complexity. In the modern pacemaker, interpretation of the paced rhythm requires knowledge of the basic timing intervals. A variety of refractory periods, including postventricular atrial refractory period (PVARP), postventricular atrial blanking period, ventricular refractory period, ventricular blanking period, and paced and sensed A-V intervals, must be considered. Some intervals may change depending on the rate, such as A-V interval, atrial escape interval (when sensor driven or with special features), and PVARP. The clinician also needs to be aware of a number of device-specific responses to protect the system from a variety of anticipated but undesirable behaviors or clinical events. These include crosstalk, the initiation of pacemaker-mediated tachycardia by a premature ventricular beat, mode switching, and multiblock upper rate behavior. To facilitate interpretation of the paced rhythm, almost all modern pacing and ICD systems incorporate the ability to transmit information regarding real-time pacing system behavior to the programmer. These data are displayed on the programmer screen and may also be printed as well. Both paced and sensed events are communicated to the programmer. Displayed as a series of positive or negative marks, with or without alphanumeric annotation, these are generically termed event markers. They have the greatest diagnostic value when superimposed above or below a simultaneously recorded surface ECG (Fig. 29-6). Some systems also display the duration of the atrial and

850

SECTION 4  Follow-up and Programming

ECG Controls

Programmed Parameters

Surface ECG ................................... On Position ........................................... 1 Gain .......................................... 0.25 Filter ............................................ On Markers ........................................... On Position .......................................... 2 IEGM ............................................... Off Position ........................................... 3 Gain ............................................... 5 Configuration ................................. -Sweep Speed ................................... 25

Mode ......................................... DDDR Base Rate ........................................ 65 A-V Delay ....................................... 300 P-V Delay ....................................... 200 Magnet Response ......... Temporary Off Temporary 30 .................................. Off

mV/div

ppm ms ms

mV/div mm/s

1.0 Second

A 273

A R

R

426

627 908

281

A R 627 901

274

A R

R

464

626 900

274

A R 627 901

274

A R 626 900

274

A R 631 896

265

R

R

449

630 908

Figure 29-6  Surface ECG and simultaneous event markers. Telemetry shows an atrial-paced rhythm with intact atrioventricular nodal conduction and isolated ventricular ectopic beats. Key programmed parameters are shown at the upper right, and recording parameters at the upper left (IEGM, intracardiac electrogram). The numbers refer to the millisecond intervals automatically measured and displayed by the programmer. The horizontal lines that follow the alphabetic label (A, atrial-paced output; R, sensed ventricular event) represent the length of the programmed or functional refractory period. Data are from a Pacesetter Trilogy DR+ Model 2360 (St. Jude Medical CRMD, Sylmar, Calif ).

ventricular refractory periods and interval measurements. Others show events that are sensed during the refractory period even though they do not play a role in altering the system timing (i.e., they are sensed but not used). Events may be displayed either in real time or after the tracing has been frozen on the programmer screen using cursors to identify the interval of interest. If the real-time monitor screen method is used to show the rhythm and event markers, the tracing may be frozen and then printed for inclusion in the medical record. Event markers (also called marker channels, annotated event markers, and main timing events by various manufacturers) are most effectively used when they are displayed with a simultaneously recorded ECG rhythm.22-25 Without the ECG, the event marker simply reports the behavior of the pacemaker. This information is valuable in showing that an output has been released or that sensing has occurred. It does not confirm that the stimulus effectively resulted in capture, or that a sensed event was a true atrial or ventricular depolarization. The presence of an output marker does not confirm that the stimulus even reached the heart. The output marker serves only to confirm that the pacemaker delivered a stimulus from its output circuit. This notation is transmitted directly from the pacemaker to the programmer by way of the telemetry module. An open circuit (e.g., a fractured conductor coil) may preclude the output pulse from reaching the heart, but the pacemaker would indicate that an output pulse was released. Similarly, a native depolarization may not be sensed, allowing the pacing stimulus to be released at a time when the myocardium is physiologically refractory. If the markers reported that an event was sensed on the atrial channel and was followed by a ventricular output pulse after a preset delay (known as P-wave synchronous ventricular pacing or tracking), the clinician would know that the pacemaker was capable of sensing in the atria and pacing in the ventricles. Without a simultaneously recorded ECG, it would be impossible to determine whether the pacemaker was responding to inappropriate signals on the atrial channel, whether the ventricular stimulus was effective, or whether a native QRS complex was present but not sensed. Therefore,

telemetered event markers are most effective when displayed with a simultaneously recorded ECG. Event Marker Displays A variety of different displays have been used over the years. Although not intended for this purpose, the simplest event marker for sensed events was achieved with triggered mode pacing, particularly if the output configuration was unipolar. A sensed event would be marked by the simultaneous release of a pacing stimulus coincident with sensing. This was easily recorded on the ECG, because the stimulus artifact distorted the morphology of the native sensed complex. The next evolutionary step in this technology involved the pacemaker emitting a series of subthreshold stimuli of varying amplitudes to represent the release of an output pulse, a sensed event, and the end of a refractory period. Both these systems, the triggered mode and the series of markers, were limited by the signals requiring an intact lead system, to allow the pulse to be delivered to the heart through the lead and subsequently recorded for display by the ECG. With a bipolar output pulse, the small artifact might not be readily visible, particularly in the triggered mode, because it would be obscured by the larger native complexes. In addition, if there were an open circuit (most often a conductor fracture) or an internal insulation failure involving a bipolar lead, no marker would be visible. The next improvement was to transmit coded signals representing paced and sensed events from the pacemaker to the programmer. The programmer reconstituted these signals into a series of varyingamplitude pulses or alphanumeric labels representing paced or sensed events. These could be either displayed on a monitor screen or recorded using a printer integral to the programming system, which allowed for the simultaneous recording of a surface ECG acquired by way of a separate set of cables. The simultaneous ECG and markers allowed the clinician to correlate the behavior of the pacemaker directly with the patient’s rhythm, to determine whether the system is functioning properly. A calibration signal composed of a series of



29  Pacemaker Troubleshooting and Follow-up Marker codes Atrial Pace (AP) Atrial Sense (AS) Atrial Refractory Sense (AR) Vent. Refractory Sense (VR) Vent. Sense (VS) Vent. Pace (VP)

→ → → → → →

A A A P S R

C H

V V V R S P

Figure 29-7  Example of formerly used event marker annotation. Lines of various amplitude are used to designate paced, sensed, and refractory events. Lines above the baseline are used to describe atrial events, and lines below the baseline to describe ventricular events. This type of annotation has been made obsolete by the current annotation systems.

different amplitude pulses or a legend of the cryptic labels allowed the clinician to interpret the various markers (Fig. 29-7). In an early series of markers, the largest pulse represented a pacing output, the intermediate one indicated a sensed event, and the smallest represented either the end of the refractory period or a sensed complex that occurred during the refractory period. With the advent of dual-chamber pacing systems, a marker pulse extending above the baseline identified atrial events, and ventricular events were labeled with a pulse extending below the baseline. This type of marker system has become obsolete, and there are very few devices remaining as active implants that use this scheme. A further refinement to this system was the addition of alphanumeric annotations, which made the simple (yet cryptic) system just described obsolete. Two common sets of notations have been used and are summarized later. These are not the only possibilities, because some manufacturers use a unique set of symbols to identify paced and sensed events, with the location of the symbol on the recording identifying whether it represents an atrial or a ventricular event. Others have expanded on the set of labels and provide, on command, a detailed explanation. One method for single-chamber pacing systems with event marker telemetry uses the letter P to reflect a paced event and S to represent a sensed event. This may cause confusion with other dual-chamber systems in which the letter P reflects a sensed atrial event indicative of a native P wave (with which most medical personnel are familiar, based on their knowledge of the standard ECG). The interpretation of the alphanumeric event markers is often product specific, and the clinic personnel who evaluate the pacing system must take this into account (Fig. 29-8). In the case of dual-chamber pacing or when the pacemaker knows that it is providing atrial pacing and sensing, a native atrial depolarization may be identified as either the letter P or the combination AS. P is taken from the standard ECG identifier for an atrial depolarization. AS is one abbreviation for an atrial sensed event. An atrial stimulus may be identified by either the letter A or the combination AP for atrial paced event. Analogous lettering is used on the ventricular channel. Again, singlechamber pacing in some systems might still use the letters P to represent a paced event and S to refer to a sensed event. Other systems use R to refer to a native ventricular depolarization, which is generically called an R wave on the standard ECG. This may also be identified by the letter combination VS for a ventricular sensed event. The letter V in one system might be used to represent a ventricular pacing stimulus, whereas the identical event may be labeled VP (for ventricular paced event) in other systems. Other symbols may be used for a paced or sensed event and are usually displayed with an identifying key on the resultant printout. Each paced or sensed event may also be identified by a vertical line, going up in the case of atrial events and down for ventricular events. In some cases, a difference in the amplitude of these lines has been retained in conjunction with the alphanumeric lettering. Indeed, as the

851

complexity of the devices increases, the variety of symbols and letters identifying specific events and behaviors is also increasing (see Fig. 29-8). In many systems, interval measurements between the various events are either calculated automatically and displayed, or measured after cursors are aligned with specific events. There may be a time delay between the actual sensed or paced event and the release of the event marker. This is caused by the finite period that is required for the pacemaker to recognize the event and then transmit the appropriate information to the programmer through the telemetry channel. In most cases, priority is given to the normal function of the pacemaker, with the diagnostic marker feature being delayed. Differences of up to 40 msec between the actual event and the resultant marker have been noted. Laddergramming Laddergramming is an advanced adjunct to the interpretation of clinical arrhythmias. It was incorporated in some programming systems by using the known programmed parameters of the pacemaker combined with the event marker information telemetry from the implanted pacemaker23-26 (Fig. 29-9). For all the elegance of these graphic interpretations of the pacemaker’s behavior, they still require the simultaneously recorded ECG rhythms. Although the pacemaker may be functioning normally, in that it is behaving properly with respect to its programmed parameters, failure to capture or properly sense would not be diagnosed from the various diagrams and markers without the simultaneously recorded surface ECG.27 Laddergramming has become a teaching tool at this time, because no programmers currently provide this level of graphic description. Event Marker Limitations Several limitations are associated with event marker telemetry. First, used alone, markers report the behavior of the pacemaker but do not allow the clinician to determine whether this behavior is appropriate for the patient.27 In this regard, markers are analogous to the hand-held digital counters that report pacing rates and intervals. The counters only detect and report the pacing stimuli, not whether these output pulses are effective in causing a cardiac depolarization, or whether native events are properly and consistently sensed. A long interval between consecutive pacing stimuli could reflect normal function because the pacemaker responded appropriately to a native complex, or it could represent a system malfunction with oversensing or no output (e.g., from intermittent lead fracture). Neither event marker telemetry nor the digital counters should be used independently of a simultaneously monitored ECG rhythm. The second limitation is that the report of a stimulus output does not mean that there was appropriate capture. Confirmation of capture requires an ECG or concomitant hemodynamic pulse monitoring. In addition, the markers may report that the pacemaker is sensing a signal, but if this signal is not visible on the surface ECG, there is cause for concern. Is it an appropriate signal that the pacemaker should be sensing (some intrinsic atrial rhythms may not be visible on the specific lead that is being monitored), or is the system responding to an inappropriate or nonphysiologic signal, such as the make-break potentials associated with a breach of the internal insulation in a coaxial bipolar lead? Most pacemaker event marker telemetry is limited to real-time recordings. The markers must be telemetered from the pacemaker to the programmer or another display system while the rhythm is being actively monitored. Neither the pacemaker nor the programmer can retrospectively provide markers for a previously recorded rhythm. If the pacemaker is responding to events that are not visible on the surface ECG, the event marker simply confirms this fact but does not identify the specific signal. An evaluation of sensed but otherwise invisible events requires intracardiac electrogram telemetry or an invasive procedure to record the signal from the implanted lead. Many premium-level pacemakers can store

852

SECTION 4  Follow-up and Programming

Event Marker Annotation Legend AS AP VS VP S P Hy PVC () Sr ↑ ↓ → Tr Ns FB MT PVP→ PMT-B Output↓ ATR↑ ATR↓ ATR-FB ATR-Dur ATR-End TN REFR Caliper

Atrial Sensed Atrial Paced Ventricular Sensed Ventricular Paced Sensed (Single Chamber) Paced (Single Chamber) Hysteresis Rate PVC after Refractory During Refractory Sensor Rate Smoothing Up Rate Smoothing Down Inserted after AFR Trigger Mode Sense Amp Noise During A-Tachy Response Atrial Tracked at MTR PVARP after PVC PMT Detection and PVARP Threshold New Parameters Active A-Tachy Sense Count Up A-Tachy Sense Count Down Fallback Started Onset Started Fallback Ended Noise Indication Refractory Interval Screen Caliper Location End of Report

AP

(AS) VP

AP

(AS) VP

AP

(AS) VP

AP

(AS) VP

(AS)

AP

VP

event markers with or without electrograms. Markers may be stored using a patient trigger (e.g., magnet application),28 a simple battery-operated radiofrequency transmitter, or on spontaneous activation of predefined algorithms or sequences of sensed or paced events. ELECTROGRAM TELEMETRY The clinician evaluates a pacing system based on an analysis of the electrocardiogram (ECG), but the pacemaker does not respond to P waves or QRS complexes. The latter are surface manifestations of the atrial and ventricular depolarizations. The recorded signal that enters the pacemaker’s sense amplifier by way of the electrode located within or on the heart is termed an electrogram or intracardiac electrogram (EGM). The EGM is composed of a number of elements. The portion that is sensed by the pacemaker is termed the intrinsic deflection; it reflects the rapid deflection that occurs when the wave of electrical cardiac depolarization passes by the electrode. The intrinsic deflection can be characterized by both amplitude and slew rate. The change in voltage amplitude divided

AP

Figure 29-8  ECG and EGM tracings with event marker legend. Lower ECG rhythm strip (top) with simultaneously recorded atrial (AEGM, middle) and ventricular (bottom) electrograms. Labels across bottom identify specific events reflecting the behavior of this Boston Scientific pacemaker. In these tracings, the atrial refractory sensed events (AS) are caused by far-field R-wave sensing that is also visible on the AEGM channel.

by the time duration of this portion of the signal is known as the slew rate, measured in volts per second. Most implanted pacemakers require a slew rate of more than 0.5 V/sec for proper sensing. The other portions of the cardiac depolarization, as reflected by the EGM, are termed the extrinsic deflection. Although the extrinsic deflection may have adequate amplitude, the slew rate is usually too low, precluding this portion of the cardiac signal from being sensed by the pacemaker. At implantation, the amplitude of the EGM is usually measured with a pacing system analyzer (PSA) that reports a millivoltage amplitude. The PSA uses its own unique set of filters, which frequently is not identical to those in the pacemaker’s sense amplifier. Therefore, the reported PSA signal, at best, provides an approximation of what the pacemaker effectively sees. Newer pacing system analyzers are now being introduced that will allow adjustment of the filters to match specific models of pacemakers and ICDs to eliminate this discrepancy. Likewise, the morphology of the EGM observed on a high-fidelity monitor is not identical to the signal as seen by the pacemaker, because filters in the pacemaker’s sense amplifier usually have a narrower bandpass and therefore block out some of the frequencies (Fig. 29-10).



29  Pacemaker Troubleshooting and Follow-up

Mode Rate Minimum Maximum RRF Auto A-V Delay Program Current

DDDR + MV 60 ppm 130 ppm 23 Normal

VMR 114 ppm 130 ppm

AMS 114 ppm 130 ppm

(140–100 ms) (#171, 5 May 93)

Longevity > Cell Impedance Magnet Rate

853

50 months 650  90 ppm

Measured RRF Rate Sense Pace

Events Pace A Sense DDDR Noise V Lead I Gain 20 mm/mV Speed 25 mm/s

Telectronics

9600 v4. 1 OUE

Pacing Systems

Figure 29-9  Laddergram from rate-modulated dual-chamber pacing system. The event markers are identified by a variety of symbols displayed in a key to the left of the tracing. In addition, battery (cell) impedance and projected longevity are reported in the upper right portion of the tracing, and selected programmed parameters are shown in the upper left quadrant. AV, Atrioventricular; RRF, rate response factor. Data from a META DDDR Model 1250 Telectronics Pacing Systems, now Pacesetter, St. Jude Medical CRMD, Sylmar, Calif.), displayed with a Model 9600 programmer.

Examining the EGM recorded with a physiologic recorder or telemetry with a wide band-pass can provide valuable information on the slew rate, splintering of the intrinsic deflection, and other morphologic abnormalities. Measurements of the peak-to-peak amplitude of the EGM, as recorded at implantation or as telemetered from an already-implanted pacemaker, are typically used to determine the sensing threshold. This approach may be inappropriate if the frequency content of the signal is outside the constraints of the band-pass filter of the sense amplifier.

If the clinician wants to determine the sensing threshold for a given patient, the sensitivity of the system should be progressively reduced until the system no longer consistently senses the native signal. The least sensitive setting (usually identified by millivolt amplitude) at which there is consistent sensing is the sensing threshold. The precision of this measurement is limited by the number and range of programmable sensitivity options in the specific model of pacemaker.29-31 All modern pacing systems now have the ability automatically to measure the EGM amplitude and report this to the clinician. This measurement

ECG Controls

ECG Controls

Surface ECG ................................... On Position ........................................... 1 Gain ................................................ 1 Filter ............................................ Off Markers ........................................... On Position .......................................... 2 IEGM ............................................... On Position .......................................... 3 Gain ............................................... 5 Configuration .................... Vtip-Vring Sweep Speed ................................. 100 1/4 Second

mV/cm

mV/cm mm/s

Surface ECG ................................... On Position ........................................... 1 Gain ................................................ 1 Filter ............................................ Off Markers ........................................... On Position .......................................... 2 IEGM ............................................... On Position .......................................... 3 Gain ............................................... 5 Configuration .............. V Sense Amp Sweep Speed ................................. 100

mV/cm mm/s

1/4 Second

P 124

P R

134

501 633

Vtip-Vring

mV/cm

R 804 929

V Sense Amp

Figure 29-10  Side-by-side display of telemetered bipolar ventricular electrograms. Before processing by the sense amplifier (Vtip-Vring) on the left and after being processed by the sense amplifier (V Sense Amp) on the right. The simultaneously recorded surface ECG and telemetered event markers are also shown (P, native atrial depolarization; R, native ventricular depolarization), with the horizontal lines representing the atrial (top) and ventricular (bottom) refractory periods. The circuitry of the sense amplifier has a narrow band-pass filter that modifies the raw signal, which can also be telemetered. These signals were telemetered from a Pacesetter Affinity DR pacemaker, Model 5330 (St. Jude Medical CRMD, Sylmar, Calif).

854

SECTION 4  Follow-up and Programming

ECG LEAD II 0.05 mV/mm

A EGM 0.2 mV/mm 0.1 mV/mm

Marker Channel A S

V S

V S

V S

A S

V S

A R

V P

V S

A S

V S

A R

A S

V S

A R

V P

AA SR

V P

V S

V S

V S

V S

V S

Figure 29-11  Dual-chamber pulse generator tracings. Simultaneous surface ECG (top), atrial electrogram (AEGM; middle), and event markers (bottom) (Medtronic). Although the “automatic mode switch” algorithm was enabled, this system did not switch modes despite the persistence of atrial fibrillation (AF); the reason is clearly identified from the AEGMs, which were telemetered before being processed by the sense amplifier. The AF signal is a predominantly low-frequency signal identified by the slow-rise deflections, even though the peak-to-peak amplitude was well above the programmed sensitivity and should have been adequate for AF to be sensed. These low-frequency signals were filtered out by the sense amplifier, as demonstrated by the event markers—very few of the fibrillatory signals are sensed (AS or AR); thus the rhythm never fulfills the rate criteria necessary to initiate mode switching. Note that the signals with a discrete rapid deflection (arrows) were properly sensed, whereas those that were not sensed had relatively slow deflections.

is done through the pacemaker’s band-pass filter and therefore is a good estimation of the EGM size. The limitation to this method occurs when there is a large beat-to-beat or respiratory variation of the EGM size. The best method available uses this automatic measurement together with a beat-by-beat digital readout of the EGM amplitude. With this approach, the range of actual EGMs can be accurately evaluated. Unfortunately, this method of measurement is not widely available. Other EGMs are obtained after the signal is processed by the pacemaker’s sense amplifier. As shown in Figure 29-10, both filtered and unfiltered EGMs may be available. Although the unfiltered telemetered EGM should not be used to determine the sensing threshold, it has many other roles.32,33 A primary value is in identifying signals that are being sensed but are not visible on the surface ECG. Another role is to facilitate analysis of the timing of the pacing system, because the sensed intrinsic deflection resets one or more timers. The intrinsic deflection at which sensing occurs can best be identified from the EGM; it is only indirectly measured from the surface ECG. In many cases, the telemetered EGM may be used to confirm capture (particularly atrial) when the evoked complex (P-wave or QRS) is not visible in any lead of the surface ECG.34,35 The evoked EGM may be enhanced by using a unique output pulse configuration to help cancel the residual polarization artifact, or by recording the signal through electrodes not directly involved with the output pulse. The output pulse tends to overload the telemetry or sense amplifier, driving the signal off scale. This is followed by a refractory period within the telemetry amplifier before anything can again be recognized. However, many of the newer pacing systems have more advanced telemetry systems that are able to blank the output pulse and quickly recover to provide high-quality EGM signals. The telemetered EGM has been effectively used to diagnose native arrhythmias, in which the pacemaker is simply an innocent bystander, or to identify retrograde P waves not visible on the surface ECG. The latter ability may facilitate programming of the PVARP to prevent pacemaker-mediated tachycardia.35-43 The telemetered EGM provides clues to why episodes of undersensing may be occurring, including splintering of the EGM and low slew rates, which may place the signal outside the tight constraints of the pacemaker’s sense amplifier, despite an adequate peak-to-peak amplitude44 (Fig. 29-11). The telemetered EGM can also be monitored periodically to follow the progression of the patient’s intrinsic disease process. A decrease in the amplitude of the telemetered EGM was reported to identify early

rejection effectively in cardiac transplantation recipients; a return to the baseline amplitude correlated with resolution of the rejection process.45 Preliminary work on the signal-averaged EGM, either atrial or ventricular, suggests that it may be helpful in identifying disease in the respective chamber that is beyond the resolution of signal-averaging the surface ECG.46 Limitations of Electrogram Telemetry The apparently adequate amplitude of the telemetered EGM for sensing does not mean that the pacemaker will sense it. The telemetry amplifier may use filters different from those in the sensing circuit, providing qualitative rather than quantitative data on the EGM (see Fig. 29-11). In most pacing systems, telemetered EGMs also have limitations similar to those of event markers. EGMs are real-time recordings and cannot be retrospectively provided by the programmer to facilitate the interpretation of an earlier ECG. Real-time telemetry allows the physician to analyze the behavior of the pacing system when the patient is in the physician’s office or clinic while these diagnostics are being accessed with the programmer. This is impractical over a long period. In addition, it does not allow the patient to move around much while these recordings are being obtained. Long-term monitoring of pacing system behavior requires a Holter monitor, a loop memory recorder, or event counter telemetry, depending on the desired degree of precision. Pacemakers with microprocessors and significant random access memory (RAM) can now store select EGMs,47,48 as well as event markers, when triggered by the patient or by a predefined set of circumstances. This may greatly reduce the need for Holter or other monitoring techniques to evaluate intermittent symptoms in patients with pacemakers. EVENT COUNTER TELEMETRY In simple terms, the pacemaker “knows” when it has released an output pulse or responded to a sensed event. The availability of high-density, low-power RAM and read-only memory (ROM) integral to microprocessors that can be incorporated in the pacemaker has given pacemakers the ability to store information about system performance for retrieval at a later date. The objective of the event counters is to facilitate the clinician’s ability to analyze and manage the patient’s pacing therapy more effectively. Although this may lengthen the evaluation, to retrieve and interpret these data, the



additional time is usually minimal. This technology can provide the clinician with information that is crucial to understanding the performance of the system over time, and consequently to directing the programming of the system and achieving optimal performance. Other techniques, such as standard Holter monitor recordings or repeated exercise tolerance tests, although valuable, are impractical, arduous, and relatively expensive to acquire on a routine or repeated basis. The first use of stored diagnostic data in cardiac pacemakers was associated with the introduction of multiparameter programmability. Simple data using codes to identify implant indications and medications could be downloaded into the pacemaker for retrieval at subsequent follow-up evaluations. This ability has been expanded, allowing entry of free text (date of implantation, lead model numbers, pharmacologic regimens, and acute implant measurements, including capture and sensing thresholds and lead impedances; see Fig. 29-1, B). This information is printed with the programmed parameters each time the pacemaker is interrogated. A variety of diagnostic event counters are now available, too numerous to detail in this chapter. Some provide information on the overall performance of the system, whereas others focus on a specific algorithm or subsystem. Still others provide detailed information on the basis of the time course of events. Select examples are used to illustrate these capabilities. Total System Performance Counters The simplest systems keep track of the number of times a pacing stimulus is released or a native complex is sensed. This allows for an assessment of the degree to which the pacemaker was used by calculating the percent pacing in each chamber. A refinement of this ability allows the pacemaker to diagnose bradycardia and, in the dual-chamber modes, to determine whether the bradycardia was the result of sinus node dysfunction or AV block. Event counters with this ability have also been termed diagnostic data, implanted Holter systems, and data logging.49-55 With the introduction of dual-chamber pacing (specifically the DDD mode), the potential interactions between the pacemaker and the patient increased from two (pacing or sensing in one chamber) to five (pacing or sensing in the atria or ventricles and sensing ventricular activity without preexisting atrial activity). The situation became even more complex with the introduction of multiple-site ventricular and atrial pacing configurations. Knowledge of how the pacing system has behaved over time, combined with the clinician’s knowledge of the patient, provides invaluable information toward assessing the overall performance of the implanted system. The various annotations described in the event marker section were combined to provide a cryptic description of the different operational states of the DDD mode. These include an atrial sensed event followed by a ventricular sensed event (AS-VS or PR), indicating that the pacemaker is inhibited on both channels. Atrial sensing followed by a ventricular paced event (AS-VP or PV) refers to P-wave synchronous ventricular pacing. Atrial pacing with intact AV nodal conduction or functional single-chamber atrial pacing is indicated by AP-VS or AR. Base-rate pacing in both chambers is represented by AP-VP or AV. A ventricular sensed event not preceded by atrial activity, either paced or sensed, is a premature ventricular event (PVE), identified by the letter R or the combination VS. Some systems label these events premature ventricular contractions, or complexes (PVCs). This information may be collected in conjunction with events occurring in specific rate bins, allowing for a detailed report of heart rate distributions. Additional data collected include the percentage of pacing in the atrium and ventricle, length of time at the maximum tracking rate, and the number of episodes in which the pacing system reached the programmed upper rate limit (Fig. 29-12). Additional data may be recorded regarding mode-switching events, pacemakermediated tachycardia (PMT) termination algorithm use, or the number of times any one of several other special features was activated. The counters are able to continue to accumulate data until one of the

29  Pacemaker Troubleshooting and Follow-up

855

pacing state bins is full and cannot accept additional information. At this point, one or more of the counters are frozen. The volume of data that can be stored depends on the memory capacity of the pacemaker that is dedicated to these features. The following example illustrates the amount of data that can be stored, or the quantity of memory. All data are stored in a binary code, represented by a series of 1s and 0s. A binary unit of memory is called a bit. Eight bits are a byte and result in 256 combinations of 1s and 0s. If each series of combinations represents a single item of data, a total of 256 pieces of information can be stored in a system with eight bits of memory. As the number of bits increases, the amount of data that can be stored increases exponentially. If each pacing state is represented by a single combination of bits, and there are 24 bits in the RAM devoted to these counters, more than 17 million events can be counted and stored in memory for retrieval at the time of routine pacing system follow-up. Reading the counters requires access to the memory banks in the pacemaker through the use of specific coded commands from the programmer. One DDD system introduced in the mid-1980s had sufficient memory to provide a summary of pacing system behavior for a period of about 6 months. As memory capacity has increased and data compression algorithms have evolved, these systems are now able to store much more data for periods longer than 1 year. Storing a simple marker of the pacing state and rate requires relatively little memory compared with storing waveform data representing the rhythm, as depicted by a consecutive series of EGMs. A theoretical 100-Hz bandwidth with 200 samples per cardiac cycle at eight bits of resolution per sample, recording the entire rhythm during a 24-hour period, would require 140,000,000 bits/day, even if the heart rate was a steady 60 beats per minute (bpm).47 Most implantable defibrillator systems store a series of EGMs preceding and following the delivery of antitachycardia therapy. Premium pacing systems use certain triggers to initiate EGM storage. These triggers may be a high atrial or a high ventricular rate, initiation of mode switching, or activation of any of several other specialized algorithms. Storage may also be triggered by application of the magnet or use of a simple transmitter device by the patient when symptoms are present. An early method to save memory was to provide “snapshots” of representative complexes; the trigger to store these data in an ICD was delivery of antitachycardia therapy. Extensive storage of cardiac rhythm data within pacemakers became possible with increasingly sophisticated data compression algorithms and more memory than previously available. Higher-bandwidth data transmission channels are required for this volume of data storage, particularly for long series of rhythms, so that transmission can be accomplished as efficiently and as quickly as possible. Implanted looping memory event recorder (implantable loop recorder, ILR) capability, complete with stored rhythms, is now available as a stand-alone device, in ICDs, and in high-end pacemakers. Most of the older pacemakers, however, continue to store only data reflecting the total number of times a pacing state was encountered and, in some systems, the distribution of rates or intervals, rate ranges, or mean rates within these pacing states. This information provides the physician with an overview of the function of the system in the patient. Predominant base-rate pacing is expected in patients with marked sinus node dysfunction and in those receiving certain medications such as beta-adrenergic blockers or some calcium channel blockers. On the other hand, predominant base-rate pacing (AP-VP) in patients whose primary indication for pacing was complete heart block suggests either the development of sinus node dysfunction or primary atrial undersensing. In these same patients with high-grade AV block, frequent counts of AS-VS and PVEs, particularly in the absence of known ventricular ectopy, suggests episodes of ventricular oversensing or resolution of the AV block. Large numbers of counts regarding PMTs warrant a reassessment of retrograde conduction and possible adjustment of the programmed PVARP or PMT prevention and termination algorithm. It may also mean only that the maximum tracking rate (MTR) is

SECTION 4  Follow-up and Programming

HEART RATE HISTOGRAM Time at max track rate Max sensor Max track

Base

A Tach detection Paced (AP-VP, AP-VS) Sensed (AP-VP, AP-VS) PVC Sensor-indicated rate

Time (%)

100

30

50

70

90

EVENTS AP counts VP counts AV conduction counts

<1%

110

130

150

100

190 200 225 255 >

170

AS-VP AS-VS AP-VP AP-VS <1% 40% 12% 47%

bpm 448d 1h 25m 12s sampled since last session <1% 126

150

200

250

300 >

bpm 0d 9h 20m 34s in AMS since last session

Duration AS

0 1 3 6 20 1 3 8 24 48 > Minutes

AMS base

100

Hours

Time (%)

Episodes

100

V Rates during AMS 100

AS

PVC <1%

448d 1h 25m 12s sampled since last session

Episodes

100

AMS SUMMARY Mode switch AMS episodes Peak A rate

55% 11% 89%

Time (%)

856

VP VS

30

65

85

110

150

>175

bpm 0d 9h 20m 34s in AMS since last session

Figure 29-12  Heart rate, event, and mode switch histograms. Data represent the performance of the pacing system over the preceding 448 days, with monitoring of every event. Patient had a St. Jude Medical device programmed to DDDR mode. The event histogram is a graphic display of the relative percentage of events within each of the five basic pacing states, whereas the heart rate histogram is a graphic display of the rate distribution based on atrial sensed or atrial paced events. This distribution reflects normal chronotropic function of the sinus node in this patient, whose pacemaker was placed for intermittent atrioventricular block (almost all the atrial paced events are at the base rate). The percentage of time per rate bin represents a normalized display of the relative percentage of atrial paced or atrial sensed events and premature ventricular sensed events in each rate bin during this period. The AMS summary and V Rates During AMS indicate the atrial rates during mode switch, the duration of the mode switch events, and the ventricular response during the mode switch events. These data can be used to manage antiarrhythmia medication as well as AV node–slowing medications.

being reached, as some devices use the MTR as the trigger for PMT intervention. A large number of counts at the MTR suggests that the upper rate limit should be reassessed, because it may be too low for the patient’s physiologic needs. It might also indicate pathologic atrial rhythms. Event counter telemetry can help reveal the overall function of the pacing system; a variation from the clinician’s knowledge of the patient may suggest the need for a further evaluation. When the additional ability to monitor a series of rates and pacing states is added, chronotropic function can be assessed by the distribution of atrial sensed rates (AS-VS or PR and AS-VP or PV; see Fig. 29-12). Furthermore, atrial pacing at rates above the programmed base rate reflects sensor drive in the DDDR pacing systems, providing an overview of the sensor behavior. The ability to report both rates and pacing states can provide the clinician with a better insight into the cause of PVEs as well as overall pacing system function. True premature ventricular contractions tend to occur at short coupling intervals, which is equivalent to a rapid rate. Large numbers of PVEs might suggest recurrent ventricular arrhythmias.56,57 If there are large numbers of PVE counts at relatively low rates, the clinician should consider episodes of atrial undersensing or accelerated junctional rhythms, which would also fulfill the pacemaker’s criteria for a PVE (i.e., a sensed R wave not preceded by an atrial event). Subsystem Performance Counters An increasing number of specific algorithms and capabilities are used either intermittently or potentially independently of the functional performance of the pacing system. An early counter representative of

this capability is the sensor-indicated rate histogram, which reports the distribution of pacing rates that would have occurred had the sensor been totally controlling the pacing rates.58,59 This counter reports the sensor-defined rates, even if the pacemaker was inhibited by a faster native rhythm or the actual functional rate was being controlled by the sensed atrial activity (Fig. 29-13). Other subsystem performance counters include automatic mode switch histograms, reports of the cumulative length of time for which the system functioned at MTR, number of times the PMT algorithm was enabled, high atrial or ventricular rate episodes (Fig. 29-14), and sudden rate-drop episodes. These diagnostic counters provide detailed information about the use of a specific algorithm or system behavior that is not activated daily or is not visible on the ECG, making identification difficult using standard recording techniques such as a Holter monitor. The principal limitation associated with the two types of counters so far described is that counts are placed in a bin, either the pacing state alone or the pacing state and rate, which provides a onedimensional view of the system’s behavior. If the period of monitoring is short, as during a casual or brisk walk, the clinician can reasonably assess the behavior of the pacing system. Longer periods of monitoring accumulate and overlap the results of many activities. This precludes an assessment of the pacing system’s behavior during a specific activity, or the identification of a symptomatic episode occurring at an earlier time. The ability of the system to store pacing state and rate data with respect to time (i.e., time-based event counters) has been variably termed event record or pacemaker Holter systems.60-62 Technically, this is not yet a true Holter monitor, because continuous rhythm



29  Pacemaker Troubleshooting and Follow-up HEART RATE HISTOGRAM Time at max track rate

<1%

Max sensor Max track

Base

A Tach detection Paced (AP-VP, AP-VS) Sensed (AP-VP, AP-VS) PVC Sensor-indicated rate

Time (%)

100

30

50

70

90

110

A

130

150

170

190 200 225 255 >

bpm HEART RATE HISTOGRAM Time at max track rate

Max sensor Max track

Base

100

0% A Tach detection Paced (AP-VP, AP-VS) Sensed (AP-VP, AP-VS) PVC Sensor-indicated rate

Time (%)

Figure 29-13  Sensor-indicated rate histograms show­ ing heart rates for two patients. The bars show the actual heart rates and are dark if atrial paced or white if atrial sensed (St. Jude Medical pacemaker). The open circles indicate what the activity sensor would have driven the heart rate to if the sensor-indicated rate was faster than the patient’s intrinsic heart rate. A, This histogram is from a patient with a normal sinoatrial (SA) node, showing that the patient’s heart rate exceeded the sensor-indicated rate in all bins except the base rate bin. B, This histogram is from a patient with sinus node incompetence; thus almost all the atrial events are paced, and at the sensor-indicated rate.

857

30

50

70

90

110

B

130

150

170

190 200 225 255 >

bpm

High rate epis-A. Tachy rate (ppm)

Detection rate–180 ppm

*EGM collected >400 202 >400 365 335 >400 >400

Feb 02 06:42 *Feb 01 18:45 Feb 01 11:37 Jan 29 08:38 Jan 28 17:25 Jan 27 01:28 Jan 23 17:34 120 80 Seconds

0

180

Rate (ppm)

High rate epis–A. data >300 250 200 510 100 50

DR

–4 –2 0 Sensed event

2

10 10 14 16 18 20 22 24 Beats

Paced event

A. EGM 2.370 Seconds of EGM Figure 29-14  High-rate episodes on AEGM. High-rate episode summary (top) and high-rate episode graphic with stored atrial electrogram (AEGM; bottom). These data facilitate the clinician’s ability to assess the behavior of the pacing system between office visits. In this case, the specific episode associated with the AEGM reported atrial paced events occurring above the trigger level for this event counter, which was also above the maximum sensor rate. The electrogram demonstrates atrial pacing with a large, far-field R-paced ventricular event; presumably the labeled high-rate episode was caused by far-field sensing. This knowledge may be helpful in further programming of the pacemaker. Data from Medtronic Thera DR Model 7940.

858

SECTION 4  Follow-up and Programming

recordings are not retained in memory, even though rate data may be available. Time-Based System Performance Counters Time-based event counters require an extensive amount of memory. Not only are the pacing state and rate stored, but these data must be stored with respect to preceding and subsequent events. The data cannot be simply dumped into a rate or pacing state bin. Each piece of data (i.e., every cardiac event) must have a time reference, which takes significantly more memory than simple histogram-type counters. Two techniques are available for storing real-time data. One is to continue to accumulate the data until the memory is full and then to freeze the recorded events. Freezing all the counters at the same time maintains the ratios between the events. A clearing function is usually provided to reset the counters. In some devices, reprogramming of any parameter or specific parameters (e.g., rate or pacing mode) can result in the automatic clearing of these data. This “initial events” or “frozen” recording technique is especially useful for short-term monitoring, as in office-based exercise evaluations. It also allows the system’s response to exercise to be evaluated, often without the need for simultaneous ECG monitoring. The other option is to collect the data continuously. As the counters fill, new data are added at the expense of the oldest data (Fig. 29-15). This has been called rolling trend, final trend, or continuous data storage and is based on the “first in, first out” (FIFO) principle. When the patient is seen in follow-up, the data acquired over the time immediately preceding the interrogation of the system are available for review. The patient can often recall symptoms and activities during this period. These can be correlated with the behavior of the pacing system at the time of the symptoms. In this manner, the clinical staff caring for the patient may further assess chronotropic function, the behavior of the pacemaker during a variety of special or usual activities, and whether the sensor and other algorithms are behaving appropriately. The clinician may gain insight into the cause of palpitations and other symptoms that may have occurred during this time by correlation of the recorded data and the patient’s complaints or activities.51,58-62 Sensor-input data have been combined with the actual rates achieved to facilitate reprogramming of the sensor parameters. Once acquired, the data from an exercise session are retained in the memory of the programmer, uploaded to the programmer, and then displayed on a screen. The system’s performance is based on a given set of sensor parameters that were in effect at that time. Because the pacemaker has the actual sensor-signal data, it can calculate how the unit would perform in response to a different set of sensor parameters. If a new set of sensor parameters is entered into the programmer, the curves that were based on the original input data are redrawn to display the system’s projected behavior in response to the new set of parameters. The clinical staff can then determine the best sensor parameters for the individual patient without having the patient perform repeated activities (Fig. 29-16). This feature has been termed redraw,63 exercise test, or prediction model.64 Limitations of Event Counter Telemetry The major value of event counters is providing a review of system performance over time. This is not available from the real-time diagnostic features of measured data and event counter and EGM telemetry. The data, however, are interpretable only after a detailed assessment of the capture and sensing thresholds, in a manner analogous to event marker telemetry. The pacemaker can only store information that it knows about: output and sensed events, sensor data, and activation of unique algorithms. If there is a problem with undersensing, the pacemaker releases a pacing pulse, and the counters report a paced rhythm. Similarly, a large number of sensed events may cause the pacemaker to be inhibited on the respective channel. The counter simply reports a large percentage of sensed events, but this may be clinically inappropriate if the cause is oversensing. With respect to pacing, a rhythm that is predominantly composed of AV- or PV-paced complexes does not necessarily indicate complete

heart block. It might result from a programmed AV delay that was not sufficiently long to allow for full conduction through the AV node. Although the ventricular complex could have been fully paced, it could also have been a fusion or pseudofusion beat. The counters cannot differentiate between these complexes, because the native complex had not yet been sensed, the timer had been completed, and an output was delivered. Another situation would be a total loss of ventricular capture with intact AV nodal conduction (Fig. 29-17). The first conducted R wave in this figure would not have been sensed, because it occurred during the refractory period that followed the ventricular output pulse. An identical result in the counters would occur with intact AV nodal conduction but with ventricular undersensing. The event counters simply report the system’s performance without making any statement or judgment about the appropriateness of this behavior. The information provided by the event counters can be interpreted only after the programmed parameters are known, the pacing and sensing thresholds have been determined, and the status of the native rhythm is known. If the pacemaker is programmed to provide a good margin of safety for both pacing and sensing, the event counters are likely to be an accurate reflection of the patient’s clinical rhythms. These data also provide insight into the degree to which the patient requires pacing support at the current programmed parameters, the chronotropic function of the sinus node, and responsiveness of the sensor. Evidence of oversensing or lead dysfunction renders the event counter data suspect with regard to these findings, although a marked change in event counter data can provide the clinician with a clue to a developing problem. The event counter data cannot be adequately interpreted without knowledge of how these data are collected, the clinical status of the patient, and any unique behavioral performance of the implanted pacemaker. This is illustrated by Figure 29-14, which is an atrial highrate graphic from a Medtronic Thera DR pacemaker. The reported rates were greater than 200 bpm, yet the graphic suggests that these were atrial paced events and that the device is not capable of being programmed to rates this high. It is essential to know how the manufacturer calculates rates. In this case, the device measures the interval between atrial events; if the event preceding the atrial output occurred during the refractory period (labeled AR by the markers), the reported atrial paced rate would be based on the AR-AP interval. With this knowledge, the graphic report can be understood. If this fact were not known, the graphic would suggest a pacing system malfunction. Atrial fibrillation (AF) is a major clinical problem that is common in patients with cardiac implantable electronic devices (CIEDs). Management can be improved by knowing whether AF is present, the frequency of AF, and the duration of AF episodes. Knowing these data allows the clinician to determine the need for antiarrhythmia therapy, for ventricular rate–slowing medication or interventions, or for anticoagulation. Several diagnostic counters are available to assist in the management of AF (Fig. 29-18). These may consist of the number and duration of the episodes, atrial rates and ventricular rates during the episodes, and specific dates and times so that patient symptoms can be correlated to events. The one caution in terms of accepting data from these counters is the possibility of oversensing in the atrial channel, which would cause inappropriate assignment of events to these diagnostics. The most common cause of false information is sensing of the far-field QRS complex by the atrial lead (Fig. 29-19). This leads to double-counting of the heart rate and incorrect classification of the event as atrial high rate. Use of stored EGMs to verify the cause of the high-rate episode is advised whenever possible, to avoid inappropriate treatment for nonexistent AF.

Pacing System Malfunction Interrogating the pacemaker about programmed parameters and measured data, retrieval of any and all event count data, and the use of the event markers and EGM telemetry capabilities are essential in a routine office-based follow-up evaluation. It is even more important when



29  Pacemaker Troubleshooting and Follow-up

859

Legend A =AV

P =PV

=PVE

A=AR

Time Scale

P=PR

S =Paced

S=Sensed V =Vent Paced

60 h

O=Off

D D D

190

Rate (ppm)

170 150 130 110 90 70 50 30 9:33:17 am

9:33:17 pm

9:33:17 am

9:33:17 pm

Time

Event Bar Graph

Event Time Graph 100% Time 91

Time (%)

PV PR AV

9

0 PV

PR

0 AV

AR

0 PVE

AR

PVE 6:33:17 am 2:03:17 am 11:03:17 pm 9:33:17 pm 3:33:17 pm 12:33:17 pm 9:33:17 am

Rate Bar Graph

Rate Time Graph

18

18

11 1 1 1 0

45

65

85

Atrial Sensed Atrial Paced

0

105 125 Rate (ppm)

0

0

145

0

0

165

0 185

Rate (ppm)

Time (%)

52

185 165 145 125 105 85 65 45

100% Time

6:33:17 am 2:03:17 am 11:03:17 pm 3:33:17 pm 9:33:17 pm 12:33:17 pm 9:33:17 am

Figure 29-15  Event record display. The sampling interval was 26 seconds, which provides a detailed overview of the behavior of the pacing system for the preceding 60 hours. The top display is an overview of the moment-to-moment behavior of the pacing system, with the vertical lines representing the maximum and minimum rates during each time period (the total displayed interval is divided into 40 equal time segments) and with the cross-bar representing the mean heart rate. The vertical line is displayed if there are two or more complexes in the specific time bin. The display scale can be expanded to display individual events, in which case a specific alphanumeric label is shown, consistent with the legend in  the upper left. The same data may be displayed as an event bar graph (equivalent to the event histogram) or as a rate bar graph (equivalent to the heart rate histogram). The solid bars represent atrial paced events; thus atrial rates greater than the programmed base rate represent sensor drive. Atrial rates lower than the programmed base rate represent “sleep mode” behavior that was also programmed. The time graphs automatically divide the overall monitoring period into six equal segments. Display is from a Pacesetter Trilogy DR+ Model 2364 (St. Jude Medical).

860

SECTION 4  Follow-up and Programming

RATE RESPONSE OPTIMIZATION Rate response model

Parameters

190 150

Rate (bpm)

Sensor Max sensor rate Threshold (Measured avg) Slope (Measured auto) Reation time Recovery time

Modeled Tested Intrinsic

110 70

Tested On 120 bpm Auto (–0.5) Auto (+3) Very fast Medium

Modeled On 120 bpm Auto (–0.5) A 2.0 16 n/a Very fast Medium

30 0

1

2

4

3

5

Exercise duration (min) Figure 29-16  Exercise test report. The lower line on the graph represents the actual behavior of the pacing system during a hall walk with the settings as noted to the right of the graph as “tested.” Patient has St. Jude Verity pacemaker. The thicker line above represents the behavior of the pacemaker under sensor drive at the proposed or “modeled” values. By using this type of feature, the patient only needs to take a single walk to set up the activity response of the device. Mode: DDDR

Rate: 50 ppm A-V Delay: 175 msec Magnet: TEMPORARY OFF ECG/IEGM PARAMETERS

Surface ECG Surface ECG Gain Surface ECG Filter Intracardiac EGM Intracardiac EGM Gain Chart Speed

ON 1.0 mv/div ON OFF 2.5 mv/div 25.0 mm/sec

evaluating a suspected pacing system malfunction. Knowledge of the present programmed settings, combined with the baseline data with which the current results can be compared, is crucial. Many devices have special programming features and idiosyncrasies that may appear to be malfunctions to clinicians who are not completely familiar with the particular system under scrutiny. It is not unusual to hear about devices being explanted and returned to the manufacturer for failure to pace at the programmed rate, only to find that hysteresis had been enabled. This is only one of many examples of “pseudomalfunctions,” as discussed later.65-69 HISTORICAL CLUES

1.0V P

P

P

V 150

V 147 690 837

V 150

P R

365 350 485

V 122

R

The first step in the evaluation of the patient with a suspected pacing system problem is to gather as much information about the patient as possible (Box 29-1). This includes the indications for the pacemaker, the operative record of the implantation, the model, and possibly the serial numbers of all portions of the implanted pacing system. In addition, one must obtain the current programmed parameters and all

377 Box 29-1 

PATIENT EVALUATION FOR POTENTIAL PACING SYSTEM MALFUNCTION Surface ECG

1.0 sec Figure 29-17  Telemetry data limitations. Although this printout was obtained during a ventricular capture threshold test, it demonstrates the limitations of some of the telemetry data in the absence of a simultaneously recorded electrocardiogram (ECG). The last two ventricular output pulses were subthreshold, resulting in a loss of capture. The endogenous P wave conducted, but with a marked first-degree atrioventricular (AV) block, placing the R wave outside the ventricular refractory period initiated by the subthreshold ventricular output, allowing it to be sensed. Based on event marker and event counter data, this patient would be interpreted as having frequent premature ventricular events (PVEs) interspersed in a stable atrial sensed, ventricular paced rhythm; however, in actuality, there was a loss of ventricular capture with intact AV nodal conduction. Key programmed and recording parameters are also included with each printout to facilitate interpretation; EGM, Electrogram. Data from Pacesetter Synchrony II Model 2022 dualchamber pacing system (St. Jude Medical CRMD, Sylmar, Calif.)

Know the Patient Cardiac and noncardiac diagnoses Exposure to environmental extremes Exposure to sources of electromagnetic interference Programming changes performed by others Know the Pacemaker Manufacturer Model and serial number Alerts or recalls Current programmed settings Device idiosyncrasies Mode and algorithm idiosyncrasies Know the Leads Manufacturer Model and serial number Alerts or recalls Connector type Polarity Insulation material Fixation mechanism Radiographic appearance



29  Pacemaker Troubleshooting and Follow-up

861

Mode Switch Episodes Date/Time

A. Max Rate

37839 37838 37837 37836 37835 37834 37833 37832 37831 37830 37829 37828 37827 37826 37825 37824 37823 37822 37821 37820

Aug 02, 2005 22:07:37 Aug 02, 2005 00:19:30 Jul 30, 2005 23:57:31 Jul 22, 2005 03:22:54 Jul 21, 2005 23:35:48 Jul 21, 2005 21:50:57 Jul 21, 2005 01:25:17 Jul 20, 2005 06:24:08 Jul 20, 2005 01:26:59 Jul 20, 2005 00:58:06 Jul 19, 2005 05:07:23 Jul 19, 2005 03:04:02 Jul 18, 2005 06:15:20 Jul 18, 2005 04:08:05 Jul 18, 2005 03:57:48 Jul 18, 2005 01:14:07 Jul 18, 2005 01:01:24 Jul 17, 2005 17:24:50 Jul 14, 2005 16:02:06 Jul 14, 2005 00:34:16

(Episode in progress) >400 bpm >400 bpm >400 bpm >400 bpm 400 bpm >400 bpm >400 bpm >400 bpm 375 bpm >400 bpm 400 bpm >400 bpm >400 bpm 400 bpm >400 bpm 400 bpm >400 bpm >400 bpm >400 bpm

Avg peak rate

PEAK FILTERED RATE

B

>300 300 275 250 225 200 175 150 125 100

1 0 1 0 0 0 0 0 0

>300 276-300 251-275 226-250 201-225 176-200 151-175 126-150 100-125

1 0 1 0 0 0 0 0 0

V. Max Rate

Duration

146 bpm 94 bpm 143 bpm 80 bpm Paced 128 bpm 102 bpm 80 bpm Paced 91 bpm Paced 95 bpm Paced Paced Paced Paced 85 bpm 154 bpm 130 bpm

22 hr 48 hr 213 hr 4 hr 2 hr 20 hr 19 hr 5 hr 28 min 20 hr 2 hr 21 hr 2 hr 10 min 3 hr 12 min 8 hr 73 hr 15 hr

MODE SWITCH DURATION

Counts

Duration

A

ID#

>48h 0m 48h 0m 24h 0m 8h 0m 3h 0m 1h 0m 20m 0s 6m 0s 3m 0s 1m 0s 0m 0s

Number of occurrences

0 0 0 0 0 0

1

1

0

0 1 0 0 0 0 0 0 1 0

Number of occurrences

CARDIAC COMPASS REPORT

P = Program I = Interrogate AT/AF total hours/day

0

Counts

>48h 0m 24h 0m-48h m 8h 0m-24h 0m 3h 0m-8h 0m 1h 0m-3h 0m 20m 0s-1h 0m 6m 0s-20m 0s 3m 0s-6m 0s 1m 0s-3m 0s 0m 0s-1m 0s

P

I

24 20 16 12 8 4 0

V. rate during >200 AT/AF (bpm) VF Max/day Avg/day

C

150 100

<50 Feb 2005

Apr 2005

Jun 2005 Aug 2005 Oct 2005

Figure 29-18  Event log and histogram. A, Event log from a Medtronic pacemaker with mode switch algorithm showing date, time, and duration of the atrial arrhythmia, presumably atrial fibrillation (AF). Maximum atrial and ventricular rates are also provided. B, Mode switch histogram from a St. Jude pacemaker showing the number of episodes, peak atrial rates, and the duration of the AF episodes. AF burden graph is also shown for a St. Jude pacemaker as well as AF trend for a Medtronic pacemaker. This can assist in the management of patients regarding need for anticoagulation or antiarrhythmia drug therapy. C, Cardiac Compass Report from a Medtronic device implanted into a patient in January 2005. The patient went into persistent AF 2 weeks after implantation. Note the presence of AF 24 hr/day on the top graph for most of the period monitored. The lower percentage of AF during June and July could have been caused by intermittent sinus rhythm or by AF undersensing. The bottom graph shows the average and maximum ventricular rates while the patient was in AF and can be used to determine whether further therapy to control the  ventricular response is needed.

862

SECTION 4  Follow-up and Programming

(1 mV) Lead II

A S ↓

A S ↓

↑ V S

A S ↓ ↑ V S

A S ↓

A S ↓ ↑ V S

A S ↓

A S ↓ ↑ V S

A S ↓

A S ↓ ↑ V S

A S ↓

A S ↓ ↑ V S

EMG2

EGM1

Figure 29-19  Far-field QRS complex. The top line displays the event marker telemetry, showing that the device is sensing both the intrinsic P wave as well as the far-field QRS complex on the atrial lead. The middle trace is the intraventricular electrogram, and the bottom trace is the intraatrial electrogram (AEGM). Note that the QRS is easily seen on the AEGM, thus causing the pacemaker to double-count the atrial rate.

measured data. The programmed parameters and measured data are crucial to the correct evaluation of the device. Even in the current high-technology environment of cardiac pacing, the history and physical examination continue to be important. The patient should be asked about symptoms relating to potential device malfunction. These include presyncope, syncope, palpitations, slow or fast pulse rates, pain or erythema around the implanted device, fevers, chills, night sweats, and extracardiac stimulation. It is also important to obtain any history of trauma to the implant area, exposure to intense electromagnetic signals (e.g., MRI), therapeutic radiation, electrocautery or defibrillation (internal or external), programming changes by other medical personnel, or exposure to environmental extremes. Information related to the actual implantation procedure can be important to clinical decision making. If the implanting physician was unable to obtain an adequate EGM in the atrium for sensing, atrial undersensing of P waves by the device would be expected. Knowledge of such a situation might prevent a second futile operation for the patient. Another common situation occurs with unusual radiographic findings. What may appear to be a lead dislodgment might actually be the intentional site of placement because of poor sensing or capture thresholds in the “standard” location. In addition, ventricular leads are

being implanted with increasing frequency in areas other than the right ventricular (RV) apex. These areas include the RV outflow tract, RV septum, and cardiac veins through the coronary sinus. An otherwise stable and normal system might be interpreted as a potential problem resulting in an inappropriate intervention in the absence of this crucial historical information. The full analysis of a suspected pacing system malfunction is facilitated by access to telemetry and programming information, allowing a detailed noninvasive evaluation. Despite this, an invasive evaluation may sometimes be required (Boxes 29-2 and 29-3). The model numbers of the pulse generator and leads should be determined before an invasive evaluation of the system is performed. There may be unique device eccentricities that are known to the manufacturer. In some cases, unique tools or replacement devices may be required. It is therefore wise to contact the manufacturer’s technical service group before an operative intervention for an unexpected behavior in an otherwise clinically stable patient. With noninvasive system evaluation followed by programming, serious errors may occur in the absence of full knowledge of the programmed parameters, measured data, and clinical information. Although most patients carry an identification card that identifies the pulse generator model, lead model(s), and serial numbers, this does

Box 29-2 

NONINVASIVE TESTING Office Evaluation Multichannel rhythm strips or 12-lead electrocardiogram Pulse generator interrogation Programmed parameters Measured data—lead and battery function Event counters Rhythm monitoring with telemetered electrograms Event markers Pacing system evaluation Capture threshold assessment Sensing threshold assessment Sensor evaluation Special algorithm evaluation Provocative maneuvers Ancillary Testing Posteroanterior and lateral chest radiographs Fluoroscopy Continuous rhythm monitoring Telemetry Holter monitoring Event or transient arrhythmia monitoring Transtelephonic or remote monitoring

Box 29-3 

INVASIVE ANALYSIS Visual inspection Connector Set screws Grommets Insulation Conductor Suturing sleeve Measurements Capture threshold Strength-duration curve Evoked-response amplitude Polarization amplitude Sensing threshold Pacing system analyzer measurement Peak-to-peak amplitude Slew rate Electrogram recording Stimulation impedance



29  Pacemaker Troubleshooting and Follow-up

not provide the current programmed settings. Some patients have more than one CIED implanted or have noncardiac stimulation devices to treat central nervous system or other diseases. These patients will have multiple identification cards. If the patient has had a device replaced, it is important to determine whether the ID card is the most recent one. Many patients keep their old and invalid ID cards as mementos of their previous pacemakers. If chronic leads were reused, the data relating to the leads may or may not be on the new card for the pulse generator. However, a large percentage of pacemaker problems are the result of lead malfunction. Certain leads are less reliable than others, and there have been multiple recalls and alerts regarding leads, making such information vital. Because the observed system problem may result from a lead malfunction, an electrode-tissue interface problem, or how the pacemaker was programmed for the individual patient, it is prudent to think about the system as a whole. Rather than labeling an observed abnormal behavior as a “pacemaker” malfunction,” it should be termed a pacing system malfunction, which expands the focus of the evaluation from the pulse generator to all components of the system. In the absence of an ID card, model and serial number information may be obtained from the operative report or from adhesive labels (provided with each pulse generator and lead) if they were included in the medical record at the time of implantation. If none of these is available, a radiograph of the patient that includes the area of the pulse generator allows the clinician to match the identification label inside the pulse generator to those in a reference source70-72 (Fig. 29-20). Although not all pulse generators have these labels, many have a distinct radiographic “skeleton” or radiopaque alphanumeric labels from which the clinician can determine at least the name of the manufacturer, if not the model. All manufacturers provide toll-free numbers that the clinician may call to obtain further information regarding the pulse generator and the implanted leads. All manufacturers’ programmers are capable of automatically identifying the model and serial number of their pacemakers and ICDs. Unfortunately, only the programmer from the manufacturer of the pacemaker or ICD can communicate with that device. Certain pulse generators are also capable of storing data concerning the patient, implantation date, and lead model (see Fig. 29-1, B). These data

A

863

need to be downloaded into the pacemaker by the clinician or support staff. If the pacemaker and programmer have this capability, the programmer provides much of the data necessary for finding additional patient data. It may be possible to obtain further information from the manufacturer’s patient-tracking database. Pulse generators often have a characteristic magnet response signature that can be recorded on an ECG strip and may provide clues to the manufacturer or model. The clinician should avoid “blindly” interrogating a device without knowing at least the name of the manufacturer. Unexpected and possibly disastrous reprogramming results have been reported when one manufacturer’s programmer was used on another manufacturer’s pacemaker, although with current-generation systems, this is unlikely. Knowing the specifics of the implanted pacing system’s components is a crucial first step. It is also important to know if any special considerations apply to the device. These might include recalls, alerts, known idiosyncrasies, and the functions of specialized programmable features and rate-modulating sensors.73-79 Any of these may affect the observed behavior and help guide further evaluation of the system, as well as any parameter adjustments. For example, a pulse generator exhibiting its elective replacement parameters would typically be replaced using the same lead system if the system had a good capture threshold, a good sensing threshold, and a normal stimulation impedance. If the lead is under a safety alert or recall, however, the clinician should follow recommended guidelines and, if appropriate, replace the vulnerable lead system at the time of generator replacement. Some patients have required a second procedure to revise another element of the pacing system simply because the implanting physician was unaware of previously reported potential product deficiencies. Virtually any device could exhibit idiosyncratic behavior that might be mistaken for a malfunction. In addition, functional undersensing as a result of a variety of normal refractory and blanking periods, pauses due to normal hysteresis and sleep rates, and changes in the spontaneous functional behavior of the pacemaker (as with automatic mode switching, rate-drop response, and endless-loop tachycardia [ELT] prevention and termination algorithms) are examples of features that could cause confusion if the clinician is not aware of these capabilities.

B

Figure 29-20  Radiographs of two pulse generators showing radiopaque identification tags. Some units do not have this helpful feature, but they can still be identified by the appearance of their unique radiographic “skeletons.” On A, also note that the terminal pins of the leads extend through the set-screw connector block, indicating that they are properly and fully inserted into the pulse generator connector. However, it cannot be determined, based on the radiograph, whether the set screw is fully secured.

864

SECTION 4  Follow-up and Programming

Box 29-4 

CAUSES OF EXTRACARDIAC STIMULATION Improper Lead Position Gastric vein Cardiac vein Diaphragmatic Stimulation Lead in cardiac vein Thin right ventricular wall combined with high output Myocardial perforation Lead position near phrenic nerve Active-fixation lead: right atrium Lead withdrawal to innominate, superior vena cava, or subclavian vein Pacemaker Pocket Stimulation Delamination of insulating coating Device movement (twiddler’s syndrome) Device inserted in pocket upside down Unipolar output configuration at high output Irritable skeletal muscles: low stimulation threshold Breach of lead external insulation Damage to set-screw seal Failure to insulate adapter set screw

PHYSICAL EXAMINATION AND TELEMETRY After the history has been obtained and the pacemaker system’s specifics are known, the patient should be examined. The implantation site is examined for proper healing or abnormalities such as erosion of suture material, leads, or the generator; erythema, hematoma, or seroma; excessive pain on palpation; evidence of trauma; pocket stimulation; device mobility; and generator displacement. The precordium is inspected for chest wall or diaphragmatic stimulation; the latter may indicate several possible problems (Box 29-4). If the system is unipolar, the pacemaker (if coated on one side) may have the anode facing the skeletal muscle or may be considered to be upside down in the pocket. The malpositioning of a pacemaker sitting upside down in the pocket may have occurred inadvertently at implantation, may have developed spontaneously (most often with lax subcutaneous tissues), or may have resulted from the patient’s manipulating the pacemaker within the pocket, a condition known as twiddler’s syndrome.80-84 Alternatively, the unidirectional insulated coating on the pulse generator or the grommets protecting the set screws may have been damaged or may have degraded over time. In some situations, pocket stimulation may occur even with the generator in the correct position and the insulation intact.85 Also, most pacemakers now produced have no coating on one side and therefore are “omnidirectional” with respect to their placement in the pocket. High-output settings, placement in or below the pectoral musculature, or high-current delivery as a result of low lead impedance may also be at fault. Outer lead insulation failure may also allow problematic current leakage and local extracardiac muscle stimulation. The neck veins should be evaluated for distention or the presence of cannon A waves. The latter might indicate an atrial lead problem, inappropriate programming in a dual-chamber system with too long or too short an AV delay assuming otherwise normal electrical function, or pacemaker syndrome in a single-chamber system. Auscultation of the heart for variable-intensity heart sounds, rubs, or gallops may also give clues to the physiology related to the patient-device interaction.86,87 Physical maneuvers may be useful to unmask an intermittent symptom or malfunction during examination. Carotid sinus massage and other vagal maneuvers may slow the intrinsic rhythm so that device function or malfunction becomes evident. Positional changes (sitting or standing up) or having the patient perform in-place exercise or isometric maneuvers may accelerate the heart rate to allow

Figure 29-21  ECG rhythm strip of patient with 100% ventricular pacing. The pace artifact is not readily identified because of the small electric potential generated by the bipolar pacing polarity.

observation for sensing (proper tracking and inhibition). Manipulation of the device and lead may disclose an intermittent lead fracture, loose connection, or insulation failure that was not evident while the patient was lying quietly on the examination table. Other helpful maneuvers include movement of the patient’s ipsilateral arm (reaching overhead, across the chest, or behind the back), isometric exercise (pressing the hands together in front of the chest or reaching around the chest to scratch the opposite side), and doing sit-ups (in the case of an abdominal implant) are helpful in identifying an intermittent problem.88,89 If the patient develops symptoms during the induced abnormal behavior and these symptoms reproduce those that occurred spontaneously, the cause of the symptoms likely has been identified. A 12-lead ECG is required to document the pacemaker-evoked morphology of the atrial and ventricular depolarizations at baseline. It may then be helpful to repeat a 12-lead ECG, or at least a multiple-lead ECG, instead of a single-lead rhythm strip, when evaluating a suspected malfunction. A myocardial infarction or progressive cardiomyopathy may have occurred, resulting in a change of capture or sensing thresholds. A change in the paced QRS axis may be a clue to lead dislodgment or loss of capture from one lead in a biventricular system, whereas a change in the intrinsic axis (a new bundle branch block) may be associated with sensing problems. Multiple ECG leads are frequently necessary to recognize the relatively low-amplitude atrial depolarization. In addition, the pacing artifact may not be visible in any given lead, especially if the pacing system is bipolar90 (Figs. 29-21 and 29-22). Care should be taken in the interpretation of the ECG tracing with regard to the type of recording system used. The olderstyle analog systems provide a consistent reproduction of the pacing stimulus, varying the relative amplitude of the stimulus with the delivered energy of the system. An unstable paced artifact on an analog ECG is a sign of potential problems. The same cannot be said for digital recording systems, which have generally replaced the older-generation

Figure 29-22  ECG rhythm strip of patient with 100% ventricular pacing. The pace artifact is easily identified because of the large electric potential generated by the unipolar pacing polarity.



analog systems. Although these allow computer interpretation of the ECG, they can introduce many artifacts and have several idiosyncrasies that have been misinterpreted as a device malfunction when they were actually recording system artifacts90-96 (Fig. 29-23). In many cases, the pace artifact is not visible in any lead. The baseline ECG rhythm strip should be closely inspected for any abnormalities of rate, sensing, loss of capture, or change in paced axis. A tracing with the magnet applied to the pulse generator should also be performed. This provides information about the status of the battery and, if the device is otherwise inhibited, allows for a quick assessment of capture and whether the output is being delivered to the appropriate chamber. If no output is seen during application of the magnet, several possibilities should be considered: the battery may be depleted, the device may be nonfunctional, or an open circuit (e.g., lead fracture) may be present. In some models, the magnet response is programmable (on or off). If the magnet function is disabled, placement of a magnet over it does not result in an overt change in its demand behavior. Alternatively, the magnet may not have been positioned properly, the reed switch may be stuck open, or a magnet with insufficient strength may have been used. The “doughnut” magnet is the strongest type and is preferred over “horseshoe” or “bar” magnets. The magnet function of each device is unique with regard to the rate and mode of response. The response may differ according to manufacturer, model, and programmed mode of the pacemaker. The magnet

Figure 29-23  Recording of the same rhythm with two different systems. The cause of the high-frequency artifact was never identified (possibly because of a poor electrical ground or defective “power-strip surge protector”), but was amplified by the design of the Medtronic 9790 programmer during evaluation of a patient with a Prodigy DR 7860 pacemaker (Medtronic). The simultaneous event markers identify atrial pacing followed by ventricular pacing. The paced output saturates the telemetry amplifier for the atrial electrogram (AEGM). The electrocardiogram (ECG) cable was disconnected from the electrodes, and the Pacesetter APS II Model 3003 programmer (St. Jude Medical) was connected to these same electrodes and used as a monitor for the pacing system evaluation. The ECG display in the APS-II programmer uses analog recording technology without artificial amplification of high-frequency transients. Therefore, the bipolar outputs are small on the atrial channel and even smaller, such that they are not visualized, on the ventricular channel in this specific lead that was being monitored.

865

29  Pacemaker Troubleshooting and Follow-up

response may also be programmable, not only as to whether a response will occur, but also as to the type of response. The clinician should not assume that a DDD device will exhibit a DOO response to application of the magnet. Some dual-chamber devices may pace VOO or may not pace asynchronously. If there are questions about the appropriate response to magnet application, the physician’s manual that is supplied with the pacemaker, other reference sources, or the manufacturer’s website may be used to view device reference material. One can also consult the manufacturer’s technical support staff. The initial action should be interrogation and printing of the programmed settings.97,98 The printout is important because it documents the initial settings and serves as a reference should the clinician want to restore the device to the same settings after the evaluation is complete. Although most programmers have a “return to initial settings” capability, if the programmer is turned off or inadvertently disconnected from the power source, these data will be lost. Virtually all currently implanted pacemakers have the ability to measure and monitor critical system functions. These data should be interrogated and printed. The same recommendation holds for models that have extensive histograms, trend data, or other diagnostic counters. If the settings are routinely retrieved at the beginning of the evaluation, the various programming changes that may be required during the evaluation and that may cause clearing of these counters will not result in loss of critical data. Indeed, on completion of this task, the counters

ECG Lead II 0.2 mV/mm

Marker Channel

V P

V P

A EGM 1 mV/mm

Surface ECG

1.0 sec

0.1 mV/mm

A P

A P

V P

A P

V P

A P

V P

A P

A P

V P

V P

V P

866

SECTION 4  Follow-up and Programming

should be cleared so that they reflect the subsequent behavior of the implanted pacing system in response to any changes made by the end of the evaluation. Some devices automatically clear the data 1 hour after the end of the programming session, or when the final report is printed. Others simply use the FIFO data storage scheme, with the newest events written to memory and the oldest deleted. When reviewing the results of the interrogation, an evaluation of the programmed setting data should be the first step. What are the mode and base rate? Are any special algorithms enabled? Many suspected device malfunctions are eliminated once the programmed parameters become known. These may have been changed by another medical professional since the last evaluation, or they may have been entered incorrectly into the patient’s record, accounting for the concern. The former situation has been referred to as phantom reprogramming, which most often occurs when another clinician does not notify those responsible for monitoring the patient about the changes made to the pacemaker. Depletion of the battery may also cause a change in the mode, rate, or other parameters. Box 29-5 lists other causes of mode changes. Some dual-chamber devices change to a single-chamber mode to conserve power if the battery’s voltage drops below a manufacturer-defined value. In other devices, the sensor, data storage, and telemetry may be disabled to slow the rate of battery depletion, in an effort to protect the patient from a no-output state. New devices that are shipped or transported via areas experiencing winter weather may cool sufficiently to allow the battery’s voltage to drop, triggering the elective replacement behavior even though the device is new. Normal function either spontaneously returns or can be reset using the programmer once the device has warmed up to at least

Box 29-6 

CAUSES OF RATE CHANGE Programming: DDD mode with atrial paced, ventricular sensed complex pacing in ventricular-based timing system Sensor drive P-wave tracking modes (DDD, VDD) Sinus node Atrial tachyarrhythmias Triggered modes Special algorithms Rate hysteresis Overdrive algorithms Atrial fibrillation suppression algorithms Rate smoothing Circuit failures: runaway Recording artifacts Paper or tape speed errors Pulse enhancement artifact Rate slowing Sensed premature (ectopic) beats Hysteresis Oversensing Open circuit Battery depletion Rate acceleration Circuit malfunction Crosstalk: ventricular-based timing Inappropriate rate sensor drive Rate-drop response

Box 29-5 

CAUSES OF APPARENT MODE AND PARAMETER CHANGES Programming Special algorithms Upper rate behavior Wenckebach Fixed block Fallback Rate smoothing Base-rate behavior Sensor drive Rate hysteresis Sudden rate-drop response Sleep or rest mode PVARP post-PVE algorithms Automatic mode switch algorithms Functional AAI[R] pacing Autointrinsic conduction search AV hysteresis search DDD with algorithm to minimize ventricular pacing PMT prevention and termination algorithms Lead surveillance and configuration change Battery depletion Recommended replacement time indicator End-of-life indicator Stuck reed switch (DOO, VOO, AOO) Electromagnetic interference Electrocautery Cardioversion and defibrillation (external/internal) Airport security systems Electronic article surveillance Cellular telephone Magnetic resonance imaging Power on reset Voltage drop caused by cold shipping temperature Electric shock or defibrillation AV, Atrioventricular; PMT, pacemaker-mediated tachycardia; PVARP, Postventricular atrial refractory period; PVE, premature ventricular event.

room temperature. Attempting to accelerate the warming of the pulse generator by placing it in an oven may damage the pacemaker. Electrocautery and defibrillation can cause mode and polarity changes to occur on some models and may also trigger the elective replacement indicator of the pacemaker. Pacing rate changes may also occur for many other reasons (Box 29-6). Therefore, no assumptions about the expected operating characteristics of a device can be made without the knowledge of the mode and rate. After the mode and rate have been verified, an evaluation of the remaining programmed parameters is appropriate. The identified output, pulse width, sensitivity, and refractory periods should be reviewed for each channel and correlated with the ECG. The presence and status of any special programmable features should be checked. These include rate-modulation behavior, ELT/PMT prevention and termination algorithms, rate and A-V interval hysteresis, time-of-daydependent or sensor-based rate changes, rate-adaptive AV delay, differential paced and sensed AV delay, rate smoothing, and others. An evaluation of the device’s function in relation to all programmed data is performed by comparing the programmed data with ECG and event counter data. In many cases, the event counter diagnostics will minimize if not eliminate the requirement for routine-screening Holter monitor studies. The most advanced devices now record high-rate episodes in the atrium and ventricle. Many even record EGMs to document further the heart rhythm at the time of the high-rate event, or when triggered by the patient with a magnet or transmitting device. The measured data are reviewed.5,44,99 Stimulation impedance for each lead is one of the most important elements of the measured data. Proper interpretation of lead impedance, however, depends on the manufacturer and model of the lead used, the method of measurement, and the historical values of an individual lead’s impedance. The other parameters of the lead’s performance, including pulse voltage, pulse charge, pulse energy, and current, should also be correlated with the measured impedance, and internal consistency assessed. A marked discrepancy between observed and expected values may identify a telemetry error or measurement error within the pacemaker rather than a primary problem with the lead. It is prudent to repeat the



29  Pacemaker Troubleshooting and Follow-up

measurements several times if a conflict is noted.15 Some devices take periodic readings of stimulation impedance and graph these over time (see Fig. 29-5). This is a highly effective tool to spot changes in a lead system. Another important dataset that may be available measures the battery’s status. This can include a measured magnet rate; measured baserate pacing; projected longevity; elective replacement indicator or status message; and the voltage, impedance, and mean current drain of the battery. The measurements of battery function may be useful to corroborate the measured data from the lead. If the mean current drain remains unchanged despite a major change in the lead’s impedance or current, a telemetry or measurement error should be suspected. Normal mean current drains vary greatly according to generator model, the lead system implanted, and the programmed settings. Once again, tracking these data over time provides the greatest clinical benefit. After the telemetry and measured data have been obtained and reviewed, a meticulous assessment of the pacing and sensing thresholds is warranted. A complete threshold evaluation should be performed for each lead present. Pacemakers that have automatic algorithms to regulate output should have their diagnostics evaluated for abrupt onset of changes or great variability (Fig. 29-24). Marked changes in capture or sensing thresholds may imply malfunction of a lead or of the lead-tissue interface when lead impedance values are stable. Other causes of both permanent and transient increases in threshold are discussed later.

Amplitude (V)

5 4

2 1 0 09/15/04 Date

A

Adapted

Threshold

Monitor Only “What If”

Aborted Search

5 Amplitude (V)

Figure 29-25  Focused view of posteroanterior chest radiograph showing attenuation of ventricular lead where it crosses between clavicle and first rib. Superimposed on this radiograph is the explanted pulse generator and both atrial and ventricular leads. The attenuation of the conductor coil visualized on the radiograph is associated with a marked disruption of the insulation and conductor coil of the explanted lead at this position (arrow), although the extraction process itself may have contributed to some of the disruption of the lead, exacerbating the abnormality seen on the radiograph. In some cases, overlapping leads or leads overlying other structures make it difficult to visualize  a deformity of the conductor coil. If a problem is suspected, multiple views, including oblique and lordotic views, using either standard radiograph techniques or fluoroscopy may be required.

3

08/14/04

4 3 2 1 0 06/04/04

07/06/04 Date

B

867

Adapted

Threshold

Monitor Only “What If”

Aborted Search

Figure 29-24  Capture management graphs. A, Patient with a normally functioning capture management algorithm. Note the consistent capture threshold and adapted output. B, Patient in whom the algorithm is not able to identify the threshold. Because the device is not able to determine capture (note the aborted searches), it will be programmed to a high output, resulting in premature battery depletion.

If a pacing system problem is suspected, posteroanterior (PA) and lateral chest radiographs should be obtained. In the “predigital” radiology era, it was best to request a slightly overpenetrated exposure to visualize the intracardiac segment of the pacing leads for position and integrity. A thoracic spine exposure technique provides optimal penetration for visualization of the pacing leads. Most radiology departments are digital, allowing manipulation of the brightness and contrast on a computer display. The radiograph should be inspected for evidence of conductor disruption; insulation failure, as inferred from a deformity in the conductor coil, because the insulation is radiolucent (Fig. 29-25); proper lead placement in the generator connector block, adequate slack in the lead system, electrode perforation, dislodgment or malposition of a lead, generator movement, and proper orientation of the coated side of the can positioned against the muscle (i.e., leads exiting in a clockwise direction, except in devices specifically designed for implantation on the left side of the chest or devices that are not coated; see Fig. 29-20).100 The latter criterion is especially important when evaluating pocket stimulation in unipolar systems or devices programmed to the unipolar pacing polarity. Because most new pacemakers and all ICDs are uncoated, leads may exit in a counterclockwise or clockwise manner, which can be confusing if the construction of the pacemaker is not known. Knowledge of the design of the specific pacemaker, lead, or adapter in question is essential to establishing the proper diagnosis. Close attention should be paid to the infraclavicular area, where pressure from structures around the clavicle and first rib can cause lead failure.101-115 On occasion, a fluoroscopic evaluation of the patient may be useful. This shows many of the mechanical or positional problems and defects listed earlier. It also provides a dynamic view of the lead system, facilitating identification of excessive electrode movement consistent with an unstable lead, or it may reveal insufficient slack, with respi­ ratory movement placing traction on the lead and tension at the

868

SECTION 4  Follow-up and Programming

electrode-tissue interface. Either of these conditions would provide an explanation for an intermittent capture or sensing problem. DIFFERENTIAL DIAGNOSIS OF PACING SYSTEM MALFUNCTION Although many pacing system malfunctions are common to singlechamber and dual-chamber devices, the latter present a greater challenge. This section deals with problems seen in single-chamber, dual-chamber, and multichamber devices. The subsequent section deals with problems unique to dual-chamber and multichamber devices. Failure of Output (No Artifact Present) In the pacemaker-dependent patient, failure to pace represents a potentially catastrophic and lethal situation. The ECG appearance in a single-chamber system is that of no pacing artifact when the intrinsic rate is below the lower rate limit of the device. This may be intermittent or continuous. In a dual-chamber device, the clinician may see an atrial pace alone, ventricular pace alone, or no pacing artifacts at all. Of course, any of the latter may be entirely normal depending on the patient’s sinus rate, AV nodal conduction, A-V interval settings, enabling of hysteresis or one of its analogs such as sleep mode or ratedrop response, and sensor settings. Box 29-7 lists the causes of a no-output condition. In evaluating this situation, the clinician must be certain that a malfunction truly exists before taking any corrective action. Remember that the ECG (especially as visualized in a single surface lead) may not display the pacing artifact because of technical factors (Fig. 29-26). This is particularly common in bipolar systems and systems programmed to a lower-than-nominal voltage output. It is important to recognize that the problem may be failure to capture rather than failure to output. Access to telemetered event markers and measured data facilitates the evaluation. Event markers identify the

Box 29-7 

FAILURE TO PACE (NO OUTPUT OR RATE SLOWING) Normal system function Hysteresis Sleep or rest mode PVARP extension after premature ventricular contraction Oversensing Electromagnetic interference (see Table 29-1) Inappropriate physiologic signals Myopotentials T waves Afterpotentials Far-field signals Make-break signals Internal insulation failure Lead chatter Partial conductor fracture Crosstalk—in the presence of atrioventricular block Safety pacing either not available or disabled Open circuit Conductor (lead) fracture Failure to tighten set screw Failure to insert lead fully in connector block Component malfunction Incompatible lead and pulse generator Air in pocket: coated unipolar pulse generator Pacemaker not in pocket: unipolar pacing polarity Battery depletion Recording artifact Isoelectric ectopic beats, properly sensed Isoelectric paced beats Rapid recording speed: longer interval between complexes PVARP (postventricular atrial refractory perioda) algorithms

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 29-26  12-lead ECG of patient with normally functioning bipolar pacing system. Note that a small pace artifact is seen in lead V4, whereas other leads do not show it at all.



869

29  Pacemaker Troubleshooting and Follow-up

release of an output pulse or recycling resulting from a sensed event, even if this is not visualized on the ECG. If lead impedance is normal (with the previously noted caveat that the problem may be intermittent and multiple measurements should be obtained), this probably reflects a capture problem if there is an output, or an oversensing problem if there is a sensed event. A high impedance suggests an open circuit, whereas a low impedance suggests an insulation failure. Both are probable mechanical problems with the lead in a chronically implanted system. In a newly placed system or when the leads have been recently replaced into the pacemaker, this may be caused by malalignment of the lead in the connector, a loose set screw, or failed spring-loaded connector. If the markers fail to demonstrate an ineffective output or an inappropriate sensed event, normal function (e.g., hysteresis) should be considered. At this point, the programmed parameters should be double-checked to determine whether hysteresis or one of its analogs was programmed. Pacemakers have been returned to their manufacturers as defective when hysteresis was enabled. In these cases, the physician was either not aware of the programming or did not understand this feature.112-114 Other causes of intermittent prolongation of the pacing interval are listed in Box 29-7. Another source of evaluation error is failure to recognize intrinsic complexes that are present and are properly sensed, causing an appropriate device inhibition. This problem may occur in the hospital’s telemetry unit, where only a single lead is monitored. Premature beats may be present, with the ectopic complexes appearing nearly isoelectric (Fig. 29-27). Although the observer may not recognize the PVC or premature atrial contraction (PAC) on casual observation, the pacemaker senses these events and is appropriately inhibited. The use of multiple leads or a 12-lead ECG recording virtually eliminates this cause of pseudomalfunction. The most common cause of lack of an output pulse in unipolar systems is oversensing. The pacemaker, for all its complexity, operates from a relatively simple set of rules. Any event that generates an electrical signal of adequate strength and frequency content (during the alert period) is sensed and resets the timing cycle. Oversensing is the sensing of a physiologically inappropriate or nonphysiologic signal. A cause of intracardiac oversensing in AAI systems is sensing of the far-field QRS complex116 (Fig. 29-28). This is most common in unipolar systems when the lead is placed close to the tricuspid valve, with high atrial sensitivity settings, and with short atrial refractory periods. In systems that can deliver antitachycardia pacing (ATP) therapy, oversensing may result in an inappropriate diagnosis of a tachycardia and therapy delivery.117 In dual-chamber systems, atrial far-field sensing is also one of the most common causes of inappropriate mode switching, because the pacemaker is seeing double the actual heart rate. Far-field sensing of the atrium is uncommon in VVI systems because of the diminutive size of the P wave, as seen electrically from the ventricle. Although reported, it is usually associated with other problems, such as an insulation abrasion on the atrial portion of the ventricular lead.15 Sensing

Mode: AAI Rate: 70 ppm Magnet: TEMPORARY OFF ECG/IEGM PARAMETERS Surface ECG Surface ECG Gain Intracardiac EGM Intracardiac EGM Gain Chart Speed

P

R

Off 1.0 mv/div A IEGM 1 mv/div 25.0 mm/sec

P

R

P

R

P

R

A IEGM Figure 29-28  Intracardiac electrogram (IEGM) recorded from unipolar atrial lead. Note the large size of the far-field ventricular electrogram (VEGM), labeled R. If the near-field atrial electrogram (AEGM), labeled P, were not as large, the device could undersense the atrium, sensing the VEGM in error. ECG, Electrocardiogram.

of the intracardiac T wave may occur in VVI systems with similar results (Fig. 29-29), although this was a more common problem in the early days of pacing, as was oversensing of the polarization artifact generated by the output pulse. Other chapters in this text provide a description of polarization and the evoked response. Oversensing of this event occurred with short refractory periods combined with high outputs on certain lead systems. This has also been reported in ICD systems that require short refractory periods and broad band-pass filters in the sense amplifier. The most common source of a physiologic extracardiac signal that causes oversensing is myopotential inhibition. The pacemaker is capable of sensing muscle depolarizations—not only those of the heart, but also those of noncardiac structures such as the pectoralis, rectus abdominis, and diaphragmatic muscles. Myopotential inhibition of pacemaker output can be seen during arm movements (pectoral implantation) or when the patient sits up or does a Valsalva maneuver (abdominal implantation; Fig. 29-30). This occurs primarily in unipolar systems, because the anode, the pacemaker’s case, remains in proximity to these muscular structures.88,89,118-124 Nonphysiologic electrical signals may also cause oversensing. Formerly, electromagnetic interference (EMI) from microwave ovens was a significant problem when pacemakers were encased in plastic or epoxy, with the relatively large antenna created by the discrete components. Newer devices are shielded from EMI by their metal cases and filters. Integrated circuits provide

1000 msec 1000 msec

Pace

PVC

Pace

PVC

Figure 29-27  ECG rhythm strip of pacemaker programmed to VVI with a demand rate of 50 bpm. This appears to show an inappropriate bradycardia. Note the low-amplitude waves that map out to the escape interval. These are premature ventricular complexes/contractions (PVC) that appeared almost isoelectric in this lead.

Figure 29-29  ECG rhythm strip of a device programmed to VVI at 60 bpm. T-wave oversensing is present. The last sensed event can always be determined by mapping back by the escape interval.

870

SECTION 4  Follow-up and Programming

V

V

V

V

R

R

R

675

675

675

557

420

357

575

Surface ECG 1.0 sec

A V

V

V

V

V

V

675

677

675

675

677

675

Surface ECG 1.0 sec

B Figure 29-30  A, ECG rhythm strip shows inappropriate inhibition caused by myopotential oversensing. B, ECG rhythm strip of the same pacing system, with a magnet placed over the pulse generator. If a loss of output were still evident with the magnet “on,” the problem likely would not be oversensing.

for a smaller antenna, although strong EMI sources can still cause oversensing. Table 29-1 summarizes EMI sources and their potential effects.125-142 It has been well documented that intermittent metal-to-metal contact can create electrical signals. These make-break signals may be of sufficient amplitude to be detected by pacing systems. Signals exceeding 25 mV have been recorded in some cases (Fig. 29-31). These large signals present a major problem: the false signal cannot be managed by programming the device to a less sensitive setting, because the nonphysiologic signal is far greater than the physiologic atrial or ventricular depolarization. The sources of these electrical signals include a loose set screw, fracture of the conductor coil, failed insulation between the anode and cathode conductors in a bipolar system, interaction between active and abandoned pacing electrodes, and a loose retractable fixation screw.142-150 Other mechanisms can also cause these signals, such as capacitance between the anode and cathode of a coaxial bipolar lead with failing insulation. Oversensing need not result in pacing system inhibition. In the dualchamber mode, if oversensing occurs on the atrial channel, it can result in ventricular pacing in response to the false P wave, which in a patient susceptible to retrograde conduction can precipitate an ELT as well. If the pacemaker was programmed to the triggered mode (which is one way to manage an oversensing problem that cannot be safely eliminated by programming to a less sensitive value), there would be periods of irregular pacing at a rate exceeding the programmed base rate in the presence of oversensing. Note that many of the biventricular devices use a trigger ventricular pacing function to pace on a sensed ventricular beat in an attempt to maintain resynchronization therapy. Oversensing can be confirmed by use of the magnet or by reprogramming to an asynchronous mode. If the cause of the pauses or slow rate is oversensing, regular pacing will resume during asynchronous pacing. If a lead failure, open circuit, or other cause exists as the cause of lack of output, these maneuvers will not result in consistent asynchronous pacing. The use of EGMs and event marker telemetry can quickly identify the cause of the pause, whether an output pulse that

Mode: VVI Rate: 70 ppm Magnet TEMPORARY OFF

Mode: VVI Rate: 70 ppm Magnet TEMPORARY OFF

ECG/IEGM PARAMETERS

ECG/IEGM PARAMETERS

Surface ECG Surface ECG Gain Intracardiac EGM Intracardiac EGM Gain Chart Speed

On 2.0 mv/div V IEGM BI 5 mv/div 25.0 mm/sec

V IEGM BI E

Surface ECG Surface ECG Gain Intracardiac EGM Intracardiac EGM Gain Chart Speed

On 2.0 mv/div V IEGM BI 5 mv/div 25.0 mm/sec

V IEGM BI E

E E

Surface ECG

Surface ECG

R

R V

A

V

V

V

V

B

Figure 29-31  A and B, Ventricular intracardiac electrograms (IEGMs) as telemetered by a pulse generator, recorded simultaneously with a surface electrocardiogram (ECG). Note the large artifacts (E) on the intracardiac channel seen without ventricular activity (R, native QRS; V, pace output). These were caused by failing inner insulation in a bipolar coaxial lead system.



29  Pacemaker Troubleshooting and Follow-up

TABLE

29-1 

871

Causes of Potential Electromagnetic Interference

Source Ablation Antitheft device (EAS) Arc welder Cardiokymography Cardioversion Citizen’s band radio Defibrillation Dental scaler Diathermy Electroconvulsive therapy Electric blanket Electric power tools Electric shaver Electric switch Electric toothbrush Electrocautery Electrolysis Electronic article surveillance Electrotome Ham radio Heating pad Lithotripsy Magnetic resonance imaging scanner Personal audio player (MP3/iPOD) Personal headphones Positron emission tomographic scanner Powerline (high voltage) Pulp tester (dental instrument) Radar Radiotransmission (AM) Radiotransmission (FM) Stun gun (TASER) Telephone, cellular Telephone, cordless Transcutaneous electrical nerve stimulation Television transmitter Ultrasound (therapeutic) Weapon detector/magnetometer

Pacer Damage Y N N N Y N Y N Y N N N N N N N Y N N N N Y§ Y N N Y N N Y N N N N N N N Y§ N

Total Inhibition Y N Y Y N N N N Y Y N N N N N N Y Y N N N Y* N N N N N Y* N N N N Y Y Y Y* N N

One-best Inhibition N Y Y Y N Y N Y* Y Y N N Y§ Y* Y Y* Y Y Y Y* Y Y* Y Y N N N Y* N Y* Y* Y Y Y N Y* Y* Y*

Asynchrony Noise N N Y N N N N Y* Y Y Y† Y§ N N N N Y Y Y N N Y* Y Y Y N Y Y N N Y* N Y Y Y Y* N N

Rate Increase Y N N Y N N N Y§ Y Y§ N N N N N N Y§ Y N N N Y‡ Y‡ N N N N N Y N N N Y‡ Y‡ Y‡ N N N

Unipolar/Bipolar U/B U U/B U/B U/B U U/B U U/B U U U U U U U U/B U/B U U U U/B U/B U/B U/B U/B U/B U U/B U U U/B U/B U/B U U U U

Data updated from Telectronics (now Pacesetter), St. Jude Medical, Sylmar, Calif., technical note. *Remote potential for interference. † Impedance-based sensors. ‡ DDD mode only. § Piezocrystal-based sensors. B, bipolar; N, No; Y, yes; U, unipolar.

failed to reach the heart or the presence of oversensing. In the case of oversensing, the telemetered EGM may provide a clue to the source of the extraneous signal. As demonstrated in Figure 29-30, this is useful for differentiating the causes of oversensing and deciding on the proper remedy. The normal refractory period timing cycle initiated by the oversensing may give the overt appearance of undersensing, because the native complex that coincides with the electrocardiographically invisible refractory period is not sensed (normal behavior), allowing for time-out of the pacing escape interval and delivery of an output pulse; this is termed functional undersensing (see Fig. 29-4). The output pulse, if delivered during a period of physiologic refractoriness initiated by the native cardiac depolarization, may not capture, a phenomenon appropriately termed functional noncapture (Fig. 29-32). The true cause of the observed behavior is readily appreciated with telemetered event markers, but it may be difficult to decipher from the freestanding ECG or rhythm strip. Primary component failure of the pulse generator circuit is the least common of all the causes of pacing system failure, but it too can result in failure to output (Box 29-8). Patients who have been lost to follow-up

V

V

F

Figure 29-32  ECG rhythm strip showing functional noncapture. The problem in this case is the pacing system’s failure to sense the QRS complex. A subsequent pace output (V) occurs during the myocardial refractory period and should not be expected to be captured. The second-to-last QRS represents fusion (F) between the pace artifact and the native QRS.

872

SECTION 4  Follow-up and Programming

Presenting cardiogram

may present with complete exhaustion of the power source (battery) and a completely inoperative and unresponsive system. As the power source begins to fail, slowing of the pacing rate and erratic behavior may occur (Fig. 29-33). This may also be associated with mode and rate changes with or without sensing problems. Several problems may be mistaken for pulse generator failure, resulting in a no-output situation. These are generally related to problems at implantation. If the lead is not positioned properly in the connector block of the pacemaker, or if an improper lead is used, the electrical connection may not be complete. This is still an open circuit, but in the presence of a technically normal pulse generator and normal lead. The two are simply not connected appropriately, which is a physician error at implantation. A transient situation has been reported in unipolar systems after wound closure. Air may be present in the pocket, especially if a large generator is replaced by a smaller one. Air is an effective insulator and prevents contact of the anterior anodal surface of the pacemaker’s case with the body’s tissues (this applies only to coated pacemakers). The result is an incomplete circuit until the air is absorbed. Subcutaneous emphysema has also been reported to be responsible for loss of anodal contact.151,152 A similar pseudofailure occurs when a unipolar pulse generator is out of the pocket. If the stimulation impedance could be measured in each of these settings, it would be extremely high and well above the standard measurement for the particular lead being used. Event markers would report the release of an output pulse, even though the circuit was open, precluding effective pacing. It is important to keep in mind that virtually all bipolar pacemakers may be programmed to function in the unipolar mode. Failure to output may also be seen with bipolar pacemakers that are connected to a unipolar pacing lead when programmed to pace in the bipolar polarity. This is more likely with IS-1 leads because the bipolar and unipolar connectors may appear identical. Most unipolar IS-1 leads have a protective metal band where the anodal screw of the pacemaker connector block is located to prevent inadvertent tightening of this screw from damaging the lead. This gives the appearance of a bipolar lead, even though no anodal conductor is present, and may be misleading (Fig. 29-34). Most polarity-programmable pulse generators allow the user to designate the lead type as “unipolar” in a separate field of the programming system. Then, when the standard programmed parameter page is accessed, the “bipolar” lead option is locked out, minimizing the chance that the device will be accidentally programmed to the bipolar configuration. Of course, this lockout feature only works if the lead type is programmed correctly. Some newer devices have the ability to verify that a bipolar circuit is present before allowing permanent programming to be completed to the bipolar polarity. This feature operates independently of any programmed lead type and also protects against programming to an ineffective polarity if the anode has failed

25 mm/sec

Figure 29-33  ECG rhythm strip from pulse generator beyond elective replacement interval. Not only is the pacing rate below the programmed rate of 70 bpm, but the device is not sensing properly. The leads were found to function normally after the device was replaced.

because of lead fracture, malalignment of the lead in the connector, or failure to secure the anode set screw. In dual-chamber systems, sensing an event on one channel triggers refractory periods on both channels. Oversensing on the ventricular channel initiates both a ventricular refractory period and a PVARP. Depending on its precise timing, the PVARP initiated by the oversensed ventricular event may result in failure to sense a native P wave— yet another example of functional undersensing. A similar phenomenon may be seen in single-chamber systems in the presence of relatively rapid intrinsic rhythms. Oversensing starts a refractory period that may coincide with a native complex. Although this same complex is otherwise perfectly capable of being sensed, the pacemaker’s refractory period precludes it being sensed, with the result apparent undersensing when the true cause of the problem is oversensing. This is most readily identified if the phenomenon occurs while the rhythm is being monitored with the simultaneous display of event markers. Programming errors by the clinician also may result in no output or the appearance of no output. Programming to an ineffective pacing mode such as ODO will not allow any pacing to occur. A similar problem might be seen in a patient with complete AV block if programmed to the AAI mode. Likewise, programming the pace outputs to zero or extremely low values may cause the appearance of failure output. Failure to Capture (Artifact Present) With the advent of the newer ECG recording systems and the use of pulse artifact enhancement, the clinician must first be certain that the pace artifact seen is truly from the pacing system. The newer recording and monitoring systems have pacemaker pulse detectors that, when enabled, generate a discrete pacemaker pulse artifact in response to any high-frequency transient. Many extraneous signals can cause the enhanced ECG, telemetry system, or Holter recorder to place an erroneous pace artifact on the ECG. EMI (including programmer

Box 29-8 

CAUSES OF PULSE GENERATOR FAILURE Battery depletion Component malfunction Direct trauma Loss of hermeticity Therapeutic radiation Electrocautery Defibrillation and cardioversion Lithotripsy

Figure 29-34  Unipolar and bipolar IS-1 connectors. Top lead is an endocardial bipolar lead, and bottom lead is an epicardial unipolar lead. Note that both leads have a pin and ring at the connector end, leading to the possibility of confusion that the unipolar lead might actually be bipolar.



29  Pacemaker Troubleshooting and Follow-up

telemetry), loose ECG electrode connections, and subthreshold pulses, as seen with the minute ventilation sensors associated with normal pacemaker function, are examples of situations associated with spurious ECG artifacts (see Fig. 29-23). The use of event marker telemetry and EGMs can assist in differentiating the true pacemaker output from a recording system artifact, whereas retrospective analysis of a recorded rhythm may prove challenging. A common cause of functional noncapture is undersensing, with a resultant delivery of the pacemaker impulse during the physiologic refractory period of the myocardium. Although the output does not elicit a depolarization, the problem in this case is related to sensing, not output, and should be evaluated as such (see Fig. 29-32). This is best identified as undersensing, but if one insists on commenting on capture, it is functional noncapture. No matter how high the energy content of the output pulse, the myocardium is physiologically refractory and incapable of being depolarized. When true noncapture is documented, the patient’s safety must be ensured. If the patient is pacemaker dependent or is intolerant of the subsequent bradycardia associated with complete or intermittent loss of capture, the device should be programmed to its highest output. This can often be rapidly achieved by activating emergency VVI mode through the programmer. In most systems, even with a dual-chamber device, this programs the pacemaker to the highest available output in a unipolar output configuration. If consistent capture is still not secured, placement of a temporary pacemaker may be required. Almost all bipolar devices allow programming to the unipolar polarity. This may acutely correct the situation, particularly in the presence of an internal insulation failure, with a resultant short circuit or an open circuit associated with a fracture of the outer (anode) conductor. Although this maneuver eliminates the need for an emergency surgical intervention, it is a temporizing measure only, and a lead with a mechanical failure should be replaced. Box 29-9 lists the causes of noncapture. The onset of noncapture in relation to implantation of the device and lead system can provide Box 29-9 

CAUSES OF LOSS OF CAPTURE* Lead dislodgment or malposition Micro-instability Macro-dislodgment Perforation Elevated capture thresholds Lead maturation Chronic Progressive cardiac disease Myocardial infarction Cardiomyopathy Metabolic abnormality Electrolyte abnormality Drugs Local damage at electrode-myocardium interface Electrocautery Defibrillation and cardioversion Battery depletion Circuit failure Capture management algorithm failure Inappropriate programming Too low a safety margin Evoked-response sensitivity set to oversensitive value Pseudomalfunction Recording artifacts mimicking a pacing stimulus Isoelectric evoked potential with visible pacing stimulus Functional noncapture: delivery of output during physiologic refractory period Functional noncapture True undersensing Functional undersensing *Pulse artifact present but no evoked potential.

873

Box 29-10 

METABOLIC FACTORS INCREASING CAPTURE THRESHOLDS Major changes Acidosis Alkalosis Hypercarbia Hyperkalemia Severe hyperglycemia Hypoxemia Myxedema Minor Changes Sleep Viral infections Eating

valuable clues to the cause. Loss of capture shortly after lead implantation suggests dislodgment, malposition, or perforation of the heart by the lead. Elevated thresholds that occur during the first several weeks after implantation were more common in the early days of pacing. Although the incidence of this problem has greatly decreased with the introduction of steroid-eluting electrodes and other electrode materials and designs, a significant rise in capture threshold may still occur. The capture threshold rise is attributed to the inflammatory reaction that results from two factors: (1) the pressure and thus trauma applied by the electrode to the endocardium and (2) a standard foreign body reaction. The peak of the early threshold rise usually occurs 2 to 6 weeks after implantation. Use of a higher output during this acute period minimizes the likelihood of noncapture until the threshold improves to its chronic level. Use of newer devices that can measure the capture threshold on a beat-to-beat or periodic basis can reduce the need for these higher outputs, yet provide the safety needed for the patient should the threshold rise. A rise in threshold more than 6 weeks after implantation is usually considered to be in the chronic phase of the lead maturation process. The threshold may rise steadily over time until noncapture occurs or until the threshold exceeds the pacemaker’s maximum output, typically referred to as exit block.153-159 Older lead models and some epicardial leads are more likely to develop elevated capture threshold levels.160-163 Some patients demonstrate repeated episodes of this phenomenon and have required multiple lead revisions or replacements. Children with epicardial implants are especially prone to this condition.153,164 Steroid-eluting leads are useful in minimizing the development of exit block.165-173 Anecdotal reports propose the use of high-dose systemic steroids to lower high thresholds, with dosing continued for months and then slowly tapered, but no prospective randomized trials have evaluated this pharmacologic intervention.174-176 Causes of capture threshold rise occur in both the acute and the chronic phase. Any severe metabolic or electrolyte derangement can lead to acute threshold changes177-188 (Box 29-10). These may occur in critically ill patients or during and immediately after cardiac arrest. Noncapture may occur secondary to the hypoxemia, acidemia, or hyperkalemia, rather than be the primary event leading to the arrest. In addition, some medications may affect capture thresholds, resulting in significant changes from the patient’s baseline189-194 (Box 29-11). Beat-by-beat capture confirmation and periodic capture threshold measurement systems are now in widespread use. These have been reported to identify patients with transient or sustained late rises in capture threshold that would have resulted in loss of capture had the implanted pacemaker been programmed to a standard 2 : 1 safety margin.195 As experience continues using systems with these capabilities, understanding of the factors that can affect chronic capture threshold will increase. Although the clinician might expect that fracture of a lead would result in the absence of any visible pacing artifact, this is frequently not the case. The ECG may display a pace artifact with failure to capture, especially in unipolar systems. This occurs because the current passes

874

SECTION 4  Follow-up and Programming

Box 29-11 

DRUGS THAT INCREASE OR DECREASE PACING THRESHOLDS Increase threshold Flecainide Propafenone Sotalol Tikosyn Mineralocorticoids Possibly increase threshold Beta-adrenergic blockers Ibutilide Lidocaine Procainamide Quinidine Decrease threshold Atropine Epinephrine Isoproterenol Glucocorticoids

across the gap in the conductor coil through the fluid in the lead; however, the resistance is high, and the delivered current is likely to be subthreshold. In unipolar systems, the anode (i.e., the pulse generator surface) is virtually always intact and provides enough of an electrical transient to trigger the artificial pace artifact circuitry of many monitoring systems. One can also see stimulus artifacts in the setting of a total disruption of both the conductor and the insulating sheath, which allows the output to be delivered to some local tissue, resulting in a stimulus on the ECG even though there is noncapture.145 Although modern pulse generators attempt to maintain the programmed voltage output until the battery is exhausted, a reduction in the delivered voltage may occur before the elective replacement indicator is activated. At advanced stages of depletion of the battery, this may result in an ineffective pacing stimulus. Latency is a finding that may be mistaken for failure to capture. Latency is defined as the delay between delivery of the pacing impulse and onset of the evoked potential or electrical systole.196 Some antiarrhythmic agents, myocardial disease, or severe electrolyte disturbances (e.g., hyperkalemia) can cause latency (Fig. 29-35). A Wenckebach type of latency prolongation, leading to a noncapture and a repeat of the cycle, has also been reported. Failure to Sense To appreciate undersensing, it is necessary to understand how the sense amplifier works and where in the cardiac cycle the sensing can and cannot occur. A prerequisite for proper sensing is a good-quality EGM; the signal must possess both an adequate amplitude and an adequate frequency content (slew rate) to be sensed properly. A signal of apparently adequate peak-to-peak amplitude may be greatly attenuated by the sense amplifier because of its poor slew rate. The resultant “filtered”

Figure 29-35  ECG rhythm strip showing latency. Note the prolonged period from the pace artifact until the evoked QRS complex. This patient had a serum potassium concentration of 7.1 mEq because of renal failure.

Box 29-12 

CAUSES OF UNDERSENSING Poor intrinsic signal from implant Signal amplitude Slew rate Deterioration of intrinsic signal over time Lead maturation Progression of disease • Cardiomyopathy • New bundle branch block • Myocardial infarction Respiratory or motion variation Ectopic complexes not present at implantation Transient decrease in signal amplitude Postcardioversion or defibrillation Metabolic derangement (e.g., hyperkalemia) Device malfunction Sensing circuit abnormality Stuck reed switch Battery depletion Mechanical lead dysfunction Insulation failure Partial open circuit Pseudomalfunction: recording artifact Normal device function: misinterpreted Triggered mode Fusion and pseudofusion beats Functional undersensing Long refractory periods Blanking period Safety pacing Oversensing DVI mode (particularly committed DVI) Oversensing-initiated functional undersensing

signal may be of insufficient size to be recognized as a valid event.197-202 Box 29-12 lists the causes of sensing failure. It is often assumed that the pacemaker senses a cardiac event at the beginning or the peak of the P wave or QRS complex, as seen on the surface ECG. This is not the case. The surface P wave or QRS is a summation of all electrical events occurring at the cellular level over a period of time (normally 80 to 120 msec, but may be longer due to conduction system disturbances). The intracardiac EGM as recorded from a pacing electrode appears as a large-amplitude, relatively rapid deflection (see Fig. 29-10). If one did not know that the recording was an EGM, an atrial signal could be easily mistaken for a QRS complex presumed to have been recorded with a standard surface ECG. It is therefore helpful to record both the atrial and the ventricular EGM simultaneously, the EGM with the simultaneous surface ECG, or telemetered event markers (nearly all pacing systems now provide all these simultaneously). This event, the intrinsic deflection of the QRS or P wave, is generated as the wave of depolarization passes by the electrode. This is the complex that is sensed, even if it occurs well after the onset of the native depolarization. An excellent example of this delayed sensing is in the patient who has right bundle branch block and a pacing electrode in the right ventricle. The native depolarization occurs late in the right ventricle because of the conduction delay. The pacemaker does not sense this event until that depolarization reaches the pacing lead, which is very late in the timing of the surface QRS complex. If it is assumed that sensing occurred earlier, this may be incorrectly labeled “late sensing.” Measurements made from the onset of the QRS complex can misinterpret the timing cycle by more than 100 msec. Therefore, an ECG with a pacing artifact in the QRS (pseudofusion and fusion) can occur in the presence of absolutely normal sensing203,204 (Fig. 29-36). The refractory and blanking periods are integral to understanding sensing and whether a native complex is even potentially capable of being sensed. A blanking period is a time during which no sensing at



29  Pacemaker Troubleshooting and Follow-up

Figure 29-36  ECG rhythm strip showing pseudofusion beats. Because the premature ventricular contractions arise from the left ventricle (right bundle branch block morphology), right ventricular depolarization occurs late within the overall cardiac activation sequence. The QRS complexes cannot be sensed by the pacemaker until late into the surface QRS, resulting in pseudofusion complexes when the escape interval “times out” before the intrinsic deflection has occurred. In these cases, even though the ventricle had started to depolarize, the pacemaker was not yet capable of sensing it.

all will occur on a given channel. A refractory period is similar to a blanking period, but events occurring during a refractory period may be used for purposes other than resetting escape intervals. These “sensed but not used” events can be used by the device to detect noise on a lead, or detection of atrial events for initiation of mode switching. Long programmed refractory and blanking periods can cause undersensing of events occurring within these periods (Fig. 29-37). This might occur in the case of a closely coupled PVC or PAC or very rapid intrinsic rhythms. Although there may be resultant competition, this is not a lead or pulse generator malfunction, in that both are functioning properly and in accord with their design. This is clinically undesirable and reflects inappropriate programmed settings in the pacemaker, a behavior amenable to correction by programming. This is also termed functional undersensing, because the pacemaker is not capable of sensing at the time the native signal occurred. On the other hand, the failure to sense the native complex allows the timing period to complete, with the resultant release of an output pulse that may prove to be ineffective because it was delivered at a time of physiologic refractoriness. Functional undersensing usually results in functional noncapture. A classic example of this phenomenon was the committed DVI pacing system, an early-generation (and now obsolete) AV sequential pacing system that was not capable of sensing on the atrial channel but, with release of an atrial output, was committed to release a ventricular output even in the presence of a native R wave.203,222 As in noncapture, the onset of undersensing in relation to implantation of the pacemaker and lead system may direct the clinician to the correct diagnosis of the malfunction. Undersensing that occurs close in time to implantation should lead the physician to suspect dislodgment, malposition, or perforation of the electrode. Problems occurring in chronic systems are frequently caused by mechanical problems with the lead or, if the lead is normal, by programming errors. Occasionally, problems are attributable to a change in the morphology of the intrinsic cardiac signal associated with myocardial disease progression. Inappropriate programmed settings do occur, particularly when sensitivity threshold testing has been performed in a nontemporary manner

875

during follow-up. The clinician may forget to return the sensitivity to the appropriate setting and leave it at or above the threshold setting. Occasionally, the sensing threshold may show a slow decline in the amplitude of the native signal as the lead-tissue interface changes over time.205-212 The vector of depolarization can affect the amplitude and slew rate of the EGM. Any change in the vector may result in significant changes in the sensing threshold. If a patient with a ventricular pacemaker has a myocardial infarction, develops a bundle branch block, or has PVCs, the intracardiac signal may be insufficient to allow sensing at a previously appropriate setting206-208 (Fig. 29-38). The same may be seen with atrial implants and PACs. Another cause of vector change is movement of the lead’s position associated with respiration. Marked changes in the intracardiac signal can be documented in some patients as the angle of the lead relative to the heart changes with body position or diaphragmatic motion209-212 (Fig. 29-39). Evaluation of the quality of the intracardiac signal associated with sensing failure is greatly facilitated by access to the telemetered EGM. As the pacemaker’s battery begins to become depleted, erratic behavior may occur, including persistent or intermittent undersensing. Failure of a circuit component may also cause sensing failure. Rarely, the reed switch that activates the magnet mode may stick in the closed position, causing (in most cases) asynchronous pacing. For the same reason, when reviewing a rhythm strip, the clinician must know whether the magnet was over the device when the recording was made. Asynchronous pacing may also be seen during the interference or noise mode function of the device. The latter obligates pacing when highfrequency, nonphysiologic electrical signals are sensed by the pulse generator (Fig. 29-40). Typically, this is defined as multiple sensed events occurring within the terminal portion of the ventricular refractory period. The device then paces asynchronously to protect the pacemaker-dependent patient against inappropriate device inhibition.142,213 One frequently misinterpreted reason for failure to sense involves pacemakers that use impedance plethysmography as a rate modulation sensor. This applies primarily to minute ventilation sensors, but now also to “lung wetness” monitoring systems. The system uses the pacemaker’s case as the anode for the impedance-sensing impulses. Therefore, when the case is out of the pocket, much electrical noise is generated because the system is not grounded. This may result in asynchronous pacing until the device is placed into the pocket. If the clinician is not aware of this idiosyncrasy, a malfunction of the pulse generator might be inappropriately diagnosed. The use of external or internal defibrillation can result in temporary or permanent loss of the sensing function. This may result from transient saturation of the sensing amplifier pacemaker, circuit damage, or lead-myocardium interface damage. This phenomenon occurs when the large electric current delivered by the defibrillator is diverted from the pacemaker’s circuitry to the pacing lead by way of Zener diodes, which are included to protect the pulse generator from large voltage surges. The result may cauterize the myocardium and thereby reduce or eliminate the local EGM. It may also cause a marked elevation in the capture threshold or result in exit block. Capacitive coupling is another mechanism that may allow a current to be induced into the pacing lead, by a defibrillation shock or nearby electrocautery use.214-216

475 ms Additional cardiogram

Lead II @ 25mm/sec

Figure 29-37  ECG rhythm strip showing undersensing of QRS complexes in patient with atrial fibrillation. The device is programmed to VVI with a demand rate of 70 bpm and a refractory period of 475 msec. Because of a long programmed ventricular refractory period, this does not represent a pacemaker malfunction. The pacemaker will not respond to intrinsic events during the refractory period, a phenomenon termed functional undersensing. The arrows indicate paced beats.

876

SECTION 4  Follow-up and Programming

PVC

ICEGM

ICEGM

I I

II II

III

Figure 29-38  Intracardiac electrogram (ICEGM) and surface ECG (I, II, III) of intrinsic beats and PVC. In this example, the premature ventricular contraction (PVC) electrogram has a peak-to-peak amplitude that is significantly lower than the normal beats and may lead to undersensing.

Exposure to magnetic resonance imaging (MRI) may result in inductive coupling with the lead system, induce a current, and cause the same problem. DUAL-CHAMBER PACEMAKER ISSUES Crosstalk Inhibition Crosstalk is a potentially catastrophic form of ventricular oversensing that can occur in any dual-chamber mode in which the atrium is paced and the ventricle is sensed and paced. Consider that the common output voltages for the atrial channel range from 2.5 to 5 V, or 2500 to 5000 mV. The ventricular lead is just several centimeters away from this atrial lead and is “looking” for an electrical event of about 2 mV, which would represent a sensed ventricular depolarization. If the ventricular channel senses the pacing impulse delivered to the atrium, it interprets the event as an R wave. The ventricular output is inhibited, and the patient is left without pacing support. If crosstalk occurs in a patient with complete AV block, ventricular asystole could result. In the absence of an escape rhythm, only paced P waves would be visible.217-220 Conversely, crosstalk is more difficult to detect when AV nodal conduction is intact. In a system that uses ventricular-based timing, the result may be an acceleration of the paced atrial rate with ventricular output inhibition, even in the presence of a first-degree AV block that exceeds the programmed AV delay.220 As demonstrated in Figure 29-41, crosstalk can be recognized by an acceleration of the atrial paced rate in a non-sensor-driven dualchamber system using ventricular-based timing. Note that ventricular sensing occurs virtually simultaneously with atrial output. The AV delay is immediately terminated with ventricular sensing, and the atrial escape interval (AEI) is started. Therefore, the pacing interval with this

III

Figure 29-39  Intra-atrial electrogram and surface ECG. Note the profound variation of the intracardiac signal without apparent change in the surface P-wave morphology. The variation was synchronous with respiratory movements. This situation may be seen in either the atrium or the ventricle. ICEGM, Intracardiac electrogram.

type of timing is equal to the AEI (programmed pacing interval minus AV delay) plus the ventricular blanking period. Rate-modulated pacing systems that use ventricular-based timing have a rate acceleration that is seen at the base pacing rate. Crosstalk may not be readily diagnosed in patients with rate-modulated pacing systems and intact AV nodal conduction if the increased atrial pacing rate is believed to be caused by the sensor.

Figure 29-40  Noise response pacing. Tracing was recorded from a patient with a St. Jude Medical pacemaker during exposure to electromagnetic interference. Note that the device goes from a normal tracking behavior to an asynchronous pacing behavior during the EMI. It then returns to normal function once the interference terminates. This feature is designed to prevent asystole in a pacemaker-dependent patient.



29  Pacemaker Troubleshooting and Follow-up

877

Delay Additional cardiogram

Lead II @ 25mm/sec

A Mode: DDD

Rate: 70 ppm A-V Delay: 200 msec Magnet: TEMPORARY OFF

C

Mode: DDD

ECG/IEGM PARAMETERS

Rate: 70 ppm A-V Delay: 200 msec Magnet: TEMPORARY OFF ECG/IEGM PARAMETERS

Surface ECG Surface ECG Gain Surface ECG Filter Intracardiac EGM Intracardiac EGM Gain Chart Speed

ON 4.0 mv/div ON OFF 2.5 mv/div 25.0 mm/sec

Surface ECG Surface ECG Gain Surface ECG Filter Intracardiac EGM Intracardiac EGM Gain Chart Speed

ON 4.0 mv/div ON OFF 2.5 mv/div 25.0 mm/sec

A

A

A

A

A

A

A

A

A

A

R 22 655 675

R 22 655 675

R 22 657 677

R 22 655 675

R 22

V 125 657 775

V 120 657 700

V 125 655 777

V 125 655 775

V 122

Surface ECG

Surface ECG

1.0 sec

1.0 sec

B

D

Figure 29-41  Crosstalk. A, Electrocardiogram (ECG) rhythm strip showing crosstalk in a patient with complete atrioventricular (AV) block, with a ventricular-based pacing system. Note the presence of an atrial output without a ventricular output. A comparison of the atrial escape interval (AEI) from the first until the second atrial pulse with that from the second until the third atrial pulse demonstrates that the pacing interval is shortened by the A-V interval minus the blanking period (120 msec). B, ECG strip from the same patient with event markers during crosstalk. Note that the ventricular sensing (R) occurs immediately after the atrial output pulse (A). Safety pacing was turned off. C, ECG rhythm strip showing crosstalk in a patient with intact AV conduction. Because this pacemaker operates with ventricular-based timing, the AEI resets with each atrial output, elevating the frequency of atrial stimulation. D, ECG rhythm strip and event markers during crosstalk and ventricular safety pacing enabled. Note that, despite the programmed setting of the AV interval to 200 msec, the event markers demonstrate the ventricular stimulus at 125 msec after the atrial output pulses. IEGM, Intracardiac electrogram.

Pacing systems that use atrial-based timing do not exhibit this rate increase. Although ventricular sensing of the atrial output inhibits the ventricular output, the portion of the AV interval not used is added to the AEI, maintaining atrial pacing at the programmed interval (Fig. 29-42). Without access to event marker telemetry, ventricular output inhibition from crosstalk cannot be differentiated from failure to output, as with an open circuit. Several factors increase the likelihood of crosstalk (Box 29-13). Programmed settings that make the ventricular channel more sensitive or that increase the atrial energy output predispose to this problem. Insulation failure on the atrial lead also increases the chances of crosstalk by increasing the pulse charge and energy. Certain pacemaker models are more prone to this phenomenon than others, related to differences in circuit designs and the degree of isolation between the two channels within the pulse generator.217 Crosstalk may occur internally, within the circuitry of the pulse generator, as a result of external oversensing Figure 29-42  ECG rhythm strip showing crosstalk with atrial-based timing in pacemaker. Note that the atrial pacing rate remains at the programmed rate of 70 bpm. The atrioventricular interval was programmed to 175 msec.

between the pacing leads. Unipolar systems are also significantly more prone to crosstalk because of the larger electrical signal, as sensed by the ventricular channel.218-223 Prevention of Crosstalk.  Prevention of crosstalk is approached by proper programming of the device and proper lead placement. Atrial Box 29-13 

FACTORS PROMOTING CROSSTALK High atrial output settings Pulse amplitude Pulse width Pulse current, as with low impedance High ventricular sensitivity setting (e.g., 1 mV) Short ventricular blanking period

878

SECTION 4  Follow-up and Programming

Figure 29-43  ECG rhythm strip showing undersensing of native QRS complex. The device was programmed to the DVI mode, so there is no atrial sensing. When the atrial escape interval expires, the atrial output coincides with the onset of the native QRS complex. The ventricular blanking period is triggered by the release of the atrial output; this precludes ventricular sensing for 38 msec after the atrial output. If the intrinsic deflection of the native QRS coincides with the ventricular blanking period, it will not be sensed, and a ventricular output will be delivered at the end of the programmed atrioventricular interval.

amplitude and pulse width settings that provide an appropriate safety margin without being excessive and ventricular sensitivity settings that are not unnecessarily sensitive are helpful. Newer circuit designs are much more resistant to this problem. Even under ideal circumstances, however, crosstalk may still occur. The use of an additional ventricular refractory period, known as the ventricular blanking period (VBP), is fundamental to prevention.221 The VBP begins with the atrial output and usually lasts from 12 to 120 msec (the “ultimate blanking period” was the now obsolete DVI-committed mode, during which no sensing occurred on the ventricular channel at any time during the A-V interval after an atrial output pulse). In most devices, this is a programmable parameter. During the VBP, nothing (including the atrial output) can be sensed on the ventricular channel. Short VBPs help to prevent the undersensing of intrinsic ventricular activity but may allow crosstalk to occur. Long VBPs virtually ensure the prevention of crosstalk but may cause intrinsic events to not be sensed, a potential problem if the native beat is a late-cycle PVC and the A-V interval is programmed to a long length. Functional failure to sense a PVC, because the intrinsic deflection of the PVC coincided with the VBP, may be followed by a ventricular output beyond the myocardial refractory period and on the vulnerable zone of the T wave. This might result in the induction of a ventricular arrhythmia, which could also occur with atrial undersensing if a normally conducted QRS complex falls into the VBP. The latter event would not be detected, and an unnecessary stimulus would be delivered (Fig. 29-43). Prevention of Crosstalk Sequelae.  The earliest approach to prevention of ventricular output loss as a result of crosstalk was the introduction of the DVI-committed mode (DVI-C). In this version of DVI, ventricular sensing is completely disabled during the AV interval that follows an atrial output pulse. After termination of the A-V interval, a ventricular output pulse is committed whether or not an intrinsic ventricular event has occurred. Thus, with DVI-C, there can never be an inhibition of the ventricular output by an atrial output. Although this approach worked, it resulted in confusing ECGs and wasted energy because of the delivery of unnecessary pacing impulses.203,222 It is also Additional cardiogram

not practical for DDD devices for similar reasons. With the development of the DDD mode, however, manufacturers were able to provide brief refractory periods (blanking periods) starting with the atrial output. Even blanking periods, however, are not a guaranteed prevention for ventricular output inhibition associated with crosstalk. To ensure patient safety, a unique circuit/algorithm has been integrated into the ventricular channel. The most common approach is the use of a safety output pulse when crosstalk is suspected by the device. This is referred to by multiple names, depending on the manufacturer of the device (e.g., safety pacing, nonphysiologic AV delay, ventricular safety standby). This method uses a brief sensing period (crosstalk sensing window) after the blanking period. Any electrical event sensed during this crosstalk sensing period is assumed to be crosstalk. A ventricular output is then triggered to be delivered after a shortened AV delay223,224 (Fig. 29-44). Other events can cause a safety output pulse to occur, including premature ventricular beats, premature junctional beats, and normally conducted ventricular events that occur after undersensed intrinsic atrial beats (see Fig. 29-43). After one of the latter events, if the safety output pulse were to be delivered using a long A-V interval, there would be a potential for delivering a tightly coupled and potentially arrhythmogenic stimulus to the ventricle. Therefore, a shortened A-V interval is used (typically 100-120 msec) to deliver the stimulus harmlessly into the depolarizing ventricle while maintaining the ability to rescue the patient in the presence of actual crosstalk. In the presence of a long programmed AV delay and intact AV nodal conduction, crosstalk is signaled by AV pacing at the abbreviated AV delay. Reducing the atrial output, reducing the ventricular sensitivity, or lengthening the VBP should reduce, if not totally eliminate, episodes of crosstalk. As in crosstalk, delivery of the safety output pulse causes a shortening of the base pacing interval because of the shortened A-V interval. If the baseline A-V interval is programmed to the same duration as that of the safety output pulse (this has become very common in biventricular devices when treating patients with congestive heart failure), or if a rate-modulated or differential A-V interval is present, the presence of safety pacing (i.e., crosstalk) may be difficult or impossible to discern on the standard ECG. The use of event marker Lead II @ 25 mm/sec

Figure 29-44  ECG rhythm strip showing safety pacing. Sensing is occurring on the ventricular channel during the crosstalk sensing window. This causes a ventricular output to be delivered at a shortened atrioventricular (A-V) interval. In a ventricular-based timing system, the pacing interval is shortened by the difference between the programmed A-V interval and the safety-paced A-V interval, because the atrial escape interval is reset by any sensed or paced ventricular event. This results in an AV paced rate of 93 bpm, even though the device is programmed DDD at 75 bpm and is not capable of rate modulation.



29  Pacemaker Troubleshooting and Follow-up Presenting cardiogram

Lead: III

25 mm/sec, 8 mm/mV

End

Magnet applied

Lead: III

25 mm/sec, 8 mm/mV

End

879

Figure 29-45  Example of “runaway pacemaker.” This device was subjected to direct, unshielded therapeutic irradiation during treatment of a breast carcinoma. The patient presented to the clinic for routine follow-up and had a normal presenting rhythm strip, as shown. She had been programmed to DDDR from 70 to 120 bpm. On placement of the magnet over the device, pacing began at the runaway protect rate of 180 bpm. The patient was taken to the operating room, and the device was replaced emergently.

telemetry documents the presence of crosstalk or safety output pulses in these situations (see Fig. 29-44). Delivery of a safety output pulse does not prevent crosstalk. It is designed to prevent the sequelae of crosstalk by preventing ventricular asystole. It is unwise to allow a patient to use this backup mechanism continually. If crosstalk is suspected or documented, the clinician should pursue the potential causes and make the necessary adjustments to terminate this condition. In some situations, such as failure of the lead’s insulation, programming changes may not be adequate, and surgical intervention may be required. Pacemaker-Mediated Tachycardia Any undesired rapid pacing rate caused by the pulse generator or by an interaction of the pacing system with the patient may be considered pacemaker-mediated tachycardia (PMT). This has classically been associated with the endless-loop tachycardia (ELT) seen in dualchamber devices. PMT, however, should be assumed to be a more general term. The following are several conditions that are welldocumented causes of PMT. Runaway Pacemaker.  The runaway pacemaker is a pacemaker malfunction that may occur in single-chamber or dual-chamber pacing systems. It is usually the result of at least two separate component failures within the pulse generator. The result is the rapid delivery of pacing stimuli to the heart, with the potential for inducing lethal arrhythmias, such as ventricular tachycardia or fibrillation. All modern devices incorporate a runaway protect circuit that prevents stimulation above a preset rate, typically between 180 and 200 bpm. Although extremely rare with modern pacing devices, this represents a medical Box 29-14 

emergency (Fig. 29-45). Emergent surgical intervention to replace the device or, if all else fails, cut the lead, must be performed. Obviously, a patient who is pacemaker dependent presents a new challenge as soon as the defective pacing system is disabled.225,226 Sensor-Driven Tachycardia.  Sensor-driven tachycardia is a rapid heart rate occurring in rate-modulated pacemakers. It can occur with any type of sensor-driven pacing system (Box 29-14). Interaction between the patient and external stimuli can cause the rate modulation system to overreact and pace at a high rate. The most common cause of this PMT type is inappropriate programming of the sensor parameters. In piezoelectric devices, a threshold setting that is too low or a slope setting that is too high results in high pacing rates for low levels of activity. It also exposes the patient to increased pacing rates for nonphysiologic events, such as riding in a car, exposure to loud noise or music, or sleeping on the ipsilateral side to the device implant.227-237 One unpublished incident concerned a patient with a bipolar piezoelectric VVIR device. The emergency medical squad had been summoned to treat an unconscious patient. They arrived to find the patient with seizure activity. On viewing the ECG, they found the patient’s condition to be wide-complex tachycardia at 150 bpm. The patient received repeated direct-current cardioversion for this tachycardia, without reversion to sinus rhythm. In this patient the seizures were caused by epilepsy, and the vibration-based sensor responded to the seizure by pacing at its upper rate. No spikes had been noted on the ECG because the output configuration was bipolar, which resulted in a diminutive artifact on the monitor (Fig. 29-46). In the past, pacing systems responsive to central venous temperature changes might have responded to a fever spike with upper rate pacing. This necessitated design of a “nulling” feature, which restores a more appropriate pacing rate after a specified time at the upper rate has

CAUSES OF SENSOR-DRIVEN PACEMAKER TACHYCARDIA Vibration sensor: piezocrystal Pressure on device • Patient lying on device (as during sleep) • Tapping on device Submuscular implantation Loud, low-frequency music Bumpy ride, as in a tractor, lawn mower, or helicopter Use of vibration-generating tools Impedance-based sensors—minute ventilation Hyperventilation Electrocautery Environmental 50- to 60-Hz electrical interference Evoked QT interval Rate-dependent QT-shortening spiral Sympathomimetic drugs

Figure 29-46  ECG rhythm strip of pseudo–ventricular tachycardia. Caused by rapid ventricular pacing using a bipolar device. Note that the pace artifact is not well seen, leading to this potential misdiagnosis.

880

SECTION 4  Follow-up and Programming

occurred. Devices that respond to changes in the evoked QT interval also use this nulling feature, although for different reasons. As the QT interval shortens because of catecholamine increases and changes in the autonomic nervous system, the pacing rate is increased by the device; however, this may cause further shortening of the QT interval by a rate-dependent mechanism. The latter change further increases the pacing rate, which may then spiral to the upper rate limit. Devices that use thoracic impedance plethysmography to determine changes in minute ventilation may pace at the upper rate during marked hyperventilation, use of electrocautery, hyperventilation during anesthesia induction, and when close to an electrical power supply. Therefore, it is strongly recommended that this type of ratemodulating feature be disabled before the patient undergoes any surgical procedure (even if electrocautery is not used, because much electrical equipment is present in most operating room suites), treatment with a mechanical ventilator, or treatment in a critical care unit.236 Magnetic Resonance Imaging.  Exposure to MRI scanners has been reported to cause inappropriately high pacing rates when tested in animals. Some pacemakers have been noted to pace at the radiofrequency (RF) pulse rate of the scanner. This situation resolves immediately with the cessation of the RF output by the scanner.238-243 MRI may also result in inhibition of the pacing output during the scanning process. Because of these issues, such scanning has been cautioned against by all manufacturers of pacemakers. This is true even though some patients have inadvertently or intentionally undergone MRI without problems. Some physicians have programmed devices in patients who are not pacemaker dependent to the OOO/ODO mode or to a subthreshold voltage output or pulse width, effectively disabling the pacemaker, and pacemaker-dependent patients have had the device programmed to an asynchronous mode. Although this may help, the induced current from having a wire in a moving magnetic field can theoretically stimulate the heart without being connected to the generator. One study reported that the induced current was subthreshold,244 even though the potential for stimulation existed. It has also been reported that the capture threshold may rise because of heating at the lead-myocardium interface. Myopotential Tracking.  Myopotential tracking is caused by oversensing of muscle potentials by the atrial channel in a dual-chamber pacing system capable of P-wave tracking. This has become much less common with the use of bipolar sensing, which is preferred by most implanting physicians. It is a greater problem with unipolar dual-chamber systems. A unique sensing modality—“combipolar” sensing, which is sensing between unipolar atrial and ventricular electrodes for a form of widedipole bipolar sensing with the entire system restricted to the heart— has the potential to reduce the incidence of atrial myopotential oversensing.245 Myopotential tracking occurs when the atrial channel senses the electrical activity of the muscle underlying the pulse generator. Those same signals, if sensed on the ventricular channel, would result in myopotential inhibition. The atrial sensitivity setting is usually

more sensitive than in the ventricular channel, and myopotential sensing is more likely in the unipolar configuration. When myopotentials are sensed on the atrial channel, the atrial output is inhibited, and a ventricular output is triggered at the end of the AV interval. This pseudo–P wave repeatedly triggers the ventricular output, and ventricular pacing may occur up to the programmed maximum P-wave tracking rate (Fig. 29-47). If the myopotentials are of sufficient amplitude, they may be sensed on the ventricular channel, in which pacing system inhibition may also occur.88,89,120 Atrial Arrhythmias.  A common cause of rapid pacing in a dualchamber pacemaker capable of tracking the atrium is atrial fibrillation. Any rapid atrial rhythm, such as flutter or ectopic atrial tachycardia, may also cause a similar situation. The pacemaker attempts to track the atrium to the upper rate limit if one of these arrhythmias occurs. This is not a pacemaker malfunction, although it may manifest as rapid ventricular pacing and may be clinically undesirable. Suppression of the arrhythmia with medication or cardioversion may be necessary. Placing a magnet over the pacemaker stops the high-rate tracking until the arrhythmia can be terminated or the device can be reprogrammed. After a programmer is obtained, a nontracking mode may be programmed, or features such as automatic mode switching may be enabled. The latter is most useful in patients with AV block and intermittent atrial arrhythmias. In other cases, modes such as DDI or VVI have proved to be effective. In some cases, mode switching is programmed on but does not activate. This is most likely with poorly sensed atrial fibrillation or with flutter or atrial tachycardia occurring at a rate that causes atrial events regularly to land in blanking or refractory periods and therefore ignored by the device. The result may be failure of the pacemaker to see a sufficient number of atrial events to engage the mode-switching algorithm. Endless-loop Tachycardia.  The classic form of PMT is ELT, which can occur in dual-chamber pacemakers that are capable of atrial tracking modes, most often DDD or VDD. Only patients who are capable of retrograde ventriculoatrial (VA) conduction through the AV node or an AV accessory pathway are capable of sustaining this rhythm. The mechanism is identical to any macro-reentrant tachycardia in which two electrical pathways exist between the atria and ventricles. Pacemaker ELT is classically initiated by a PVC. The depolarization is conducted retrograde to the atria. If the PVARP has ended and the retrograde complex is of sufficient amplitude to be sensed, the atrial channel senses the event and initiates an A-V interval. At the end of the A-V interval, the pacemaker delivers a stimulus to the ventricle, and the loop is reinitiated (Fig. 29-48). Although PVC is the classic cause of PMT initiation, any situation that results in AV dissociation, allowing a ventricular depolarization to occur without a normally coupled atrial-paced or atrial-sensed event, may begin the loop (Box 29-15). Examples include atrial noncapture, oversensing, and undersensing. In addition, if the programmed AV interval is long (some units allow programming of an interval of up to 400 msec), it may be possible for the AV node to recover in time to conduct the subsequent

Figure 29-47  ECG rhythm strip of myopotential tracking. The electrical activity of the muscle adjacent to the pacemaker case in a unipolar system is sensed by the atrial channel. This causes repeated initiation of the atrioventricular interval up to the maximum tracking rate. Higheramplitude myopotentials may also cause inhibition of the ventricular channel.



29  Pacemaker Troubleshooting and Follow-up PVC sensed by RV lead, starts PVARP

Conducts retrograde to atrium

LA

LA

AVN

RA

LV

RA

LV

RV

RV

RP

B

Retrograde P-wave sensed by atrial channel since PVARP expired

Paced into RV after A-V interval continues cycle

LA

LA RA

RA LV

RV

RV

Box 29-15 

ENDLESS- LOOP TACHYCARDIA (ELT) SUMMARY Initiation Premature ventricular ectopic beat Atrial undersensing Atrial oversensing Atrial noncapture Long programmed AV delay with echo beats Prevention PVARP PVARP extension after ventricular ectopic beat detection Differential atrial sensing Rate-responsive AV delay allowing longer base-rate PVARP Adaptive PVARP High maximum tracking rate (MTR): retrograde fatigue Atrial pace on PVE detection

PVC

A

881

LV

Detection P tracking at upper rate limit P tracking at intermediate rate Atrioventricular (A-V) interval modulation Discrepancy between sensed atrial rate and sensor-indicated rate Termination PVARP extension Withhold of ventricular output Withhold of ventricular output with early atrial pace Atrial pace during ELT AV, Atrioventricular; PVARP, postventricular atrial blanking period; PVE, premature ventricular event.

PVARP AVI

C

D

Figure 29-48  Classic initiation of endless-loop tachycardia by PVC in patient with retrograde AV conduction. A, Premature ventricular contraction (PVC) occurs. B, The event is conducted retrograde to the atrium, as seen by the inverted (retrograde) P wave (RP). C, The retrograde event is sensed by the atrial channel, which causes an atrioventricular (A-V) interval (AVI) to be started. D, At the end of the AVI, a stimulus is delivered to the ventricle (if the maximum rate limit is not violated), resulting in retrograde conduction and the perpetuation of this cycle. AVN, Atrioventricular node; LA, left atrium; LV, left ventricle; PVARP, postventricular atrial refractory period; RA, right atrium; RV, right ventricle.

ventricular-paced event in a retrograde direction, thus initiating another ELT (Fig. 29-49). The absence of anterograde AV nodal conduction does not rule out retrograde conduction over the AV node or a concealed AV accessory pathway. Patients may also exhibit intermittent retrograde conduction or have variations in the retrograde conduction time based on their sympathetic tone and catecholamine status.246-255 The rate of ELT depends on the conduction velocity and refractory period of the retrograde AV pathway. If the retrograde AV conduction is the same as or shorter than the upper rate interval (but not shorter than the PVARP), the tachycardia rate is at the programmed upper rate. If the retrograde AV conduction time is slower than the upper rate interval, the tachycardia rate is below the upper programmed rate (Fig. 29-50). Therefore, although the rate of the ELT can never exceed the programmed upper rate of the pacemaker, it may be lower.254,256 When the rate is lower than the MTR, the rhythm has been termed a balanced ELT. Prevention.  The main defense against ELT is the use of an appropriate PVARP interval. During the PVARP, the atrial channel cannot

Atrial Non-capture

A

Atrial Oversense

B

Atrial Undersense

C

Long AVI

D Figure 29-49  Initiating events leading to retrograde P-wave conduction and potential for endless-loop tachycardia. A, Atrial noncapture causes ventricular stimulation without the atrioventricular (AV) node being blocked by an anterograde event. B, Atrial oversensing inhibits atrial output and provides just a ventricular output, with the same results as in A. C, Atrial undersensing results in a long A-V interval, allowing the AV node time to recover and conduct retrograde. D, A long programmed A-V interval may also allow the AV node to recover.

882

SECTION 4  Follow-up and Programming

A V

V

P

V

P

V

P

B Figure 29-50  Endless-loop tachycardia (ELT). A, Electrocardiogram (ECG) rhythm strip of ELT with fast ventriculoatrial (VA) conduction, which resulted in a rapid ELT at the upper programmed rate of 155 beats per minute (bpm). The lower rate was 60 pulses per minute (ppm); the sensed atrioventricular (A-V) interval, 150 msec; the postventricular atrial refractory period (PVARP), 275 msec; and the VA time, 300 msec. B, ECG rhythm strip of ELT with slow VA conduction, which resulted in ELT below the upper programmed rate. Because of the slow retrograde conduction, the ELT rate is significantly slower than the programmed upper rate. The lower rate was 60 bpm; the upper rate, 145 bpm; the AV interval, 165 msec; and the PVARP, 250 msec. P, Retrograde P wave; V, ventricular output.

respond to the retrograde depolarization that would initiate the ELT. This is independent of the source of that atrial event. If retrograde conduction is present during implantation or follow-up, it is a simple matter to measure the VA time and program the PVARP to an interval that is longer.250 Many patients, however, exhibit only intermittent VA

conduction, making an accurate assessment difficult. The major limitation of using a long PVARP is that it limits the upper tracking rate of the device (2 : 1 blocking rate). Some patients in our clinics have VA times in excess of 430 msec. If a PVARP of 450 msec and an A-V interval of 150 msec are used, the total atrial refractory period (TARP) is 600 msec. This causes 2 : 1 blocking at an atrial rate of 100 bpm, which is much too low for most patients. One solution to this problem is the use of ELT prevention algorithms.257,258 The most common algorithm is PVARP extension on PVE detection. A premature ventricular event is defined as a ventricular sensed event that is not preceded by an atrial paced or atrial sensed event. When a PVE is detected, the device prolongs PVARP by a fixed or programmable value for the next cycle. It allows a shorter baseline PVARP to be used, with associated higher 2 : 1 blocking rates. A variation on this technique is to initiate one DVI cycle after the PVE. This is the ultimate PVARP extension, because the atrial channel remains refractory to sensing throughout the entire AEI. A problem with most of the PVARP extension algorithms is that functional atrial noncapture may occur. Because there was an atrial output, the system returns to the shorter PVARP, thus allowing for retrograde conduction to be sensed after the AV paced cycle, simply postponing the ELT for one cycle. In the latter case, the pacemaker does not maintain the long PVARP because it has delivered an atrial stimulus (although ineffective) before a ventricular event. The subsequent ventricular paced event then leads to ELT (Fig. 29-51). A refinement to the standard PVARP extension algorithm is to extend the atrial alert interval at the end of the extended PVARP.246 On release of the atrial output at the end of the longer AEI, the atrial myocardium will have recovered, allowing for capture, thus precluding retrograde conduction on the next ventricular cycle. Newer approaches have been made possible by the advent of sensordriven pacing systems. With a DDDR system, even though the MTR may be limited by a long PVARP, faster AV sequentially paced rates may be possible through the sensor. Even though atrial sensing does not occur during the PVARP, sensor-driven atrial pacing may occur. Another alternative in some DDDR pulse generators is to use an adaptive PVARP that is long when the sensor determines that the patient is at rest. When the patient’s sensor-indicated rate increases along with the need for higher heart rates, the PVARP is shortened proportionately, allowing higher rates before a 2 : 1 block upper rate behavior occurs. This approach allows the device to discriminate between early

MAGNET FEB 12 1986

DEMAND FEB 12 1986 TRANSTELEPHONIC EVALUATION

J.M. 283-01-03155

Figure 29-51  Dual-chamber pulse generator programmed with PVARP extension on premature ventricular event detection. Top tracing shows behavior of pacemaker with magnet application. The atrioventricular (AV) delay is programmed to a long value to allow functional singlechamber atrial pacing. Bottom tracing shows demand mode. A ventricular premature complex/contraction (PVC) occurred (arrow), causing postventricular atrial refractory period (PVARP) extension. The retrograde P wave coincided with the extended PVARP and, appropriately, was not sensed and not tracked. When the atrial output was delivered at the end of the atrial escape interval, it was ineffective (functional noncapture), because the native atrial depolarization had rendered the atrial myocardium physiologically refractory. The delivery of the atrial output caused the pacemaker to shorten the PVARP with the next ventricular paced event, by which time atrial refractoriness had resolved; retrograde conduction followed the paced ventricular complex and initiated an endless-loop tachycardia (ELT). Thus, the PVARP extension simply postponed the initiation of the ELT rather than preventing it. Data from Cosmos Model 283-01 (Sulzer Intermedics, Angleton, Texas, now Boston Scientific). (From Levine PA, Selznick L: Prospective management of the patient with retrograde ventriculoatrial conduction: prevention and management of pacemaker mediated endless loop tachycardias, Sylmar, Calif, 1990, Pacesetter Systems.)



atrial depolarizations at rest (possibly retrograde beats or PACs) and sinus tachycardia with exertion.259-261 Even in the absence of rate modulation, rate-responsive AV delay algorithms allow a shorter TARP and therefore a higher MTR, even with a fixed, long PVARP. A comparison of P-wave morphology can allow discrimination between sinus and retrograde atrial depolarizations in some cases; this is referred to as differential atrial sensing.262-266 Mapping of the atrium may allow positioning of the lead at a site that has a large P wave when generated by the sinus node and retrograde P waves that appear small in comparison. The pacemaker sensitivity may be programmed to allow sensing of the anterograde P wave but not the retrograde P wave. Therefore, ELT cannot be initiated or sustained because the loop cannot be completed. Although the retrograde P wave is usually of lower amplitude than the anterograde P wave, this is not always the case; the individual situation needs to be evaluated before any attempt to use atrial sensitivity as a discriminating factor. In addition, the atrial EGM may decrease in amplitude as the sinus rate increases under physiologic stress. Programming a reduced atrial sensitivity to facilitate discrimination between anterograde and retrograde P waves could compromise sensing of rapid intrinsic atrial rhythms.246 Another preventive mechanism has been to program a high MTR, in the hope of inducing retrograde fatigue and spontaneous termination of any ELT that is allowed to start. Careful assessment of the patient’s ability to conduct retrograde should be performed, however, because some patients have superior retrograde conduction (compared with anterograde conduction) and are able to sustain extremely rapid ELTs.246 Detection and Termination.  The most difficult aspect of applying an ELT termination protocol is having the device determine whether ELT is present as opposed to a native atrial tachycardia that is being appropriately tracked. This has been approached differently by different manufacturers. Some criteria used are simple and others more complex. The following are some of the most common techniques for identifying the presence of ELT. The first criterion is sustained P-wave tracking at the upper rate. This is the most common method of ELT detection. If the pacemaker tracks the P waves at the upper rate for a specific number of intervals, then the PVARP is prolonged for one cycle, DVI is used for one cycle, or the ventricular output is withheld. The number of events at the upper rate that trigger an ELT termination attempt depends on the particular pulse generator. Some algorithms use a fixed number of beats; in other systems, this is a programmable option. The method of ELT termination may also be programmable (PVARP extension, DVI cycle, or atrial pace).267,268 The second method used to identify ELT is sustained P-wave tracking at a specific rate that is lower than the upper rate. As previously noted, not all ELTs occur at the upper programmed tracking rate. An ELT rate is always limited by the slowest point in the loop. If the patient has a VA conduction time that is longer than the upper tracking interval, the resulting ELT is slower than the programmed upper tracking rate. This manifestation of ELT is not identified by the sustained upper rate method. Some devices allow initiation of the ELT termination algorithm at a P-wave tracking rate that is lower than the upper tracking rate. This lower rate is typically a programmable option, to provide for termination of ELT in this subset of patients. The third approach to identifying ELT is modulation of the A-V interval during sustained P-wave tracking at or above a specific rate. The technique is based on the observation that the VA conduction time in an individual patient is relatively constant. When the device is P-wave tracking at a high rate, the system first assesses the stability of the retrograde interval. The A-V interval is then either shortened or lengthened, and the effect on the subsequent retrograde interval is assessed. If an ELT is present and the V-pace to P-sense interval remains constant (i.e., atrial cycle length is shortened by shortening of A-V interval), the device confirms ELT and initiates a termination algorithm (Fig. 29-52), either by withholding the ventricular output or by delivering an atrial output after a period sufficient to allow for atrial recovery.260,261 However, if the V-pace to A-sense interval changes by

29  Pacemaker Troubleshooting and Follow-up (V → P)1

AVI

883

(V → P)2

AVI Modified

AVI

A (V → P)1

AVI

(V → P)2

AVI

AVI Modified

B Figure 29-52  Diagram of endless-loop tachycardia (ELT) detection scheme. A, Rapid tracking of sinus tachycardia. The device causes the atrioventricular interval (AVI) to be varied. When the interval is shortened (AVI modified), there is a prolongation of the V-P interval (V-P2 is longer than V-P1) because the sinus node rate is not affected. B, ELT caused by tracking of retrograde P waves. The device again causes the AVI to be varied. In this case, shortening of the AVI has no effect on  the next retrograde event (V-P2 is the same as V-P1). This is defined by the device as ELT, and a termination algorithm is activated. System is used by ELA Medical (Sorin Group, Milan).

more than a preset amount (i.e., atrial cycle length is unaffected by A-V interval shortening), ELT is not confirmed, and the device continues to track the atrium normally. CROSS-STIMULATION Cross-stimulation can be defined as stimulation of one cardiac chamber when stimulation of the other is expected (Fig. 29-53). An embarrassing cause of this phenomenon is inadvertent placement of the ventricular lead into the atrial connector and the atrial lead into the ventricular connector of the pulse generator. Dislodgment of either lead into the other chamber may also be a cause. Coronary sinus A

V

A

V

A

V

Figure 29-53  ECG rhythm strip of cross-stimulation from lead reversal caused by misconnection at implantation. Although the leads were properly situated in the heart, the atrial lead was placed into the ventricular connector, and the ventricular lead was placed into  the atrial connector. Note that the first output delivered stimulated the ventricle, and the second fell into the ST segment when it was delivered into the atrium at the end of the atrioventricular interval, because it was delivered through the atrial lead.

884

SECTION 4  Follow-up and Programming

placement of either lead, either intentionally or accidentally, can cause continued or intermittent cross-stimulation. For all of these situations, surgical revision of the pacing system is the only option for correction. There have been several reports of cross-stimulation not related to these situations.269-272 Internal crossover within the pulse generator circuitry may be the cause. This can be seen in dual-chamber unipolar systems with the leads connected but before placement in the pocket, as the current crosses from one electrode to the other and then back to the pulse generator through the other lead. In this case, because the atrial output is first, atrial capture is obscured by ventricular capture. Because the impedance in this system is high, it requires a high output with a very low capture threshold. After the pulse generator is implanted, this phenomenon ceases. (There is also a system that has internal energy crossover when a magnet is applied to the pacemaker. Here, too, the amount of energy crossover is minimal, and capture can be demonstrated only when the capture threshold is very low. In all cases, crossover resolved after several weeks, as lead maturation resulted in a rise in the capture threshold.) REPETITIVE NON-REENTRANT VENTRICULOATRIAL SYNCHRONOUS RHYTHM The repetitive non-reentrant VA synchronous rhythm is becoming increasingly common with the growth of the DDDR and DDIR modes. It represents a classic example of an adverse interaction between a normally functioning dual-chamber pacemaker and a patient. A prerequisite for this rhythm is intact retrograde conduction. Further, the pacemaker must be programmed with a PVARP that is sufficiently long so that retrograde conduction does not induce ELT. The second prerequisite is a sufficiently high base rate such that there is a relatively short atrial escape interval and an even shorter interval from the retrograde atrial depolarization that renders the atrial tissue physiologically refractory. The retrograde P wave is not sensed because it coincides with the PVARP. This represents functional undersensing. Because of the relatively high rate and the failure to reset the atrial timing cycle (because the retrograde P wave is not sensed), an atrial output is delivered when the atrial myocardium is physiologically refractory. This results in functional atrial noncapture. Thus, after the ineffective atrial output, the A-V interval times out, and a ventricular paced event occurs, by which time the AV node and atrial myocardium have fully recovered, allowing retrograde conduction. The result is an AV paced rhythm with repeated functional atrial noncapture and functional atrial undersensing, all caused by a coincidence of various key timing intervals. This rhythm is called either repetitive non-reentrant VA synchrony or AV desynchronization arrhythmia.273-275 The effect on the patient is the same as that of ventricular pacing with retrograde conduction but in a DDDR/DDIR pacing system. This can lead to symptoms of palpitations, dyspnea, and even syncope. Effectively, the resultant rhythm is a classic rhythm associated with pacemaker syndrome, but unless one recognizes the problem, either normal pacemaker function is diagnosed and the symptoms are unexplained, or the disorder is labeled atrial noncapture and inappropriate efforts are directed toward correcting this “malfunction.” Management requires allowing sufficient time for the atrial tissue to recover. This means either providing a short AV delay at the higher rates, using a lower base rate, or limiting of the specific rates. When AV nodal conduction is intact, the clinician may consider singlechamber AAIR pacing, which would totally avoid this rhythm. If the rhythm is repeatedly triggered by a PVC with retrograde conduction, use of a PVARP extension algorithm that also slows the escape rate, allowing time for the atrium to physiologically recover, is indicated. It is absolutely essential that the clinician fully understand the interaction between the timing circuits in the pacemaker and those in the heart. The author knows of a patient who was taken back to the operating room for an atrial lead repositioning on two additional occasions after the initial implantation because of this rhythm and the

implanting physician’s failure to understand the adverse interaction between the various programmed parameters and the patient’s intrinsic rhythms. This was not a lead dislodgment or malposition, although the latter was the working diagnosis. The problem could not be solved by repositioning of the lead, yet that was the diagnosis by the referring physicians because of repeated failure to capture on the atrial channel at the highest outputs that the pacemaker would allow. When evaluated by a knowledgeable physician, this rhythm was suspected because the referring physician described losing atrial capture at 0.5 V and then not being able to regain it at 7.5 V when the base rate was 90 pulses per minute (ppm), but having absolutely no problems with capture when the base rate was 60 ppm. The referring physician sought advice about where the lead could be positioned (on a fourth operative procedure) to prevent repeated loss of atrial capture. Rather than reoperate, it was advised to leave the rate low and disable the rate modulation. The patient was then sent for a detailed evaluation, at which time it was easy to induce and demonstrate this phenomenon with the aid of the telemetered atrial EGM and event markers (Fig. 29-54). Management was more of a challenge, in that the maximum sensor rate had to be limited to preclude atrial pacing at a high rate, which meant that there would be a relatively short atrial escape interval. This patient’s adverse rhythm was triggered by early atrial premature beats.

A 274

A V 476 750

274

A V 476 750

274

A V 476 745

269

A V 476 750

274

A V 476 750

274

A V 476 749

273

V

Figure 29-54  Functional atrial noncapture induced during atrial capture threshold test persists when output returned to previously effective programmed level. This is an example of repetitive nonreentrant ventriculoatrial (VA) synchronous rhythm. The retrograde P wave seen as a negative deflection in the ST segment of the paced QRS complex (long arrow), as shown on the surface electrocardiogram (top) and the rapid deflection on the atrial electrogram (bottom), coincides with the atrial refractory period, as identified by the event markers. This is consistent with the programmed settings of the pacemaker. Therefore, the failure to sense this P wave is normal, allowing delivery of an atrial output pulse (functional undersensing). The atrial output pulse occurs at a time when the atrial myocardium is still physiologically refractory from the native atrial depolarization; thus there is failure to capture, but on a functional basis, not as a sign of a malfunction. By the time the ventricular output is delivered, the atrium has recovered, allowing retrograde conduction to occur again. This rhythm persists until the base rate slows or is reduced, allowing the atrium physiologically to recover so that the atrial output effectively captures the atrium.



FOLLOW-UP RECOMMENDATIONS Follow-up of pacing systems has evolved with their increased complexity. The newest devices are able to report automatically determined capture and sensing thresholds. Although these are quite accurate, they are not always reliable. Some capture management algorithms can be foiled by high polarization leads, or frequent fusion beats caused by AF, or programmed A-V intervals that allow fusion and pseudofusion. Review of the graph showing the capture thresholds over time will show intermittent high thresholds or many aborted searches (see Fig. 29-24). If this is seen, reprogramming of the AV interval to avoid fusion or turning off the algorithm may be necessary to avoid sustained highoutput pacing. If a device is not capable of automatically reporting capture and sensing thresholds, these must be done manually, using the features of the programmer. Capture and sensing thresholds should be determined for each lead implanted. Programming of appropriate safety margins is then performed. After these basic but critical determinations have been made, additional data from the device are evaluated to determine whether arrhythmias have been present (i.e., atrial high rate, ventricular high rate, mode switching). Retrieval of any supporting information, such as EGMs associated with these events, is advised to verify that the counters correctly classified the event and that the event was not caused by oversensing or other extraneous signals, as described earlier in this chapter. It is also important to evaluate the sensor indicated rate histogram to determine whether the rate modulation sensor is performing appropriately. A flat response may indicate a sensor programmed to an insensitive setting, or it may reflect an inactive patient. It is therefore important to correlate the sensor findings to the patient’s condition, then adjust the device accordingly. Evaluation of the percentage of ventricular pacing should be a regular part of the evaluation. Recent studies have shown that unnecessary pacing of the right ventricle can lead to a higher incidence of AF, heart failure, and mortality. Use of longer A-V intervals as well as modes that do not track the atrium (e.g., DDI) can help to minimize ventricular pacing. Special modes allow extremely long A-V intervals or even intermittent, nonconducted P waves to occur (e.g., Medtronic MVP, St. Jude VIP). These modes should not be reserved for patients with intact AV conduction and should be avoided in patients with high-grade AV block. It is also important to recognize that there is a balance in any individual patient between the detrimental effect of right ventricular pacing and a properly timed A-V interval to optimize atrial preload of the ventricles. Very long A-V intervals may prevent ventricular pacing but may sacrifice optimal end-diastolic preload by the atria. The frequency of follow-up visits to the device clinic should be based on the needs of the individual patient and not on how frequently an insurance carrier will pay for these visits. A common standard of practice is to evaluate the patient in the office setting 1 month after implantation, 6 and 12 months after implantation, and then annually thereafter. Additional visits may be necessary if the patient has symptoms or complaints related to the heart rhythm or the implantation site. Transtelephonic monitoring (TTM) was virtually unchanged for the past 40 years until the recent introduction of home interrogation devices capable of retrieving the same information as the programmer. Classic TTM involves the use of a device that can transmit a rhythm strip over any standard telephone to a receiving station. The receiving station converts the tones sent by the TTM transmitter to an ECG tracing. Using this simple technique, a baseline heart rhythm, magnet strip, and final heart rhythm strip can be recorded. This provides a very basic check of the heart rhythm, whether the device is able to pace, and the condition of the battery as can be determined by the magnet rate. However, because of the limited fidelity of the recording and the single lead that is transmitted, it can be difficult to determine atrial capture and sensing, or even the atrial rhythm. Although many centers do TTM transmission monthly, it has been recommended that a TTM once every 3 months (skipping any time when a clinic visit is due) is adequate until the device begins to show significant wear. At that time,

29  Pacemaker Troubleshooting and Follow-up

885

TTMs can be increased to monthly, to determine when the elective replacement indicator has been tripped. In addition, a patient with a pacemaker or lead system that is on alert may warrant more frequent monitoring. Lastly, should a patient have a symptomatic event such as palpitations or lightheadedness, a TTM may be done to evaluate the heart rhythm and pacing function. Manufacturers of pacing systems have now introduced interrogation devices that can be placed in the patient’s home for remote monitoring. These are capable of retrieving all the programmed settings, telemetry and diagnostic data, and even stored EGMs. These data are then transmitted over a telephone line, cell phone, or Internet connection to a receiving center. Devices require the patient or caregiver to place a wand over the device and initiate the interrogation, or wandless “long range” communication interrogation may occur automatically or on demand. New devices with long-range telemetry can interrogate the pacemaker from a distance of 20 feet (6 m) or more. These systems can be set to download data automatically on a regular basis and send it to the receiving center. Patients can also send data by pressing a button if they suspect a problem with the device or their heart rhythm. Devices can also automatically initiate a transmission if the device has detected an arrhythmia or an out-of-range diagnostic value such as battery depletion or high lead impedance. The receiving center prepares a report that is faxed or e-mailed to the clinician. Alternatively (or in combination), the report may be viewed through a Web portal from any standard Internet browser. By having access to this detailed information, the pacemaker follow-up center can make much more informed decisions about the nature of a patient’s complaints, the status of the pacing system, and the actual rhythms present at that time. Currently, remote programming is not an option. Therefore, should a patient need an adjustment to the device, a trip to the pacemaker center is still necessary. The frequency of monitoring with these more extensive systems is still evolving. Follow-up may occur routinely at weekly to quarterly intervals. In addition, pacemakers continue to expand their selfdiagnostic capabilities and are able to self-determine atrial and ventricular capture and sensing thresholds. They are also able to adjust their sensitivity and output settings automatically. Therefore, the patient may not need to come to the pacemaker center except to reprogram certain parameters or to perform more advanced diagnostic testing.

Conclusion Pacing system malfunction, although seemingly difficult to assess, can be categorized in relation to the dysfunction of the leads or the generator and apparent dysfunction related to the idiosyncratic characteristics of the pacemaker’s timing algorithms. In contrast to the relative frequency of lead failure as a result of implantation error or deterioration of the lead materials, primary malfunction of the pulse generator is rare. Patient-specific problems or inappropriate program settings are relatively common. Consequently, the keys to understanding unexpected pacemaker behavior are meticulous evaluation of the integrity of the leads, assessment of capture and sensing thresholds, and an understanding of the timing cycles of the specific pacemaker, which is facilitated by access to event marker telemetry. Clues to the problem and its cause are found in the patient’s history, physical examination, and the various diagnostic tests integral to the pacemaker that are retrieved through bidirectional telemetry. With respect to the hardware, the answer is usually lead dysfunction or a behavioral eccentricity detailed in the pacemaker’s technical manual. The clinician must always keep the patient’s physiology and pathophysiology in mind, because these also affect the function of the pacing system. Furthermore, even if all components of the system are normal, the pacemaker may be programmed to a set of parameters that are no longer optimal for the patient. When the clinician is presented with a suspected pacing system malfunction, it is essential to proceed in a meticulous and orderly manner, carefully assessing each component of the system, including the pulse generator, the programmed settings, any unique algorithms,

886

SECTION 4  Follow-up and Programming

the leads, and the patient. If a complete assessment of capture and sensing thresholds, lead impedance, sensor response, and the behavior of any unique algorithms is performed periodically as part of the routine surveillance of the patient’s pacing system, baseline data will be available for comparison with the results of evaluation when and if a problem is suspected.

Acknowledgment The author would like to acknowledge the previous contribution to this work by Dr. Paul A. Levine, who due to time constraints was not able to participate in the preparation of the current revision of this chapter. His significant work in the past, as well as his friendship and mentoring, remain part of the foundation of the material presented in this chapter.

REFERENCES 1. Furman S: Pacemaker programmability. Pacing Clin Electrophysiol 1:161, 1978. 2. Furman S, Escher DJW, Fisher JD: Seven-year experience with programmable pulse generators. In Meere C, editor: Cardiac pacing, Montreal, 1979, Pacesymp. 3. Levine PA: Why programmability? Indications for and clinical utility of multiparameter programmability, Sylmar, Calif, 1981, Pacesetter Systems. 4. Gold RD, Saulson SH, MacGregor DC: Programmable pacing systems: the medium and the message. Pacing Clin Electrophysiol 5:777, 1982. 5. Sholder J, Levine PA, Mann BM, Mace RC: Bidirectional telemetry and interrogation in cardiac pacing. In Barold SS, Mugica J, editors: The third decade of cardiac pacing: advances in technology and clinical applications, Mt Kisco, NY, 1982, Futura, pp 145-166. 6. Levine PA, editor: Proceedings of the Policy Conference of the North American Society of Pacing and Electrophysiology on Programmability and Pacemaker Follow-up Programs. Clin Prog Pacing Electrophysiol 2:145, 1984. 7. Del Marco CJ, Tyers GFO, Brownlee RR: Lithium pacers with self-contained multiparameter telemetry: First year followup. In Meere C, editor: Cardiac pacing, Montreal, 1979, Pacesymp. 8. Tanaka S, Nanba T, Harada A, et al: Clinical experience with telemetry pacing systems and long-term followup: clinical aspects of lead impedance and battery life. Pacing Clin Electrophysiol 6:A30, 1983. 9. Castellanet MJ, Garza J, Shaner SP, Messenger JC: Telemetry of programmed and measured data in pacing system evaluation and followup. J Electrophysiol 1:360, 1987. 10. Marco D: Pacemaker output settings for lowest current drain and maximum longevity. Reblampa 8:159-162, 1995. 11. Crossley GH, Gayle D, Simmons TW, et al: Reprogramming pacemakers enhances longevity and is cost-effective. Circulation 94(suppl II):245-247, 1996. 12. Freedman RA, Marks ML, Chapman P, King C: Telemetered pacemaker battery voltage preceding generator elective replacement time: use to guide utilization of magnet checks [abstract]. Pacing Clin Electrophysiol 18:863, 1995. 13. Ben-Zur UM, Platt SB, Gross JN, et al: Direct and telemetered lead impedance. Pacing Clin Electrophysiol 17:2004-2007, 1994. 14. Danilovic D, Ohm OJ: Pacing impedance variability in tined steroid eluting leads. Pacing Clin Electrophysiol 21:1356-1363, 1998. 15. Levine PA: Clinical manifestations of lead insulation defects. J Electrophysiol 1:144, 1987. 16. Clarke M, Allen A: Early detection of lead insulation breakdown. Pacing Clin Electrophysiol 8:775, 1985. 17. Winoker P, Falkenberg E, Gerard G: Lead resistance telemetry: insulation failure prognosticator. Pacing Clin Electrophysiol 8:A85, 1985. 18. Phlippin F, O’Hara GE, Gilbert M: Lead impedance measured bipolar vs unipolar: a method to identify lead insulation failure [abstract]. Pacing Clin Electrophysiol 18:817, 1995. 19. Pickell D, Siegler K, Brewer L, et al: Suspect polyurethane insulated bipolar pacing leads: clinical management [abstract]. Pacing Clin Electrophysiol 18:866, 1995. 20. Schmidinger H, Mayer H, Kaliman J, et al: Early detection of lead complications by telemetric measurement of lead impedance. Pacing Clin Electrophysiol 8:A23, 1985. 21. Mauser JF, Huang SKS, Risser T, et al: A unique pulse generator safety feature for bipolar lead fracture. Pacing Clin Electrophysiol 16:1368-1372, 1993. 22. Kruse I, Markowitz T, Ryden L: Timing markers showing pacemaker behavior to aid in the follow-up of a physiologic pacemaker. Pacing Clin Electrophysiol 6:801, 1983. 23. Olson W, McConnell M, Sah R, et al: Pacemaker diagnostic diagrams. Pacing Clin Electrophysiol 8:691, 1985. 24. Levine PA, Schuller H, Lindgren A: Pacemaker ECG: utilization of pulse generator telemetry, Solna, Sweden, 1988, Siemens Elema AB. 25. Furman S: The ECG interpretation channel [editorial]. Pacing Clin Electrophysiol 13:225, 1990. 26. Olson WH, Goldreyer BA, Goldreyer BN: Computer-generated diagnostic diagrams for pacemaker rhythm analysis and pacing system evaluation. J Electrocardiol 1:376, 1987. 27. Levine PA: Pacemaker diagnostic diagrams [letter]. Pacing Clin Electrophysiol 9:250, 1986. 28. Machado C, Johnson D, Thacker JR, Duncan JL: Pacemaker patient-triggered event recordings: Accuracy, utility and cost for the pacemaker follow-up clinic. Pacing Clin Electrophysiol 19:1813-1818, 1996.

29. Furman S, Hurzeler P, DeCaprio V: Cardiac pacing and pacemakers. III. Sensing the cardiac electrogram. Am Heart J 93:794, 1977. 30. Levine PA, Klein MD: Discrepant electrocardiographic and pulse analyzer endocardial potentials: a possible source of pacemaker sensing failure. In Meere C, editor: Cardiac pacing, Montreal, 1979, Pacesymp. 31. Levine PA, Podrid PJ, Klein MD, et al: Pacemaker sensing: comparison of signal amplitudes determined by electrogram telemetry and noninvasively measured sensing thresholds [abstract]. Pacing Clin Electrophysiol 12:1294, 1989. 32. Levine PA, Sholder J, Duncan JL: Clinical benefits of telemetered electrograms in the assessment of DDD function. Pacing Clin Electrophysiol 7:1170, 1984. 33. Clarke M, Allen A: Use of telemetered electrograms in the assessment of normal pacemaker function. J Electrophysiol 1:388, 1987. 34. Edery T: Clinical applications of pacemaker-telemetered intracardiac electrograms. Technical concept paper, Minneapolis, 1991, Medtronic. 35. Hughes HC, Furman S, Brownlee RR, Del Marco C: Simultaneous atrial and ventricular electrogram transmission via a specialized single-lead system. Pacing Clin Electrophysiol 7:1195, 1984. 36. Feuer J, Florio J, Shandling AH: Alternate methods for the determination of atrial capture thresholds utilizing the telemetered intracardiac electrogram. Pacing Clin Electrophysiol 13:1254, 1990. 37. Sarmiento JJ: Clinical utility of telemetered intracardiac electrograms in diagnosing a design dependent lead malfunction. Pacing Clin Electrophysiol 13:188, 1990. 38. Marco DD, Gallagher D: Noninvasive measurements of retrograde conduction times in pacemaker patients. J Electrophysiol 1:388, 1987. 39. Nalos PC, Nyitray W: Benefits of intracardiac electrograms and programmable sensing polarity in preventing pacemaker inhibition due to spurious screw-in lead signals. Pacing Clin Electrophysiol 13:1101, 1990. 40. Halperin JL, Camunas JL, Stern EH, et al: Myopotential interference with DDD pacemakers: Endocardial electrographic telemetry in the diagnosis of pacemaker-related arrhythmias. Am J Cardiol 54:97, 1984. 41. Gladstone PJ, Duxbury GB, Berman ND: Arrhythmia diagnosis by electrogram telemetry: involvement of dual-chamber pacemaker. Chest 91:115, 1987. 42. Hassett JA, Elrod PA, Arciniegas JG, et al: Noninvasive diagnosis and treatment of atrial flutter utilizing previously implanted dual-chamber pacemaker. Pacing Clin Electrophysiol 11:1662, 1988. 43. Luceri RM, Castellanos A, Thurer RJ: Telemetry of intracardiac electrograms: applications in spontaneous and induced arrhythmias. J Electrophysiol 1:417, 1987. 44. Levine PA: The complementary role of electrogram, event marker, and measured data telemetry in the assessment of pacing system function. J Electrophysiol 1:404, 1987. 45. Pirolo JS, Tweddel JS, Brunt EM, et al: Influence of activation origin, lead number, and lead configuration on the noninvasive electrophysiologic detection of cardiac allograft rejection. Circulation 84(suppl III):344, 1991. 46. Berbari EJ, Lander P, Geselowitz DB, et al: Correlating late potentials from the body surface with epicardial electrograms. Eur J Card Pacing Electrophysiol 2:A156, 1992. 47. Barold SS, Bornzin G, Levine P: Development of a true pacemaker Holter. In Vardas PE, editor: Cardiac arrhythmias, pacing and electrophysiology: the expert view, Dordrecht, The Netherlands, 1998, Kluwer Academic, pp 421-426. 48. Sermasi S, Marconi M: Temporary RAM programming of pacemaker capabilities. In Santini M, editor: Progress in clinical pacing 1996, Armonk, NY, 1997, Futura, pp 85-91. 49. Sanders R, Martin R, Frumin H, et al: Data storage and retrieval by implantable pacemakers for diagnostic purposes. Pacing Clin Electrophysiol 7:1228, 1984. 50. Levine PA, Lindenberg BS: Diagnostic data: an aid to the follow-up and assessment of the pacing system. J Electrocardiol 1:396, 1987. 51. Levine PA: Utility and clinical benefits of extensive event counter telemetry in the follow-up and management of the rate-modulated pacemaker patient, Sylmar, Calif, 1992, Siemens-Pacesetter. 52. Newman D, Dorian P, Downar E, et al: Use of telemetry functions in the assessment of implanted antitachycardia device efficiency. Am J Cardiol 70:616, 1992. 53. Wang PJ, Manolis A, Clyne C, et al: Accuracy of classification using a data log system in implantable cardioverter defibrillators. Pacing Clin Electrophysiol 14:1911, 1991. 54. Luceri RM, Puchferran RL, Brownstein SL, et al: Improved patient surveillance and data acquisition with a third-generation

implantable cardioverter defibrillator. Pacing Clin Electrophysiol 14:1870, 1991. 55. Stangl K, Sichart U, Wirtsfeld A, et al: Holter functions for the enhancement of the diagnostic and therapeutic capabilities of implantable pacemakers [Vitatext], Dieren, The Netherlands, 1987, Vitatron Medical, pp 1-6. 56. Lascault GR, Frank R, Fontaine G, et al: Ventricular tachycardia using the Holter function of a dual-chamber pacemaker [abstract]. Pacing Clin Electrophysiol 16:918, 1993. 57. Lascault GR, Frank R, Barnay C, et al: Clinical usefulness of a “diagnostic” dual-chamber pacemaker [abstract]. Pacing Clin Electrophysiol 16:918, 1993. 58. Hayes DL, Higano ST, Eisinger G: Utility of rate histograms in programming and follow-up of a DDDR pacemaker. Mayo Clin Proc 64:495, 1989. 59. Levine PA, Sholder JA, Florio J: Obtaining maximal benefit from a DDDR pacing system: a reliable yet simple method for programming the sensor parameters of Synchrony, Sylmar, Calif, 1990, Siemens-Pacesetter.60. Levine PA: Holter and pacemaker diagnostics. In Aubert AE, Ector H, Stroobandt R, editors: Cardiac pacing and electrophysiology: a bridge to the 21st century, Dordrecht, The Netherlands, 1994, Kluwer Academic, pp 309-324. 61. Novak M, Smola M, Kejrova E: Pacemaker built-in Holter counters match up to ambulatory Holter recordings. In Sethi KK, editor: Proceedings of the Sixth Asian-Pacific Symposium on Cardiac Pacing and Electrophysiology, Bologna, Italy, 1997, Monduzzi, pp 61-64. 62. Limousin M, Geroux L, Nitzsche R, et al: Value of automatic processing and reliability of stored data in an implanted pacemaker: initial results in 59 patients. Pacing Clin Electrophysiol 20:2893-2898, 1997. 63. Relay DDDR pacing system technical manual, Angleton, Texas, 1992, Intermedics. 64. Trilogy DR+ 2364L pulse generator technical manual, Sylmar, Calif, 1996, Pacesetter. 65. Garson A, Jr: Stepwise approach to the unknown pacemaker ECG. Am Heart J 119:924, 1990. 66. Furman S: Cardiac pacing and pacemakers. VI. Analysis of pacemaker malfunction. Am Heart J 94:378, 1977. 67. Mond HG: The cardiac pacemaker: function and malfunction, New York, 1983, Grune & Stratton. 68. Barold SS: Modern cardiac pacing, Mt Kisco, NY, 1983, Futura. 69. Levine PA: Pacing system malfunction. In Ellenbogen KA, editor: Cardiac pacing, Boston, 1992, Blackwell Scientific, pp 309-382. 70. Morse DP, Steiner RM, Parsonnet V: A guide to cardiac pacemakers, Philadelphia, 1983, Davis. 71. Morse DP, Steiner RM, Parsonnet V: A guide to cardiac pacemakers: supplement 1986-1987, Philadelphia, 1986, Davis. 72. Morse DP, Parsonnet V, Gessment LJ, et al: A guide to cardiac pacemaker, defibrillator and related products, Durham, NC, 1991, Droege Computing Services. 73. Van Gelder LM, El Gamal MIH: Myopotential interference inducing pacemaker tachycardia in a DVI programmed pacemaker. Pacing Clin Electrophysiol 7:970, 1984. 74. Lindenberg BS, Hagan CA, Levine PA: Design dependent loss of telemetry: uplink telemetry hold. Pacing Clin Electrophysiol 12:823, 1989. 75. Levine PA, Lindenberg BS: Upper rate limit circuit-induced rate slowing. Pacing Clin Electrophysiol 10:310, 1987. 76. Levine PA, Lindenberg BS, Mace RC: Analysis of AV universal (DDD) pacemaker rhythms. Clin Prog Pacing Electrophysiol 2:54, 1984. 77. Bertuso J, Kapoor A, Schafer J: A case of ventricular undersensing in the DDI mode: cause and correction. Pacing Clin Electrophysiol 9:685, 1986. 78. Erlbacher JA, Stelzer P: Inappropriate ventricular blanking in a DDI pacemaker. Pacing Clin Electrophysiol 9:519, 1986. 79. Ajiki K, Sagara K, Namiki T, et al: A case of a pseudomalfunction of a DDD pacemaker. Pacing Clin Electrophysiol 14:1456, 1991. 80. Meyer JA, Fruehan CT, Delmonico JE: The pacemaker twiddler’s syndrome: a further note. J Thorac Cardiovasc Surg 67:903, 1974. 81. Veltri EP, Mower MM, Reid PR: Twiddler’s syndrome: a new twist. Pacing Clin Electrophysiol 7:1004, 1984. 82. Lal RB, Avery RD: Aggressive pacemaker twiddler’s syndrome: dislodgment of an active fixation ventricular pacing electrode. Chest 97:756, 1990. 83. Roberts JS, Wenger NK: Pacemaker twiddler’s syndrome. Am J Cardiol 63:1013, 1989. 84. Ellis GL: Pacemaker twiddler’s syndrome: a case report. Am J Emerg Med 8:48, 1990. 85. Ekbom K, Nilsson BY, Edhag O: Rhythmic shoulder girdle muscle contractions as a complication in pacemaker treatment. Chest 66:599, 1974.



86. Gelleri D: Retrograde (ventriculoatrial) conduction, premature beats, pseudotricuspid regurgitation, systolic atrial sounds, and pacemaker sounds observed together in two patients with ventricular pacing. Acta Med Hung 48:157, 1991. 87. Flickinger AL, Peller PA, Deran BP, et al: Pacemaker-induced friction rub and apical thrill. Chest 102:323, 1992. 88. Jalin P, Kaul U, Wasir HS: Myopotential inhibition of unipolar demand pacemakers: utility of provocative maneuvers in assessment and management. Int J Cardiol 34:33, 1992. 89. Levine PA, Caplan CH, Klein MD, et al: Myopotential inhibition of unipolar lithium pacemakers. Chest 82:461-465, 1982. 90. Levine PA: Electrocardiography of bipolar single- and dualchamber pacing systems. Herzschrittmacher 8:86-90, 1988. 91. Cherry R, Sactuary C, Kennedy HL: The question of frequency response. Ambulatory Electrocardiol 1:13, 1977. 92. Sheffield LT, Berson AL, Bragg Remschel D, et al: AHA special report: recommendation for standards of instrumentation and practice in the use of ambulatory electrocardiography. Circulation 71:626A, 1985. 93. Lesh MD, Langberg JJ, Griffin JC, et al: Pacemaker generator pseudomalfunction: an artifact of Holter monitoring. Pacing Clin Electrophysiol 14:854-857, 1991. 94. Van Gelder LM, Bracke FA, El Gamal MI: Fusion or confusion on Holter recordings. Pacing Clin Electrophysiol 14:760-763, 1991. 95. Engler RL, Goldberger AL, Bhargava V, Kapelusznik D: Pacemaker spike alternans: an artifact of digital signal processing. Pacing Clin Electrophysiol 5:748-750, 1982. 96. Slack JP: Identification of recording artei fact in a dual chamber (DDD) paced rhythm: clues from the electrocardiogram. Clin Prog Pacing and Electrophysiol 2:384-387, 1984. 97. Schüller H, Faajhraeus T: Pacemaker EKG: a clinical approach, Solna, Sweden, 1980, Siemens Elema. 98. Levine PA, Schüller H, Lindgren A: Pacemaker ECG: an introduction and approach to interpretation, Solna, Sweden, 1986, Siemens-Pacesetter. 99. Wilkoff BL, Firstenberg MS, Moore S, Ching B: Lead impedance velocity as a predictor of pacing lead instability. Pacing Clin Electrophysiol 16:930, 1993. 100. Karis JP, Ravin CE: Counterclockwise exit of cardiac pacemaker leads: sign of pulse-generator flip. Radiology 174:711, 1990. 101. Suzuki Y, Fujimori S, Sakai M, et al: A case of pacemaker lead fracture associated with thoracic outlet syndrome. Pacing Clin Electrophysiol 11:326, 1988. 102. Stokes K, Staffenson D, Lessar J, et al: A possible new complication of subclavian stick: conductor fracture. Pacing Clin Electrophysiol 10:748, 1987. 103. Anonymous: Subclavian puncture procedure may result in lead conductor fracture. Medtronic News Winter 16:27, 1986-87. 104. Magney JE, Flynn DM, Parsons JA, et al: Anatomical mechanisms explaining damage to pacemaker leads, defibrillator leads, and failure of central venous catheters adjacent to the sternoclavicular joint. Pacing Clin Electrophysiol 16:445, 1993. 105. Jacobs DM, Fink AS, Miller RP, et al: Anatomical and morphological evaluation of pacemaker lead compression. Pacing Clin Electrophysiol 16:434, 1993. 106. Arakawa M, Kambara K, Ito HA, et al: Intermittent oversensing due to internal insulation damage of temperature sensing rateresponsive pacemaker lead in subclavian venipuncture method. Pacing Clin Electrophysiol 12:1312, 1989. 107. Antonelli D, Rosenfeld T, Freedberg NA, et al: Insulation lead failure: is it a matter of insulation coating, venous approach or both? Pacing Clin Electrophysiol 21:418-421, 1998. 108. Fyke FE: Simultaneous insulation deterioration associated with side-by-side subclavian placement of two polyurethane leads. Pacing Clin Electrophysiol 11:1571, 1988. 109. Kranz J, Crystal DK, Wagner CL, et al: Thoracic outlet compression syndrome: the first rib. Northwest Med 68:646, 1969. 110. Witte A: Pseudofracture of pacemaker lead due to securing suture: a case report. Pacing Clin Electrophysiol 4:716, 1981. 111. Deering JA, Pederson DN: A case of pacemaker lead fracture associated with weightlifting. Pacing Clin Electrophysiol 15:1354, 1992. 112. Schuger CD, Mittleman R, Habbal B, et al: Ventricular lead transection and atrial lead damage in a young softball player shortly after the insertion of a permanent pacemaker. Pacing Clin Electrophysiol 15:1236, 1992. 113. Papa LA, Abkar KB, Chung EK: Pacemaker hysteresis. Heart Lung 3:982-984, 1974. 114. Bornzin GA, Arambula ER, Florio J, et al: Adjusting heart rate during sleep using activity variance. Pacing Clin Electrophysiol 17:1933-1938, 1994. 115. Gammage MD, Hess M, Markowitz T: Initial experience with a rate drop algorithm in malignant vasovagal syndrome. Eur J Cardiac Pacing Electrophysiol 5:45-48, 1995. 116. Brandt J, Fåahraeus T, Schüller H: Far-field QRS complex sensing via the atrial pacemaker lead. I. Mechanism, consequences, differential diagnosis and countermeasures in AAI and VDD/DDD pacing. Pacing Clin Electrophysiol 11:1432-1438, 1988. 117. Wolpert C, Jung W, Scholl C, et al: Electrical proarrhythmia: induction of inappropriate atrial therapies due to far-field R wave oversensing in a new dual chamber defibrillator. J Cardiovasc Electrophysiol 9:859-863, 1998. 118. Halperin JL, Camunas JL, Stern EH, et al: Myopotential interference with DDD pacemakers: endocardial electrographic telemetry in the diagnosis of pacemaker-related arrhythmias. Am J Cardiol 54:97, 1984.

29  Pacemaker Troubleshooting and Follow-up 119. Williams DO, Thomas DJ: Muscle potentials simulating pacemaker malfunction. Br Heart J 38:1096, 1976. 120. Ohm OJ, Morkrid L, Hammer E: Amplitude-frequency characteristics of myopotentials and endocardial potentials as seen by a pacemaker system. Scand J Thorac Cardiovasc Surg 22(suppl):41-46, 1978. 121. Ohm OJ, Bruland H, Pedersen OM, et al: Interference effect of myopotentials on function of unipolar demand pacemakers. Br Heart J 35:77, 1974. 122. Gabry MD, Behrens M, Andrews C, et al: Comparison of myopotential interference in unipolar-bipolar programmable DDD pacemakers. Pacing Clin Electrophysiol 10:1322, 1987. 123. Gross JN, Platt S, Ritacco R, et al: The clinical relevance of electromyopotential oversensing in current unipolar devices. Pacing Clin Electrophysiol 15:2023, 1992. 124. Volosin KJ, Rudderow R, Waxman HL: VOOR: Nondemand rate-modulated pacing necessitated by myopotential inhibition. Pacing Clin Electrophysiol 12:421, 1989. 125. Dodinot B, Godenir JP, Costa AB: Electronic article surveillance: a possible danger for pacemaker patients. Pacing Clin Electrophysiol 16:46, 1993. 126. Inbar S, Larson J, Burt T, et al: Case report: nuclear magnetic resonance imaging in a patient with a pacemaker. Am J Med Sci 305:174, 1993. 127. Marco D, Eisinger G, Hayes DL: Testing of work environments for electromagnetic interference. Pacing Clin Electrophysiol 15:2016, 1992. 128. Toivonen L, Valjus J, Hongisto M, et al: The influence of elevated 50 Hz electric and magnetic fields on implanted pacemakers: the role of the lead configuration and programming of the sensitivity. Pacing Clin Electrophysiol 14:2114, 1991. 129. Mellenberg DE, Jr: A policy for radiotherapy in patients with implanted pacemakers. Med Dosim 16:221, 1991. 130. Mangar D, Atlas GM, Kane PB: Electrocautery-induced pacemaker malfunction during surgery. Can J Anaesth 38:616, 1991. 131. Teskey RJ, Whelan I, Akyurekli Y, et al: Therapeutic irradiation over a permanent pacemaker. Pacing Clin Electrophysiol 14:143, 1991. 132. Salmi J, Eskola HJ, Pitkanen MA, et al: The influence of electromagnetic interference and ionizing radiation on cardiac pacemakers. Strahlenther Onkol 166:153, 1990. 133. Chin MC, Rosenqvist M, Lee MA, et al: The effect of radiofrequency catheter ablation on permanent pacemakers: an experimental study. Pacing Clin Electrophysiol 13:23, 1990. 134. McDeller AG, Toff WD, Hobbs RA, et al: The development of a system for the evaluation of electromagnetic interference with pacemaker function: hazards in the aircraft environment. J Med Eng Technol 13:161, 1989. 135. Godin JF, Petitot JC: STIMAREC report: pacemaker failures due to electrocautery and external electric shock. Pacing Clin Electrophysiol 12:1011, 1989. 136. Belott P, Sands S, Warren J, et al: Resetting of DDD pacemakers due to EMI. Pacing Clin Electrophysiol 7:169, 1984. 137. Erdman S, Levinsky L, Strasberg B, et al: Use of the new Shaw scalpel in pacemaker operations. J Thorac Cardiovasc Surg 89:304, 1985. 138. Gascho JA, Newton MC: Electromagnetic interference in dynamic electrocardiography caused by an electric blanket. Am Heart J 95:408, 1978. 139. Irnich W: Interference in pacemakers. Pacing Clin Electrophysiol 7:1021, 1984. 140. Kuan P, Kozlowski J, Castellanet MJ, et al: Interference with pacemaker function by cardiographic testing. Am J Cardiol 58:362, 1986. 141. Leeds CJ, Akhtar M, Damato AN, et al: Fluoroscope-generated electromagnetic interference in an external demand pacemaker. Circulation 55:548, 1977. 142. Warnowicz-Papp M: The pacemaker patient and the electromagnetic environment. Clin Prog Pacing Electrophysiol 1:166, 1983. 143. Van Gelder LM, El Gamal MIH: False inhibition of an atrial demand pacemaker caused by insulation defect in a polyurethane lead. Pacing Clin Electrophysiol 6:834, 1983. 144. Sanford CF: Self-inhibition of an AV sequential demand pulse generator due to polyurethane lead insulation disruption. Pacing Clin Electrophysiol 6:840, 1983. 145. Salem DN, Bornstein A, Levine PA, et al: Fracture of pacing electrode mimicking failure of pulse generator. Chest 74:673, 1978. 146. Coumel P, Mujica J, Barold SS: Demand pacemaker arrhythmias caused by intermittent incomplete electrode fracture. Am J Cardiol 36:105, 1975. 147. Barold SS, Scovil J, Ong LS, et al: Periodic pacemaker spike attenuation with preservation of capture: An unusual electrocardiographic manifestation of partial pacing electrode fracture. Pacing Clin Electrophysiol 1:375, 1978. 148. Sarmiento JJ: Clinical utility of telemetered intracardiac electrograms in diagnosing a design dependent lead malfunction. Pacing Clin Electrophysiol 13:188, 1990. 149. Nalos PC, Nyitray W: Benefits of intracardiac electrograms and programmable sensing polarity in preventing pacemaker inhibition due to spurious screw-in lead signals. Pacing Clin Electrophysiol 13:1101, 1990. 150. Chew PH, Brinker JA: Oversensing from electrode “chatter” in a bipolar pacing lead: a case report. Pacing Clin Electrophysiol 13:808, 1990.

887

151. Santomauro M, Ferraro S, Maddalena G, et al: Pacemaker malfunction due to subcutaneous emphysema: a case report. Angiology 43:873, 1992. 152. Giroud D, Goy JJ: Pacemaker malfunction due to subcutaneous emphysema. Int J Cardiol 26:234, 1990. 153. Shepard RB, Kim J, Colvin HC, et al: Pacing threshold spikes months and years after implant. Pacing Clin Electrophysiol 14:1835, 1991. 154. Trautwein W: Electrophysiological aspects of cardiac stimulation. In Schaldach M, Furman S, editors: Advances in pacemaker technology, New York, 1975, Springer-Verlag, pp 11-23. 155. Siddons H, Sowton E: Threshold for stimulation. In Siddons H, Sowton E, editors: Cardiac pacemakers, Springfield, Ill, 1967, Charles C Thomas, pp 145-174. 156. Ohm OJ, Breivik K, Anderssen KS: Strength-duration curves in cardiac pacing. In Meere C, editor: Proceedings of the Sixth World Symposium on Cardiac Pacing, Montreal, 1979. 157. Irnich W: The chronaxy time and its practical importance. Pacing Clin Electrophysiol 3:292, 1980. 158. Davies JG, Sowton E: Electrical threshold of the human heart. Br Heart J 28:231, 1966. 159. Furman S, Hurzeler P, Mehra R: Cardiac pacing and pacemakers. IV. Threshold of cardiac stimulation. Am Heart J 94:115, 1977. 160. Helguera ME, Maloney JD, Woscoboinik JR, et al: Long-term performance of epimyocardial pacing leads in adults: comparison with endocardial leads. Pacing Clin Electrophysiol 16:412, 1993. 161. Esperper HD, Mahmoud PO, von der Emde J: Is epicardial dualchamber pacing a realistic alternative to endocardial DDD pacing? Initial results of a prospective study. Pacing Clin Electrophysiol 15:155, 1992. 162. Bianconi L, Boccadamo R, Toscano S, et al: Effects of oral propafenone therapy on chronic myocardial pacing threshold. Pacing Clin Electrophysiol 15:148, 1992. 163. Szabo Z, Solti F: The significance of the tissue reaction around the electrode on the late myocardial threshold. In Schaldach M, Furman S, editors: Advances in pacemaker technology, New York, 1975, Springer-Verlag, pp 273-287. 164. DeLeon SY, Ilbawi MN, Backer CL, et al: Exit block in pediatric cardiac pacing: comparison of the suture-type and fishhook epicardial electrodes. J Thorac Cardiovasc Surg 99:905, 1990. 165. Stojanov P, Djordjevic M, Velimirovic D, et al: Assessment of long-term stability of chronic ventricular pacing thresholds in steroid-eluting electrodes. Pacing Clin Electrophysiol 15:1417, 1992. 166. Karpawich PP, Hakimi M, Arciniegas E, et al: Improved epicardial pacing in children: steroid contribution to porous platinized electrodes. Pacing Clin Electrophysiol 15:1551, 1992. 167. Johns JA, Fish FA, Burger JD, et al: Steroid-eluting epicardial pacing leads in pediatric patients: encouraging early results. J Am Coll Cardiol 20:395, 1992. 168. Stamato NJ, O’Tolle MF, Petter JG, et al: The safety and efficacy of chronic ventricular pacing at 1.6 volts using a steroid-eluting lead. Pacing Clin Electrophysiol 15:248, 1992. 169. Hamilton R, Gow R, Bahoric B, et al: Steroid-eluting epicardial leads in pediatrics: improved epicardial threshold in the first year. Pacing Clin Electrophysiol 14:2066, 1991. 170. Anderson N, Mathivanar R, Skalsky M, et al: Active fixation leads: long-term threshold reduction using a drug-infused ceramic collar. Pacing Clin Electrophysiol 14:1767, 1991. 171. Kruse IM, Terpstra B: Acute and long-term atrial and ventricular stimulation thresholds with a steroid-eluting electrode. Pacing Clin Electrophysiol 8:45, 1985. 172. Mond H, Stokes K, Helland J, et al: The porous titanium steroideluting electrode: a double-blind study assessing the stimulation threshold effects of steroid. Pacing Clin Electrophysiol 11:214, 1988. 173. Klein HH, Steinberger J, Knake W: Stimulation characteristics of a steroid-eluting electrode compared with three conventional electrodes. Pacing Clin Electrophysiol 13:134, 1990. 174. Beanlands DS, Akyurekli Y, Keon WJ: Prednisone in the management of exit block. In Meere C, editor: Proceedings of the Sixth World Symposium on Cardiac Pacing, Montreal, 1979. 175. Nagatomo Y, Ogawa T, Kumagae H, et al: Pacing failure due to markedly increased stimulation threshold two years after implantation: Successful management with oral prednisolone: a case report. Pacing Clin Electrophysiol 12:1034, 1989. 176. Preston TA, Judge RD, Lucchesi BR, et al: Myocardial threshold in patients with artificial pacemakers. Am J Cardiol 18:83, 1966. 177. Schlesinger Z, Rosenberg T, Stryjer D, et al: Exit block in myxedema, treated effectively with thyroid hormone therapy. Pacing Clin Electrophysiol 3:737, 1980. 178. Lee D, Greenspan K, Edmands RE, Fisch C: The effect of electrolyte alteration on stimulus requirement of cardiac pacemakers. Circulation 38:VI124, 1968. 179. Gettes LS, Shabetai R, Downs TA, et al: Effect of changes in potassium and calcium concentrations on diastolic threshold and strength-interval relationships of the human heart. Ann NY Acad Sci 167:693, 1969. 180. O’Reilly MV, Murnaghan DP, Williams MB: Transvenous pacemaker failure induced by hyperkalemia. JAMA 228:336, 1974. 181. Dohrmann ML, Godschlager N: Metabolic and pharmacologic effects on myocardial stimulation threshold in patients with cardiac pacemakers. In Barold SS, editor: Modern cardiac pacing, Mt Kisco, NY, 1985, Futura, pp 161-170. 182. Sowton E, Barr I: Physiologic changes in threshold. Ann NY Acad Sci 167:679, 1969.

888

SECTION 4  Follow-up and Programming

183. Finfer SR: Pacemaker failure on induction of anaesthesia. Br J Anaesth 66:509, 1991. 184. Hughes JC, Jr, Tyers GFO, Torman HA: Effects of acid-base imbalance on myocardial pacing thresholds. J Thorac Cardiovasc Surg 69:743, 1975. 185. Preston TA, Judge RD: Alteration of pacemaker threshold by drug and physiologic factors. Ann NY Acad Sci 167:686, 1969. 186. Preston TA, Fletcher RD, Lucchesi BR, et al: Changes in myocardial threshold: physiologic and pharmacologic factors in patients with implanted pacemakers. Am Heart J 74:235, 1967. 187. Emilsson K, Oddsson H, Allared M, Brorson L: An unusual cause of high threshold values at pacemaker implantation. Pacing Clin Electrophysiol 20:366-367, 1977. 188. Perry GY, Parsonnet V, Werres R, Flowers NC: Transient loss of sensing and capture during coronary angiography in two patients with permanent pacemakers. Pacing Clin Electrophysiol 18:108-112, 1995. 189. Hellestrand KJ, Burnett PJ, Milne JR, et al: Effect of the antiarrhythmic agent flecainide acetate on acute and chronic pacing thresholds. Pacing Clin Electrophysiol 6:892, 1983. 190. Levick CE, Mizgala HF, Kerr CR: Failure to pace following highdose antiarrhythmic therapy: reversal with isoproterenol. Pacing Clin Electrophysiol 7:252, 1984. 191. Nielsen AP, Griffin JC, Herre JM, et al: Effect of amiodarone on acute and chronic pacing thresholds. Pacing Clin Electrophysiol 7:462, 1984. 192. Montefoschi N, Boccadamo R: Propafenone-induced acute variation of chronic atrial pacing threshold: a case report. Pacing Clin Electrophysiol 13:480, 1990. 193. Salel AF, Seagren SC, Pool PE: Effects of encainide on the function of implanted pacemakers. Pacing Clin Electrophysiol 12:1439, 1989 194. Guarnieri T, Datorre SD, Bondke H, et al: Increased pacing threshold after an automatic defibrillatory shock in dogs: effects of class I and class II antiarrhythmic drugs. Pacing Clin Electrophysiol 11:1324, 1988. 195. Clarke M, Liu B, Schüller H, et al: Automatic adjustment of pacemaker stimulation output correlated with continuously monitored capture thresholds: a multicenter study. Pacing Clin Electrophysiol 21:1567-1575, 1998. 196. Grant SC, Bennett DH: Atrial latency in a dual-chambered pacing system causing inappropriate sequence of cardiac chamber activation. Pacing Clin Electrophysiol 15:116, 1992. 197. Furman S, Hurzeler P, DeCaprio V: Cardiac pacing and pacemakers III: Sensing the cardiac electrogram. Am Heart J 93:794, 1977. 198. Ohm OJ: The interdependence between electrogram, total electrode impedance, and pacemaker input impedance necessary to obtain adequate functioning demand pacemakers. Pacing Clin Electrophysiol 2:465, 1979. 199. Kleinert M, Elmqvist H, Strandberg H: Spectral properties of atrial and ventricular endocardial signals. Pacing Clin Electrophysiol 2:11, 1979. 200. Myers GH, Kresh YM, Parsonnet V: Characteristics of intracardiac electrograms. Pacing Clin Electrophysiol 1:90, 1978. 201. Evans GL, Glasser SP: Intracardiac electrocardiography as a guide to pacemaker positioning. JAMA 216:483, 1971. 202. Levine PA, Klein MD: Discrepant electrocardiographic and pulse analyzer endocardial potentials: A possible source of pacemaker sensing failure. In Meere C, editor: Proceedings of the Sixth World Symposium on Cardiac Pacing, Montreal, 1979. 203. Levine PA, Seltzer JP: Fusion, pseudofusion, pseudopseudofusion and confusion: normal rhythms associated with atrioventricular sequential “DVI” pacing. Clin Prog Pacing Electrophysiol 1:70, 1983. 204. Barold SS, Falkoff MD, Ong LS, et al: Characterization of pacemaker arrhythmias due to normally functioning AV demand (DVI) pulse generators. Pacing Clin Electrophysiol 3:712, 1980. 205. Breivik K, Ohm OJ, Engedal H: Long-term comparison of unipolar and bipolar pacing and sensing, using a new multiprogrammable pacemaker system. Pacing Clin Electrophysiol 6:592, 1983. 206. Ohm OJ: Demand failures occurring during permanent pacing in patients with serious heart disease. Pacing Clin Electrophysiol 3:44, 1980. 207. Griffin JC, Finke WL: Analysis of the endocardial electrogram morphology of isolated ventricular beats. Pacing Clin Electrophysiol 6:315, 1983. 208. Barold SS, Gaidula JJ: Failure of demand pacemaker from lowvoltage bipolar ventricular electrograms. JAMA 215:923, 1971. 209. Van Mechelen R, Hart CT, De Boer H: Failure to sense P waves during DDD pacing. Pacing Clin Electrophysiol 9:498, 1986. 210. Bricker JT, Ward KA, Zinner A, Gillette PC: Decrease in canine endocardial and epicardial electrogram voltage with exercise: implications for pacemaker sensing. Pacing Clin Electrophysiol 11:460, 1988. 211. Frohlig G, Schwerdt H, Schieffer H, et al: Atrial signal variations and pacemaker malsensing during exercise: A study in the time and frequency domain. J Am Coll Cardiol 11:806, 1988. 212. Van Gelder BM, van Mechelen R, den Dulk K, et al: Apparent P-wave undersensing in a DDD pacemaker post exercise. Pacing Clin Electrophysiol 15:1651, 1992. 213. Sager DP: Current facts on pacemaker electromagnetic interference and their application to clinical care. Heart Lung 16:211, 1987.

214. Lau FYK, Bilitch M, Wintroub HJ: Protection of implanted pacemakers from excessive electrical energy of DC shock. Am J Cardiol 23:244, 1969. 215. Levine PA, Barold SS, Fletcher RD, Talbot P: Adverse acute and chronic effects of electrical defibrillation and cardioversion on implanted unipolar cardiac pacing systems. J Am Coll Cardiol 1:1413-1422, 1993. 216. Van Lake P, Levine PA, Mouchawar GA: Effect of implantable nonthoracotomy defibrillation system on permanent pacemakers: an in-vitro analysis with clinical implications. Pacing Clin Electrophysiol 18:182-187, 1995. 217. De Keyser F, Vanhaecke J, Janssens L, et al: Crosstalk with external bipolar DVI pacing: a case report. Pacing Clin Electrophysiol 14:1320, 1991. 218. Sweesy MW, Batey RL, Forney RC: Crosstalk during bipolar pacing. Pacing Clin Electrophysiol 11:1512, 1988. 219. Coombs WJ, Reynolds DW, Sharma AJ, Bennett TD: Crosstalk in bipolar pacemakers. Pacing Clin Electrophysiol 12:1613-1621, 1989. 220. Levine PA, Venditti FJ, Podrid PJ, Klein MD: Therapeutic and diagnostic benefits of intentional crosstalk mediated ventricular output inhibition. Pacing Clin Electrophysiol 11:1194-1201, 1988. 221. Batey FL, Calabria DA, Sweesy MW, et al: Crosstalk and blanking periods in a dual-chamber pacemaker. Clin Prog Pacing Electrophysiol 3:314, 1985. 222. Barold SS, Falkoff MD, Ong LS, et al: Interpretation of electrocardiograms produced by a new unipolar multiprogrammable “committed” AV sequential demand (DVI) pacemaker. Pacing Clin Electrophysiol 4:692, 1981. 223. Levine PA: Normal and abnormal rhythms associated with dualchamber pacemakers. Cardiol Clin 3:595-616, 1985. 224. Barold SS, Belott PH: Behavior of the ventricular triggering period of DDD pacemakers. Pacing Clin Electrophysiol 10:12371252, 1987. 225. Heller LI: Surgical electrocautery and the runaway pacemaker syndrome. Pacing Clin Electrophysiol 13:1084, 1990. 226. Mickley H, Andersen C, Nielsen LH: Runaway pacemaker: a still existing complication and therapeutic guidelines. Clin Cardiol 12:412, 1989. 227. Snoeck J, Beerkhof M, Claeys M, et al: External vibration interference of activity based rate-responsive pacemakers. Pacing Clin Electrophysiol 15:1841, 1992. 228. Lamb LS, Jr, Judson EB: Maximal rate response in a permanent pacemaker during chest physiotherapy. Heart Lung 21:390, 1992. 229. Lau CP, Tai YT, Fong PC, et al: Pacemaker-mediated tachycardias in single-chamber rate-responsive pacing. PACE 13:1575, 1990. 230. Madsen GM, Andersen C: Pacemaker-induced tachycardia during general anaesthesia: a case report. Br J Anaesth 63:360, 1989. 231. Fetter J, Patterson D, Aram G, et al: Effects of extracorporeal shock wave lithotripsy on single-chamber rate-response and dual-chamber pacemakers. Pacing Clin Electrophysiol 12:1494, 1989. 232. Lau CP, Linker NJ, Butrous GS, et al: Myopotential interference in unipolar rate-responsive pacemakers. Pacing Clin Electrophysiol 12:1324, 1989. 233. French RS, Tillman JG: Pacemaker function during helicopter transport. Ann Emerg Med 18:305, 1989. 234. Volosin KJ, O’Connor WH, Fabiszewski R, et al: Pacemakermediated tachycardia from a single-chamber temperaturesensitive pacemaker. Pacing Clin Electrophysiol 12:1596, 1989. 235. Fearnot NE, Kitoh O, Fujita T, et al: Case studies on the effect of exercise and hot water submersion on intracardiac temperature and the performance of a pacemaker which varies pacing rate based on temperature. Jpn Heart J 30:353, 1989. 236. Seeger W, Kleinert M: An unexpected rate response of a minute ventilation dependent pacemaker [letter]. Pacing Clin Electrophysiol 12:1707, 1989. 237. Hayes DL: Rate adaptive cardiac pacing: Implications of environmental noise during craniotomy. Anesthesiology 87:12431245, 1997. 238. Holmes DR, Hayes DL, Gray JE, Merideth J: The effects of magnetic resonance imaging on implantable pulse generators. Pacing Clin Electrophysiol 9:360, 1986. 239. Hayes DL, Holmes DR, Gray JE: Effect of 1.5 Telsa nuclear magnetic resonance imaging scanner on implanted permanent pacemakers. J Am Coll Cardiol 10:782, 1987. 240. Erlebacher JA, Cahill PT, Pannizzo F, Knowles RJR: Effect of magnetic resonance imaging on DDD pacemakers. Am J Cardiol 57:347, 1986. 241. Gimbel JR, Johnson D, Levine PA, Wilkoff BL: Safe performance of magnetic resonance imaging on five patients with permanent cardiac pacemakers. Pacing Clin Electrophysiol 19:913-919, 1996. 242. Achenbach S, Moshage W, Diem B, et al: Effects of magnetic resonance imaging on cardiac pacemakers and electrodes. Am Heart J 134:467-473, 1997. 243. Shellack F, Kanal E: Politics, guidelines and recommendations for MR imaging safety and patient management. J Magn Reson Imaging 11:97-104, 1991. 244. Lauck G, von Smekal A, Wolke S, et al: Effects of nuclear magnetic resonance imaging on cardiac pacemakers. Pacing Clin Electrophysiol 18:1549-1555, 1995. 245. Schüller H, Binner L, Linde C, et al: Combipolar sensing in DDD pacemakers: do we still need bipolar atrial leads? In Sethi KK, editor: Proceedings of the Sixth Asian Pacific Symposium on

Cardiac Pacing and Electrophysiology, Bologna, Italy, 1997, Monduzzi, pp 75-79. 246. Levine PA, Selznick L: Prospective management of the patient with retrograde ventriculoatrial conduction: prevention and management of pacemaker mediated endless loop tachycardias, Sylmar, Calif, 1990, Pacesetter Systems. 247. Limousin M, Bonnet JL: A multicentric study of 1816 endless loop tachycardia (ELT) responses. Pacing Clin Electrophysiol 13:555, 1990. 248. Oseran D, Ausubel K, Klementowicz PT, et al: Spontaneous endless loop tachycardia. Pacing Clin Electrophysiol 9:379, 1986. 249. Rubin JW, Frank MJ, Boineau JP, et al: Current physiologic pacemakers: a serious problem with a new device. Am J Cardiol 52:88, 1983. 250. Levine PA: Postventricular atrial refractory periods and pacemaker-mediated tachycardias. Clin Prog Pacing Electrophysiol 1:394, 1983. 251. Furman S, Fisher JD: Endless loop tachycardia in an AV universal (DDD) pacemaker. Pacing Clin Electrophysiol 5:486, 1982. 252. Den Dulk K, Lindemans FW, Bar FW, et al: Pacemaker-related tachycardias. Pacing Clin Electrophysiol 5:476, 1982. 253. Luceri RM, Castellanos A, Zaman L, et al: The arrhythmias of dual-chamber cardiac pacemakers and their management. Ann Intern Med 99:354, 1983. 254. Ausubel K, Gabry MD, Klementowicz PT, et al: Pacemakermediated endless loop tachycardia at rates below the upper rate limit. Am J Cardiol 61:465, 1988. 255. Denes P, Wu D, Dhingra R, et al: The effects of cycle length on cardiac refractory periods in man. Circulation 49:32, 1974. 256. Amikam S, Furman S: Programmed upper rate limit dependent endless loop tachycardia. Chest 85:286, 1984. 257. Haffejee C, Murphy J, Gold R, et al: Automatic extension vs. programmability of the atrial refractory period in the prevention of pacemaker-mediated tachycardia. Pacing Clin Electrophysiol 8:A56, 1985. 258. Den Dulk K, Hamersa M, Wellens HJJ: Role of an adaptable atrial refractory period for DDD pacemakers. Pacing Clin Electrophysiol 10:425, 1987. 259. Rognoni G, Occhetta E, Perucca A, et al: A new approach to the prevention of endless loop tachycardia in DDD and VDD pacing. Pacing Clin Electrophysiol 14:1828, 1991. 260. Nitzsche R, Gueunoun M, Lamaison D, et al: Endless-loop tachycardias: description and first clinical results of a new fully automatic protection algorithm. Pacing Clin Electrophysiol 13:1711, 1990. 261. Cameron DA, Gentzler RD, Love CJ, et al: Initial clinical experience with a new automatic PMT detection and termination algorithm to discriminate between pacemaker-mediated tachycardia due to ventriculoatrial conduction and normal sinus tachycardia. HeartWeb 2(1), article 96110035, 1996. http:// www.webaxis.com/heartweb/1196/pacing0018.htm. 262. Klementowicz PT, Furman S: Selective atrial sensing in dualchamber pacemakers eliminates endless loop tachycardias. J Am Coll Cardiol 7:590, 1986. 263. Pannizzo F, Amikam S, Bagwell P, et al: Discrimination of antegrade and retrograde atrial depolarization by electrogram analysis. Am Heart J 112:780, 1986. 264. McAlister HF, Klementowicz PT, Calderon EM, et al: Atrial electrogram analysis: antegrade versus retrograde. Pacing Clin Electrophysiol 11:1703, 1988. 265. Bernheim C, Markewitz A, Kemkes BM: Can reprogramming of atrial sensitivity avoid endless loop tachycardia? Pacing Clin Electrophysiol 9:293, 1986. 266. Throne RD, Jenkins JM, Winston SA, et al: Discrimination of retrograde from anterograde atrial activation using intracardiac electrogram waveform analysis. Pacing Clin Electrophysiol 12:1622, 1989. 267. Van Gelder LM, El Gamal MIH, Sanders RS: Tachycardiatermination algorithm: a valuable feature for interruption of pacemaker-mediated tachycardia. Pacing Clin Electrophysiol 7:283, 1984. 268. Duncan JL, Clark MF: Prevention and termination of pacemaker-mediated tachycardia in a new DDD pacing system (Siemens-Pacesetter Model 2010T). Pacing Clin Electrophysiol 11:1679, 1988. 269. Puglisi A, Ricci R, Azzolini P, et al: Ventricular cross stimulation in a dual-chamber pacing system: phenomenon analysis. Pacing Clin Electrophysiol 13:993, 1990. 270. Goldschlager N, Francoz R: Ventricular cross stimulation using a pacing system analyzer. Pacing Clin Electrophysiol 13:986, 1990. 271. Doi Y, Takada K, Nakagaki O, et al: A case of cross stimulation. Pacing Clin Electrophysiol 12:569, 1989. 272. Levine PA, Rihanek BD, Sanders R, et al: Cross-stimulation: the unexpected stimulation of the unpaced chamber. Pacing Clin Electrophysiol 8:600, 1985. 273. Van Gelder LM, El Gamal MIH: Ventriculoatrial conduction: a cause of atrial malpacing in AV universal pacemakers—a report of two cases. Pacing Clin Electrophysiol 8:140-143, 1985. 274. Barold SS: Repetitive non-reentrant ventriculoatrial synchrony in dual chamber pacing. In Santini M, Pistolese M, Alliegro A, editors: Progress in clinical pacing 1990, Amsterdam, 1990, Exerpta Medica, pp 451. 275. Levine PA: Pacing system malfunction: evaluation and management. In Podrid PJ, Kowey P, editors: Cardiac arrhythmia, mechanisms, diagnosis and management, Baltimore, 1995, Williams & Wilkins, pp 582-610.

30  30

Troubleshooting of Implantable Cardioverter-Defibrillators ANDREW E. EPSTEIN  |  MICHAEL P. RILEY

Since its introduction into clinical practice in the early 1980s, the

implantable cardioverter-defibrillator (ICD) has evolved from a treatment of last resort for aborted cardiac arrest to the treatment of choice for the management of resuscitated cardiac arrest and, more recently, for the primary prevention of sudden cardiac death. The original device (AID, Intec Systems, Pittsburgh) lacked programmability except for turning the device on or off. Its detection rate was fixed, and it had no diagnostic capabilities except to indicate that a charging cycle had been initiated. With the emergence of additional therapeutic capabilities, including bradycardia and antitachycardia pacing, the need for diagnostic capabilities and features has increased exponentially with growth in the rate of ICD implantation. The need to recognize and define the initiating events and resulting rhythms at the time of ICD intervention has led to the development of sophisticated telemetry features. Other requirements include diagnosing ICD malfunction noninvasively and evaluating the performance of the ICD components (e.g., battery and lead integrity). This chapter reviews the available methods for the diagnosis of ICD malfunction using the programmer and noninvasive techniques. Only conventional ICDs are discussed here; Chapter 31 discusses biventricular devices.

Troubleshooting Principles Malfunction of ICDs is uncommon. The most common reasons for inappropriate therapy or the absence of expected therapy relate to inappropriate programming, lead-related complications, imperfect diagnostic specificity, insufficient understanding of the technical specifications of device function, and drug-device interactions. Devicedevice interactions and true component malfunctions now rarely occur.1 Troubleshooting of suspected ICD malfunction follows logically from analysis of the index clinical event, whether from a patient report or from a device’s diagnostics. By evaluation of the clinical history, physical examination, radiographic techniques, device memory, and online telemetry, the cause of malfunction can usually be determined. The analysis must take into account the specifics of the ICD as well as the sensing and treatment algorithms used to arrive at an accurate diagnosis. Therapy may be delivered or withheld because of true malfunction of a component or because the device is responding appropriately according to its programming and interaction with the environment (e.g., responses to electromagnetic interference). Analysis of ICD problems begins with identification of the problem, followed by analysis of its possible cause. Presentation falls into four general areas: multiple shocks, failure to convert ventricular tachycardia (VT) or ventricular fibrillation (VF), failure to detect VT or VF, and problems with pacing.2 INITIAL EVALUATION AND TOOLS Clinical History As in all other areas of medicine, the keystone to diagnosis is the clinical history. Historical clues suggesting ICD malfunction, although by themselves nondiagnostic, provide the basis for a presumptive diagnosis and suggest further avenues of inquiry. For example, repeated shocks in an asymptomatic patient suggest false signal detection or an atrial arrhythmia. Certain body positions associated with ICD shocks

suggest the possibility of lead fracture or lead instability. ICD model, manufacturer, date of implantation, lead type and location, antiarrhythmic drug history, presence or absence of symptoms of heart failure or angina preceding therapy, and other clues are important, because any or all of these factors may have relevance and can be related to ICD therapy. The presence of an implanted pacemaker with an ICD raises the specter of device-device interaction. Therapy during exercise suggests sinus tachycardia or atrial fibrillation with a rapid ventricular response. Palpitations may signal either supraventricular tachycardia (SVT) or VT. Physical Examination The physical examination may be helpful in pinpointing the exact cause of ICD malfunction. For example, for a patient who reports that certain body positions or movements elicit ICD shocks, reproducing the precise maneuver or the exact circumstances known to elicit the shocks, while simultaneously telemetering the device, may prove the diagnosis of lead failure. Occasionally, patients are reluctant to allow the examiner to do this because the prospect of an ICD shock is psychologically threatening.3 In such circumstances, the ICD may be placed in a monitor mode, either by programming or using a magnet to suspend tachyarrhythmia detection, while assuring the patient that shock delivery will not occur. The assessment of recordings from the ICD in these situations is discussed later. Because a common point of lead fracture occurs where transvenous ICD leads pass between the clavicle and first rib,4,5 manipulation of the device pocket or the lead entry point in the pectoral area may elicit electrical noise artifact, indicating lead conductor fracture.6,7 Similar artifacts may occur with a loose connection of the set screw to the lead terminal pin in the ICD pulse generator header. Again, make-break potentials can be demonstrated by noninvasive telemetry, as discussed later. Other diagnostic clues may be provided by the physical examination, such as detection of an irregular pulse suggestive of atrial fibrillation, which may be readily confirmed by an electrocardiogram. Congestive heart failure is often associated with exacerbation of ventricular arrhythmias.8-10 Therefore, eliciting symptoms and signs of left ventricular decompensation suggests a possible cause for worsening arrhythmias. Electrocardiographic Recordings Objective evidence of the event precipitating ICD therapy, or of an arrhythmia with absence of the expected ICD response, can be extremely helpful and is usually diagnostic (Fig. 30-1). In the days before the availability of stored electrograms (EGMs), such evidence was rarely available unless the patient was hospitalized and monitored at the time of the event. Fortunately, this is now a problem of the past. Nevertheless, even when available, EGMs can sometimes be inconclusive or confusing. In addition, if multiple ICD detections have occurred for any reason, including lead failure, SVT, or a VT or VF storm, EGM documentation of the initial event leading to detection may be overwritten because of limited device memory. Device Telemetry The advent of device telemetry has revolutionized and greatly simplified analysis of arrhythmias and events suspected of representing ICD

889

890

SECTION 4  Follow-up and Programming

Trigger S

S

914 1289

S

895 531

R

895 1259

R

8

* R

* R

* R

* R

883 895 254 297 285 293 273 227 297 R

16

R

R

R

R

R

R

17

R

R

11

* * * * * * * R R R RRR R 887

* R

F

R

18

19

R

F

F

F

R

* R

* R

R

* R

R

R

R

R

* R

R R

F

F

R

R

R

F

F

R

R

R

R

15

H V

F

R

16

S

679V 1193

R

20

F

14

266

R R R

F

875 883 281 273 266 281 285 273 242

13

891 891 277 281 266 273 281 238

R R R RR R

R

12

* R

F

887 883 422 289 297 273 281 281 281

R

10

* R

S

879 527

R

9

* R

S

906

R

21

22

23

24

Figure 30-1  Electrogram (EGM) shows sinus rhythm with premature ventricular complexes (PVCs) in a pattern of bigeminy, followed by a rapid, irregular ventricular arrhythmia, then a high-voltage (HV) shock delivered by a Model V193 defibrillator (St. Jude Medical, Sunnydale, Calif.). The three recordings are from the atrial channel (top), marker channel (middle), and ventricular pace/sense channel (bottom). Note that the EGM of the ventricular arrhythmia has a different morphology from that of the preceding sinus rhythm. The first and third beats are PVCs. The second and forth beats are sinus in origin. The fifth beat is a PVC that initiates ventricular fibrillation, typified by a rapid, polymorphic EGM.

VEGMs, to be telemetered11 (Fig. 30-2). The complexity and sophistication of these diagnostic tools are increasing with the new generation of ICDs. The addition of the atrial channel has greatly simplified analysis of arrhythmic events (Fig. 30-3). Other diagnostic information is now routinely available from all ICDs, including battery voltage, pacing and sensing lead impedances, charge times, capacitor re-formation times, high-voltage lead

malfunction. Early devices (e.g., Ventak, Cardiac Pacemakers [CPI/ Guidant], St. Paul, Minn.) were able to emit sounds or beeps synchronous with ventricular electrogram (VEGM) detection, enabling identification of oversensing or undersensing. When recorded with a phonocardiogram, a so-called “beep-o-gram” was produced. Although helpful, these crude attempts at telemetry were quickly supplanted by advances that enabled detailed information, such as R-R intervals and

S 100

S 100

1047 R

1047 R 3

S 100 1063 R

4

S 100 1063 R

5

S 100

6

1063 R 7

100 1063 R 8

Figure 30-2  The first line of this tracing is an EGM recorded from a single-chamber St. Jude Medical Model V193 ICD. This device monitors the heart rate and has the capability of analyzing the EGM morphology. The bottom lines annotate the ICD sensing function. The checks and 100 numbers indicate the degree of matching of the EGM morphology to a sinus rhythm template that can be used to distinguish atrial from ventricular arrhythmias. The 1047 and 1063 numbers indicate cycle length. S indicates sinus rhythm; R, sensed R waves; and the numbers at the bottom count the seconds of the recording.



891

30  Troubleshooting of Implantable Cardioverter-Defibrillators

S

S

S

100 871 867

3

100 887 879

R

8

S 100 801 543

R

X 0

10

S 100 879 891

977 1227

R

9

S

R

S 100 863 867

R

11

12

R

13

S 100 867 871 R

14

S 100 879 875 R

15

100

R

16

Figure 30-3  As in Figure 30-2, this tracing EGM recorded at a routine clinic follow-up visit shows the ventricular EGM (fourth tracing) as well as an atrial EGM (third tracing) from a dual-chamber Model V242 ICD (St. Jude Medical). The first and second tracings are, respectively, a surface electrocardiogram (ECG) and a marker channel. In the marker channel, the checks indicate a template match with sinus rhythm (100% registered below the horizontal marker line). The fourth beat, marked x, is a premature ventricular depolarization with a different morphology than sinus; it is logged as a 0% match. The next two rows of numbers are the P-P and R-R intervals. S indicates sinus rhythm, as defined by the ICD, as opposed to T or F if ventricular tachycardia or fibrillation were present, respectively. R indicates sensed ventricular activity. The data on atrial and ventricular EGM timing and ventricular EGM morphology allow this device to use discrimination algorithms to differentiate supraventricular from ventricular arrhythmias. It can also function as an atrial, ventricular, or dual-chamber pacemaker.

impedance, and frequency and timing of ventricular events. The finding of a depleted battery, lead impedance out of range (either too high or too low), and R-R intervals can lead to correct diagnoses. The latter is extremely important, because nonphysiologic intervals (short) raise the suspicion of make-brake electrical noise artifact. One device (Medtronic, Minneapolis) records information regarding both impedance changes (Fig. 30-4) and nonphysiologic R-R intervals.12 Newer ICDs from all major manufacturers are capable of remote device telemetry from the patient’s home.13,14 This capability offers two advantages over exclusively office-based interrogation. The first advantage is the ability to interrogate the ICD more quickly and easily after a shock. The second advantage is that most remote monitoring frequently assesses lead impedance changes and other parameters that may herald lead failure. The Lumos-T Reduces Routine Office Device Follow-Up Study (TRUST) showed that remote monitoring

Impedance (ohms)

30 25 20 15 10

7 wks

5 0 0

5

10

15

20

25

30

35

40

45

50

Time (weeks) Figure 30-4  The plot shows decreasing ring-coil impedances logged in a GEM ICD (Medtronic, Minneapolis). The first four impedances readings of less than 15 ohms are circled. The arrow indicates that the lowimpedance trigger would have provided an alarm 15 weeks before this patient received an inappropriate shock. (From Gunderson BD, Patel AS, et al: An algorithm to predict implantable cardioverter-defibrillator lead failure. J Am Coll Cardiol 44:1898-1902, 2004.)

with automatic daily surveillance provides early detection of device events.15-17 Once a potential lead failure is identified by the device, the physician can be notified quickly, often quickly enough to intervene before lead failure produces a clinical event (i.e., shock for lead fracture). The CONNECT Trial demonstrated that remote follow-up of ICD significantly reduced the time from onset of clinical events (newonset atrial or ventricular arrhythmias, lead or device integrity problems) to clinical decisions compared with usual outpatient clinic follow-up.18 Unfortunately, some device failures occur with adverse events happening so rapidly, such as inappropriate shocks, that early notification is impossible.19 Notably, even if mechanisms such as audible tones are available for patient notification, with increasing age, more patients are unable to hear the alerts.20 Radiographic Evidence Radiographic evidence is helpful if lead malposition, dislodgment, or fracture is suspected.7 It is recommended, whenever possible, that chest radiographs taken immediately after ICD implantation be compared with radiographs obtained at the time of a problem. Such comparisons may reveal lead malposition and displacement when none is suspected. Radiographs can also be helpful in demonstrating conductor fracture or pin connectors improperly positioned in the header. Examining the radiographic “signature” of the device can help identify the device type when the patient is unaware of the ICD model or type. Knowledge of unique failure modes such as “migration” of set screws (travel of the right ventricular fixation screw into the channel lumen during shipment) in particular families of ICDs is of course desirable.21 Figures 30-5 and 30-6 show examples of lead dislodgment. Because the distal end of the lead is close to the tricuspid anulus (Fig. 30-5, A), both atrial and ventricular signals are recorded (B). This leads to “double-counting” such that, for a given heart rate, the ventricular channel registers twice the actual heart rate, satisfying the high rate detection requirement and leading to administration of a shock. Figure 30-6 shows a similar example, but the electrical artifacts are more disorganized and irregular, presumably because the lead is more free floating. Figure 30-7 shows an example of disruption of a transvenous ICD lead as it passes between the clavicle and first rib. Care must be taken to learn the appearance of the welds of the springs, because they

892

TABLE

30-1 

SECTION 4  Follow-up and Programming

Box 30-1 

Multiple Shocks

Cause Incessant/repetitive VT or VF Supraventricular tachycardia (SVT) Change in substrate Ischemia Drug change Sensing Malfunction Lead failure (conductor or insulation) Loose connection (e.g., set screw) T-wave sensing P-wave sensing External Signals Electromagnetic interference (EMI) Device-device interaction

Management Judicious use of magnet and/or programming ICD off. Reprogram; treat arrhythmia; slow ventricular response to AF. Treat precipitating factor. Revascularize; administer drug therapy. Reprogram, or change drug. Replace lead. Reoperate, and reseat screw. Reprogram as feasible. Reprogram as feasible, but often requires reoperation. Avoid cause. Reprogram, or reoperate.

AF, Atrial fibrillation; VF, ventricular fibrillation; VT, ventricular tachycardia.

can be mistaken for fracture if their usual appearance of being offset from the central axis of the lead is not appreciated22 (Fig. 30-8). An unusual cause of lead failure, and sometimes failure of telemetry, occurs in twiddler’s syndrome; in these cases, a lead is twisted and fractured or the ICD is inverted23,24 (Fig. 30-9). Lead perforation can occur subacutely or rarely chronically, leading to several problems, including undersensing of ventricular arrhythmias, failure to convert ventricular arrhythmias, and failure of pacing as the lead tip exits the myocardium (Fig. 30-10).

Multiple Shocks Multiple shocks may be the result of incessant VT/VF, repetitive VT/ VF, oversensing of T waves, electromagnetic interference, electrical noise artifacts from a fractured conductor or myopotentials (in the case of insulation failure), or SVT, including sinus tachycardia, atrial fibrillation, atrial flutter, or another mechanism (Table 30-1). Sometimes the ICD itself can be proarrhythmic (Box 30-1). The occurrence of multiple shocks leads to myriad problems. Shocks are poorly tolerated by patients, families, and referring physicians and can create long-lasting fear and distrust of the ICD requiring professional help. Furthermore, shocks lead to significant increases in cost of therapy by repeated hospitalizations and testing sessions; shocks may jeopardize the physician-patient relationship. ICD shocks, both appropriate and inappropriate, have also been associated with increased mortality.25-27 The occurrence of repetitive shocks for whatever reason represents a medical emergency. The management of multiple ICD shocks must address multiple factors: First, the patient must be comforted, and to do so, the underlying rhythm must be determined. Is it sinus, supraventricular, or ventricular? If it is not ventricular, the ICD can be disabled by a magnet or programmer. If it is ventricular, is there a precipitating cause, such as ischemia, heart failure, or lead malfunction? If so, can the shocks be stopped with treatment of the cause, or are antiarrhythmic drugs, β-blockers, or other interventions (e.g., reprogramming, ablation) needed? Usually, the occurrence of multiple shocks requires hospital admission, because a monitored environment is not only helpful diagnostically but also for patient safety and support. Perhaps the most difficult causes of multiple shocks to treat are incessant VT and VF. On the one hand, delivered therapy is appropriate; on the other hand, it is not only a horrible experience for patients but also reflects a substrate problem. ICDs do not treat heart disease, only its consequences. Initial management centers on the administration of drug therapy,8,9,28,29 and the ICD usually should be disabled by programming or magnet application. Although antiarrhythmic drugs may be useful, particularly intravenous amiodarone, the judicious use

CLASSIFICATION OF ICD-INDUCED PROARRHYTHMIA ICD-Induced Tachyarrhythmias Clinically Appropriate Therapies ATP or shocks leading to: • Acceleration of VT • Deceleration of VT • Induction of supraventricular tachyarrhythmias Clinically Inappropriate Therapies Antitachycardia therapies (ATP, cardioversion, defibrillation) Failure to discriminate between SVT and VT Committed behavior for nonsustained VTs Signal oversensing • Electrical noise artifact • T or P waves • Electromagnetic interference (EMI) Antibradycardia pacing Undersensing of spontaneous beats ICD-Induced Bradyarrhythmias Postshock bradyarrhythmias Postshock increase in pacing threshold leading to noncapture Postshock reset of a separate pacemaker Inhibition of antibradycardia pacing caused by T-wave oversensing Modified from Pinski SL, Fahy GJ: The proarrhythmic potential of implantable cardioverter-defibrillators. Circulation 92:1651-1664, 1995. ATP, Antitachycardia pacing; ICD, implantable cardioverter-defibrillator; SVT, supraventricular tachycardia; VT, ventricular tachycardia.

of β-blockers has been found to be extremely beneficial.9,29 If VT or VF episodes are repetitive or incessant despite drug therapy, it is often advisable to intubate and sedate the patient, disable the ICD, and use an external defibrillator to manage the arrhythmia events. Intra-aortic balloon counterpulsation has been used on occasion with success. With the increased efficacy of radiofrequency ablation, incessant arrhythmias may be so treated.30 Text continued on page 897

A Figure 30-5  Lead dislodgment. A, Right ventricular pacing-sensingdefibrillation lead displaced to the tricuspid anulus in biventricular pacing-ICD system (St. Jude Medical Model V340).



893

30  Troubleshooting of Implantable Cardioverter-Defibrillators

DDI Trigger F

F

645 492

465

P R R

RR

8

F

F

F

648

641

648

453

P R R

9

465

P R R

F

461

P R R

10

645 496 P R R

F

F

648

648

453

P R R

11

F

P R R

12

* R

D 648 477 P R R

648 480 P R R

453

*

F

13

* R

*

652 496 P R R

14

*

652

648 680 P R

453

P R R

15

16 D

* S

*

* S

*

*

* S

*

S

R

S

S

S

R

R

R

R

H v 619

656

652 504 P R R

488 P R R

16

652 645 P R

652

461 P R R

18

17

656 488 P R R

652 656 P R R

19

648 500 P R

20

652 496 P RR

652 496 P RR

21

652 504 P RR

22

652 484 P R R

23

24

3510P Serial: 09885 (3307_4.8.1m) Stored EGM Report

V-340 Serial:

Page 1 or 2

EGM 1: (24-33 sec) Dec 16, 2004 9:03 PM

Page 2 or 2

DDI

DI

S

S

S

S

1047 P

742 BV

25

918 A

652

R R

26

707 527 P R R

27

S RS 703

V

24

P R

656 684 P R

A R

28

B

S

S

B A

758 BV

29

672 P

672 BV

30

656 P

508

R

660

496

P R R

31

648

453 P R R

32

B Figure 30-5, cont’d  B, Recordings from the ICD. Top to bottom, Atrial EGM, the marker channels, and the ventricular EGM. In the marker channel area, F indicates fibrillation detection, trigger denotes episode detection and asterisks (*) indicate device charging. During the charging and reconfirmation period, R indicates an interval fast enough to reconfirm, and S indicates an interval below the VT/VF rate. The numbers are atrial and ventricular cycle lengths. Below the numbers, P stands for P wave and R for R wave. Because the distal end of the lead is close to the tricuspid annulus, both atrial and ventricular signals are recorded in the ventricular channel, such that the ventricular rate counter registers twice the actual heart rate. The R-R labels reflect double-counting from the EGM in the bottom tracing recorded from the right ventricular distal tip. This doublecounting satisfied high rate detection, and a shock was delivered (HV).

894

SECTION 4  Follow-up and Programming

V-V interval (ms)

V-V

VF  330 ms

2000 1700 1400 1100 800

20.2J

600 400 200

50 45 40 35 30 25 20 15 10

A

V F F F F V S S S S D S 1 1 2 2 1 7 5 5 5 6 0 0 0 0 0

B

0

5

5

10

15

20

25

Time (sec) [0  Detection]

6 8 0

V V S S 1 4 0

VF VF Rx 1 Defib

V S 6 7 0

V V S S 1 1 7 2 0 0

V S 5 7 0

8 7 0

V S

6 3 0

V S

1 8 0

V S

1 7 0

C D

8 0 0

V S

1 8 0

F S

1200

V P

1200

20.2 J

Figure 30-6  Lead dislodgment. A, Interval plot; B, stored EGM; the right ventricular defibrillation lead was dislodged to the tricuspid valve. Random electrical signals generated by lead movement in the ventricle provided very rapid and irregular artifacts that were interpreted by the Model 7230 ICD (Medtronic) as ventricular fibrillation, and a shock was delivered (CD, charge delivered) in B.



30  Troubleshooting of Implantable Cardioverter-Defibrillators

A

895

B

Figure 30-7  Clavicle–first rib lead discontinuity. A, Posteroanterior chest radiograph of an ICD system from a patient who presented with multiple shocks. The lower lead has a discontinuity where it travels between the clavicle and the first rib. B, Close-up view of a different patient with an identical presentation. The fracture again is at the junction between the clavicle and first rib and is easily identified where the superior, high-voltage lead is bent with a discontinuity at the inferior margin. (Courtesy of Dr. Paul A. Levine.)

A

B

Figure 30-8  Lead fracture. A, Posteroanterior chest radiograph that was interpreted to show a lead fracture (Endotak, Cardiac Pacemakers, St. Paul, Minn.). The area is the distal portion of the defibrillation coil with apparent lateral displacement of the electrode (arrowhead). B, Coned-down view of the lead, documenting a continuous metallic connection at the level of the transition from a central electrode to the outer coil. This is the typical appearance of a Guidant Endotak lead, and no fracture is present. (From Kratz JM, Schabel S, Leman RM: Pseudo fracture of a defibrillating lead. Pacing Clin Electrophysiol 18:2225-2226, 1985.)

896

SECTION 4  Follow-up and Programming

A

B Figure 30-9  Two examples of “twiddling.” A, Dramatic example of multiple twists of leads in an ICD implanted in the abdomen. B, Subtler example of twiddler’s syndrome; the ICD has been rotated 180 degrees. This patient’s presentation was inability to interrogate the ICD.



30  Troubleshooting of Implantable Cardioverter-Defibrillators

Figure 30-10  Lead perforation. Chest radiograph obtained 6 weeks after dual-chamber ICD implantation shows subacute lead perforation. The device was implanted uneventfully for primary prevention and to manage sinus node dysfunction. At routine 6-week follow-up, the patient was asymptomatic, the R-wave amplitude had deteriorated, and there was failure to capture. Lead revision was performed without complication.

Oversensing of P waves, T waves, and even atrial flutter may lead to repetitive shocks.31-33 Atrial oversensing in the ventricle is uncommon; it is usually seen with integrated bipolar leads when the proximal spring is close to or straddling the tricuspid valve31,32 (Fig. 30-11). P-wave sensing may also be seen when a lead is dislodged to the right atrioventricular junction, as in Figure 30-5. More often, T waves are sensed because of their large size relative to the R wave, but sometimes simply because the T wave is huge, as in a patient with hypertrophic cardiomyopathy (Fig. 30-12). Rarely, T-wave oversensing occurs during rate-related bundle branch block,34 hyperglycemia,35 and the Brugada syndrome.36 First reported in the mid-1990s, myopotentials can also be sensed and interpreted as a ventricular arrhythmia, leading to inappropriate shock therapy. These may arise from the pectoral muscles37,38 or from the diaphragm.39,40 The latter has occurred with integrated bipolar leads that presumably lie near the respiratory muscles (Fig. 30-13). An unusual case of inappropriate shock therapy caused by pectoral muscle myopotential oversensing involving an integrated bipolar lead occurred with high-voltage pin reversal in the device header41 (Fig. 30-14). Oversensing can often be rectified by altering the sensitivity or refractory period of the ICD. However, if T waves are large and R waves are small, changing the sensitivity will not suffice. If the sensitivity is decreased, VF may not be identified (Fig. 30-15). Similarly, lockouts imposed by the device to ensure arrhythmia detection limits programming of device refractory periods. One manufacturer provides greater programmability to overcome these problems. Because ICDs, in contrast to pacemakers, vary their sensitivity to identify ventricular activity, altering the amplitude and timing at which sensitivity is adjusted can address this problem. For the patient with hypertrophic cardiomyopathy shown in Figure 30-12, the R wave was greater than 25 mV and the T wave greater than 4 mV. If the sensitivity were decreased significantly, VF might not be reliably sensed. Furthermore, because of prolonged repolarization and sensing of the terminal portion of the T wave, prolonging the ventricular refractory period would not suffice to correct this problem. In this case, avoidance of T-wave oversensing was achieved by altering the threshold start, the decay delay, and the sensitivity. Alternatively, on rare occasions an ICD lead may need to be repositioned or a separate sensing lead placed in a different area of the right ventricle. In anticipation of T-wave oversensing in the future, one approach that may be useful is to test VF detection at low sensitivity at implantation. If oversensing occurs, sensitivity may be decreased without the need for retesting of defibrillation sensing. On the other hand,

897

whenever sensitivity is decreased from a level that has not been tested and shown to provide adequate detection of VF, it is imperative to retest VF detection with an electrophysiologic study to demonstrate adequate sensing (see Fig. 30-15). The sensing of external electrical activity may lead to false detection. Because of the increased use of ICDs and relatively low lead failure rates, the most common cause (after lead failure, discussed later) is probably electrocautery42,43 (Fig. 30-16). Other causes include electronic surveillance systems,42,44 razors,45 radiofrequency handheld remote controls,46 ungrounded electrical tools,42 fluid in a connector port,47 transcutaneous electrical nerve stimulation (TENS; Fig. 30-17),48 personal digital assistants (PDAs),49 and even slot machines50 and washing machines.51 A common cause of multiple shocks is lead failure.6,28,52-60 When make-break potentials are recorded by the ICD, the rapid electrical activity is interpreted as VF. This is one of the easiest and most characteristic problems encountered (Fig. 30-18). Note the nonphysiologic (extremely rapid) electrical activity that is the signature of this phenomenon. Lead failure may become apparent after shocks.55 ICD leads have a higher failure rate than pacemaker leads because they are an order of magnitude more complex. In addition, some models have especially high failure rates, including both epicardial leads53 and endocardial leads.54-56 One reported case had a 37% failure rate (confidence interval, 24%-54%) at 68.6 months; the study showed that failure may not become apparent until late follow-up, but also that a “signature” of failure is the occurrence of electrical noise artifact after shock delivery.55 Failure is not predicted by R-wave changes or changes in pacing characteristics. However, combining the occurrence of an abnormal impedance with a counter showing R-R intervals shorter than 140 msec can identify ICD lead failure with high sensitivity and specificity.12 The most recent lead to manifest a higher-than-anticipated failure rate is the Medtronic 6949.56 Conductor fracture causing make-break potentials interpreted as VF is the most frequent mode of failure for this lead, although high-voltage conductor failure has also been reported. Both inappropriate shocks and inhibition of pacing can occur. As expected, changes in lead impedance and nonphysiologic R-R intervals precede lead failure. For patients with the Medtronic 6949 lead, recommended changes to device programming improved early detection of lead failure and minimized inappropriate shocks. Early detection changes included narrowing the acceptable range for normal lead impedance and tracking the number of sensing integrity counter (SIC) events.57 Lead impedances falling outside the established limits or too many SIC events triggered both an audible patient alarm and physician notification by the patient’s remote monitor. Because the make-break signals usually generated by a lead fracture tend to be nonsustained in character, increasing the number of R-R intervals to Text continued on page 902 P

P

P

P

P

P

R P

P

P

R P

Figure 30-11  Recordings showing counting of both the atrial (P) and ventricular (R) signals from an integrated bipolar ventricular lead (Model RV-1101, Ventritex, Sunnyvale, Calif.) in a radiographically ideal apical position. Because the patient and her heart were small, the distal spring, used both for defibrillation and as the anode for sensing, came to straddle the tricuspid valve, allowing atrial signals to be recorded.

898

SECTION 4  Follow-up and Programming

DDD

DDI Trigger

S 4

RS 726 726 P R

S

8

B P

R

9

S

S

F

F F

F

S

F F

S F F

F

F F

S

S

F

726 722 726 722 722 741 765 741 339 448 249 354 241354 601 249 351 237 358 616 249 390 P P P V R R R R R R R RR RR R RR R RR RR R R

10

11

12

13

14

15

16

DDI * S

* * R R

* * * S R R

H V R 801V

R R

S

753 749 765 612 249 374 245 382 249 394 P R R R R RR R R R R R

702 827

792

V

R

16 17 18 19 20 V-240 Serial: 56397, EGM 3: (0-24 sec), 24 Jul 2002 11:59 Stored EGM Report DDD

S

B P

24 A

R

B 706 702 P V

25

B

26

694 694 P V

B

B 687 686 P V

27

608 P

B 812 1007 P R

765 999

B

V

RS 726 769 P V

21 22 23 3610P Serial: 06368 (3307-3.1.1a)

V-240 Serial: 56397

698 694 P V

S

24 Page 1 of 2

EGM 3: (24-29 sec), 24 Jul 2002 11:59

Page 2 of 2

690 P V

28

P

29

30

31

32

Figure 30-12  Oversensing in patient with hypertrophic cardiomyopathy. The system comprises a Model V145AC ICD (Ventritex), a bipolar atrial lead, and a Model 6936 defibrillation lead (Medtronic). A, Tracings from top to bottom show the atrial EGM, the marker channels, and the ventricular EGM. There is both double-counting of the R and T waves (registered as VR in third beat in first tracing) and double-counting of multiple components of the R wave itself (registered as RR in both first and second continuous tracings). In addition, there is triple-counting of both R-wave components and the T wave (registered as RR-R) that leads to fibrillation detection (labeled F) and an ICD shock (labeled HV) in sinus rhythm. The R wave was greater than 25 mV, and the T wave greater than 4 mV. Oversensing was corrected by programming; the threshold start (signal amplitude at which sensing sensitivity begins) and the decay delay (time after sensed beat when sensitivity begins to increase) were extended, and the sensitivity was decreased. To ensure proper function, ventricular fibrillation was induced after programming to show that, with more restrictions on sensing, VF could still be sensed appropriately by the ICD.



899

30  Troubleshooting of Implantable Cardioverter-Defibrillators

I

aVR

V1

V4

V2

V5

aVL II

III

V3

aVF

V6

V1

II

V5 B Figure 30-12, cont’d  B, The 12-lead ECG from this patient shows marked left ventricular hypertrophy and voltage.

AS 640

VF 173

PVP

VS 533

AS 815 VP 928

AS 813

VP 813

AS 620 VP 620

AS 755

VP 755

AS 763

[AS] 633

PVP

PVP

PVP

VF zone 86 bps 238 bps

[AS] 825

[AS] 683

VS VF VF VF 600 165 218 165 VF VF VF 170 195 243

Initial detection Pre-attempt Avg A Rate Pre-attempt Avg V rate

Pre-attempt EGM (10 sec max)

25 mm/s

VF 198

VS 563

PVP

VT 305 Epsd

AS 663 VF 153 VF 143

AS AS 823 AS 328 345

VS VF VF 458 158 203 VF VF 163 233 Detct

AS AS 135 470

VP 858

AS 780 VF 858

Chrg

Figure 30-13  Diaphragmatic sensing in patient with high-grade AV block. The three recordings show the atrial EGM (top), bipolar ventricular EGM from the sensing lead (middle), and the shock EGM (bottom). The marker channel is shown at the bottom. During deep respiration, rapid, high-frequency activity is recorded on the sensing channel and is judged by the ICD as ventricular fibrillation (VF) and triggers ICD charging. This ventricular oversensing also inhibits bradycardia pacing (Guidant ICD, Boston Scientific).

900

SECTION 4  Follow-up and Programming

[AS]

[AS] [AS]

PVC VF 360 138 VF 153

VP --

PVP

[AS]

VF 213 PVC 518

VF 148 PVC 408

PVP

PVP

PVP

[AS] --

[AS]

PVP

VF zone 41 bpm 338 bpm

AS 1305

VF VF VF VF 143 323 143 150 PVC VF VF VF VF 390 238 140 280 270 Epsd PVP

Initial detection Pre-attempt Avg A Rate Pre-attempt Avg V rate

Pre-attempt EGM (10 sec max)

25 mm/s

AS 1305

[AS] AS 685 VF VF VF VF VF VF VF VF 195 158 143 158 248 243 155 160 VF VF VF VF VF VF VF 135 255 158 140 205 165 135 Detct

PVP

AS 655

VF 650

Chrg

Figure 30-14  Myopotential sensing. Caused by reversal of the high-voltage pins in the ICD header of a Guidant Model H175 biventricular ICD. The three tracings are electrograms from the right atrial lead, the right ventricular pacing/sensing system, and the high-voltage lead system. Annotation at the bottom indicates transient inhibition of (biventricular) pacing, and the detection of ventricular fibrillation (VF). Reversal of the high voltage pins in the header alters the sensing circuit in such a way as to make the ICD housing a component of the sensing circuit (the other being the ICD lead tip) permitting pectoral myopotentials to be recorded as rapid electrical activity whenever the left arm is raised. (From Allison JS, Epstein AE, Plumb VJ: Electrical noise artifact: from without or within? J Cardiovasc Electrophysiol 18:332-333, 2007.)

S

S

FF S 0 0 0 0 0 0 0 0 633 633 633 633 633 633 820 629 324 320 883 A A A A A A R 303 501 330

S

R

483

R R 71

R

RRR 87 679

S

S

S

0 0 0 0 633 633 633 418 555 1189 A A A R

R

373

R R 1117

*

S 633 A

0

633 730 A R

579

RS 0 0 633 633 246 1461 A A R R R 133 1211

* S 0 A

664 A

* S 0

* S

* S

0 0 664 664 602 500 359 1087 A A A

R R R 407 257

R 1039

Figure 30-15  Ventricular fibrillation (VF). Made during ICD testing, this recording shows VF that was not detected by a Model V232 ICD (St. Jude Medical) because the electrogram (EGM) amplitude was below the sensitivity for detection. The tracings show the surface electrocardiogram (ECG), the marker channel, the atrial EGM, and the ventricular EGM. Notice that in the marker channel, only two intervals labeled F are shown that signified VF detection; for some appropriately detected short intervals, hash marks are present without F annotation since the printer function cannnot accommodate the typed letters. S indicates an EGM interval longer than the tachycardia detection interval. Also note that the zeroes under the marker channel line indicate the absence of a template match with sinus rhythm, but VF is still not diagnosed, because the cycle length is not short enough as assessed by the ICD sensing circuit. The gain of the ventricular EGM recording was 6.0 mV/cm, indicating that many VF signals were less than 0.5 mV.



30  Troubleshooting of Implantable Cardioverter-Defibrillators

901

Continuous AS 1408 AS VS VF 131 471 217 VF VT 268 320

AS 695

AS 201 AS AS 566 180 VF VF 146139 VS VF 639 229

AS AS 182 1506 AS AS VP 730 295 VF VF VP 882 291 143 VS 778 VS VF 581 481 258

AS 930

AS AS AS AS 121 279230 1098 AS AS AS AS VF 266 162 174 170 VP 152 VF 858 VS VS 213 VF VF 509 703 137 217

AS AS AS 715 AS 412 AS 645 1199 238 VF VS VF VF 150 547 252 146 VS VS VS VT VT 547 512 721 314 422

AS AS AS 760 88 111 AS AS AS VF 746 229100 VP VF VP 858 295 170 VT VF 858 VS VF VF 513222137 442 162 AS 1605

VS 760

AP AS 496 1962 VS VS 633

854

Figure 30-16  This stored electrogram (EGM) was recorded from a Guidant Model 1831 ICD (Boston Scientific, Natick, Mass.) when bipolar cautery was delivered to the patient’s ear lobe to remove a skin cancer. Note the electrical noise artifact in the atrial and ventricular sensing-pacing channels (top two EGMs on each tracing, respectively) but only minimally on the EGM from the high-voltage circuit (bottom electrograms), in which sensing does not occur. The atrial and ventricular intrinsic activity can be seen on all channels.

Figure 30-17  Electrogram shows electrical noise artifact from a Guidant ICD (Boston Scientific) recorded as the patient applied his spouse’s transcutaneous electrical nerve stimulation (TENS) to himself in an attempt to treat muscle aches.

902

SECTION 4  Follow-up and Programming

0

1

2

s

10

17

25

3

11

18

26

4

12

19

27

5

13

20

28

6

14

21

29

7

15

22

30

8

16

23

31

24

32

Figure 30-18  Electrogram from one of the early devices capable of storing EGMs, a Model V100 ICD (Ventritex/St. Jude Medical), shows nonphysiologic, rapid make-break potentials characteristic of conductor fracture.

trigger device detection of a sustained ventricular arrhythmia serves to minimize inappropriate ICD shocks. The safety of such an extension in arrhythmia detection time is discussed later. However, as previously discussed, despite these programming changes, lead failure can occur quickly, and inappropriate ICD shocks might still be delivered.18 Supraventricular arrhythmias conducting to the ventricles above the ICD detection rate are common causes of multiple shocks.61 In this instance, device therapy does not reflect malfunction, but rather an appropriate response to tachycardia. The incidence of inappropriate shocks is higher in patients receiving an ICD for primary prevention than in those receiving secondary prevention.62,63 In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), 829 patients with class II or III congestive heart failure received an ICD for primary prevention. Of those, 259 (31%) received an ICD shock, and 32% of the shocks were inappropriate. Therefore, 10% of the population receiving a prophylactic ICD received inappropriate shocks.64 Atrial fibrillation (AF) is the most common cause of multiple shocks in patients undergoing ICD implantation for primary prevention.63 AF can be recognized by its EGM characteristics; the VEGM most often has the same morphology as in sinus rhythm (or AF, if it is the baseline) and is irregularly irregular (Fig. 30-19). In contrast, polymorphic VT, although irregularly irregular, has varying EGM morphologies (Fig. 30-20). Detection of atrial arrhythmias may be managed by both drug therapy and device programming. Beta-adrenergic blockers are a mainstay of therapy to decrease atrioventricular (AV) conduction and are antiarrhythmic themselves. Antiarrhythmic drugs may be prescribed to decrease the frequency of arrhythmia recurrence. Sotalol65 and azimilide66 have been efficacious in this regard, and although they avoid the organ toxicities associated with amiodarone, azimilide was

never market released because it caused neutropenia. ICD programming to avoid inappropriate therapies for supraventricular arrhythmias depend in part on whether a single- or dual-lead system is present.67-69 For single-lead systems, detection enhancements to recognize rate stability and sudden onset are useful. For dual-lead systems, these parameters are used in addition to functions that assess AV relationships. It is controversial whether the addition of an atrial lead improves tachycardia discrimination.70-72 Multiple reports beginning in the 1990s, when stored EGMs became available, consistently show that the most common cause of inappropriate shocks is SVT.61 Despite the presence of an atrial lead, the risk of inappropriate shocks from atrial arrhythmias remains about 20% to 30%. In the Antiarrhythmics Versus Implantable Defibrillators (AVID) study, in which singlechamber ICDs were primarily used, the incidence of shocks was 11% for AF and 9% for other SVTs.62 In a randomized trial that compared the incidence of inappropriate therapies from single-chamber versus dual-chamber ICDs, 21% of dual-chamber patients received inappropriate therapy despite having detection enhancements enabled. Theuns et al.71 randomly assigned patients with dual-chamber ICDs to singleor dual-chamber detection. Overall, there was no difference in atrial and ventricular arrhythmia discrimination between the two settings. Figure 30-19 shows an EGM recorded from a patient in whom AF triggered an ICD shock despite a 100% template match with a supraventricular rhythm; despite the match, the timer withholding therapy expired, overriding the discriminator. Multiple shocks may also be a proarrhythmic response to drugs or to the ICD itself. Repetitive VT and VF can be a consequence of antiarrhythmic drug proarrhythmia. In addition, attention to the history may reveal the ingestion of a cardiac stimulant.73,74 Proarrhythmia may



30  Troubleshooting of Implantable Cardioverter-Defibrillators

* * T T T T R T T T T T T 100 100 100 100 100 100 100 100 100 100 100 100 D 395 324 371 406 457 414 387 363 406 398 348 387 379 582 R R R R R R R R R R R R R R 40 41 42 43 44 45 T

*

* R

R

R

R

H V 605V

453 375 418 367 352 R R R R R 48 49 50

51

S

S

S

480 V

453 R 52

492 R

*

*

*

* R

* R

903

* R

422 395 422 379 313 402 R R R R R R 46 47 48

S

T T T F T RS 100 85 88 100 71 90 422 516 402 410 332 289 R R R R R R R R 53 54 55 56

Figure 30-19  Electrogram shows atrial fibrillation above the ventricular tachycardia detection rate leading to an ICD shock (Model V199 ICD, Ventritex/St. Jude Medical). The EGM morphology is constant (top tracing), and the notations in the marker channel below signify a 100% match to an EGM template of a signal produced by conduction from the atria to the ventricles (i.e., a “sinus beat”). Therapy was delivered because this device has a timer which, when expired, overrides the supraventricular tachycardia discriminator and releases shock therapy as a safety measure so that therapy, if withheld in error, will not be withheld indefinitely.

Sinus rhythm

Torsades de pointes

Ventricular fibrillation and sinus rhythm

Discharge Figure 30-20  This stored electrogram (EGM) is from a 12-year-old boy with the familial long QT syndrome who had an ICD implanted after resuscitation from a cardiac arrest. After he collapsed in school, ICD interrogation showed sinus rhythm (note long QT even on EGM) followed by torsades de pointes ventricular tachycardia (VT), characterized by a polymorphic and constantly changing morphology, and degeneration to ventricular fibrillation (VF). The VF was terminated by a shock, which is labeled on the third tracing. In contrast to the tracing shown in Figure 30-1, there was no monomorphic VT preceding VF. (From Moss AJ, Daubert JP: Images in clinical medicine: Internal ventricular defibrillation. N Engl J Med 342:398, 2000.)

904

SECTION 4  Follow-up and Programming

I

II

N V

V

q

V

V

V

V A

V

V

q

V

V

V

V

q

V

A

V

A

B Figure 30-21  Two examples of pacing-induced ventricular tachycardia (VT). A, Telemetry recordings from a hospitalized patient. A premature ventricular contraction (second beat) is not sensed by the ICD; the ICD then delivers two pulses for bradycardia backup pacing, which induce VT. B, Sinus rhythm with a P wave blocked in the atrioventricular conduction system, leading to a pause in the ventricular rhythm. The next ventricular depolarization induces VT. The three tracings show EGMs from, respectively, the atrial and ventricular pace/sense channels and the high-voltage channel of a dual-chamber ICD (Guidant, Boston Scientific).

also be caused by the ICD itself.75-77 Pinski and Fahy76 review types of device proarrhythmia (see Box 30-1). A common cause of VT induction is undersensing of an ectopic beat, followed by a paced beat and subsequent induction of the ventricular arrhythmia (Fig. 30-21). Himmrich et al.77 studied patients with a history of tachycardia caused by right ventricular backup pacing and randomized them to no pacing or to VVI backup pacing at 60 bpm. No further pacemaker-induced tachycardias occurred in patients with pacing turned off, but did occur in five of six patients with pacemaker turned on. The induced arrhythmias were both monomorphic and polymorphic VTs. A recent development in programmability to decrease the delivery of shock therapy for VT is the option for antitachycardia pacing (ATP) for extremely rapid VTs. Previously it was believed that such an approach would not only be inefficacious but also unsafe. In a prospective randomized trial comparing ATP with simple shock therapy for fast VTs, however, Wathen et al.78,79 showed that, for VTs in the range of 188 to 250 beats per minute, ATP was effective in terminating 81% (72% adjusted). Also, empirical ATP was equally safe and associated with improved quality of life compared with shock therapy for fast VTs. The morbidity of inappropriate shocks, both from supraventricular arrhythmias and from nonsustained ventricular arrhythmias, led to further efforts to define the most appropriate programming for patients receiving ICDs for primary prevention. Wilkoff et al.80 showed that empirical programming designed to reduce ICD shocks for SVT and nonsustained VTs as well as empirical ATP performed at least as well as programming tailored to the individual patient by the implanting physician, in terms of reducing unnecessary shocks and avoiding undertreatment of sustained VTs. The authors then extended these findings to a more diverse group of patients undergoing ICD implantation.81 The effectiveness of longer detection times (30 of 40 beats) was further tested in terms of avoiding unnecessary shocks, as well as the safety of such a detection time in terms of arrhythmic syncope and undertreated ventricular arrhythmias. Compared with a control group of patients with devices programmed to treat much slower arrhythmias, the longer detection times and use of ATP did reduce the number

of patients receiving inappropriate therapy, but at a slight increase in the number of patients experiencing arrhythmic syncope. These findings demonstrate that longer detection times and the use of ATP can, in primary prevention patients, safely reduce the incidence of inappropriate ICD therapy for supraventricular arrhythmias and nonsustained ventricular arrhythmias. As mentioned, these longer detection times can also be used to reduce the incidence of lead fracture associated ICD shocks. Additional trials are under way to further define the programming parameters that will reduce inappropriate ICD shocks. A strategy of prophylactic catheter ablation was recently shown to reduce ICD therapy by 65% in a group of patients with ischemic cardiomyopathy who received an ICD after presenting with sustained ventricular arrhythmias.82 The generalizability of this finding to patients with nonischemic cardiomyopathy and prior sustained ventricular arrhythmias, or patients receiving ICDs for primary prevention, has not been examined. In some situations, ICDs have been implanted in patients who failed therapy or were deemed poor candidates for medical therapy to treat sustained idiopathic VT. With the increased availability and effectiveness of catheter ablation, many of these patients can now undergo curative ablation procedures, with minimal residual risk of recurrent ventricular arrhythmias. Discontinuing ICD therapy should be discussed with the patient. In these situations the risks and benefits of header and lead extraction must be weighed against continuing therapy.

Other Presentations FAILURE TO CONVERT VENTRICULAR TACHYCARDIA OR VENTRICULAR FIBRILLATION Problems related to the myocardial substrate, ICD programming, or ICD function are the usual reasons for failure to convert an arrhythmia. Changes in substrate may include ischemia resulting in



30  Troubleshooting of Implantable Cardioverter-Defibrillators

TABLE

30-2 

Nonconversion of Ventricular Tachycardia (VT) or Ventricular Fibrillation (VF)

Cause Problems with VT therapy   Pacing algorithm   Elevated pacing/cardioversion threshold   Incessant VT Problems with VF therapy   Elevated defibrillation threshold   Fixed voltage/pulse width   Incessant VF Faulty lead system: Dislodgment, fracture, loose connector ICD failure Battery depletion ICD-pacemaker interaction Abandoned electrode shunting energy

Management For both VT and VF problems:   Change therapy prescription.   Decrease time to therapy.   Reverse polarity.   Change current path.   Change waveform.   Change drugs that affect rate or DFT.   Treat myocardial substrate. Revise lead system Replace ICD. Replace ICD. Revise system or reprogram if feasible. Extract extra lead.

DFT, Defibrillation threshold.

polymorphic ventricular arrhythmias or VF, worsened heart failure that causes new arrhythmias or conversion to incessant ones, and any combination of events that may increase the pacing, cardioversion, or defibrillation thresholds (Table 30-2). Problems with therapy most often include the programming of ineffective pacing or shock therapies. ATP may be either underaggressive or overaggressive, resulting in failure of conversion or arrhythmia acceleration.75-77 If ventricular arrhythmias persist, they may become self-perpetuating because of ischemia and myocardial stretch exacerbated by hemodynamic compromise. These factors, as well as the arrhythmia duration itself, may also elevate the defibrillation threshold (DFT).83 Other factors that may affect shock efficacy relate not only to the amount of delivered energy but also to the shock waveform. For example, efficacy may be improved by altering the tilt of the shock waveform. Evidence indicates that a 50%/50% tilt is more efficacious than the nominal 65%/65% waveform.84 St. Jude Medical devices allow for optimization of the biphasic waveform by varying the duration of

905

each phase of the shock to accommodate the individual patient’s DFT. These observations are not transferable to the waveforms of all manufacturers. For Medtronic devices, a randomized comparison of biphasic waveforms with 65%/65% versus 42%/42% tilt found no difference in the DFT.85 A related factor is the position of the ICD lead in the right ventricle. Although adequate defibrillation can occur with many different lead positions, failure to convert VF can sometimes be addressed by moving the lead to a more apical position that then encompasses more of the heart in the shock vector.86 Likewise, the efficacy of placement of a subcutaneous lead or array on lowering the DFT can be influenced by the placement of the array and its relation to the heart.87 Lead perforation can lead to inadequate defibrillation by altering the shock vector (see Fig. 30-10). Therapy may also fail if there is component failure of either the ICD (uncommon but reported)1 or any of its leads. In the past, defective crystal oscillators led to rapid ventricular pacing, VF, and inability to deliver shock therapy.88 More recently, electrical overstress (EOS) has led to ICD failure.89 EOS is the damage to electrical components caused by high voltages or currents that arc within a pulse generator. In addition, recent occurrences of disabling of ICDs have been caused not only by electromagnetic interference but also by health care professionals unaware that magnet application might permanently inactivate tachycardia detection.90 Although interactions between separately implanted pacemakers are less common today, in the past they did interfere with ICD function. Although it was more common for a pacemaker to inhibit detection by asynchronously pacing during VF62 (Fig. 30-22), pacing may also reinitiate VT or VF after ICD therapy. Antiarrhythmic drugs are often used in conjunction with ICD therapy (Box 30-2). These agents not only have beneficial effects of decreasing arrhythmia occurrence, but also may affect ICD detection and therapy (Figs. 30-23 and 30-24). Sodium channel blockers and amiodarone may increase the DFT, rendering therapy ineffective.91-93 Because remote monitoring has not been available until recently for ICD follow-up94,95 and warning features (e.g., beeping by the ICD on achievement of the elective replacement indicator),96 battery depletion may also prevent delivery of effective therapy.

1 sec 58

I

DCCV

VF II Pacer Artifact V1 AFL

Sinus brady

HRA

LRA RV Figure 30-22  Electrogram shows result of intraoperative testing of ICD implanted with unipolar pacemaker. The pacemaker was not fully inhibited during ventricular fibrillation (VF), and the large pacemaker artifacts (arrows in lead V1) were randomly delivered. The ICD failed to recognize VF because it interpreted these large artifacts as a supraventricular rhythm not in the tachycardia detection zone. Sinus rhythm was restored by an external shock (DCCV). (From Kim SG, Furman S, Waspe LE, et al: Unipolar pacer artifacts induced failure of an automatic implantable cardioverter/ defibrillator to detect ventricular fibrillation. Am J Cardiol 57:881-882, 1986.)

906

SECTION 4  Follow-up and Programming

Box 30-2 

TABLE

EFFECTS OF ANTIARRHYTHMIC DRUGS ON ICDS Beneficial Reduce inappropriate shocks Suppress sustained VT/SVT Suppress nonsustained VT/SVT Enhance antitachycardia pacing efficacy Reduce symptoms by slowing VT rate Lower DFT (e.g., dofetilide, sotalol) Adverse Increase DFT Increase pacing threshold Worsen LV function Proarrhythmia Increase frequency of VT and/or VF Organize atrial fibrillation to atrial flutter with a rapid ventricular response Sensing interference Increase tachycardia cycle length such that VT not detected Increase VT cycle length variability so that therapy is inappropriately withheld Create bradycardia or conduction disturbances, leading to: Increased pacing and earlier battery depletion Pacemaker syndrome Worsened CHF by right ventricular pacing-provoked LV dyssynchrony Cost Constitutional side effects CHF, Congestive heart failure; DFT, defibrillation threshold; LV, left ventricular; VF, ventricular fibrillation; VT/SVT, ventricular tachycardia/supraventricular tachycardia.

FAILURE TO DETECT VENTRICULAR TACHYCARDIA OR VENTRICULAR FIBRILLATION The first question to ask when an arrhythmia is not detected is whether the ICD system is activated. Is a magnet over the device, or has one been used to permanently turn it off?90 Second, if the arrhythmia is ongoing, is its rate below the ICD detection rate? Has a new drug been started (e.g., amiodarone or a class IC agent) that has slowed the tachycardia rate below the detection rate (see Fig. 30-24)? Has a new drug provoked a new VT, such as torsades de pointes VT? Is the battery depleted?

30-3 

Nondetection of Ventricular Tachycardia (VT) or Ventricular Fibrillation

Cause Improper/phantom programming (e.g., is system activated?) VT below detection rate: New VT VT slowed by drug(s) Detection enhancements Undersensing: Deterioration of R wave Oversensing of pacemaker stimulus artifacts Magnet application Battery depletion

Management Reprogram. Reprogram detection rate. Change drugs. Disable; reprogram. Increase sensitivity. Decrease sensitivity; reposition lead. Remove magnet. Replace device.

The most common reasons for nondetection are inappropriate programming (Table 30-3). Lead dysfunction may also prevent arrhythmia detection. As previously noted, the presence of a second device (e.g., pacemaker) may lead to detection inhibition if sensing of separate pacemaker stimulus artifacts is interpreted by the ICD as a “normal rhythm.” VT and VF may be undersensed97-99 (see Fig. 30-15). VF nondetection or underdetection is usually caused by low-amplitude VF signals (i.e., below sensitivity of device). This is more common with integrated bipolar leads than with dedicated bipolar leads.78 As mentioned, lead perforation can result in both undersensing of ventricular arrhythmias and failure of pacing as the lead tip exits the myocardium (see Fig. 30-10). Detection enhancements were developed to decrease the frequency of inappropriate shocks caused by SVT (Table 30-4); the literature is mixed on their efficacy. However, the requirement that criteria other than rate must be satisfied before initiation of arrhythmia therapy increases the possibility of falsely failing to detect a VT. Swerdlow et al.99 identified six mechanisms of underdetection of VT caused by algorithms to discriminate VT from supraventricular rhythms and nonsustained VT: (1) onset not satisfied (e.g., gradual onset, especially slower ones in sinus tachycardia), (2) stability not satisfied (e.g., irregular-cycle VT length not satisfying a rate stability criterion to exclude a false diagnosis of AF with a rapid ventricular response as VT or VF), (3) isolated long intervals, (4) VT-VF competition, (5) failure

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V6

V3 Figure 30-23  This 12-lead electrocardiogram (ECG) was recorded in the early 1980s, when ICD rate criteria were not programmable. The slow ventricular tachycardia with a rate 113 beats per minute (bpm) was well below the ICD detection rate of 156 bpm. Despite symptoms, the patient drove for 4 hours to seek help. Even today, if rate criteria are not satisfied, arrhythmia detection will not occur.



907

30  Troubleshooting of Implantable Cardioverter-Defibrillators VF detection

A R

8 0 0

ICD shock with 15.2 J

7 9 0

A R

V V V V V V V V C S S S S S S S S E 2 1 1 1 1 1 2 1 0 8 6 3 5 5 1 9 0 0 0 0 0 0 0 0

1160

A S

V V C R S D 1 1 9 9 0 0 152J

4 7 0

8 7 0

A S

7 5 0

A S

T P

1200

VF detection

V P

5 3 0

7 1 0

A S V P

7 5 0

8 6 0

7 1 0

2 1 0

A

V S

ICD shock with 19.4 J

1760

A R

2 8 0

V S

1 9 0

V S

2 3 0

V S

2 1 0

V S

2 2 0

V S

5 7 0

V V C R S D 2 1 0 3 0 0

A R V S

6 0 0

9 1 0

2 3 0

F S

2 3 0

F S

2 3 0

F S

2 2 0

F S

2 2 0

F S

B Continuous VF

8 7 0

8 6 0

A R

V S

2 4 0

V S

2 3 0

V S

2 2 0

V S

2 1 0

V S

ICD shock with 33.6 J

1760

A R 2 1 0

V C S E 1 5 0

4 6 0

C D

6 6 0

V S

2 4 0

External shock

9 0 0

A R F S

2 3 0

F S

2 2 0

F S

2 1 0

F S

2 2 0

F S

2 0 0

F S

9 3 0

A R 2 4 0

F S

2 4 0

F S

2 4 0

F D

2 3 0

V S

4 2 A 0 R 2 1 0

V S

2 5 0

V S

1 9 0

V S

A R 2 1 0

V S

6 7 0

7 8 0

T P 7 8 0

T P

C Figure 30-24  Amiodarone increasing defibrillation threshold (DFT). In the absence of amiodarone, DFT was 14 J (A). After amiodarone was started for atrial fibrillation, follow-up testing with shocks of 19.4 J (B) and 33.6 J (C) were ineffective. An external shock was required for restoration of sinus rhythm. The three tracings in all plates show, top to bottom, atrial EGM, ventricular EGM, and marker channel. (From Rajawat YS, Patel VV, Gerstenfeld EP, et al: Advantages and pitfalls of combining device-based and pharmacologic therapies for the treatment of ventricular arrhythmias: Observations from a tertiary referral center. Pacing Clin Electrophysiol 27:1670-1681, 2004.)

to reconfirm VT, and (6) post-VF suspension of VT detection. Currently, another reason for nondetection is morphology of the endocardial EGM similar to that of supraventricular origin. Importantly, the degree of morphology “match” used to distinguish between the template “normal” EGM and the “arrhythmia” EGM is both programmable and as a nominal value less than 100%, often much less, to account TABLE

30-4 

Detection Enhancements

Manufacturer Biotronik (Berlin) ELA Medical (Sorin Group, Milan) Guidant (Boston Scientific, Natick, Mass.) Medtronic (Minneapolis, Minn.) St. Jude Medical (St. Paul, Minn.)

Dual-Chamber Discrimination Enhancements SMART Detection Algorithm: Ventricular versus atrial rates, P-P and R-R stability, AV relationship and multiplicity, and suddenness of onset PARAD Algorithm: R-R stability, P-R association, and ventricular acceleration Suddenness of onset, rate stability, atrial fibrillation rate and stability, and ventricular rate versus atrial rates, Rhythm ID PR Logic Algorithm: Pattern of A-V and V-A intervals; atrial and ventricular rates; evidence for atrial fibrillation, AV dissociation, and ventricular R-R irregularity; analysis for R-wave sensing in atrial channel; VEGM morphology Suddenness of onset, AV association and relation of atrial and ventricular rates, interval stability, and VEGM morphology

AV, Atrioventricular; VEGM, ventricular electrogram.

for rate-related changes in EGM morphology.100,101 Experience with these algorithms, however, suggests that there may be errors in classification resulting from morphology changes with time, after shocks, or caused by bundle branch block.102,103 A newly recognized cause of underdetection is the application of algorithms to smooth and stabilize the ventricular rate during pacing.104-107 The common denominator of this mechanism of underdetection is intradevice interaction between pacing parameters and tachycardia detection, which usually leads to the undersensing of ventricular events during blanking periods while pacing. For example, during rate smoothing, to avoid ventricular sensing of atrial stimuli, after each atrial stimulus the ventricular channel is blanked for a fixed interval. In addition, after each ventricular stimulus, the ventricular channel is blanked again. When rate smoothing is activated to decrease symptoms secondary to varying heart rates, ventricular blanking after rapid atrial pacing can lead to nondetection of VT. PROBLEMS WITH PACING Current ICDs provide both bradycardia and antitachycardia pacing therapies. Pacing for either indication may fail because of lead dysfunction or a change in the pacing threshold resulting from a change in substrate or physiologic milieu, such as addition of a drug (e.g., flecainide) that increases pacing threshold.93 Radiofrequency ablation may cause not only inappropriate shock therapy but also inhibition of

908

TABLE

30-5 

SECTION 4  Follow-up and Programming

Problems with Pacing

Cause Increased pacing threshold T-wave sensing inhibits ventricular pacing R-wave sensing inhibits atrial pacing Atrial electrical activity inhibits ventricular pacing Faulty lead system

Management Reprogram, occasionally replace lead. Reprogram ventricular refractory period or sensitivity. Reprogram atrial refractory period or sensitivity. Decrease sensitivity or replace lead. Revise lead system.

pacing. Although theoretically radiofrequency energy may alter the lead-tissue interface and increase the pacing threshold, this has not been observed.108 However, magnetic resonance imaging (MRI) can increase the pacing threshold and alter component function.109 As in arrhythmia nondetection, the most common cause of abnormal pacing for bradycardia is inappropriate programming (Table 30-5). Pacing may be inhibited by T-wave110 and even far-field P-wave sensing in the ventricular channel. As described earlier, oversensing usually leads to inappropriate shock therapy rather than inhibition of pacing.31-33,111-113 Programming may be both the cause and the remedy for sensing problems. Certain St. Jude Medical ICDs permit separate sensitivity programming for bradycardia and tachycardia detection. This can be an important consideration for patients who are pacemaker dependent and at risk for ventricular oversensing of either P waves or noncardiac electrical signals. A serious cause of abnormal pacing is lead failure, as discussed earlier with regard to the production of electrical noise artifact and inappropriate shocks.6,28,52-60 ICD leads are complex, with more components than simple pacing leads. This complexity increases the chance for failure. Failure may occur in the conductor, insulation, or connector pins. The fault may be in the header, the yoke, or body of the lead within the vascular system. With subclavian approaches to lead implantation, crush is possible.4,5 Although the devices are large, “twiddling” may occur23,24 (see Fig. 30-9). Also, leads may become dislodged (see Figs. 30-5 and 30-6).

Other Issues

minimize device malfunction are used at centers evaluating the safety and efficacy of MRI scanning on ICD patients.109,114-116,119 To extrapolate these findings to the general population would require much greater numbers. Furthermore, even proponents of MRI safety with ICDs acknowledge that “minimal” changes in pacing threshold and battery function may occur.109 Although a small change in pacing threshold or battery function may be acceptable most of the time, it can be disastrous if safety margins are small, as when batteries are near their end of life or in patients with borderline pacing thresholds. Safety concerns such as those listed must be carefully weighed against the usefulness of information obtained from the MRI scan. Interactions with new scanners having field strengths greater than 1.5 tesla remain unknown. Rarely, ICD programmers can malfunction. They are slow, and programming is sometimes not intuitive. In the operating room, these issues are frustrating, and malfunction sometimes can be handled only by powering down and rebooting the system or obtaining a new programmer. Current ICDs are well shielded from external shocks. Nevertheless, cardioversion or defibrillation may injure the device. Therefore, whenever external shocks are given, paddles must be placed as far from the ICD as possible. In an emergency situation, patient resuscitation obviously takes precedence over saving the device. In addition, other medical equipment may injure an ICD, specifically shock wave lithotripsy.121 The beam should always be aimed away from the ICD if possible. Importantly, psychological issues must be considered when taking care of patients with ICDs, and psychological problems certainly fall into the realm of troubleshooting.122,123 With patients who have received shocks, imagined shocks, and “phantom shocks,” the shock may cause concern for them and their families. Explanation is usually satisfactory, but sometimes fear of shocks can be debilitating, similar to a posttraumatic stress disorder. Indeed, patients receiving ICD shocks can have a worse prognosis than ICD patients who have not received an ICD shock.25-27 Besides counseling, drug therapy may be warranted to decrease anxiety and depression. Further investigation is needed to determine ways to reduce the morbidity associated with ICD shocks. The combination of a benzodiazepine and serotonin reuptake inhibitor is especially useful.

Conclusion

As in all fields of medicine, technologic advances and progress in defibrillation and pacing bring new and unanticipated problems. The use of MRI has expanded, and although its use generally is contraindicated in patients with an ICD, studies now report on its safety. A completely protected ICD has yet to be developed. Although some clinicians suggest MRI scanning may be safe with newer devices,109,114-116 it is probably premature to make this a general conclusion.117,118 Not only have interactions been reported,120 but series purporting device safety have included only small numbers of patients with relatively few devices. Indeed, specific device programming protocols designed to

Implantable cardioverter-defibrillator troubleshooting requires systematic analysis of evidence based on history, physical examination, and analysis of retrieved ICD information. Problems may be approached from the perspective of multiple shocks or other clinical presentation (failure to detect, failure to convert, problems with pacing) or as those of the system components (ICD battery, programming, integrity, and lead integrity and function). With the remarkable diagnostic capabilities of current devices, the reason for an ICD system problem can usually be identified and, in the absence of component failure, remedied by reprogramming.

REFERENCES 1. Hauser RG, Kallinen L: Deaths associated with implantable cardioverter defibrillator failure and deactivation reported in the United States Food and Drug Administration Manufacturer and User Facility Device Experience Database. Heart Rhythm 4:399405, 2004. 2. Epstein AE: Approach to the patient with suspected implantable cardioverter-defibrillator system malfunction. J Cardiovasc Electrophysiol 2:330-333, 1998. 3. Ballas SL, Rashidi R, McAlister H, et al: The use of beep-o-grams in the assessment of automatic implantable cardioverter defibrillator sensing function. Pacing Clin Electrophysiol 12:1737-1745, 1989. 4. Magney JE, Parsons JA, Flynn DM, Hunter DW: Pacemaker and defibrillator lead entrapment: case studies. Pacing Clin Electrophysiol 18:1509-1517, 1995.

5. Gallik DM, Ben-Sur U, Gross JN, Furman S: Lead fracture in cephalic versus subclavian approach with transvenous implantable cardioverter defibrillator systems. Pacing Clin Electrophysiol 19:1089-1094, 1996. 6. Lawton JS, Ellenbogen KA, Wood MA, et al: Sensing lead-related complications in patients with transvenous implantable cardioverter-defibrillators. Am J Cardiol 78:647-651, 1996. 7. Gupta A, Zegel HG, Dravid VS, et al: Value of radiography in diagnosing complications of cardioverter defibrillators implanted without thoracotomy in 437 patients. AJR Am J Roentgenol 168:105-108, 1997. 8. Exner DV, Pinski SL, Wyse DG, et al: Electrical storm presages nonsudden death: the Antiarrhythmics versus Implantable Defibrillators (AVID) Trial. AVID Investigators. Circulation 103:2066-2071, 2001.

9. Credner SC, Klingenheben T, Mauss O, et al: Electrical storm in patient with transvenous implantable cardioverter-defibrillators: incidence, management and prognostic implications. J Am Coll Cardiol 32:1909-1915, 1998. 10. Whang W, Mittleman MA, Rich DQ, et al: Heart failure and the risk of shocks in patients with implantable cardioverter defibrillators: results from the Triggers of Ventricular Arrhythmias (TOVA) study. TOVA Investigators. Circulation 109:1386-1391, 2004. 11. Marchlinski FE, Callans DJ, Gottlieb CD, et al: Benefits and lessons learned from stored electrogram information in implantable defibrillators. J Cardiovasc Electrophysiol 6:832-851, 1995. 12. Gunderson BD, Patel AS, Bounds CA, et al: An algorithm to predict implantable cardioverter-defibrillator lead failure. J Am Coll Cardiol 44:1898-1902, 2004.



30  Troubleshooting of Implantable Cardioverter-Defibrillators 13. Jung W, Rillig A, Birkemeyer R, et al: Advances in remote monitoring of implantable pacemakers, cardioverter-defibrillators and cardiac resynchronization therapy systems. J Interv Card Electrophysiol 23:73-85, 2008. 14. Orlov MV, Szombathy T, Chaudhry GM, Haffajee CI: Remote surveillance of implantable cardiac devices. Pacing Clin Electrophysiol 32:928-939, 2009. 15. Varma N: Rationale and design of a prospective study of the efficacy of a remote monitoring system used in implantable cardioverter defibrillator follow-up: the Lumos-T Reduces Routine Office Device Follow-Up Study (TRUST). Am Heart J 154:1029-1034, 2007. 16. Varma N, Epstein AE, Irimpen A, et al: Early detection of ICD events using remote monitoring: the TRUST trial [abstract]. Heart Rhythm 6:S125, 2009. 17. Varma N, Epstein AE, Schweikert RA, et al: Evaluation of efficacy and safety of remote monitoring for ICD follow-up: the TRUST trial [abstract]. Circulation 118:2316, 2008. 18. Crossley GH et al: The Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT) trial: the value of remote monitoring. Abstract presented at American College of Cardiology’s 59th Annual Scientific Session’s Late Breaking Clinical Trials, 2010. 19. Kallinen LM, Hauser RG, Lee KW, et al: Failure of impedance monitoring to prevent adverse clinical events caused by fracture of a recalled high-voltage implantable cardioverter-defibrillator lead. Heart Rhythm 5:775-779, 2008. 20. Simons EC, Feigenblum DY, Nemirovsky D, Simons GR: Alert tones are frequently inaudible among patients with implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 32:12721275, 2009. 21. Prickett RA, Saavedra P, Ali MF, et al: Implantable cardioverterdefibrillator malfunction due to mechanical failure of the header connection. J Cardiovasc Electrophysiol 14:1095-1099, 2004. 22. Kratz JM, Schabel S, Leman RM: Pseudo fracture of a defibrillating lead. Pacing Clin Electrophysiol 18:2225-2226, 1985. 23. Beauregard LAM, Russo AM, Heim J, et al: Twiddler’s syndrome complicating automatic defibrillator function. Pacing Clin Electrophysiol 18:735-738, 1995. 24. Boyle NG, Anselme F, Monahan KM, et al: Twiddler’s syndrome variants in ICD patients. Pacing Clin Electrophysiol 21:26852687, 1998. 25. Moss AJ, Greenberg H, Case RB, Zareba W, et al: Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) Research Group. Circulation 110:3760-3765, 2004. 26. Poole JE, Johnson GW, Hellkamp AS, Anderson J, et al: Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 359:1009-1017, 2008. 27. Sweeney MO, Sherfesee L, DeGroot PJ, et al: Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients. Heart Rhythm 7:353-360, 2010. 28. Miller JM, Hsia HH: Management of the patient with frequent discharges from implantable cardioverter defibrillator devices. J Cardiovasc Electrophysiol 7:278-285, 1996. 29. Nademanee K, Taylor R, Bailey WE, et al: Treating electrical storm: sympathetic blockade versus advance cardiac life support–guided therapy. Circulation 102:742-747, 2000. 30. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E: Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation 101;1288-1296, 2000. 31. Peters W, Kowallik P, Wittenberg G, et al: Inappropriate discharge of an implantable cardioverter-defibrillator during atrial flutter and intermittent ventricular antibradycardia pacing. J Cardiovasc Electrophysiol 8:1167-1174, 1997. 32. Scaglione J, Socas AG, De Palma C, Kreutzer E: Inappropriate single chamber ICD discharges due to supraventricular tachycardia with high degree atrioventricular block. J Interv Card Electrophysiol 11:73-76, 2004. 33. Kelly PA, Mann DE, Damle RS, Reiter MJ: Oversensing during ventricular pacing in patients with a third-generation implantable cardioverter-defibrillator. J Am Coll Cardiol 23:1531-1534, 1994. 34. Coyne RF, Man DC, Sarter BH, et al: Implantable cardioverterdefibrillator oversensing during periods of rate-related bundle branch block. J Cardiovasc Electrophysiol 8:807-811, 1997. 35. Krishen A, Shepard RK, Leffler JA, et al: Implantable cardioverter defibrillator T wave oversensing caused by hyperglycemia. Pacing Clin Electrophysiol 24:1701-1703, 2001. 36. Porres JM, Brugada J, Marco P, et al: T wave oversensing by a cardioverter defibrillator implanted in patient with the Brugada syndrome Pacing Clin Electrophysiol 27:1563-1565, 2004. 37. Sandler MJ, Kutalek SP: Inappropriate discharge by an implantable cardioverter defibrillator: recognition of myopotentials sensing using telemetered intracardiac electrograms. Pacing Clin Electrophysiol 17:665-671, 1994. 38. Karanam S, John RM: Inappropriate sensing of pectoral myopotentials by an implantable cardioverter-defibrillator system. Pacing Clin Electrophysiol 27:688-689, 2004. 39. Sweeney MO, Ellison KE, Shea JB, Newell JB: Provoked and spontaneous high-frequency, low-amplitude, respirophasic noise transients in patients with implantable cardioverterdefibrillators. J Cardiovasc Electrophysiol 12:402-410, 2001.

40. Schulte B, Sperzel J, Carlsson J, et al: Inappropriate arrhythmia detection in implantable defibrillator therapy due to oversensing of diaphragmatic myopotentials. J Interv Card Electrophysiol 5:487-493, 2001. 41. Allison JS, Epstein AE, Plumb VJ: Electrical noise artifact: from without or within? J Cardiovasc Electrophysiol 18:332-333, 2007. 42. Pinski SL, Trohman RG: Interference in implanted cardiac devices. Part 1. Pacing Clin Electrophysiol 25:1367-1381, 2002. 43. Casavant D, Haffajee C, Stevens S, Pacetti P: Aborted implantable cardioverter-defibrillator shock during facial electrosurgery. Pacing Clin Electrophysiol 21:1325-1326, 1998. 44. Matthew P, Lewis C, Neglia J, et al: Interaction between electronic article surveillance systems and implantable defibrillators: insights from a fourth-generation ICD. Pacing Clin Electrophysiol 20:2857-2859, 1997. 45. Seifert T, Block M, Borggrefe M, Breithardt G: Erroneous discharge of an implantable cardioveter-defibrillator caused by an electric razor. Pacing Clin Electrophysiol 18:1592-1594, 1995. 46. Man KC, Davidson T, Langberg JJ, et al: Interference from a hand-held radiofrequency remote control causing discharge of an implantable defibrillator. Pacing Clin Electrophysiol 16:17561758, 1993. 47. Heif C, Podczeck A, Krohner K, et al: Cardioverter discharges following sensing of electrical artifact due to fluid penetration in the connector port. Pacing Clin Electrophysiol 18:1589-1591, 1995. 48. Crevenna R, Stix G, Pleiner J, et al: Electromagnetic interference by transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverter defibrillators: a pilot safety study. Pacing Clin Electrophysiol 26:626-629, 2003. 49. Tri JL, Trusty JM, Hayes DL: Potential for personal digital assistant interference with implantable cardiac devices. Mayo Clin Proc 79:1527-1530, 2004. 50. Madrid A, Sánchez A, Bosch E, et al: Dysfunction of implantable defibrillators caused by slot machines. Pacing Clin Electrophysiol 20:212-214, 1997. 51. Sabaté X, Moure C, Nicholás J, et al: Washing machine associated 50 Hz detected as ventricular fibrillation by an implanted cardioverter-defibrillator. Pacing Clin Electrophysiol 24:12811283, 2001. 52. Lawton JS, Wood MA, Gilligan DM, et al: Implantable transvenous cardioverter-defibrillator leads: the dark side. Pacing Clin Electrophysiol 19:1273-1278, 1996. 53. Brady PA, Friedman PA, Trusty JM, et al: High failure rate for an epicardial implantable cardioverter-defibrillator lead: implications for long-term follow-up of patients with an implantable cardioverter-defibrillator. J Am Coll Cardiol 31:616-622, 1998. 54. Stambler BS, Wood MA, Damiano RJ, et al: Sensing/pacing lead complications with a newer generation implantable cardioverterdefibrillator: worldwide experience from the Guardian ATP 4210 Multicenter Clinical Trial. J Am Coll Cardiol 23:123-132, 1994. 55. Ellenbogen KA, Wood MA, Shepard RK, et al: Detection and management of an implantable cardioverter-defibrillator lead failure: Incidence and clinical implications. J Am Coll Cardiol 41:73-80, 2003. 56. Hauser RG, Kallinen LM, Almquist AK, et al: Early failure of a small-diameter high-voltage implantable cardioverterdefibrillator lead. Heart Rhythm 4:892-896, 2007. 57. Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008. 58. Dorwarth U, Frey B, Dugas M, et al: Transvenous defibrillation leads: high incidence of failure during long-term follow-up. J Cardiovasc Electrophysiol 14:38-43, 2003. 59. Hauser RG, Cannom D, Hayes DL, et al: Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads. Pacing Clin Electrophysiol 25:879-882, 2002. 60. Kettering K, Mewis C, Dörnberger V, et al: Long-term experience with subcutaneous ICD leads: a comparison among three different types of subcutaneous leads. Pacing Clin Electrophysiol 27:1355-1361, 2004. 61. Grimm W, Flores BF, Marchlisnski FE: Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 15:1667-1673, 1992. 62. Klein RC, Raitt MH, Wilkoff BL, et al: Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics versus Implantable Defibrillators (AVID) Trial. The AVID Investigators. J Cardiovasc Electrophysiol 14:940-948, 2003. 63. Daubert JP, Zareba W, Cannom DS, et al: Frequency and mechanism of inappropriate implantable cardioverter-defibrillator therapy in MADIT-II. J Am Coll Cardiol 43:132A, 2004. 64. Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. N Engl J Med 352:225-237, 2005. 65. Pacifico A, Hohnloser SH, Williams JH, et al: The d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group. N Engl J Med 340:1855-1862, 1999. 66. Singer I, Al-Khalidi H, Niazi I, et al: Azimilide decreases recurrent ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators. J Am Coll Cardiol 43:39-43, 2004. 67. Swerdlow CD, Chen PS, Kass RM, et al: Discrimination of ventricular tachycardia from sinus tachycardia and atrial fibrillation

909

in a tiered-therapy cardioverter-defibrillator. J Am Coll Cardiol 23:1342-1355, 1994. 68. Dorian P, Philippon F, Thibault B, et al: Randomized controlled study of detection enhancements versus rate-only detection to prevent inappropriate therapy in a dual-chamber implantable cardioverter-defibrillator. The ASTRID Investigators. Heart Rhythm 1:540-547, 2004. 69. Hintringer F, Deibl M, Berger T, et al: Comparison of the specificity of implantable dual chamber defibrillator detection algorithms. Pacing Clin Electrophysiol 27:976-982, 2004. 70. Swerdlow CD: Supraventricular tachycardia–ventricular tachycardia discrimination algorithms in implantable cardioverterdefibrillators: state-of-the-art review. J Cardiovasc Electrophysiol 12:606-612, 2001. 71. Theuns DA, Klootwijk AP, Goedhart DM, Jordaens LJ: Prevention of inappropriate therapy in implantable cardioverterdefibrillators: results of a prospective, randomized study of tachyarrhythmia detection algorithms. J Am Coll Cardiol 44:2362-2367, 2004. 72. Theuns DA, Rivero-Ayerza M, Boersma E, Jordaens L: Prevention of inappropriate therapy in implantable defibrillators: A meta-analysis of clinical trials comparing single-chamber and dual-chamber arrhythmia discrimination algorithms. Int J of Cardiology 125:352-357, 2008. 73. Goldstein DS, Epstein AE: A shocking case of pseudoephedrine use. J Interv Card Electrophysiol 3:343-344, 1999. 74. McBride BF, Guertin D, White CM, Kluger J: Inappropriate implantable cardioverter-defibrillator discharge following consumption of a dietary weight loss supplement. Pacing Clin Electrophysiol 27:1317-1320, 2004. 75. Johnson NJ, Marchlinski FE: Arrhythmias induced by device antitachycardia therapy due to diagnostic nonspecificity. J Am Coll Cardiol 18:1418-1425, 1991. 76. Pinski SL, Fahy GJ: The proarrhythmic potential of implantable cardioverter-defibrillators. Circulation 92:1651-1664, 1995. 77. Himmrich E, Przibille O, Zellerhoff C, et al: Proarrhythmic effect of pacemaker stimulation in patients with implanted cardioverter-defibrillators. Circulation 108:192-197, 2003. 78. Wathen MS, Sweeney MO, GeGroot PJ, et al: Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease. The PainFREE Rx Investigators. Circulation 104:796-801, 2001. 79. Wathen MS, GeGroot PJ, Sweeney MO, et al: Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: pacing fast ventricular tachycardia reduces shock therapies (PainFREE Rx II) Trial results. Circulation 110:2591-2596, 2004. 80. Wilkoff BL, Ousdigian KT, Sterns LD, Wang ZJ, et al: A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective randomized multicenter EMPIRIC trial. J Am Coll Cardiol 48:330-339, 2006. 81. Wilkoff BL, Williamson BD, Stern RS, Moore SL, et al: Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 52:541-550, 2008. 82. Reddy VY, Reynolds MR, Neuzil P, Richardson AW, et al: Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med 357:2657-2665, 2007. 83. Windecker S, Ideker RE, Plumb VJ, et al: The influence of ventricular fibrillation duration on defibrillation efficacy using biphasic waveforms in humans. J Am Coll Cardiol 33:33-38, 1999. 84. Sweeney MO, Natale A, Volosin KJ, et al: Prospective randomized comparison of 50%/50% versus 65%/65% tilt biphasic waveform on defibrillation in humans. Pacing Clin Electrophysiol 24:60-65, 2001. 85. Shepard RK, DeGroot PJ, Pacifico A, et al: Prospective randomized comparison of 65%/65% versus 42%/42% tilt biphasic waveform on defibrillation thresholds in humans. J Interv Card Elecrophysiol 8:221-225, 2003. 86. Usui M, Walcott GP, KenKnight BH, Walker RG, et al: Influence of malpositioned transvenous leads on defibrillation efficacy with and without a subcutaneous array electrode. Pacing Clin Electrophysiol 18: 2008-2016, 1995. 87. Baker JH, Epstein AE, Voshage-Stahl L: A prospective, randomized evaluation of a nonthoracotomy implantable cardioverterdefibrillator lead system. Endotak/PRX Investigator Group. Pacing Clin Electrophysiol 20:72-78, 1997. 88. Carpenter CM, Galvin J, Guy M, McGovern BA: Runaway pacemaker in an implantable cardioverter defibrillator. J Cardiovasc Electrophysiol 9:1008-1011, 1998. 89. Hauser R, Hayes DL, Almquist AK, et al: Unexpected ICD pulse generator failure due to electronic circuit damage caused by electrical overstress. Pacing Clin Electrophysiol 24:1046-1054, 2001. 90. Rasmussen MJ, Friedman PA, Hammill SC, Rea RF: Unintentional deactivation of implantable cardioverter-defibrillators in health care settings. Mayo Clin Proc 77:855-859, 2002. 91. Brode SE, Schwartzman D, Callans DJ, et al: ICD-antiarrhythmic drug and ICD-pacemaker interactions. J Cardiovasc Electrophysiol 8:830-842, 1997. 92. Singer I, Guarnieri T, Kupersmith J: Implanted automatic defibrillators: effects of drugs and pacemakers. Pacing Clin Electrophysiol 11:2250-2262, 1988.

910

SECTION 4  Follow-up and Programming

93. Rajawat YS, Patel VV, Gerstenfeld EP, et al: Advantages and pitfalls of combining device-based and pharmacologic therapies for the treatment of ventricular arrhythmias: observations from a tertiary referral center. Pacing Clin Electrophysiol 27:1670-1681, 2004. 94. Anderson MH, Paul VE, Jones S, et al: Transtelephonic interrogation of the implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 15:1144-1150, 1992. 95. Joseph GK, Wilkoff BL, Dresing T, et al: Remote interrogation and monitoring of implantable cardioverter-defibrillators. J Interv Card Electrophysiol 11:161-166, 2004. 96. Becker R, Ruf-Richter J, Senges-Becker JC, et al: Patient alert in implantable cardioverter-defibrillators: toy or tool? J Am Coll Cardiol 44:95-98, 2004. 97. Sarter BH, Callans DJ, Gottlieb CD, et al: Implantable defibrillator diagnostic storage capabilities: evolution, current status, and future utilization. Pacing Clin Electrophysiol 21:1287-1298, 1998. 98. Natale A, Sra J, Axtell K, et al: Undetected ventricular fibrillation in transvenous implantable cardioverter-defibrillators: prospective comparison of different leads system-device combinations. Circulation 93:91-98, 1996. 99. Swerdlow CD, Ahern T, Chen PS, et al: Underdetection of ventricular tachycardia by algorithms to enhance specificity in a tiered-therapy cardioverter-defibrillator. J Am Coll Cardiol 24:416-424, 1994. 100. Swerdlow CD, Brown ML, Lurie K, et al: Discrimination of ventricular tachycardia from supraventricular tachycardia by a downloaded wavelet-transform morphology algorithm: a paradigm for development of implantable cardioverter-defibrillator detection algorithms. J Cardiovasc Electrophysiol 13:432-441, 2002. 101. Theuns DA, Rivero-Ayerza M, Goedhart DM, et al: Evaluation of morphology discrimination for ventricular tachycardia diagnosis in implantable cardioverter-defibrillators. Heart Rhythm 3:1332-1338, 2006. 102. Duru F, Bauersfeld U, Rahn-Schonbeck M, Candinas R: Morphology discriminator feature for enhanced ventricular tachycardia discrimination in implantable cardioverter defibrillators. Pacing Clin Electrophysiol 23:1365-1374, 2000.

103. Unterberg C, Stevens J, Vollmann D, et al: Long-term clinical experience with the EGM width detection criterion for differentiation of supraventricular and ventricular tachycardia in patients with implantable cardioverter defibrillators. Pacing Clin Electrophysiol 23:1611-1617, 2000. 104. Shivkumar K, Feliciano Z, Boyle NG, Wiener I: Intradevice interaction in a dual-chamber implantable cardioverter-defibrillator preventing ventricular tachycardia detection. J Cardiovasc Electrophysiol 11:1285-1288, 2000. 105. Glickson M, Beeman AL, Luria DM, et al: Impaired detection of ventricular tachyarrhymias by a rate-smoothing algorithm in dual-chamber implantable-defibrillators: intradevice interactions. J Cardiovasc Electrophysiol 13:312-318, 2002. 106. Wood MA, Ellenbogen KA, Shepard RK, Clemo HS: Atrioventricular sequential pacing by an implantable cardioverterdefibrillator during sustained ventricular tachycardia: what is the mechanism? J Cardiovasc Electrophysiol 13:1309-1310, 2002. 107. Grönefeld GC, Israel CW, Padmanabhan V, et al: Ventricular rate stabilization for the prevention of pause dependent ventricular tachyarrhythmias: results from a prospective study in 309 ICD recipients. Pacing Clin Electrophysiol 25:1708-1714, 2002. 108. Chin MC, Rosenqvist M, Lee MA, et al: The effect of radiofrequency catheter ablation on permanent pacemakers: an experimental study. Pacing Clin Electrophysiol 13:23-29, 1990. 109. Martin ET, Coman JA, Shellock FG, et al: Magnetic resonance imaging and cardiac pacemaker safety at 1.5 tesla. J Am Coll Cardiol 43:1315-1324, 2004. 110. Cossú SF, Hsia HH, Simson MB, et al: Inappropriate pauses during bradycardia pacing in a third-generation implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 20:22712274, 1997. 111. Sticherling C, Klingenheben T, Hohnloser SH: An unusual cause of ICD shock. Pacing Clin Electrophysiol 20:2265-2267, 1997. 112. Hsu SS, Mohib S, Schroeder A, Deger FT: T wave oversensing in implantable cardioverter-defibrillators. J Interv Card Electrophysiol 11:67-72, 2004. 113. Mann DE, Damle RS, Kelly PA, et al: Comparison of oversensing during bradycardia pacing in two types of implantable cardioverter-defibrillator systems. Am Heart J 136:658-663, 1998.

114. Nazarian S, Roguin A, Zviman MM, et al: Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable cardioverter-defibrillators at 1.5 tesla. Circulation 114:1277-1284, 2006. 115. Gimbel JR: Magnetic resonance imaging of implantable cardiac rhythm devices at 3.0 tesla. Pacing Clin Electrophysiol 31:795801, 2008. 116. Naehle CP, Strach K, Thomas D, et al: Magnetic resonance imaging at 1.5-T in patients with implantable cardioverterdefibrillators. J Am Coll Cardiol 54:549-555, 2009. 117. Levine GN et al: Safety of magnetic resonance imaging in patients with cardiovascular devices: an American Heart Association scientific statement from the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and Council on Cardiovascular Radiology and Intervention. Endorsed by the American College of Cardiology Foundation, North American Society for Cardiac Imaging, and Society for Cardiovascular Magnetic Resonance. Circulation 116:2878-2891, 2007. 118. Faris OP, Shein M: Food and Drug Administration perspective: magnetic resonance imaging of pacemaker and implantable cardioverter-defibrillator patients. Circulation 114:1232-1233, 2006. 119. Nazarian S, Halperin HR: How to perform magnetic resonance imaging on patients with implantable cardiac arrhythmia devices. Heart Rhythm 6:138-143, 2009. 120. Anfinsen OG, Berntsen RF, Aass H, et al: Implantable cardioverter-defibrillator dysfunction during and after magnetic resonance imaging. Pacing Clin Electrophysiol 25:1400-1402, 2002. 121. Vassolas G, Roth RA, Venditti FJ: Effect of extracorporeal shock wave lithotripsy on implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 16:1245-1248, 1993. 122. Sears SF, Conti JB: Quality of life and psychological functioning of ICD patients. Heart 87:488-493, 2002. 123. Schron EB, Exner DV, Yao Q, et al: Quality of life in the Antiarrhythmics versus Implantable Defibrillators Trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. The AVID Investigators. Circulation 105:589-594, 2002.

31  31

Troubleshooting of Biventricular Devices MICHAEL O. SWEENEY

O

ptimal programming of implanted electrical devices for cardiac resynchronization therapy (CRT) requires a sophisticated understanding of the pathophysiologic electrical and mechanical substrates that occur in patients with asynchronous heart failure. Furthermore, it cannot be overemphasized that optimal CRT programming is an active process that requires sustained vigilance for the remainder of the patient’s life and must anticipate the potential for dynamic and related changes in patient condition or device system operation. This is a critically important distinction to conventional pacemakers, which reliably provide bradycardia support with minimal need for periodic programming intervention, particularly with recent enhancements to automaticity. Similarly, although conventional implantable cardioverter-defibrillators (ICDs) require a slightly higher level of surveillance than pacemakers, because of possible clinically silent but important ventricular detections and therapies and several other considerations, ICDs primarily are passive for the patient’s lifetime. The hybridization of CRT pacing (CRT-P) with defibrillation systems (CRT-D) therefore invokes all the complex considerations of optimal CRT and ICD programming. This introduces particularly unique challenges because the device must simultaneously exist in two fundamentally opposed states of operation: continuous delivery of ventricular pacing and continuous surveillance for ventricular tachyarrhythmia.

Electromechanical Events and Cardiac Pump Function Optimal cardiac pump function depends on ordered mechanical events that are precisely and dynamically orchestrated by electrical timing. The term applied to this electromechanical ordering, or coupling, is synchrony. This electromechanical coupling occurs at multiple anatomic levels: within atria, between atria and ventricles, between ventricles, and within especially the left ventricle. Such disruptions to proper electrical timing result in disordered mechanical events (desynchronization, or dyssynchrony), occur in isolation or in various combinations at any level, and degrade cardiac pump function. These disruptions or uncoupling of normal mechanical ordering result from fixed or functional conduction blocks and can be generated spontaneously by myocardial disease or can be induced by cardiac pacing. CONSEQUENCES OF UNCOUPLING AT VARIOUS LEVELS Uncoupling at the Atrial Level The right atrium and left atrium are activated nearly simultaneously (within 50-80 milliseconds) during sinus rhythm. Preferential sites of interatrial conduction exist at the posterior-superior interatrial septum (Bachmann’s bundle region), fossa ovalis, and coronary sinus ostium.1,2 Significant interatrial conduction delays (up to 200 msec or greater) can occur in myopathic atria. Similar conduction delays can be also be induced, or exacerbated, by right atrial (RA) pacing. Delayed left atrial (LA) contraction can disrupt optimal left-sided atrioventricular (AV) coupling. Severe atrial decoupling and delayed LA contraction reverses the left-sided AV contraction sequence, resulting in atrial transport block.3 This causes increased LA pressures, retrograde flow in the pulmonary veins, and counterphysiologic neurohormonal responses termed pseudo–pacemaker syndrome.4-6

Uncoupling at the Atrioventricular Level Optimal AV coupling contributes to ventricular pump function through Starling’s law. The normal intrinsic atrioventricular interval (iAVI) results in atrial contraction just before the preejection (isovolumetric) period of ventricular contraction that maximizes left ventricular (LV) filling (LV end-diastolic pressure, or preload) and cardiac output. Appropriately timed AV coupling maintains a low mean atrial pressure, increases LV filling time, maximizes preload and pump function (Starling mechanism), and positions the mitral valve for closure during the isovolumetric phase of ventricular systole (Fig. 31-1). Delayed AV coupling resulting from AV conduction delay displaces atrial contraction earlier in diastole (Fig. 31-2). Atrial contraction occurs during ventricular filling, which shortens diastolic filling time, and in extreme situations, occurs immediately after or coincident with the preceding ventricular contraction. This situation is aggravated by ventricular conduction delay, which increases ventricular ejection time and delays diastolic filling, increasing the probability of collision with atrial contraction. Atrial contraction before completion of venous return reduces preload stretching of the left ventricle, which reduces ventricular volume and contractile force. Delayed AV coupling reduces diastolic filling time and may result in diastolic mitral regurgitation when elevated LV end-diastolic pressure exceeds LA pressure. Partial closure of the mitral valve may also occur, further shortening diastolic filling time. Delayed AV coupling may be worsened or induced by atrial pacing. This is a consequence of atrial capture latency, increased atrial conduction time resulting from altered activation, and increased AV nodal conduction time from altered atrial input. These effects of atrial pacing are enhanced by increased heart rates during atrial pacing and autonomic changes during sleep.7 Severe AV decoupling coexists with ventriculoatrial (VA) coupling. In extreme conditions LA contraction occurs immediately after, within, or preceding the LV contraction, causing reversal of the left-sided AV contraction sequence,3 which initiates counterphysiologic circulatory and neurohumoral reflexes. These derangements (pseudo–pacemaker syndrome) have been rarely described during marked first-degree AV block and atrial pacing.4 The identical pathophysiology occurs during AV synchronous ventricular pacing when LV contraction timing is too early, resulting in LA transport block (Fig. 31-3). This situation is corrected by proper timing of ventricular contraction with pacing (see Atrioventricular Optimization). Atrial fibrillation disrupts atrial coupling (atrial desynchronization) and eliminates AV coupling (AV uncoupling). VENTRICULAR LEVEL Normal LV electrical activation is rapid and homogeneous with minimal temporal dispersion throughout the wall.8 This elicits a synchronous mechanical activation and ventricular contraction.9 The resulting coordinated myocardial segment activation maximizes ventricular pump function. Wiggers10 established the linkage between pacing-induced alterations in ventricular conduction and pump function with two seminal observations in 1925: (1) pacing at virtually any ventricular site disturbs the natural pattern of activation and contraction, because the evoked electrical wavefront propagates slowly through ventricular myocardium rather than through the His-Purkinje system, and (2) altered ventricular activation causes an immediate reduction

911

912

SECTION 4  Follow-up and Programming

ic

ir

ic

ir

E

A

in pump function, and some sites are worse than others (site selectivity). In general, right ventricular (RV) pacing sites appear to be more detrimental than LV pacing sites, and the right ventricular apex (RVA) is among the worst sites within the right ventricle.11 Optimal interventricular and intraventricular coupling is more important than AV coupling for maximum ventricular pumping function.12,13 RVA pacing and left bundle branch block (LBBB) both induce delays in transseptal and intraventricular conduction.14 Consequently, the hemodynamic effects of altered ventricular activation during RVA pacing and LBBB are comparable. These effects can be attributed to disturbed interventricular as well as intraventricular coupling. RVA pacing also disturbs RV activation as a result of slow intramyocardial conduction. Interventricular decoupling refers to a sequential RV-LV activation delay. In LBBB the earliest ventricular depolarization is recorded over the anterior RV surface and generally latest at the posterior or posterolateral basal LV surface.15-20 Interventricular dyssynchrony can be quantified by the time delay between the upslopes of LV and RV systolic pressure,12 as well as time delay between opening of the pulmonic and ir

ic

LV pressure

ir Ejection

Filling time

E

ic

A

Diastolic MR-systolic MR Figure 31-2  Schematic of hemodynamic effects of AV decoupling on LV pump function. Same arrangement as in Figure 31-1. Atrial contraction truncates passive diastolic filling (E-A fusion). A late diastolic left ventricular–left atrial (LV-LA) pressure gradient before mitral valve closure results in diastolic mitral regurgitation. LV filling is reduced and pump function declines (reduced LV pressure during ejection).

ir Ejection

Filling time

E

Figure 31-1  Schematic representation of optimal atrioventricular (AV) coupling. Atrial contraction (A) occurs just before isovolumetric contraction (ic); ir, isovolumetric relaxation. Passive diastolic left ventricular (LV) filling (E) is unimpeded, and total diastolic filling time (E + A) is maximized. Left atrial pressure (blue line) remains low during diastole, LV pressure (orange line) is high during ejection.

Ejection

ir Ejection

LV pressure

Filling time

ic

ic

Ejection

LV pressure

Ejection

A

Premature ventricular pacing stimulus Figure 31-3  Hemodynamic effects of short A-V interval on LV pump function. Same arrangement as in Figures 31-1 and 31-2. Ventricular contraction triggered by premature pacing stimulus (arrow) truncates atrial emptying (atrial transport block). Atrial pressure increases, LV filling decreases, and pump function declines (reduced LV pressure during ejection).

aortic valves.21 Similar changes occur during RV pacing. This disruption to ventricular interdependence is a determinant of paradoxical septal motion. Presumably this reduction in ventricular septal contribution to LV ejection is an important factor in the reduction of pump function during LBBB.12,22 Delayed intraventricular activation is presumably the most important determinant of reduced pump function. In RVA pacing and LBBB, electrical activation starts in the interventricular septum, with the posterior or posterolateral basal LV wall activated more than 100 msec later. Such considerable intraventricular delay during RVA pacing and LBBB pacing is caused by slow spread of the depolarization wavefront through the working myocardium rather than through the Purkinje system. Slow intramyocardial conduction during RVA pacing prolongs QRS duration (QRSd) from the normal values of about 80 msec to values of 140 msec in otherwise normal hearts, to about 200 msec in infarcted left ventricles.14 Furthermore, the delay in LV activation relative to QRSd during RVA pacing is greater in failing ventricles.23 Left bundle branch block is a complex electrical disease resulting from LV conduction delay at multiple anatomic levels (fixed or functional) and is exhibited differently according to substrate characterization (ischemic vs. nonischemic dilated cardiomyopathy [DCM]). Early endocardial activation mapping studies of LBBB concluded that conduction delay resided entirely within the ventricular septum, and that LV endocardial activation was rapid after single-point breakthrough in nonischemic DCM, whereas activation was slowed across regions of scar throughout the left ventricle in ischemic DCM.15 In both situations the posterior or posterolateral basal left ventricle is the latest activated region. Higher-resolution endocardial and epicardial mapping studies have revealed that LV activation during LBBB, despite a similar surface electrocardiographic appearance, is considerably heterogeneous. At least three patterns of delayed LV activation have been characterized: (1) transseptal delay with or without LV endocardial delay, (2) normal transseptal conduction with slow conduction velocities in peri-infarct regions and globally slow in nonischemic DCM, and (3) slowed U-shaped activation around a line of functional block on the anterior wall.16-20 Generally, QRSd of 120 to 150 msec indicates delay confined specifically to the specialized conduction system, whereas QRSd greater



than 150 msec usually indicates additional conduction delay in diseased myocardium. The pattern of transseptal activation delay varies and influences LV endocardial activation. Significantly prolonged transseptal conduction times through a diseased left bundle branch result in midseptal LV or septoapical breakthroughs and unidirectional wavefront propagation throughout the left ventricle. Rapid transseptal conduction times typify conduction through septal branches of the His-Purkinje system, with basal breakthroughs from the anterior or posterior fascicle and bidirectional wavefront propagation from base to apex and high septum. Breakthrough from both fascicles results in a double wavefront that fuses on the posterolateral wall. Single-site breakthrough from the high septum caused by right-to-left muscular conduction (no conduction system present) results in a single wavefront that propagates from base to apex.16 The pattern of septal activation may affect ventricular mechanics differently. High septal activation may result in simultaneous RV and LV activation in opposite directions, and papillary muscle activation may be influenced by the earliest site of LV activation.16,20,24,25 The pattern of LV endocardial and epicardial activation is also influenced by the location and size of lines of fixed or functional conduction block. Fixed conduction block is caused by replacement of normal myocardium by interstitial fibrosis. The physiologic basis for functional conduction blocks has not been elucidated but could relate to stretch, heart rate, and spontaneous diastolic depolarization. Anterior locations of the line of functional block are characterized by a U-shaped LV activation pattern,17-19 more prolonged QRSd (>150 msec), and longer time to LV breakthrough.18 Late activation of the posterior or posterolateral basal left ventricle occurred by wavefront propagation around the line of block using the apical or inferior LV walls. Lateral locations of the line of block are characterized by less prolonged QRSd (<150 msec) and shorter time to LV breakthrough. Pacing maneuvers shift either line of block, indicating their functional nature. Noninvasive mapping of epicardial activation using body surface potentials extended these observations and demonstrated that electrical activation patterns in LBBB are highly heterogeneous and unpredictable.20 Lines of conduction block do not correlate with regions of wall motion abnormality or scarring. Some lines of block arose only during pacing and were site dependent (functional), whereas other lines of block could not be manipulated with pacing maneuvers, indicating these were caused by slow or absent conduction (fixed). Latest activation most often occurred in the posterior or posterolateral basal wall, but was also observed in the anterior and inferior walls in some patients. Effects of Asynchrony on Left Ventricular Mechanics and Structure Regions that are activated early also start to contract early. Accordingly, in RVA pacing and LBBB, earliest and latest sites of segmental LV activation correlate well with time to peak systolic velocity by Doppler imaging19 and strain by tagged magnetic resonance imaging (MRI),9,2628 providing evidence that ventricular conduction delay is responsible for heterogeneous mechanical performance (asynchrony). The mechanical effect of asynchronous electrical activation is dramatic, because the various regions differ not only in the time of onset of contraction, but also in the pattern of contraction (Fig. 31-4). Contraction of early-activated myocardium is energetically inefficient because LV pressure is low and ejection has not begun. Instead, stretching of remote regions not yet activated absorbs the energy generated by the early-activated regions. This stretching further delays shortening of these late activation regions and increases their force of local contraction by virtue of the Frank-Starling mechanism (locally enhanced preload). Vigorous late systolic contraction at delayed sites occurs against high LV cavity pressures (locally enhanced afterload) and imposes loading on the earlier activated regions, which now undergo systolic paradoxical stretch.29 This reciprocated stretching of regions within the LV wall causes a less effective and energetically efficient contraction.30

31  Troubleshooting of Biventricular Devices

913

The hemodynamic consequences of the asynchronous LV contraction are reductions in contractility and relaxation. These changes occur immediately on initiating RVA pacing in humans and animals,11,31 and induction of LBBB in animals12 (see Fig. 31-4). The loss of pump function is indicated by decreases in stroke volume, stroke work, and slower rate of rise of LV pressure (Fig. 31-5). Moreover, the LV end-systolic pressure-volume relationship shifts rightward, indicating that the left ventricle operates at a larger volume in order to recruit the FrankStarling mechanism.11 Premature relaxation in early-activated regions, and delayed contraction in others also causes abnormal relaxation,11 as expressed as slower rate of fall of LV pressure, increase in the relaxation time constant tau, and decrease of E-wave velocity amplitude on Doppler echocardiograms.32 These changes also lead to prolongation of the isovolumetric contraction and relaxation times, which are characteristic for asynchronous hearts.33 The prolongation of the isovolumetric times occurs mainly at the expense of the diastolic filling time, leading to reduced preload. The redistribution of the mechanical load within the ventricular wall also leads to reduction of regional myocardial perfusion and oxygen consumption near the RVA pacing site30,34,35 and in the septum during LBBB.36,37 Such perfusion defects and wall motion abnormalities have been demonstrated in up to 70% of patients with angiographically normal coronary arteries exposed to chronic RVA pacing.38-41 These defects are reversible on cessation of RVA pacing39,41 and after biventricular pacing.36,37,42 Accordingly, such perfusion “deficits” do not necessarily indicate coronary heart disease, because they may simply express the regional differences in myocardial workload. Similar to the situation after myocardial infarction, acute loss of pump function initiates compensatory responses (Figs. 31-6 and 31-7). Some of these responses, after a certain time and or degree of asynchrony, may result in further impairment of pump function and clinical heart failure. There are various triggers for these “remodeling” processes. As for other conditions of hemodynamic overload, RVA pacing and LBBB lead to stimulation of the sympathetic system, resulting in elevated myocardial catecholamine levels,43 and activation of the renin-angiotensin-aldosterone system. Regional differences in stretch and mechanical load heterogeneity are most likely important stimuli for remodeling processes. Chronic asynchronous LV activation results in regional and global structural changes indicated by asymmetric hypertrophy, increased end-diastolic volume, and reduced ejection fraction36,44 (see Fig. 31-6), as well as locally different molecular abnormalities, including reductions in sarcoplasmic reticulum calciumATPase and phospholamban.45 Even stronger regional differences in gene expression are found in failing hearts with conduction abnormalities.46 Dystrophic calcifications, disorganized mitochondria, and myofibrillar cellular disarray47 have been described with RVA pacing, especially in immature hearts. Early signs of cellular and molecular adaptation to disturbed ventricular activation are manifest as reduction in ejection fraction (EF) within the first week of RVA pacing. In patients with normal EF, Nahlawi et al.31 showed an immediate drop in EF of about 7%, followed by another 7% drop during the subsequent week. Suppression of RVA pacing returned EF to baseline values, but only after several days.48 Also, ventricular repolarization abnormalities have been observed within hours of RVA pacing. Alterations in potassium and calcium channels likely play a role in these phenomena. Mechanistic Basis for Development of Asynchronous Heart Failure Caused by Ventricular Conduction Delay As mentioned, synchronous activation consistently leads to acute and long-term adverse effects on cardiac pump function, which create a vicious cycle of deterioration. Accordingly, the pacing-induced ventricular conduction delay has been linked to increased risks of atrial fibrillation, heart failure, ventricular tachyarrhythmia, and death in large, randomized clinical trials of pacemakers and ICDs.49-56 Similar risks have been reported for LBBB and cardiac morbidity and mortality.57

SECTION 4  Follow-up and Programming

Synchronous contraction

Asynchronous contraction

Ejection

Ejection

Local strain

Normalized pressure

LV RV –5 ms

0

0

100 200 300 400 Time (ms)

0

200

400 600

Time (ms)

1

120

← ← ← ← ← ← ← ←

Normalized pressure

1

LV pressure [mmHg]

B

Lateral septum

80 40 0

–35 ms

0

40

60

80

LV volume (mL)

0

100 200 300 400 Time (ms)

0

200

400 600

Time (ms)

LV pressure [mmHg]

A

Aortic flow

LV pressure

914

120 80 40 0 0 40

60

80

LV volume (mL)

C-E Figure 31-4  Effects of synchronous (left panel) and asynchronous (right panel) ventricular activation on LV and aortic pressure (A), regional strain (B), ventricular conduction (C), electrocardiographic tracings), RV and LV pressure signals (D), and pressure-volume loops (E). Asynchronous contraction causes reduction in ejection time and slows rates of rise and fall of LV pressure and aortic pressure and increases duration of isovolumetric contraction (ic) and relaxation (ir) (A). Onset of LV shortening (strain) is regionally delayed (negative deflection of curve) (B). Asynchronous electromechanical activation induces increased QRSd (C) and interventricular/intraventricular activation times (D), which instantaneously reduce stroke volume, stroke work, dP/dtmax, and dP/dtmin, indicating an acute reduction in pump function (E). (Modified from Sweeney MO, Prinzen FW: Ventricular pump function and pacing: physiological and clinical integration. Circ Arrhythmia Electrophysiol 1:127-139, 2008.)

Multiple factors may contribute to heart failure associated with ventricular asynchrony. At least three candidate factors are readily identified: (1) reduced pump function caused by asynchronous contraction (dyssynchrony), (2) adverse remodeling caused by long-term dyssynchrony, (3) left-sided AV desynchronization, and (4) functional mitral regurgitation (fMR). The first three factors are discussed earlier. The fMR frequently accompanies pacing-induced or spontaneous asynchronous heart failure and has multiple mechanisms.24,25,58,59 Assuming the anterior mitral leaflet is structurally normal, the immediate cause of fMR is delayed activation of the LV posterior “apparatus” caused by ventricular conduction delay.25,60 This apparatus consists of the posterior leaflet and annulus, the LV summit it sits on, the chordae, the papillary muscles, and the LV wall from which they emanate. Rapid activation of the posterior apparatus requires normal ventricular conduction. Early closure of the mitral valve is arguably the most important accomplishment of the entire conduction system because it facilitates Starling’s law; that is, it permits isovolumetric systole to occur when the ventricle is as full as it can be given the filling conditions. Delayed ventricular conduction prevents mitral valve coaptation and induces fMR during isovolumetric contraction. Ventricular conduction delay

instantaneously reduces the transmitral pressure gradient (systolic LV pressure–LA pressure difference) or mitral valve closing force, by reducing contractility (↓LV dP/dt). Chronically, volumetric remodeling contributes to fMR by further reductions in contractility (closing forces) and increasing papillary muscle tethering forces59,61,62 (Fig. 31-8). Tethering strongly depends on alterations in ventricular shape because the tethering forces that act on the mitral leaflets are higher in dilated, more spherical ventricles. Ventricular dilation and increased chamber sphericity increase the distance between the papillary muscles to the enlarged mitral annulus as well as to each other, restricting leaflet motion and increasing the force needed for effective mitral valve closure. Under these conditions, the mitral regurgitant orifice area will be largely determined by the phasic changes in transmitral pressure. There is some intriguing evidence that LBBB may be the primary cause of DCM in some patients. Progressive LV enlargement after the emergence of LBBB unaccompanied by any other explanation has been documented in case series.63 Furthermore, complete recovery of ventricular function shortly after initiation of biventricular pacing in “hyperresponders” suggests that LBBB may be a primary and reversible trigger of DCM in some patients.64,65

S

Normalized pressure

Pre

P

L

Post

Normalized pressure

A

0 0

10 20 Time [ms] Intra VA

A

30

100 200 300 400 Time [ms]

1

LV RV –5 ms

0 1

← ← ← ← ← ← ← ←

–35 ms

0 0

200 400 600 Time [ms]

LV pressure [mmHg]

31  Troubleshooting of Biventricular Devices

LV pressure [mmHg]



915

120 80 40 0

120 80 40 0 40

60

80

LV volume [ml]

Total VA

Inter VA

PV loops

B

C

D

Figure 31-5  Left bundle branch block (LBBB)–induced asynchrony causes immediate reduction in LV contractility. A, Left ventricular (LV) endocardial activation maps. Inner circle represents LV apex and outer circle represents LV base. S, A, L, and P indicate the septum, anterior, lateral, and posterior walls, respectively. Arrows indicate activation delay vectors, the amplitude of which reflects the degree of intraventricular asynchrony (intra VA). B, Surface electrocardiogram (ECG) tracings, where QRS duration indicates total ventricular asynchrony (total VA). C, Right ventricular (RV) and LV pressure signals normalized to reveal pressure differences (interventricular asynchrony, inter VA). D, Pressure-volume (PV) loops. Loop area is stroke work, loop width is stroke volume. During normal ventricular conduction (top row, pre-LBBB) intraVA and interVA are minimized, QRSd is normal and LV contractility is greater (larger PV loop). After induction of LBBB (bottom row, post-LBBB), intra VA, inter VA, and total VA are increased, which immediately reduces LV pump function (smaller PV loop indicating declines in stroke work, stroke volume, and LV pressure generation). (Modified from Vernooy K et al: Left bundle branch block induces ventricular remodeling and functional septal hypoperfusion. Eur Heart J 26:91-98, 2005.)

Several studies also showed that LBBB is associated with increased mortality, with greater impact in sicker patient populations. The relative risk associated with the presence of LBBB varied between 1.5 and 2.0, even after adjustment for covariates.57 The only study rejecting the association of LBBB with increased mortality drew this conclusion after adjustments for LV EF as a covariable.66 However, the conclusion that LBBB is not an independent predictor of mortality after the adjustment for EF can be understood because LBBB directly reduces EF because of its acute and chronic effect on LV pump function (see earlier). MECHANISMS OF CARDIAC RESYNCHRONIZATION THERAPY Fixed and functional disruptions to normal electromechanical ordering caused by conduction delay are targeted for electromechanical reconstitution of pump function. CRT has two immediate effects on electromechanical ordering: ventricular activation sequence and chamber timing. The basis of this therapeutic strategy is to restore coordinated contraction by minimizing the conduction delay, thereby restoring interventricular and intraventricular coupling. A secondorder effect is the reduction of left-sided AV decoupling, which may improve diastolic performance and thus LV pumping function. As part of this effect, fMR may be reduced. These acute beneficial hemodynamic effects may lead to even more beneficial long-term effects, because many adverse molecular and cellular derangements elicited by chronic RVA pacing or LBBB appear to be reversible. This property of CRT is remarkable; many pharmacologic therapies tend to lose effectiveness over time, whereas the beneficial effects of CRT are maintained for many years. The best explanation of the lasting benefit of CRT is that it largely restores the normal electromechanical coupling of the heart with LBBB. This idea is supported by studies in the canine

models in which CRT abolished all adverse effects of LBBB.42 Thus, CRT may be “curative” of LBBB-induced ventricular “desynchronapathy” in some situations. Improved Atrioventricular Mechanics from Optimal AV Resynchronization When LV contraction timing is delayed, even when AV conduction times are normal, the hemodynamic consequences are similar to a prolonged AV interval, as shown in Figure 31-2. Left-sided AV decoupling, due to LV conduction delay and/or AV conduction delay, is corrected with LV pacing. Optimal AV timing improves LV pump function, but the primary mechanism of improved ventricular mechanics during CRT is reduction in ventricular conduction delay. AV timing considerations during CRT are considered in detail later. Improved Ventricular Mechanics from Reduced Ventricular Conduction Delay Reduction of intraventricular delay during atrial-synchronous LV or biventricular pacing has an immediate positive effect on ventricular mechanics and is the dominant therapy effect of CRT. Instantaneous improvement in pump function is indicated by increases in LV +dP/ dtmax, stroke volume, stroke work, arterial pulse pressure and peak systolic pressure,67,68 and reduced end-systolic volume (Fig. 31-9). Moreover, unlike the inotropic effects of dobutamine, systolic augmentation with ventricular resynchronization increases efficiency of conversion of myocardial oxygen consumption to mechanical work.69 This positive contractile response demonstrates a modestly positive correlation with increasing baseline QRSd67-69 and is strongly correlated with baseline mechanical dyssynchrony.69,70 Conversely, neither improved contractility nor reverse volumetric remodeling requires QRS narrowing during LV or biventricular pacing.68,71,72 However, unlike the inotropic effects of dobutamine, systolic augmentation with ventricular

916

SECTION 4  Follow-up and Programming

160

LV end-diastolic volume

140

*

120 Baseline

Acute LBBB

Chronic LBBB

B

Base

Apex

30 20 L

10 0

A

300

Time to maximal shortening (msec)

200 100 0 15 10

Systolic circumferential shortening (%)

*

* †

0 BL

2

4

130 Normalized to baseline

Activation S time (ms)

*

100

ECG P

*

C

8

10 12 14 16

LV wall mass

†

120 110

*

100 90

*

BL

5 0

100

–5

80

*

* †

*

* ratio * Septal-to-lateral wall mass

80

2

120

A

6

4

6

8

10 12 14 16

LV ejection fraction

*

*

60

*

† *

*

*

*

*

40 BL

2

D

4

6 8 10 12 14 16 Time (weeks)

Figure 31-6  Left bundle branch block (LBBB). *P, 0.05 compared to baseline. †Significant change over time by ANOVA. A, Effects of induced LBBB on electromechanics. Dashed lines on surface electrocardiogram (ECG) indicate earliest and latest left ventricular (LV) endocardial activation times. Bull’s-eye plots indicate septal (S), posterior (P), lateral (L), and anterior (A) LV wall, where outer ring indicates LV base and inner ring indicates LV apex. Activation is color-coded where lighter shades indicate later activation times. During normal ventricular conduction (Baseline), QRSd is narrow and LV electromechanical activation is simultaneous throughout. During LBBB, QRS is prolonged and LV electrical and mechanical activation is delayed with lateral wall latest. B-D, Change in LV end-diastolic volume (increase), LV septal-lateral wall mass ratio (decrease, indicating asymmetrical hypertrophy), and ejection fraction (decrease) after 16 weeks of LBBB in a canine model. The purple and red lines in B and D indicate the time course for two individual dogs that were most and least sensitive to the adverse electromechanical effects of LBBB. (Modified from Vernooy K et al: Left bundle branch block induces ventricular remodeling and functional septal hypoperfusion. Eur Heart J 26:91-98, 2005.)

Efficiency ↓

Stretch (locally different)

Wall stress

↓

al or m n hu tio ro va eu cti a

Is in ch fa em rc i tio a n

N Contractile remodeling

Coronary reserve ↓

Io n fu ch nc an tio ne n l

ar ul ric ion nt tat Ve ila d Pump function

Hypertrophy (asymmetric) Figure 31-7  Mechanisms of ventricular remodeling and progressive reduction in pump function during mechanical dyssynchrony induced by ventricular conduction delay (LBBB, RVA pacing). For details, see text. (Modified from Sweeney MO, Prinzen FW: Ventricular pump function and pacing: physiological and clinical integration. Circ Arrhythmia Electrophysiol 1:127-139, 2008).



31  Troubleshooting of Biventricular Devices SYSTOLE

MAXIMAL DIASTOLIC OPENING

LV

Papillary muscle

Tethering force

Tethering force TMP

Flow

LA Incomplete mitral leaflet closure (IMLC)

Reduced opening and abnormal flow direction

Figure 31-8  Effects of augmented mitral valve leaflet tethering in dilated cardiomyopathy. Functional mitral regurgitation (fMR) results from an imbalance between the closing and tethering forces that act on the mitral leaflets. When the mitral valve is tethered, mitral regurgitant orifice area is largely determined by phasic changes in transmitral pressure (TMP). Reductions in LV pump function (↓dP/dt) results in decreased rate of LV (and thus transmitral) pressure, which will increase MR severity because of the impaired closing force. (Modified from Otsuji Y, et al: Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering. J Am Coll Cardiol 32:398-404, 1998.)

resynchronization does not increase detrimental myocardial oxygen consumption. These acute improvements in ventricular mechanics are maintained chronically and are accompanied by reverse volumetric remodeling of the LV (see later).73 Abrupt discontinuation of LV pacing results in immediate reduction in indices of improved contractility and regression of reverse remodeling over several weeks,73,74 as well as recurrence of fMR.25 Maximally effective ventricular resynchronization occurs at the midpoint of the interventricular (V-V) interval (Fig. 31-10), which is the conduction time from RV to LV pacing site during native activation. A single optimum AV delay will achieve maximally effective ventricular resynchronization by advancing LV activation sufficiently to minimize the V-V interval. The AV delay and the V-V interval have an interactive relationship. The effect of AV delay on acute hemodynamic response to CRT is best understood in terms of the effect on ventricular

LV pressure [mm Hg]

100 80 60

CRT

LBBB

40 20 0 0

20

30

40

50

60

LV volume [mL] Figure 31-9  Pressure-volume loops during LBBB and LV pacing. Correction of regional mechanical delay results in immediate reduction in left ventricular (LV) volumes (leftward shift of pressure-volume relationship) and increases in stroke work (larger loop), stroke volume (width of loop), and dP/dtmax. CRT, Cardiac resynchronization therapy. (Modified from Verbeek XA, Vernooy K, Peschar M: Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block. J Am Coll Cardiol 42:558-567, 2003.)

917

resynchronization during biventricular (BiV) or left univentricular pacing (Fig. 31-11). During LBBB, the right ventricle is activated by right bundle branch conduction (RBBc) before the left ventricle, and the time difference between RV and LV activation is the interventricular conduction delay.13 BiV pacing at short atrioventricular delay (AVD) results in complete replacement of intrinsic activation, allowing complete control of chamber timing with sequential ventricular stimulation. Intermediate AVDs result in fusion among RBBc, RV paced activation, and LV paced activation. Long AVDs result in “pure” fusion between RBBc and LV paced activation since LV preexcitation is still possible because of interventricular conduction delay.13,75,76 Modification of the AVD alone can therefore achieve (1) BiV paced fusion, (2) BiV paced fusion with sequential ventricular stimulation (LV first), and (3) “pure” RBBc-LV pacing fusion. Therefore, LV preexcitation is possible across a range of AVDs because LV time is delayed relative to RV time. RV pacing is not necessary to achieve fusion, and AVD can be used to time the relative prematurity of LV preexcitation. At very short AVDs, this requires sequential VV timing. At very long AVDs, this occurs spontaneously because of the native V-V interval. Early acute hemodynamic studies demonstrated that the relationship between AVD and LV dP/dtmax in patients with an acute improvement in contractile response to simultaneous BiV pacing is positive and unimodal, with a peak effect at approximately 50% of the native P-R interval, resulting in complete replacement of native ventricular conduction with paced activation67,68,77 (Fig. 31-12). This doseresponse relationship between AVD and acute contractile response shown is interpreted as follows. The magnitude of the acute contractile response depends on the magnitude of baseline asynchrony (ventricular conduction delay, QRSd) and the AVD, which titrates how much intrinsic ventricular activation is replaced by pacing activation. Patients with greater ventricular conduction delay (QRS >150 msec) benefit from near-complete replacement of intrinsic activation with BiV or LV pacing (i.e., short AVDs). Patients with less ventricular conduction delay (QRS <150 msec) benefit from limited replacement of intrinsic activation (e.g., long AVDs). Typically, programmed short AVDs of 100 to 120 msec, although near-optimal for some patients, may result in decreased contractile function in patients with less baseline asynchrony (e.g., QRS <150 msec) because even BiV pacing induces asynchrony.9 LV dP/dtmax increased 15% to 45% across a narrow range of AVDs and declined at very short AVDs (truncated filling times) or very long AVDs (inadequate correction of LV conduction delay). This maximum improvement in pump function (LV +dP/ dtmax and stroke volume) occurs at minimal intraventricular asynchrony and unchanged LV end-diastolic pressure (preload).13 This indicates that the acute contractile response is explained by ventricular resynchronization, not by better filling, and that the dose of resynchronization is titrated by the AVD. The best ventricular resynchronization occurs when the wavefronts from the RV pacing site (or originating from RBBc) and the LV pacing site collide halfway.78 Experimental evidence suggests that optimal hemodynamic effect can be achieved using LV pacing at certain AVDs as well as using simultaneous and sequential BiV pacing because fusion of electrical wavefronts can be achieved by either approach13,79 (see Fig. 31-10). Although this and other experimental studies show a clear mechanism of action for optimizing the interaction between AV and VV timing, confusion surrounds this area, and a clinical advantage of patient-specific timing optimization has not been convincingly demonstrated in clinical trials80-82 (see later). Reverse Volumetric Left Ventricular Remodeling Mechanical resynchronization reduces mechanical load heterogeneity throughout the left ventricle. Sustained improvement in ventricular mechanics results in regression of adverse LV remodeling, termed reverse remodeling. This is indicated by reductions in LV volumes and mass, reduced mitral orifice size, regression of asymmetric hypertrophy, and increased EF.73,83-90 The magnitude of the reduction in endsystolic volume ranges between 10% and 30%,83,87,91,92 which is equivalent or greater than the effects of beta-adrenergic blockers and

918

SECTION 4  Follow-up and Programming

Short AVD

Opt AVD

LBBB (long AVD) 30 Septum

20 15 10

Time [ms]

25

5 0

1 0.8 0.6 0.4 0.2 0

InterVA

–11ms

20ms

–41ms

PLV

PRV 0

200 100 Time [ms]

300 0

100 200 Time [ms]

300 0

100 200 Time [ms]

300

0 Interventricular asynchrony (ms)

Normalized pressure

IntraVA

Max

–10 –20

(Min+Max)/2

–30 Min –80

–40

0

40

–80

–40

0

40

∆% LV dP/dtmax

10

BiVS BiVO LV

8 6 4 2 0 Effective VV-interval (ms)

Figure 31-10  Relationship between intraVA and interVA under various LV pacing conditions. At long atrioventricular delay (AVD), ventricular conduction delay persists (large intraVA and interVA). At very short AVD, large intraVA and interVA persist because complete reversal of LV activation has occurred. At the optimal AVD, intraVA is minimized and interVA resides at the midpoint of the interVA during either extreme condition, which yields the maximum improvement in pump function. (Modified from Verbeek XA, Vernooy K, Peschar M: Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block. J Am Coll Cardiol 42:558-567, 2003; and Vernooy K, et al: Calculation of effective VV interval facilitates optimization of AV delay and VV interval in cardiac resynchronization therapy. Heart Rhythm 4:75-82, 2006.)

angiotensin-converting enzyme (ACE) inhibitors. These hemodynamic effects are chronically sustained assuming LV pacing is continuously maintained.73 Although improvement in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk tests may be confounded by placebo effects and reporting bias, reverse remodeling is a completely objective measure. More importantly, it appears to be related to better survival.92,93 Evidence of greater baseline electromechanical asynchrony and acute mechanical resynchronization appears to be necessary for reverse remodeling to occur, and the greater the reduction in asynchrony, the higher the probability of remodeling.72,90,94 Likewise, absence of electromechanical resynchronization acutely eliminates the possibility of chronic reverse remodeling.72,90 In canine hearts with induced LBBB, 8 weeks of CRT was sufficient to reverse almost completely the about 25% LV cavity dilation and asymmetric LV hypertrophy induced by

dyssynchrony to pre-LBBB baseline values.42 This observation has been replicated in clinical studies where in some cases, reverse remodeling results in complete normalization of LV volumes and EF.64 This suggests that ventricular conduction delay may be the primary cause of DCM in some patients,63-65 as it was to a more moderate degree in the LBBB dogs. Reduction in Functional Mitral Regurgitation In many patients, CRT reduces fMR, which likely accounts for immediate reduction in symptoms in advance of possible reverse volumetric remodeling. This can be attributed to the following complex factors: 1. Correction of left-sided AV timing, which helps position the mitral leaflets in the coaptation plane before isovolumetric systole. If the AV time is too long, the leaflets begin to drift back toward the atrium and out of the coaptation plane.

31  Troubleshooting of Biventricular Devices

Simultaneous

+

+

O

RV first

VV-interval

LV first



Short

–

O

–


O

–

=TRV AV-delay

–

>TRV

919

3 types of LV pacing fusion

1.

No RBB fusion

2.

RBB/RV pacing fusion

3.

Pure RBBB fusion RV pacing activation LV pacing activation Intrinsic activation RV pacing/intrinsic activation

Long

Fusion beats during left ventricular (LV) pacing. A: LV paced activation sequence without fusion. B-D: Fusion beats with progressively earlier intrinsic right ventricular (RV) activation (time of RV breakthrough) relative to LV pacing as a consequence of increasing atrial-ventricular delay (indicated in each panel). Earlier intrinsic activation results in greater degree of fusion. B: Right ventricular breakthrough at 153 ms after LV pacing. C: RV breakthrough at 132 ms after LV pacing. D: RV breakthrough at 45 ms after LV pacing.

Figure 31-11  Top, Interaction between atrioventricular delay (AVD) and V-V interval to determine LV activation fusion. T-RV is time to intrinsic RV activation (RA sense to RV sense, or P-R interval). During short AVD pacing (AVD < T-RV), biventricular pacing completely replaces native activation (surrogate fusion), and relative timing of ventricular activation is determined by sequential ventricular stimulation (RV first, simultaneous, LV first). When AVD = T-RV, RV pacing occurs simultaneously with intrinsic conduction, resulting in a combination of RV pacing and intrinsic conduction, whereas left ventricle is still activated earlier than would have occurred due to LBBB. When AVD > T-RV, LV-only pacing occurs with true fusion of native and paced activation. Bottom, Epicardial isochrone maps are shown during LV-only pacing at increasing pacemaker A-V intervals (pAVIs). Activation times relative to QRS onset are color-coded with red earliest and blue latest; framed numbers indicate earliest and latest activated sites. Asterisk, LV stimulation site. Black lines indicate line/region of conduction block, which influences activation wavefront propagation (see Fig. 31-77). A, pAVI = 0 msec. Note sequential ventricular activation (LV→RV): LV is activated earliest, and latest activation occurs at posterobasal right ventricle. B to C, Progressive fusion of paced LV activation with intrinsic LV activation via RBB as pAVI is increased from 65 to 86 msec. Note also progressively early RV activation from RBB conduction. D, Maximum ventricular activation wavefront fusion at pAVI = 173 msec. Note right and left ventricles are simultaneously activated (Esyn, electrical synchrony, = −18 msec). (Modified from Jia P et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006.)

920

SECTION 4  Follow-up and Programming

pacing/sensing vector (Figs. 31-15 and 31-16). With two unipolar leads, the bipolar setting results in no pacing or sensing. If both leads are bipolar, both rings act as the common electrode. If one lead is bipolar (RV) and the other lead is unipolar (typically LV), the ring on the bipolar lead acts as the common electrode (nonstimulating anode). This configuration results in shared-ring bipolar pacing and sensing. This hybrid bipolar/unipolar stimulation configuration (“dual cathodal”) is employed in most contemporary CRT pacing systems. In a dual-unipolar configuration, the lead tips are the active electrodes; the noninsulated device case is the common electrode. This polarity configuration is infrequently used in CRT pacing systems and is not feasible in CRT-D systems because of the concerns regarding ventricular oversensing associated with the unipolar pacing stimulus.

Type I response QRS >150 ms

25 20 dP/dtmax (%)

15 10 5 0 –5 –10 –15

Type II response QRS 120-150 ms

–20 –20

0

20

40

60

80

100

AV delay (% of IAVi) Figure 31-12  Interaction between atrioventricular delay (AVD), magnitude of LV conduction delay, and acute improvement in contractility during CRT. Mean (±SEM) change in LV dP/dtmax when BiV pacing at various AVDs in patients with QRS duration greater than 150 msec (diamonds) or 120 to 150 msec (triangles). The AVDs tested were fixed percentages of the intrinsic A-V interval (iAVI) determined individually for each patient. Acute hemodynamic responders (type I) demonstrate improvement across a broad range of AVDs, whereas hemodynamic nonresponders (type II) may worsen because of very short AVDs. (Modified from Auricchio A et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 99:2993-3001, 1999.)

2. Improved contractility reduces fMR instantaneously and is quantitatively related to an increase in LV dP/dtmax and transmitral pressure59 (Fig. 31-13). 3. Earlier delivery of the posterior apparatus in isovolumetric systole (Fig. 31-14). 4. Reverse volumetric LV remodeling reduces fMR chronically by reducing LV volumes and sphericity, which reduces tethering forces on the mitral valve. Factors 1 to 3 are acute effects and unrelated to geometrical changes (reverse remodeling). Factors 2 to 4 are the primary determinants of reduction in fMR and are directly related to reduction in ventricular conduction delay. It is not well understood what part of the benefit of CRT is caused by reduction in fMR versus resynchronization of contraction directly, because few studies quantitatively measure regurgitant flow. Improved Heart Rate Profile Ventricular resynchronization favorably modifies autonomic balance, as evidenced by reduced mean heart rate and increased heart rate variability, which correlate with improved functional capacity, reverse remodeling, and reduced mortality.95

Cardiac Resynchronization Therapy Systems HARDWARE SYSTEMS Leads and Electrodes: Non–Independently Programmable Ventricular Polarity Configurations Transvenous and epicardial LV pacing leads may be either unipolar or bipolar, although the former dominates current applications. Multiple ventricular pacing polarity configurations are therefore possible. Because programmed polarity settings are common to both ventricular leads, and the type (bipolar or unipolar) of these leads may not be the same, the following considerations apply. In a dual-bipolar configuration, both lead tips are the active electrodes (cathodes) and the rings are the common (nonstimulating) anode. However, the type of ventricular leads implanted defines the

Pulse Generators Conventional dual-chamber pulse generators or specially designed multisite pacing pulse generators may be used for CRT applications (Fig. 31-17). A conventional dual-chamber pulse generator is well suited for CRT in patients with permanent atrial fibrillation. In this situation, the ventricular port is used for the RV lead and the atrial port is used for the LV lead. This permits programming of independent outputs and ventricular-ventricular timing by manipulation of the AV delay. The programming mode can be either DDD/R or DVI/R (see later). A conventional dual-chamber pulse generator can also be used for atrial-synchronous BiV pacing. The single ventricular output must be divided to provide simultaneous stimulation of the RV and LV (dual cathodal system with parallel outputs). This is achieved with a Y adapter and results in simultaneous RV and LV sensing, which may result in ventricular double-counting and loss of CRT, or pacemaker

1

EROA

LV

↓dP/dt 0.5

0

↓Transmitral pressure gradient (TMP) LA

OFF

Time 1

EROA

↓V wave preserves TMP during latter systole

LV

↑dP/dt 0.5

0

CRT

↑Transmitral pressure gradient (TMP)

LA Time

Shaded area = time EROA <50% of initial value Figure 31-13  One mechanism for acute reduction in severity of functional mitral regurgitation during CRT. Schematic representation of the relationship between the increase in transmitral pressure (TMP) and the decrease in effective mitral valve regurgitant orifice area (EROA). Top, Left bundle branch block (LBBB). Left ventricular (LV) contractility is low, indicated by a slow rate of rise and delayed peak in LV pressure. This results in delayed and reduced TMP such that EROA remains large throughout systole. Bottom, Cardiac resynchronization therapy (CRT). Acute improvement in contractility, indicated by rapid rate of rise and early peak of LV pressure, results in higher TMP earlier in systole, which reduces EROA. Shaded area represents the time in systole during which EROA is below 50% of its initial value. Reduction in regurgitant V wave preserves TMP. (Modified from Breithardt OA, et al: Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol 203:765-770, 2003.)



31  Troubleshooting of Biventricular Devices

921

Anterolateral papillary muscle

Baseline

After CRT

Strain (%) 0 4-chamber view

–5

Postermedial papillary muscle

Mid-lateral site Mid-inferior site

–15 –15 800 –20 0

2-chamber view

1.0

2.0

0

1.0

Time (sec)

2.0

Time (sec)

Baseline: LBBB Moderate MR

After CRT Mild MR Anterior

Anterior AL P

520 ms

Septal

AL P

Lateral

400 ms PM P

Lateral

300 ms Posterior

Inferior

300 ms

Septal

PM P

250 ms

650 ms

Posterior Inferior

Figure 31-14  Effect of earlier delivery of posterior apparatus on functional mitral regurgitation (fMR). Echocardiographic strain images from the four-chamber view and two-chamber view (top), with corresponding time-strain plots from sites adjacent to papillary muscles before and after CRT (bottom). Baseline plots demonstrate delayed peak strain occurring in the anterolateral papillary muscle site compared with the posteromedial papillary muscle site. CRT results in time alignment of peak strain at papillary muscles (top). Time to peak systolic strain is color-coded, with lines representing isochrones of mechanical activation times at 50-msec intervals. The X indicates sites of lead placement, and the arrow indicates the direction of the propagating mechanical activation. Time to peak strain of sites adjacent to anterolateral (AL P) and posteromedial (PM P) papillary muscles are shown. A decrease in interpapillary muscle time delay was associated with decreased fMR. (Modified from Kanzaki H, et al: A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy: insights from mechanical activation strain mapping. J Am Coll Cardiol 44:1619-1625, 2004.) DUAL BIPOLAR

BIPOLAR/UNIPOLAR

DUAL UNIPOLAR PM can (anode)

Cathode

Cathode

Non-stimulating anode

Shared or common ring (non-stimulating anode)

Cathode

Figure 31-15  Biventricular pacing configurations. (From Barold SS, Stroobandt RX, Sinnaeve AF: Cardiac pacemakers step by step: an illustrated guide. Malden, Mass, 2004, Blackwell.)

922

SECTION 4  Follow-up and Programming

TRANSVENOUS LV PACING Unipolar LV lead Bipolar RV lead

Bipolar RA lead

Tip electrode in RA appendage pacing/sensing the RA

Ring electrode in RA

Coronary sinus

– + –

+ Ring electrode in RV

Tip electrode in CS pacing/sensing the LV

– Tip electrode in RV apex pacing/sensing the RV

EPICARDIAL LV PACING Bipolar RA lead

Bipolar RV lead

Ring electrode in RV

Tip electrode in RA appendage pacing/sensing the RA – + – +

Epicardial electrodes pacing/sensing the LV

+ Ring electrode in RV

–

Figure 31-16  Leads and electrodes for biventricular pacing. (From Barold SS, Stroobandt RX, Sinnaeve AF: Cardiac pacemakers step by step: an illustrated guide. Malden, Mass, 2004, Blackwell.)

Tip electrode in RV apex pacing/sensing the RV

inhibition in the case of LV lead dislodgment into the coronary sinus with sensing of atrial activity.96 First-generation multisite pacing pulse generators similarly provide a single ventricular output for simultaneous RV and LV stimulation. However, two separate ventricular channels internally connect in parallel. This connection is made for both the lead tip and ring connections and eliminates the need for a Y adapter. This configuration still provides simultaneous RV and LV sensing with associated limitations. Second-generation multisite pacing pulse generators have independent ventricular ports. Each ventricular lead therefore has separate sensing and output circuits. This arrangement permits optimal programming of outputs and time delay between RV and LV stimulation for each patient. It also eliminates the potential complications of BiV sensing.

PROGRAMMING CONSIDERATIONS Pacing Modes It is axiomatic that for maximal delivery of CRT, ventricular pacing must be continuous. The DDD mode (atrial and ventricular pacing/sensing) guarantees AV synchrony by synchronizing ventricular pacing to all atrial events, except during episodes of atrial tachycardia or atrial fibrillation. However, DDD mode increases the probability of atrial pacing (depending on programmed lower rate limit) that may alter the leftsided AV timing relationship because of interatrial conduction time and atrial pacing latency. The VDD mode (atrial sensing only, ventricular pacing and sensing) guarantees the absence of atrial pacing and synchronizes all atrial events to ventricular pacing at the programmed AV delay. However, if



31  Troubleshooting of Biventricular Devices

923

Traditional DDDR pacemaker as a reference Atrial port

PM

Bipolar

Ventric port

Bipolar

AVI Conventional DDDR pacemaker used for biventricular pacing Atrial port PM

This can only be used in patients with permanent atrial fibrillation.

Bipolar

Ventric port

LV

Bipolar

The shortest AV interval (0-30 ms) should be programmed.

RV Shortest possible AV delay Biventricular pacing with interconnected ventricular ports Internal Atrial connection port

PM

LV port

RV port

LV

Bipolar RV Bipolar

A single ventricular output is divided to provide simultaneous pacing of RV and LV (dual cathodal system with parallel outputs). The pacemaker senses RV and LV activity simultaneously.

Unipolar Biventricular pacing with independent ventricular ports Atrial port

PM

LV port

RV port

LV

Bipolar RV

The time delay between the LV and RV stimuli may be programmed and optimized for each patient. Each ventricle has its own sensing and output circuits.

Bipolar Unipolar

Figure 31-17  Pulse generators for biventricular pacing. (From Barold SS, Stroobandt RX, Sinnaeve AF: Cardiac pacemakers step by step: an illustrated guide. Malden, Mass, 2004, Blackwell.)

the sinus rate is below the lower programmed rate limit, AV synchrony is lost because the VDD mode is operationally VVI (ventricular-only sensing and pacing). Although conventional dual-chamber pacing systems are not designed for BiV pacing and generally do not allow programming of an AV delay of zero, or near zero, they are being increasingly used with their shortest AV delay (0-30 msec) for CRT in patients with permanent atrial fibrillation. The advantages include programming flexibility, elimination of the Y adapter (required for conventional VVIR devices), protection against far-field sensing of atrial activity (an inherent risk of dual cathodal devices with simultaneous sensing from both ventricles), and cost. When a conventional dual-chamber pacemaker is used for CRT, the LV lead is usually connected to the atrial port and the RV lead to the ventricular port. This provides LV stimulation before RV activation (LV preexcitation) and protection against ventricular asystole related to oversensing of far-field atrial activity, when the LV lead is dislodged toward the AV groove. The DVIR mode is ideally suited for this application. The DVIR mode (committed atrial pacing, ventricular pacing and sensing) behaves similar to the VVIR mode, except that there are always two

closely coupled independent ventricular stimuli, thereby facilitating comprehensive evaluation of RV and LV pacing and sensing performance. The DVIR mode also provides absolute protection against far-field sensing of atrial activity in case of LV lead dislodgment, because no sensing occurs on the “atrial” (LV) lead in the DVIR mode. Determining LV and RV Capture: Importance of Electrocardiography The 12-lead electrocardiogram (ECG) is essential to ascertain RV and LV capture during follow-up of CRT systems without separately programmable ventricular outputs. It is recognized that at least six distinct 12-lead ventricular activation patterns may be seen during threshold determination: (1) intrinsic rhythm during loss of RV and LV capture or pacing inhibition (native QRS), (2) isolated RV stimulation, (3) isolated LV stimulation, (4) BiV stimulation with complete replacement of native ventricular activation by paced activation, (5) BiV stimulation with fusion between native activation (RBB conduction) and paced activation, and (6) BiV stimulation with anodal capture. Further, fusion between paced and native activation may result in a wide range of unique global activation patterns on the 12-lead ECG (see later).

924

SECTION 4  Follow-up and Programming

Ventricular pacing thresholds should ideally be performed independently and in the VVI mode at a rate exceeding the prevailing ventricular rate so as to obtain continuous ventricular capture uncontaminated by fusion with native activation. Alternately, thresholds can be performed in the VDD or DDD mode at very short AV delays (e.g., 50% of P-R interval) to ensure full ventricular capture without fusion. In older devices without separately programmable ventricular outputs, RV and LV capture can only be determined by ECG analysis during common ventricular voltage decrement. In this situation it is advisable to initiate threshold determinations at maximum output (voltage and pulse duration) because a significant differential often exists in capture thresholds between RV (lower) and LV (higher). Knowledgeable analysis of the ventricular activation sequence using the 12-lead surface ECG reliably establishes univentricular capture. Monochamber RV apical (RVA) pacing generates right (R) → left (L) activation in the frontal plane and anterior (A) → posterior (P) activation in the horizontal plane, resembling LBBB activation (Fig. 31-18). Consequently, mean QRS frontal plane axis is usually left superior and is infrequently right superior. Pacing from the midsuperior RV septum also generates right (R) → left (L) activation in the frontal plane and anterior (A) → posterior (P) activation in the horizontal plane, but the mean QRS frontal plane axis is typically left inferior. Monochamber LV pacing produces a variety of activation sequences depending on stimulation site and conduction blocks. A few

generalizations are possible. Posterior wall stimulation usually generates an L → R, P → A activation, and mean QRS frontal plane axis is usually right superior, less often right inferior. A detailed discussion of ventricular activation sequences during monochamber LV and BiV pacing is provided later. Figure 31-19 shows a typical example of ventricular activation during monochamber RVA versus monochamber LV capture threshold determination. The majority of current CRT-P/CRT-D systems use either dual cathodal or dedicated bipolar pacing configuration. Anodal capture refers to the situation when myocardial capture occurs at the RV anode in a dual cathodal arrangement. This could theoretically occur in isolation with the LV cathode, but most often occurs with both RV and LV cathodes, and is referred to as “triple-site” pacing, an unfortunate misnomer; a more accurate descriptor would be “capture at three sites during biventricular pacing.” Anodal capture is more common at highvoltage outputs and with true bipolar RV leads because of the small surface area and higher current density of the ring electrode, as opposed to the larger surface area and lower current density of the coil electrode in integrated bipolar leads. Anodal capture results in a distinct change in activation pattern compared to BiV pacing that can only be appreciated on the 12-lead ECG (Fig. 31-20). The change in QRS morphology related to loss of anodal capture as voltage output is decremented during a temporary threshold test using a single ECG lead may be misinterpreted as loss

During pacing the mean frontal plane QRS axis reflects the site of the pacing: • for RV pacing: apex vs outflow tract • for biventricular pacing: RV only, LV only, or biventricular aVL aVR

I

RV apical pacing

Biventricular pacing Right superior quadrant axis

(90°) (60°)

(120°)

(30°) aVL

(150°) aVR

Left (superior) axis

I(0°)

(180°) LV pacing

Right axis

(30°)

(150°) III (120°)

aVF (90°)

II (60°)

Normal axis

RV outflow tract pacing

II

III aVF

Figure 31-18  Mean frontal plane QRS axis during various conditions of ventricular pacing. (From Barold SS, Stroobandt RX, Sinnaeve AF: Cardiac pacemakers step by step: an illustrated guide. Malden, Mass, 2004, Blackwell.)



31  Troubleshooting of Biventricular Devices

RVO

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

925

LVO

Figure 31-19  Typical ventricular activation sequences during monochamber RV and LV pacing threshold determination. Top, Right ventricular (RV) apex pacing. Activation is R → L, A → P; frontal plane axis is left superior. Bottom, Left ventricular (LV) posterior wall pacing. Activation is L → R, P → A; frontal plane axis is right superior.

of LV capture and may result in erroneous overestimation of the LV threshold. The physiologic consequences of anodal capture are uncertain. One study demonstrated that anodal capture might be advantageous during CRT by counteracting the regional activation delay located at the inferior wall of the left ventricle and improving regional measures of intraventricular dyssynchrony.97 Programming Pacing Outputs.  It is critically important that voltage output be adjusted to exceed ventricular capture threshold for left and right ventricles in common cathodal devices. Differences in capture thresholds between ventricular chambers means that the voltage output must exceed capture threshold in the chamber with highest threshold (usually the left ventricle). Newer pulse generators that permit independent programming of ventricular outputs provide

Automatic Adjustment of Left Ventricular Pacing Output Left ventricular capture management (LVCM) provides automatic adjustment of LV pacing output voltage based on periodic assessment of LV capture (Medtronic). As with all automatic threshold adjusting protocols, the intent of LVCM is to deliver continuous LV pacing at the minimum output of voltage that yields 100% capture. The primary purpose of LVCM is battery conservation. This is clinically relevant because LV voltage thresholds are typically higher than RV thresholds, rendering a single voltage output for both sites inefficient.

aVR

V1

V4

aVL

V2

V5

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I BVO+ anodal capture, II LV output 5.0 V III

BVO, no anodal capture, LV output 2.0 V

greater flexibility in this regard. Similarly, RV and LV voltage outputs may be separately programmable in the situation where a standard DDD device is used to provide RV and LV stimulation in the DVI mode for CRT in permanent atrial fibrillation (see earlier).

Figure 31-20  Effect of anodal capture on ventricular activation sequence during simultaneous biventricular (BiV) pacing. Same patient as in Figure 31-19. RV apex and LV posterior wall capture thresholds are less than 1 V. Top, Simultaneous BiV pacing when LV output is 5 V (5 times > threshold) resulting in anodal capture. Bottom, Simultaneous BiV pacing when LV output is 2 V and no anodal capture. Note change in activation sequence. During high-LV-output BiV pacing, anodal capture is indicated by attenuation of monophasic R wave in V1 and loss of R (QS) in V2 (horizontal plane) and attenuation of QS in lead I and aVL (frontal plane). QRS duration is shorter. During lower-output BiV pacing, loss of anodal capture is indicated by dominant QS in I, aVL, and dominant R (V1) and RS (V2). QRS duration is longer.

926

SECTION 4  Follow-up and Programming

performance trends. Trend displays include the maximum and minimum LV capture threshold values for the last 80 weeks along with higher-resolution details for the last 14 days.

An ancillary value is the possibility of overcoming phrenic stimulation when the voltage differential between phrenic nerve capture (higher) and LV capture (lower) is sufficiently differentiated. In this situation, LV output voltage can be automatically “capped” beneath the phrenic nerve capture voltage without compromising LV capture. Provision of long-term threshold behavior as a dedicated diagnostic measure might reduce follow-up time by eliminating the need for in-office real-time determinations, and is particularly useful during remote surveillance. When LVCM is enabled, the device automatically monitors the pacing amplitude threshold at periodic intervals, nominally 01:00 am daily. The minimum amplitude that consistently results in ventricular capture (threshold) is stored and reported. If LVCM is programmed to “adaptive,” LV output voltage is automatically reprogrammed toward a selectable maximum output voltage defined by the desired “maximum amplitude safety margin” and reported. Alternately, if LVCM is programmed to “monitor,” LV output is not adjusted, although data regarding threshold determinations are recorded.

Operating Details.  Unlike automatic RV pacing threshold adjusting algorithms in conventional pacemakers, LVCM does not use the evoked response to determine ventricular capture. Rather, LVCM determines LV capture by recording RV sensed events in response to LV monochamber pacing. This requires timing methods to ascertain whether RV sensed events during monochamber LV pacing are caused by native AV conduction, ventricular premature beats, electromagnetic interference (EMI), or other extraneous conditions. RV sensed events outside the “expected” timing window for native AV conduction, or loss of RV sensing during monochamber LV pacing, is used to indicate loss of LV capture (e.g., threshold voltage). The LVCM operation consists of four stages: (1) ventricular rate and stability check, (2) LV-RV conduction check, (3) AV conduction check, and (4) LV pacing threshold search (LVPTS). The order of these stages is not arbitrary. Ventricular rhythm must be stable (<200 msec R-R interval variability) and rate less than about 90 beats per minute (bpm) for 12 cycles. The reason for this is the need to ensure stable AV conduction timing and LV-RV conduction timing during atrial-synchronous monochamber LV pacing in tracking modes and/or 100% overdrive ventricular pacing during atrial fibrillation (nontracking modes). The LV (paced) → RV (sensed) conduction time is determined during cycles of up to eight (atrial synchronous) monoventricular pacing sequences (Fig. 31-21). To enhance accurate measurement of unidirectional ventricular conduction time, this test is initiated approximately 15 bpm above the ventricular rate measured during the rate and stability check. In dual-chamber modes, the pacemaker atrioventricular interval (pAVI) is shortened to 30 msec. These two adjustments are intended to guarantee complete replacement of AV and VV

Programming Options.  LVCM has three programmable settings: operating status, LV amplitude safety margin, and LV maximum adapted amplitude. Operating status exists in three programmable states: Off, Adaptive (indicated by an adaptive parameter icon on the programmer interface), and Monitor-only. Diagnostics are provided for Adaptive or Monitor-only states. LV Amplitude Safety Margin applied to the pacing threshold search results is selectable in 0.5-V increments (+0.5, +1.0, +1.5, +2.0, +2.5 V). Similarly, the LV maximum adapted amplitude is selectable (0.5, 1.0, … 4.0, 5.0, 6.0 V). Diagnostic Reporting.  LVCM provide diagnostics for specific conditions (high threshold, possible high threshold, high output, inadequate safety margin, and no measurement in the last 7 days) and long-term LV-RV conduction test

AV conduction test

A P

A P

A P

A P

V V P S

V V P S

V V P S

V V P S

180 ms

180 ms

180 ms

180 ms

A P

A P

B V

V P

A P

V S

Ignore

A P

B V

B V

260 ms 260 ms

Measured LV-RV interval Loss of capture (0.5 v @ 0.9 ms)

A P

A P

B V

260 ms

260 ms

PAV setting (LV-RV + 80 ms) Capture (1.0 v @ 0.9 ms)

A P

B V

A P

B V

Capture

A P

B V

Loss of capture

V V P S

A P

Figure 31-21  Left ventricular capture management (LVCM) operation. Top, Surface ECG, event markers, right ventricular electrogram (RV EGM). Successful LV-RV and AV conduction checks. During overdrive atrial pacing and LV monochamber pacing, the LV-RV interval is 180 msec (left). During AV conduction check (right) PAV is set to 180 msec + 80 msec (260 msec). Note that this example was obtained from a prototype RAMware download; in the market-released application, the PAV would be set to 180 + 60 (240 msec); see text for details. Absence of intrinsic AV conduction within this timing window is confirmed, satisfying the condition for LV Pacing Threshold Search (LVPTS). Bottom, Surface ECG, event markers for LVPTS. The expected LV-RV conduction time is 180 msec, which sets the capture detection window 150 to 200 msec (30 msec earlier—20 msec later than the expected LV-RV conduction time) from the LV test pace. The first LV test pace (0.5V/0.9 msec) is ineffectual; loss of LV capture is indicated by emergence of native AV conduction (conduction time = 300 msec). The second LV test pace (1.0V/0.9 msec) is effective with LV-RV conduction time 180 msec, satisfying the capture detection window. (Modified from Crossley GH, et al: Automated left ventricular capture management. Pacing Clin Electrophysiol 30:1190-1200, 2007.)



conduction with paced activation. Additionally, the blanking period on the RV sense amplifier is minimized to enhance RV sensing. LV-RV conduction is performed with LV output at the prevailing programmed setting. If RV sensing does not occur in response to a LV-only test stimulus, a backup BV pacing stimulus with LV at maximum amplitude occurs on the following cycle, and LV output remains at maximum amplitude except for single-test cycles. Atrioventricular conduction time is determined during overdrive (atrial pacing) simultaneous BiV pacing at a long pAVI sufficient to yield BiV sensing. This pAVI is set to 30 msec (nominal during LV-RV conduction check) + measured LV-RV conduction time + 30 msec. If no VS events during atrial pacing are seen during this time window, LVPTS can proceed. If any VS events occur within this time window, the test aborts. The difference between LV → RV and AV conduction time must therefore be consistently greater than about 60 msec to proceed with LV capture threshold determination. If the time difference between LV → RV and AV conduction is similar (e.g., <60 msec), loss of capture during LV monochamber pacing cannot be differentiated from native AV conduction. Anticipated increases in AVIs during overdrive atrial pacing increases the probability that AV conduction times will be sufficiently longer than LV-RV times. If AV conduction is absent (heart block), LVPTS proceeds. The AV conduction test is not performed in nontracking modes. If these conditions are satisfied, LVPTS is initiated at the overdrive rate applied during VV and AV conduction tests (tracking modes). In nontracking modes (e.g., VVI/R) the overdrive rate on test cycles depends on the rate of the previous three “support” cycles. Biventricular pacing is initiated in a series of three or more support cycles at programmed ventricular voltage outputs, followed by single monochamber LV pacing “test” cycles (at pAVI 30 msec in dual-chamber modes), with progressively increasing LV output starting at 0.5 V per programmed pulse width below the last measured threshold. Consequently, a single ineffectual monochamber LV paced event resulting in a ventricular pause can occur in each test sequence, which explains the pacing “support” cycles. The LV capture detection window is defined as 30 msec earlier and 20 msec later than the longest observed LV-RV conduction time. LV capture is indicated by RV sense events within the capture window, whereas absent RV sensed events or events outside (either direction) the capture window of 30 msec or longer are interpreted as loss of LV capture. Loss of LV capture is defined as the output voltage in which two thirds of test stimuli fail. Reciprocally, LV capture is defined as the output voltage in which two thirds of test stimuli succeed. The LV capture amplitude threshold is the voltage at which three consecutive test cycles result in capture (see Fig. 31-21). If LVCM is programmed to Adaptive, the programmed Amplitude Safety Margin is added to the determined threshold with an upper limit defined by the Maximum Adapted Safety Margin parameter. If the new threshold has decreased with respect to the previously measured value, the LV amplitude is decreased by 1 programmable value. If the new threshold has increased with respect to the previously measured value, the LV amplitude is set to the measured threshold plus the LV amplitude safety margin. However, if the measured threshold plus the LV amplitude safety margin exceeds the LV maximum adapted amplitude, the LV amplitude is set to the LV maximum adapted amplitude. If a highthreshold condition occurs (e.g., capture is not determined at LV maximum adapted amplitude), LV amplitude is set to LV maximum adapted amplitude. Notably, LVCM threshold determination is performed at 01:00 (1 am) (device clock). The reason for this is to minimize symptoms associated with intermittent loss of ventricular capture (single-cycle pauses), particularly in pacemaker-dependent patients. Clinical Performance.  Performance of LVCM has been investigated using downloaded RAMware.98 In 107 patients, 307 LV capture threshold measurement pairs (manual and LVCM) were analyzed. LVCM thresholds were within 1 voltage step of manually determined thresholds for 99.7% of tests (two-sided 95% confidence interval: 98.2, 100.0). Erroneously high LV thresholds were not recorded.

31  Troubleshooting of Biventricular Devices

927

Potential Limitations and Complications.  A variety of clinical conditions must be satisfied for LVCM operation. Failure to differentiate AV versus VV conduction times is probably more likely to occur in patients with relatively normal AV conduction times, since VV conduction times are generally less than 100 msec. Overdrive atrial pacing reduces this possibility by stressing AV conduction. Extraneous sensed events in the AV and VV conduction detection windows (ventricular premature depolarization [VPDs], noise) may result in spurious LV threshold determinations. Intermittent loss and recovery of atrial capture during the AV conduction test can result in spurious LV threshold determinations. Consequently, another “test abort” criterion for uncertain atrial capture was added to the LCVM algorithm. Single-cycle loss of ventricular capture during LVCM threshold determinations create ECG mimicry of pacing inhibition (crosstalk, conductor or insulation failure, EMI)99 (Fig. 31-22). This may not be simply a cosmetic issue. Short-long-short sequences (“pauses”) terminated by single ventricular paced beats have been linked to ventricular tachycardia/fibrillation (VT/VF) onset and constitute a unique form of bradycardia pacing-induced ventricular proarrhythmia.100 It seems likely that an example of VT/VF onset preceded by a short-long-short sequence during LVCM threshold determination will eventually be recorded. Operating Constraints.  A number of programming conditions must be satisfied before LVCM threshold determination can be enabled. The programmed LV amplitude voltage cannot exceed the maximum adapted amplitude voltage. Additionally, the programmed LV amplitude must be less than 8 V; LV pulse width must be 0.4 msec or greater; and PVARP must be static. Also, overdrive of the programmed lower rate may not be possible in some conditions of pacing and tachycardia detection zone programming. Once enabled, LVCM threshold determination will not be performed if a telemetry session or fluid status measurement is in progress, if programmed pacing mode is other than DDD, DDDR, or VVIR, or if ventricular pacing configuration is RV only. Similarly, a number of clinical conditions must be satisfied before LVCM threshold determination is performed. This requires that the rhythm be stable (<200 msec R-R interval variability), less than about 90 bpm, and no VT/VF detection or therapy within the prior 30 minutes. The reasons for these exemptions are (1) the need to ensure stable AV conduction and VV timing during monochamber LV pacing and/or 100% overdrive ventricular pacing during atrial fibrillation and (2) to prevent ventricular pacing during VT/VF, which could result in detection delays or failure caused by blanking. If any of these conditions is present, LVCM threshold determination is rescheduled for 30 minutes, or until four failed attempts are recorded, after which further attempts are suspended to the next calendar day. Also, several pacing features are suspended during LVCM operation (atrial rate stabilization, atrial pacing preference, ventricular rate stabilization, atrial tracking recovery, ventricular sense response, and conducted atrial fibrillation response). Left ventricular capture management can be applied with either unipolar or bipolar LV leads. However, LV pacing polarity must be bipolar or dual cathodal where the RV cathode is restricted to the RV coil. LV tip to RV ring is not permitted because anodal RV capture will interfere with the LV-RV conduction check (simultaneous BiV pacing). RV lead type (integrated bipolar vs. true bipolar) is irrelevant. However, RV blanking is extended to 90 msec for integrated bipolar leads during LV-RV conduction check to minimize RV oversensing caused by local afterpotential decay. TAILORING CRT PROGRAMMING TO IMPROVE CARDIAC MECHANICS AND MAXIMIZE PROBABILITY OF REVERSE VOLUMETRIC LV REMODELING Methods to Guarantee Ventricular Electromechanical Resynchronization The translational mechanism of CRT is ventricular activation wavefront fusion.12,72 Resynchronization of ventricular activation restores part or all of the LBBB-induced impairment in LV mechanics. The

928

SECTION 4  Follow-up and Programming

LV-RV test

Support cycles

Support cycles Test pace

A-V test

Support cycles Test pace

Test pace

Figure 31-22  Short-long-short sequences (pauses) and pseudo-crosstalk during LVCM operation. Top left, Continuous AV sequential BiV pacing, followed by LV-RV conduction check and AV conduction check. The underlying rhythm was complete AV block, and therefore the AV conduction check was satisfied (absence of VS events within detection window). A sequence of pacing support cycles (indicated by increase in pacing rate) precedes the LV Pacing Threshold Search (LVPTS). The first LV test pace is ineffectual; in the absence of AV conduction and a ventricular escape mechanism, a pause occurs. This is followed by a pacing support cycle and another ineffectual LV test pace resulting in a second pause. The third LV test pace is effective, preventing a pause. Because of the short PAV (30 msec) and low-output voltage (0.5 V) during the LVPTS, only the atrial pacing stimulus is visible, mimicking true-crosstalk inhibition of ventricular output. (Modified from Ho R, Mark GE, Rhim ES, Shorrock SM: Pseudo crosstalk behavior in a patient with atrio-ventricular block and implanted biventricular defibrillator. Pacing Clin Electrophysiol 30:1555-1557, 2007.)

immediate consequence is improvement in contractility (pump function),12,13,67,68 followed by reductions in global and regional structural abnormalities (reverse remodeling).83,92,93,101,102 Therefore, the primary goal of CRT programming is maximal and continuous correction of LV conduction delay. Maximal means the greatest achievable correction of the delayed LV activation sequence and continuous means on every cardiac cycle for the patient’s lifetime. The following conditions must be specified to achieve this goal: (1) LV stimulation is delivered from a site capable of reversing LBBB conduction delay, (2) LV stimulation threshold is within the output capacity of the pulse generator, (3) LV pacing occurs on every cardiac cycle, and (4) LV timing is adjusted to guarantee ventricular activation fusion on every cardiac cycle. Conditions 1 and 2 are determined primarily by selection of a specific site for LV pacing and are largely fixed. Condition 3 is a dynamic process that requires continuous updating but is directly addressed by programming strategies and automaticity. Condition 4 is the intended end result of satisfying conditions 1 to 3 and provides evidence that maximal and continuous correction of LV conduction delay has been achieved. Generating Ventricular Activation Wavefront Fusion during CRT.  Analysis of ventricular activation using the standard 12-lead surface ECG accurately predicts the probability of LV reverse volumetric remodeling during CRT in patients with ventricular-asynchronous heart failure and LBBB.72 The probability of reverse remodeling is explained by interactions between substrate conditions and pacinginduced changes in ventricular activation before and after CRT. The main findings are that (1) the translational mechanism for volumetric remodeling is activation wavefront fusion, evident on the paced ECG, and (2) the probability of remodeling is positively influenced by LV conduction delay (maximum left ventricular activation time, LVATmax) and negatively influenced by LV scar volume (QRS score) on the baseline ECG (Fig. 31-23). Longer LVAT and smaller LV scar volume during LBBB on the baseline ECG predict higher probability of reverse modeling (Fig. 31-24). Evidence for activation wavefront fusion on the CRTpaced ECG, indicating conduction defect reversal, also predicts higher probability of reverse remodeling (Fig. 31-25). The framework for

analysis of ventricular activation using the 12-lead surface ECG has direct application to CRT programming. Characterization of Ventricular Activation during LBBB Using QRS Hieroglyphic Analytic Framework Derived from Surface ECG.  Typical LBBB activation is registered as R → L (frontal plane), A → P (horizontal plane), and variable axis. This yields a QRS Predictor

Odds ratio (95% confidence intervals) for >10% ESV reduction

Pvalue

Baseline (pre-CRT) LVATmax (ms)

1.30 (1.11, 1.52) per 10 ms increase

QRS score (%LV scar volume)

0.49 (0.27, 0.88) for each 1 point increase from 0 to 4 0.92 (0.83, 1.01) for each 1 point increase above 4

0.001 0.0022

Post-CRT QRS hieroglyphs R wave change in expected direction

2.76 (1.01, 7.51) for each 1 mV increase above 4.5

0.048

LADEV>RADEV

2.00 (0.99, 4.02)

0.052

Figure 31-23  Predicting reverse volumetric remodeling during CRT using analysis of ventricular activation on 12 lead surface ECG. Baseline ventricular activation analysis during left bundle branch block (LBBB): longer maximum LV activation time (LVATmax; LV conduction delay) predicts greater odds of reverse remodeling (30% relative increased odds for each 10-msec increase), whereas higher QRS scores (indicating % LV scar volume) predicts reduced odds of reverse remodeling (50% relative decreased odds for 1-point increase in QRS score of 1-4, 10% relative decreased odds for each 1-point increase above 4). Post-CRT analysis of ventricular activation using QRS hieroglyphs: Emergence of R waves in leads V1-V2 (indicating posterior → anterior activation reversal) predicts greater odds of reverse remodeling (2.76 relative increased odds for each 1-mV increase above 4.5 mV). Emergence of QR, Qr, or QS in lead I (indicating left → right activation reversal) resulting in frontal axis quadrant shift predicts greater odds of reverse remodeling (2.0 relative increased odds of reverse remodeling).



31  Troubleshooting of Biventricular Devices BY MEAN R CHANGES (mV), LEADS V1 AND V2 Predicted probability of response (ESV reduction ≥10%)

0.8 0.6 0.4 0.2 0.0

Predicted probability of response (ESV reduction ≥10%)

75

100

125

150

Mean change = 7

0.8

Mean change = 5 Mean change <4.5

0.6 0.4 0.2 0.0 50

75

100

125

150

Maximum LVAT (ms)

Maximum LVAT (ms)

BY LADEV TO RADEV SHIFT

BY QRS SCORE

1.0 Shift

0.8 0.6

No shift

0.4 0.2 0.0 50

1.0

175

75

100

125

150

175

Maximum LVAT (ms)

Predicted probability of response (ESV reduction ≥10%)

Predicted probability of response (ESV reduction ≥10%)

ALL PATIENTS

50

929

175

1.0 Score = 2 Score = 6

0.8 0.6

Score = 10

0.4 0.2 0.0 50

75

100

125

150

175

Maximum LVAT (ms)

Figure 31-24  Probability of LV reverse remodeling by baseline and post-CRT predictors. Top left, Increasing probability of response with greater maximum left ventricular activation time (LVATmax). Line represents predicted probability of response for each value of LVATmax. Diamonds represent actual response rates among LVATmax quartiles. Top right, Increasing probability of response with greater LVATmax and post-CRT evidence of ventricular fusion (P→A activation reversal). Bottom left, Increasing probability of response with greater LVATmax and post-CRT evidence of ventricular fusion (L→R activation reversal). Bottom right, Increases in QRS score reduce response probability for any value of LVATmax. (From Sweeney MO, et al: Analysis of ventricular activation using surface electrocardiography to predict left ventricular reverse volumetric remodeling during cardiac resynchronization therapy. Circulation 121:626-634, 2010.)

Predicted probability of response (>10% ESV reduction)

1 0.9 0.8 0.7 This point represents 158 pts with mean R change values <1, all of which have equivalent probability of response.

0.6 0.5 1

1.5

2

2.5

3

3.5

4

4.5

Mean change in R amplitude in expected direction as a proportion of baseline, leads 1, L, V1–V6 Figure 31-25  Predicting LV reverse remodeling during CRT using a global measure of ventricular fusion. Greater changes in R-wave amplitudes after CRT, indicative of wavefront fusion, predict higher probability of response. The points along the line are individual predicted values. (From Sweeney MO, et al: Analysis of ventricular activation using surface electrocardiography to predict left ventricular reverse volumetric remodeling during cardiac resynchronization therapy. Circulation 121:626-634, 2010.)

hieroglyphic signature with dominant positive forces in I, aVL (R, Rs), negative forces in aVR (QS), variable forces in II, III, aVF (R, Rs, rS, QS), dominant negative forces in V1-V2 (QS, rS), transition V3-V5 (rS→Rs, R), and dominant positive forces in V5-V6 (R, Rs) (Fig. 31-26). QRS Notching.  Left bundle branch block is characterized by sequential ventricular activation (RV → LV)12,18,20 and registered as fragmented QRS complexes with RSR′ configuration (“notch”). QRS notching was defined as 1 notch or more in the R or S wave present in 2 or more adjacent anterior, lateral, or inferior leads103 (Fig. 31-27). Right and Left Ventricular Activation Time.  Because multiple notches in the R and S wave during LBBB may result from myocardial scar,103 the first notch was assumed to indicate the transition between RV and LV depolarization (see Fig. 31-27). Notching in the first 40 msec of the S wave in V1-V2 was excluded because this indicates scar in the QRS score. Right ventricular activation time (RVAT) was measured as time (msec) between QRS onset and first notch in any of two or more adjacent leads. LVAT was QRSd − RVAT (msec). For modeling purposes, the longest LVAT (LVATmax) recorded in any lead and region was used. A numerical relationship between QRSd and LVATmax was derived using linear regression [LVATmax (msec) = −35.839 + 0.763*QRSd (msec) + 0.000619*QRSd (msec)∧2], permitting estimation of LVATmax in the absence of QRS notching (40 patients). Quantification of Left Ventricular Scar.  Myocardial scar has been linked to reduced CRT response104 (Fig. 31-28). ECG quantification of LV scar volume was calculated using the Selvester QRS score for LBBB.105,106 The effects of scar on LBBB surface registration translate as specific QRS hieroglyphic signatures, manifest as unopposed rightward electrical forces by infarct region: qR, QR, rS in I, aVL (anteriorsuperior); qR, QR, rS in I, V5-V6 (apical); qR, QR, rS in II, aVF (inferior); QS → rS, RS, or Rs in V1-V2 (anterior-septal). Notching on the ascending limb of the S wave in V1-V2 indicates posterolateral infarct.

930

SECTION 4  Follow-up and Programming

I

BIR

II

aVR

V1

aVL

III

BLR

aVF

BV1QS

V2

V4 – V5

BV2QS

V3

V6

BFQS V1 Figure 31-26  Characterization of ventricular activation during LBBB using QRS hieroglyphs. Typical LBBB with dominant R in I (BIR glyph) and L (BLR glyph), indicating R → L activation; rS or QS in II, III, F, and rS or QS in V1-V3 (BV1QS, BV2QS glyphs), indicating anterior → posterior activation). In some patients, RS and Rs emerge in V4-V6. Left superior axis is caused by QS glyphs in leads II, III, aVF. LV activation plot (upper right) indicates R → L activation (red arrows, RV pacing wavefront; blue arrows, LV pacing wavefront).

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

V1

Lead II. RVAT = 45.3 ms

Lead V6. RVAT = 52.8 ms

Figure 31-27  Calculation of LV and RV activation time using surface ECG. First downward arrow indicates QRS onset. Second downward arrow indicates first QRS notch, which represents transition between RV and LV activation. Time difference (msec) between first and second arrows is right ventricular activation time (RVAT). RVAT is measured in multiple anatomic regions determined by distribution of QRS notching. Shown are RVAT determinations for inferior and apical regions. LVATmax is QRSd − RVATmin = 160 msec − 45.3 msec = 114.7 msec.

I

aVR

V1

V4 AS: Notching, initial 40 ms, +1 pt

II

aVL

V2

PL: S/S′ ≥2, +3 pt

V5

INF: R/S ≤0.5, +1 pt

III

AP: R/S ≤2, +1 pt

aVF

ASUP: Q ≥50 ms, +2 pts

V3

PL: S/S′ ≥2, +3 pt

V6

INF: R/S ≤0.5, +1 pt

V1

AP: R/S ≤2, +1 pt, R <6, +1 pt

Figure 31-28  Quantification of percentage LV scar volume using QRS score. This patient has inferior (INF), anterosuperior (ASUP), anteroseptal (AS), posterolateral (PL), and apical (AP) scar, yielding QRS score = 14 (LV scar volume 32%).



31  Troubleshooting of Biventricular Devices

Evidence for Ventricular Activation Fusion during CRT.  Experimental models of LBBB demonstrate maximum improvement in LV pump function occurs when intra-LV electrical asynchrony is minimized by wavefront fusion12 (see Figs. 31-29 to 31-44). Wavefront opposition and reversal during BiV pacing should yield ECG evidence of fusion: (1) expected change in frontal plane electrical axis (normal or LADEV→RADEV) and (2) expected changes in QRS hieroglyphic signatures. Rightward forces emerge in leads with dominant leftward forces (R in I, aVL → qR, QR, QS). Anterior forces emerge in leads with dominant posterior forces (QS in V1 → rS, RS, Rs, R; QS or rS in V2 → RS, Rs, R; rS or RS V3→ Rs or R, etc). Monochamber LV pacing generates specific ventricular activation patterns generally in accordance with stimulation site (see Figs. 31-29 to 31-31). Anterior vein stimulation most often results in LBBB activation sequence; infrequently, very proximal sites in the anterior vein yield RBBB activation. Middle cardiac vein stimulation always results in LBBB activation sequence, duplicating RVA pacing. Lateral cardiac vein (posterior wall) typically results in complete reversal of the LBBB activation sequence (e.g., RBBB, rightward axis). However, nearly identical ECG activation sequences may be registered at widely spaced sites,107 and electrical resynchronization during CRT correlates unpredictably with stimulation site because of conduction blocks.20 For these reasons, knowledge of specific LV stimulation site is not relevant to this approach for generating evidence of ventricular activation fusion, which emphasizes changes in ventricular activation indicated by analysis of QRS hieroglyphic patterns. CRT Programming to Generate Maximum Evidence of Ventricular Activation Fusion As discussed previously, optimal ventricular resynchronization occurs when the wavefronts from the RV pacing site (or originating from

RA

RBBc) and the LV pacing site collide halfway78 (see Fig. 31-10). Experimental and human evidence indicates that optimal hemodynamic effect can be achieved using LV pacing at certain atrioventricular delays (AVDs) as well as using simultaneous and sequential BiV pacing, because fusion of electrical wavefronts can be achieved by either approach13,79 (see Figs. 31-32 and 31-33; see also Fig. 31-11). The interaction among AVD, VV timing, and generation of activation fusion is most easily understood during “LV only” (LVO) pacing (see Fig. 31-34). In this situation, ventricular activation is controlled by fusion between LV pacing and RBBB conduction. The P-R interval is a surrogate for left-sided AV timing. Any AVD shorter than the baseline P-R interval will advance LV activation. Partial correction of LV conduction delay at a relatively long AVD < PR is registered on the surface ECG as incomplete ventricular fusion and delayed time to peak strain on the posterior wall relative to septum (see Fig. 31-35). Complete correction of LV conduction delay at shorter AVD is registered as ventricular activation fusion and synchronization of time to peak strain between septum and posterior wall (see Fig. 31-36). Overcorrection of LV conduction delay (complete reversal of activation) at even shorter AVD is registered as L → R, P → A activation on the surface ECG and delayed time to peak strain on the septum relative to posterior wall (see Fig. 31-37). More often, CRT is delivered with biventricular pacing. In this situation, evidence for generation of ventricular activation fusion on the surface ECG consists of two pacing wavefronts with unique ECG signatures. Certainty regarding maximal ventricular activation fusion during BiV pacing therefore requires characterization of ventricular activation during monochamber RV and LV pacing (see Figs. 31-19 and 31-20). This is most accurately accomplished in the ventricularonly pacing mode at a rate exceeding the prevailing ventricular rate, Text continued on page 936

LV

RA

RV

RA

LV

RV

RVA

LV

RA

LV RV

RV

RVA

RVA

Right anterior oblique

Left anterior oblique

RVA

Left anterior oblique

Right anterior oblique

I

aVR

V1

V4

I

aVR

V1

V4

II

aVL

V2

V5

II

aVL

V2

V5

III

aVF

V3

V6

III

aVF

V3

V6

A

931

B

Figure 31-29  Ventricular activation during monochamber LV pacing from anterior coronary vein. A, Approximately 75% of patients had LBBB activation sequence with minimal or absent PV1R during mid-distal anterior vein stimulation. B, Approximately 25% had right bundle branch block (RBBB) activation but only during very proximal anterior vein stimulation. (Modified from Giudici MC, et al: Electrocardiographic patterns during pacing the great cardiac and middle cardiac veins. Pacing Clin Electrophysiol 30:1376-1380, 2007.)

932

SECTION 4  Follow-up and Programming

CS RA

RA

CS

RV RV

LV LV

I

v5

aVR

II

aVL

v2

v4

III

aVF

v3

v6

Figure 31-30  Ventricular activation during middle cardiac vein pacing. 100% of patients had LBBB activation with left superior axis. (Modified from Giudici MC, et al: Electrocardiographic patterns during pacing the great cardiac and middle cardiac veins. Pacing Clin Electrophysiol 30:13761380, 2007.)

I

aVR

v1

v4

II

aVL

v2

v5

III

aVF

v3

v6

V II V5 Figure 31-31  Ventricular activation during lateral cardiac vein pacing (posterior wall). 100% of patients had RBBB activation with rightward axis. (Modified from Giudici MC, et al: Electrocardiographic patterns during pacing the great cardiac and middle cardiac veins. Pacing Clin Electrophysiol 30:1376-1380, 2007.)



31  Troubleshooting of Biventricular Devices

I

BIR → PIQS

aVR

V1

BV1QS → PV1R

933

V4 O

II

aVL

III

aVF

V2

BLR → PLqR

BV2QS → PV2rS

V3

V5

V6

V1 Figure 31-32.  Evidence for ventricular activation fusion during CRT. Same patient as in Figure 31-26. Note the following changes in global ventricular activation as compared to LBBB. R-wave emergence where there were previously S waves; Q, QS, or S wave emergence where there were previously R waves. R waves in leads I (BIR) and aVL (BLR) have been replaced by QS and qR complexes (PIQS and PLqR, respectively); indicating reversal of activation in the frontal plane (L→R). QS waves in V1 (BV1QS) and V2 (BV2QS) have been replaced by R waves (PV1R, PV2rS), indicating reversal of activation in the horizontal plane (P→A). LV activation plot (upper right) indicates fusion (red arrows, RV pacing wavefront; blue arrows, LV pacing wavefront).

LBBB I

BIR

aVR

II

aVL

III

aVF

V1

BLR

BFQS

V2

BV1QS

BV2QS

V3

V4 – V5

V6

V1 CRT I

BIR → PIQS

V1

aVR

II

aVL

III

aVF

BLR → PLqR

V2

V3

BV1QS → PV1R

BV2QS → PV2rS

V4 O

V5

V6

V1 Figure 31-33  Generation of ventricular activation fusion after CRT. Side-by-side comparison global LV activation during LBBB (top) and postCRT (bottom). Same patient as in Figures 31-26 and 31-30. Note reversal of activation by regions which yields a global pattern of ventricular activation fusion. This patient had QRS score = 1 (inferior scar), LVATmax = 147 msec, and robust evidence of fusion post-CRT (left → right, posterior → anterior reversal). Predicted probability of ≥10% reduction in ESV at 6 months was 90%, actual ESV reduction was 24%. (Modified from Sweeney MO, et al: Analysis of ventricular activation using surface electrocardiography to predict left ventricular reverse volumetric remodeling during cardiac resynchronization therapy. Circulation 121:626-634, 2010.)

934

SECTION 4  Follow-up and Programming

I

v1

aVR

v4

II

aVL

v2

v5

III

aVF

v3

v6

Local: longitudinal strain (%)=13.12 T=1070 msec AVC

18.0 12.0 6.0 0.0 –6.0 –12 –18

0

300

600

800

Figure 31-34  Typical LBBB ventricular activation and corresponding LV longitudinal strain map. LV conduction delay is registered as regional mechanical delay, indicated by early septal activation and delayed posterior wall activation.

I

aVR

v1

II

aVL

v2

v4 –
III

aVF

v3

v6

Local: transverse strain (%) 57.0

AVC

38.0 19.0 0.0 –19.0 –38.0 –57.0 0

200

400

600

800

Figure 31-35  Effect of “LV only” LVO pacing on ventricular activation (surface ECG) and LV strain map. Same patient as in Figure 31-34. Baseline P-R interval is 240 msec. LVO pacing is delivered at atrioventricular delay (AVD) 160 msec. Note changes on the surface ECG indicative of incomplete ventricular fusion. QS in lead V1 has been replaced by rS; R in lead I has been replaced by qR. Frontal plane axis shift has not occurred. Corresponding strain maps demonstrate reduction in posterior wall delay; however, L→R, A→P activation persists.



31  Troubleshooting of Biventricular Devices

I

aVR

v1

v4

II

aVL

v2

v5

v3

v6

III

aVF

935

0

Local: transverse strain (%)=28.08 T=1086 msec

57.0

AVC

38.0 19.0 0.0 –19.0 –38.0 –57.0 0

300

600

900

Figure 31-36  Effect of LVO pacing on ventricular activation (surface ECG) and LV strain map. Same patient as in Figures 34-34 and 34-35. Baseline P-R interval is 240 msec. LVO pacing is now delivered at AVD 120 msec. Note changes on the surface ECG indicative of ventricular activation fusion. QS in lead V1 has been replaced by RS; R in lead I has been replaced by QS. Right superior axis has replaced normal axis. Corresponding strain maps demonstrate synchronization of septal and posterior wall activation. LV volume is visually reduced.

I

aVR

v1

v4

II

aVL

v2

v5

–
aVF

v3

v6

57.0

Local: Transverse strain (%) AVC

38.0 19.0 0.0 –19.0 –38.0 –57.0 0

300

600

900

Figure 31-37  Effect of LVO pacing on ventricular activation (surface ECG) and LV strain map. Same patient as in Figures 34-34 to 34-36. Baseline P-R interval is 240 msec. LVO pacing is now delivered at AVD 100 msec. Note changes on the surface ECG indicative of complete reversal of ventricular activation: QS persists in lead I, qR in lead AVL has been replaced by qr (R regression), and QS in leads V1-V3 have been replaced by Rs. Corresponding strain map demonstrates early activation of posterior wall and delayed activation of septum. Activation is now R → L, P → A.

936

SECTION 4  Follow-up and Programming

so as to eliminate the possibility of fusion with native activation. Once the ECG signatures of monochamber RV and LV pacing have been characterized, simultaneous BiV pacing is initiated at an AVD sufficiently short to preempt native ventricular activation (e.g., 50% of baseline P-R interval). This allows complete control of ventricular activation timing by replacing intrinsic activation with paced activation. Since LV activation is always delayed relative to RV activation during LBBB, and the pacemaker AVD is recorded between the right atrium and right ventricle, shortening the AVD advances the LV activation and titrates the dose of resynchronization. Further advancement of LV activation is possible with sequential ventricular stimulation. The ECG is then examined for evidence of activation fusion using a similar QRS analytic architecture as previously described. Occasionally, maximal attainable sequential ventricular stimulation does not achieve ventricular activation fusion, even when the AVD is substantially shorter than the P-R interval. In this situation, further shortening of the AVD is necessary to advance the LV activation sufficiently and achieve maximal evidence of ventricular activation fusion (see Figs. 31-38 to 31-41). In this manner, the AV delay and V-V interval display a necessary and logical interaction as control parameters for ventricular activation timing. Generally, RVA pacing produces a ventricular activation sequence that duplicates the QRS hieroglyphic signature of LBBB. Under these conditions, typical changes in frontal plane axis and QRS hieroglyphs indicative of ventricular activation fusion are observed (see Figs. 31-29 to 31-32). Occasionally, atypical ventricular activation patterns occur during monochamber RVA and LV pacing and confound the typical QRS hieroglyphic signature for ventricular activation fusion during BiV pacing (see Figs. 31-42 to 31-44). In this situation, typical QRS glyph changes in the expected direction during BiV pacing are not observed. Evidence for ventricular activation fusion must therefore rely on the principle of “activation wavefront reversal” in pivotal leads. The

use of a global measure of activation fusion is particularly useful in this situation (see earlier) because this eliminates directionality, which can be confounded by atypical pacing activation patterns, in favor of magnitude of change opposite the initial forces in pivotal ECG leads. Methods to Guarantee Optimal Atrioventricular Resynchronization Correction of ventricular conduction delay to improve ventricular mechanics and induce reverse volumetric remodeling is the primary target of CRT. Resynchronization of ventricular electromechanical timing directly influences systolic performance. Since the timing of ventricular stimulation is primarily controlled with the pacemaker A-V interval, CRT also has direct effects on AV timing, which influences ventricular loading conditions and diastolic function. Diastolic dysfunction is common in systolic heart failure and contributes to symptoms. Optimal AV resynchronization can reduce diastolic dysfunction and improve symptoms. The interaction among the pAVI, ventricular electromechanical resynchronization, and AV resynchronization has resulted in much confusion and debate regarding CRT programming considerations. This confusion has two sources: (1) failure to understand the interaction between pAVI, AV timing, and VV timing (see earlier) and (2) a long-standing historical interest in improving pump function by optimizing diastolic function during conventional dualchamber, monoventricular (RV) pacing. In the latter situation, the effects of changes in pAVI were not confounded by simultaneous effects on ventricular resynchronization and therefore easier to understand. Some generalizations regarding the pacemaker AVI, ventricular resynchronization, and AV resynchronization during CRT are useful, as follows: 1. Interpretation of the effects of changes in AV timing on pump function is difficult because diastolic function and systolic function are simultaneously altered.

LV LV RV

RV

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 31-38  Lead positions and baseline LBBB activation. Same patient as in Figure 39-41. Top, RVA and LV posterior wall (lateral coronary vein) stimulation sites. Bottom, Typical R → L (frontal), A → P (horizontal) activation sequence during LBBB.



31  Troubleshooting of Biventricular Devices

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

937

Figure 31-39  QRS hieroglyphic signatures during monochamber RV and LV pacing. Top, Monochamber RVA pacing activation is typical. Bottom, Monochamber LV pacing from posterior wall (lateral coronary vein) demonstrates typical dominant R leads V1-V3, indicating P→A activation. Atypical dominant qR in lead I, aVL is caused by “lead I paradox.”

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 31-40  Incomplete ventricular activation fusion during simultaneous biventricular pacing. Top, Intrinsic AVI (P-R interval surrogate) is 160 msec, AVD is 100 msec. Monochamber RV paced → LV sensed = 120 msec; monochamber LV paced → = 120 msec (equivalent sequential ventricular conduction times between pacing sites). Global activation closely resembles monochamber RV activation (see Fig. 31-39, top). Incomplete fusion is indicated by slight QRS narrowing, most evident in leads V1-V3. Overall activation pattern remains R→L, A→P. Bottom, AVD remains fixed at 100 msec. Persistent incomplete fusion despite sequential BiV stimulation with LV 80 msec preceding RV. Minimal change in activation sequence compared to simultaneous BiV pacing. Note slight attenuation of lead I and aVL R, emergence of small monophasic R in V4-V6, and further shortening of QRS duration in V1-V2.

938

SECTION 4  Follow-up and Programming

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 31-41  Maximal evidence of ventricular activation fusion during sequential biventricular (BiV) pacing at shortened atrioventricular delay (AVD). Sequential BiV pacing with LV 80 msec preceding RV. AVD shortened from 100 msec → 80 msec. Evidence of activation reversal in pivotal leads is now present. Note leads I and aVL R → qR, leads V1-V2 QS → RS, lead V3 rQr′ → R. Since LV is always delayed relative to RV during LBBB, shortening AVD advances LV further than maximally achievable with sequential ventricular pacing at longer AVD.

2. The systolic response to positive changes in loading conditions is reduced in the failing ventricle (Fig. 31-45). 3. Positive changes in loading conditions from improved diastolic function can have a dramatic effect on symptoms, even in the absence of any significant systolic augmentation, particularly in the failing ventricle (see Fig. 31-45). 4. Atrioventricular optimization for diastolic function is not required for ventricular electromechanical resynchronization and plays no role in reverse ventricular remodeling. 5. Reverse ventricular remodeling can occur even when AV timing is not optimized. Consequently, persistent diastolic dysfunction, despite improvement in LV size and contractility, is an important and frequently unrecognized source of symptoms in asynchronous heart failure patients treated with CRT.

Effects of Pacemaker Atrioventricular Interval on Loading Conditions, Diastolic Function, and Systolic Function The events of the cardiac mechanical cycle are again displayed in Figure 31-46. Ventricular filling occurs during diastole and has two components: early passive filling (E wave) and later active filling (A wave). The velocity of the diastolic filling waves is determined by the LA-LV transmitral pressure (TMP) gradient, which is phasic. The timing of the E wave is controlled by the preceding ventricular contraction. The timing of the A-wave is fixed by the sinus rate (or atrial pacing rate). The timing of the E wave relative to the A wave is influenced by the preceding ventricular contraction and the AV conduction time (e.g., P-R interval). Diastolic function is impaired in asynchronous heart failure. The left ventricle operates at higher diastolic pressures with the consequence

LV LV

RV RV

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 31-42  Lead positions and baseline LBBB activation. Same patient as in Figures 31-43 and 31-44. Top, Radiographs of RVA and LV posterior wall (lateral coronary vein) stimulation sites. Bottom, Typical R → L (frontal), A → P (horizontal) activation sequence during LBBB.



31  Troubleshooting of Biventricular Devices

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

939

Figure 31-43  Atypical QRS hieroglyphic signatures during monochamber RV, LV, and BiV pacing. Top, Monochamber right ventricular apex (RVA) pacing activation. Note unexpected lead I rS, V1 R, and V2 Rs. Frontal plane axis is right superior. This activation pattern is likely explained by conduction blocks caused by extensive myocardial scar (coronary artery disease). Bottom, Monochamber left ventricular (LV) pacing from posterior wall (lateral coronary vein). Note atypical lead I RS, whereas lead aVL QR and lead V1-V5 R are typical. The predominantly positive force in lead I during LV posterior wall stimulation may be caused by scar. This can also occur without scar (lead I paradox), however, most likely explained by a basal location of the LV lead and more horizontal anatomic axis of the LV or posterior rotation of the heart. Consequently, LV activation proceeds paradoxically from R → L, which yields a dominant R in lead I.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

Figure 31-44  Generating evidence for ventricular activation fusion during BiV pacing for atypical monochamber RV and LV activation patterns. Top, Simultaneous biventricular (BiV) pacing. Global activation closely resembles monochamber right ventricular (RV) activation (see Fig. 31-43, top). Incomplete fusion is indicated by slight attenuation of the dominant component of lead I rS, lead aVL R, and slight QRS narrowing, most evident in leads V1-V2. Note that dominant R in V1-V2 (present during monochamber RV and LV pacing) persists. Bottom, Sequential BiV pacing with LV 60 msec preceding RV. Activation directionality is reversed in multiple leads. Note BIQS → PI qRs, BaVLR → PAVL qR, BII, aVF, III QS → PII, aVF, III rS. Note emergence of Rs in V3-V5.

940

SECTION 4  Follow-up and Programming

LEFT VENTRICULAR DIASTOLIC PRESSURE-VOLUME RELATION

Stroke volume

Normal ventricle

Myopathic ventricle

LV diastolic pressure

LEFT VENTRICULAR SYSTOLIC FUNCTION CURVE

Myopathic ventricle Normal ventricle

∆P ∆p ∆V

∆V LV diastolic volume

Preload

Figure 31-45  Different effects of change in loading conditions in normal and failing ventricles. Left, The failing ventricle operates on a depressed Frank-Starling relationship where smaller increases in stroke volume are observed for any increase in preload compared to the normal ventricle. Right, At the same time, larger increases in left ventricular (LV) diastolic pressures are observed for any increase in diastolic volume for failing ventricles compared to normal ventricles. This diastolic dysfunction results in increased LV diastolic volumes from ventricular enlargement (remodeling), causing higher LV pressures, which do not augment contractility but worsen symptoms. (Modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009.)

Diastolic filling Velocity of forward blood flow into the LV (filling) Velocity of forward blood flow out of the LV (ejection)

E

Isovolumetric contraction

dysfunction, relaxation abnormality). The compensatory response to maintain LV filling is an increase in LA pressure, resulting in higher E-wave velocity and E/A ratio. Stage II diastolic dysfunction is characterized by E/A more than 1, isovolumetric relaxation time less than 90 msec, and deceleration time less than 220 msec, termed pseudonormalization. Progression of diastolic dysfunction is indicated by a

IR

Rapid filling

Slow filling

Atrial contr.

Systole

20 Pressure (mm Hg)

that filling times are shortened (Fig. 31-47). Ventricular conduction delay and reduced pump function result in prolonged isovolumetric contraction and relaxation times, which shorten diastole (Fig. 31-48). These derangements worsen at the higher heart rates typically observed in heart failure patients. On the standard echocardiogram, LV inflow velocities are used to characterize diastolic function. Characteristic changes in mitral inflow are observed in response to changes in the TMP gradient (Fig. 31-49). The mitral E-wave velocity is determined by the early-diastolic LA-LV pressure gradient and reflects preload and alterations in LV relaxation. The mitral A-wave velocity is determined by late-diastolic LA-LV pressure gradient and reflects LV compliance (pressure-volume relationship) and LA contractile function. E-wave deceleration time reflects LV relaxation, LV diastolic pressures, and LV compliance. Changes in preload modify the echocardiographic patterns of diastolic function (Figs. 31-50 and 31-51). In the normal pattern, the majority of forward flow occurs in early diastole, yielding E/A ratio greater than 1.5 and short E-wave deceleration time (<180 msec) and isovolumetric relaxation time (<80 msec). Incomplete relaxation caused by myocardial disease results in higher early-diastolic LV pressures and reduced TMP gradient. Consequently, E-wave velocity and E/A ratio decrease (<1), and isovolumetric relaxation time (>90 msec) and E-wave deceleration time (>220 msec) increase (stage I diastolic

Normal EDP

10

High EDP 20 10 0

200 Time (ms)

400

LV LA

A

E Aortic flow

A

Isovolumetric relaxation

Systolic ejection

Figure 31-46  Left ventricular diastolic event timing relationships. Forward flow in diastole is composed of early passive LV filling (E wave) and late active LV filling (A wave). The E wave is always timed to the prior ventricular contraction, whereas the timing of the A wave is fixed to atrial systole. Isovolumetric contraction time is the interval between mitral valve closure and aortic valve opening. Isovolumetric relaxation time is the interval between aortic valve closure and mitral valve opening.

Figure 31-47  Diastolic events and pressure gradients under different loading conditions. Pressure-time curves from an anesthesized dog are shown. The first LA-LV crossover indicates the end of isovolumetric relaxation (IR), mitral valve opening, and early rapid filling when LA pressure exceeds LV pressure (E wave on the mitral inflow velocity). The solid arrow indicates minimum LV pressure. Peak mitral E-wave velocity corresponds to the second pressure crossover; LV pressure now exceeds LA pressure, decelerating mitral inflow, and concluding the early rapid filling phase. The slow filling phase is characterized by equalization of pressures and minimal LV filling. During atrial contraction, LA pressure exceeds LV pressure and mitral flow increases (active filling phase). The dotted arrow indicates the LV pressure preatrial contraction; the dashed arrow indicates LV end-diastolic pressure (EDP). The upper tracing was obtained at normal LVEDP (~8 mm Hg), the lower panel at high LVEDP (~24 mm Hg). Pressure differences are larger because of reduced compliance; LA contraction barely exceeds LVEDP, reducing active LV filling. (Modified from Nagueh et al: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22:107-133, 2008.)



941

31  Troubleshooting of Biventricular Devices

LV A

A

IVCT

LA IVRT

0

C E E

Normal

Impaired relaxation Figure 31-49  Changes in LV inflow velocity patterns in response to changes in transmitral pressure gradient. Left, Normal LA-LV pressure relationships and corresponding LV inflow velocity pattern. Note high E-wave velocity with rapid deceleration, E/A > 1. Middle, Impaired relaxation results in higher LV diastolic pressures, which reduce E-velocity (E/A < 1) and increase E-wave deceleration time. Note, a small E-velocity could also be caused by low left atrial pressure (LAP), which must be excluded by independent assessment of LA pressure. Right, Compensatory increase in LA pressure to maintain LV filling results in “pseudonormalization,” indicated by high E-wave velocity (E/A >1) and very rapid E-deceleration time. (Modified from Nagueh, et al: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22:107-133, 2008.)

stage II diastolic dysfunction in this example (Fig. 31-53). In extreme cases, atrial transport block and pulmonary flow reversal can occur, triggering counterphysiologic neurohormonal responses (Fig. 31-54). Inappropriate long pAVIs result in collision of early and late diastolic filling (Figs. 31-54 and 31-55). The physiologic consequences are identical to first-degree AV block. Early passive diastolic filling collides with late active filling because the atrial contraction is displaced leftward in time relative to the next ventricular paced beat. Increase in left atrial

E

E

A A

A

A E Normal

High LAP

Normal LAP

E

Mitral annulus velocity

40 0

Dec time

A E

A

cm/s

restrictive filling pattern, characterized by E/A over 1, isovolumetric relaxation time under 70 msec, and deceleration time under 150 msec, termed restrictive (stage III). A restrictive LV inflow pattern unresponsive to preload reduction is termed irreversible (stage IV). Stages II to IV are associated with increased LV filling pressures. The response of these LV inflow velocity patterns to preload reduction can be used to understand the relationship between diastolic function and changes in pacing rate and pAVI. Higher pacing rates combined with delayed isovolumetric relaxation time result in fusion of early and late LV filling, simulating stage III (restrictive) diastolic dysfunction (Fig. 31-52). Reduced pacing rates delay atrial contraction, displace late LV filling relative to delayed early filling, and increase diastolic filling time. Inappropriately short pAVIs result in truncation of late-diastolic active LV filling, indicated by minimization of the A-wave velocity, simulating stage III diastolic dysfunction. In extreme cases, atrial transport block and pulmonary flow reversal can occur. Increases in pAVI increase diastolic filling time, allowing for emergence of late-diastolic active LV filling (A-wave velocity emergence) and transformation to

Mitral inflow

E

A

Figure 31-48  Effect of increased contraction/relaxation times on diastolic function in failing ventricle. IVCT, Isovolumetric contraction time; IVRT, isovolumetric relaxation time; A, mitral regurgitation flow duration; B, left ventricular (LV) outflow duration; C, LV inflow duration (diastole). Index of diastolic performance = A − B/C. (Modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009.)

80

A

Index of diastolic performance = A – B/C

mmHg

20

B

E A Relaxation abnormality

E A

E A Pseudonormalization

Restrictive physiology

Figure 31-50  Echocardiographic filling patterns of diastolic dysfunction. See text for details. (Modified from Swedberg K, et al: Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J 26(11):1115-1140, 2005.)

942

SECTION 4  Follow-up and Programming

LV inflow

LV inflow velocity E

E

A

Grade I

Rest

E A

E

D

Grade I LV inflow

Rest D

S D

A

E

Grade II

Grade III

Pulmonary venous flow velocity S

A

A

Grade II

Valsalva

Valsalva

E

S

E

A

A

A

Grade III

Grade II LV inflow

Rest

Valsalva

E

E A

B

A

Grade III

Grade IV

Figure 31-51  Echocardiographic patterns of diastolic function before and after preload reduction. A, LV inflow velocity patterns as described in Figure 31-49. Pulmonary venous flow is determined by the pressure gradient between the pulmonary veins and the left atrium. Systolic forward flow (S) occurs during LA relaxation, diastolic forward flow (D) follows early LV filling. During LA contraction in late diastole, flow reversal into the pulmonary veins occurs (not shown). Increased early diastolic filling pressure results in decreased systolic flow and increased diastolic flow in the pulmonary veins. B, Response of diastolic filling patterns to preload reduction (Valsalva maneuver). Reduced preload results in reduced E-wave velocity and prolongation of E-deceleration time, whereas A-wave velocity is unchanged or increases. A ≥50% decrease in E/A ratio with Valsalva maneuver is highly specific for increased LV filling pressures. Failure of the LV inflow pattern to change with preload reduction is indicative of severe diastolic dysfunction (stage IV, irreversible). (Modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009.) IVCT 90

IVRT 200

DFP 200

E-A fusion

Paced rate 70 ppm IDP = 1.45

IVCT 90

IVRT 200

DFP 400

E-A separation

Paced rate 60 ppm IDP = 0.73

Figure 31-52  Effect of change in pacing rate on diastolic function. Left, Pacing rate 70 pulses per minute (ppm). Prolonged IVRT results in delayed early filling resulting in E-A fusion. This simulates a stage III (“restrictive”) filling diastolic pattern. Right, Pacing rate 60 ppm. E wave is tied to prior ventricular contraction; A wave is now displaced rightward in time; consequently, diastolic filling periods increase from 200 → 400 msec, and E-A separation emerges (stage III → stage I diastolic dysfunction). Note index of diastolic function decreased from 1.45 → 0.73 (reflecting increase in C term in equation in Fig. 31-48). (Modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009.)



31  Troubleshooting of Biventricular Devices

E

E

943

E A

A A

AVI = 100 msec

AVI = 150 msec

AVI = 200 msec

Figure 31-53  Changes in LV inflow velocity patterns in response to changes in transmitral pressure gradient during manipulation of the pacemaker AVI. Left, Pacemaker atrioventricular interval (AVI) of 100 msec results in truncation of late-diastolic active filling (A wave is abolished). Progressive increase of pacemaker AVI to 150 msec (middle) and 200 msec (right) restores late-diastolic active filling (A-wave emergence). (Modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009.)

(LA) pressure with atrial contraction interrupts pulmonary vein diastolic forward flow; late-diastolic LV → LA pressure gradient results in diastolic mitral regurgitation. In extreme cases, atrial contraction occurs during the preceding ventricular contraction, resulting in atrial transport block. This duplicates the situation of inappropriate short pAVI. A shorter pAVI moves early LV filling leftward (earlier) in time, since the E wave is “tied” to the prior ventricular contraction. This has the effect of separating the E wave and the oncoming A wave, which is fixed to atrial systole.

AVI 100 ms

D

Methods for titrating optimal AV resynchronization during multisite pacing therapy include echocardiographic analysis of LV inflow velocity patterns, EGM timing analysis derived from invasive hemodynamic monitoring, and real-time hemodynamic monitoring during manipulation of the pAVI. The common goal of these methods is to identify

Pressure (mmHg)

LV inflow velocity

AVI 100 ms

D S

Aortic flow LA volume PV flow LA pressure (r min–1) (ml) (mr min–1) (mmHg)

S

A

Optimization of AV Resynchronization

AVI 200 ms E A

PV inflow velocity

E

APPROACHES TO ATRIOVENTRICULAR RESYNCHRONIZATION

AVI 200 ms AVI 300 ms

100 50 0 14

ABP LVP

7 0 150 0 –150 15 12 9 20 10 0

Figure 31-54  Atrial transport block caused by inappropriately short pacemaker AVI. Left and middle, Left ventricular (LV) inflow velocities and corresponding pulmonary vein velocities at long and short atrioventricular interval (AVI). Right, Catheter measurements of left-sided heart pressures at various representative pacemaker AVIs (short, optimal, long) in an animal model. Pacemaker AVI 100ms results in atrial contraction after the onset of ventricular systole (note sudden deceleration in A-velocity, top left panel). LV contraction against a closed mitral valve results in marked increase in atrial pressure (downward arrow bottom left panel and first downward arrow in right panel where LA pressures are shown in green) and reversal of pulmonary venous flow (downward arrow bottom left panel and first upward arrow right-hand panel where pulmonary venous pressures shown in blue). Increase in pacemaker AVI to 200 msec allows emergence of late active filling (A wave) before onset of ventricular systole (note slower deceleration of A wave, top middle panel) and restoration of pulmonary venous forward flow (bottom middle panel, right-hand panel where pulmonary venous pressures are shown in blue). Diastolic dysfunction pattern changes from stage II → stage I when pacemaker AVI 100 → 200 msec. Note, long pacemaker AVI 300 msec duplicates counterphysiology of short AVI 100 msec (increase in LA pressure, pulmonary venous flow reversal caused by atrial contraction coincident with prior ventricular contraction). (Left and middle panels modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009; right panel courtesy Douglas Hettrick, PhD, Minneapolis.)

944

SECTION 4  Follow-up and Programming

AVI 120 msec

S D

A E

S D

MR flow velocity

D

PV flow velocity

LV inflow velocity

AVI 250 msec

Figure 31-55  Atrioventricular decoupling caused by excessively long pacemaker AVI. Left, Pacemaker atrioventricular interval (AVI) 250 msec results in fusion of early and late diastolic filling (E-A fusion). Atrial contraction during early LV filling interrupts pulmonary vein diastolic forward flow (downward arrow). Diastolic mitral regurgitation results from late diastolic LV → LA pressure gradient. Right, Pacemaker AVI 120 msec results in emergence of late diastolic active filling (A-wave velocity emergence), normal pulmonary vein diastolic forward flow, and elimination of diastolic mitral regurgitation. (Modified from Marcus RH, Harry MJ, Lang RM: Pacemaker therapy in refractory heart failure: a systematic approach to electromechanical optimization of diastolic function. JACC Cardiovasc Imaging 2:908-913, 2009.)

the single pAVI that yields (1) maximum improvement in LV preload and (2) maximum diastolic filling time. This requires that the timing of LA contraction to LV contraction be optimized. When LA contraction occurs too early relative to LV contraction, late diastolic active filling (A wave) fuses with early diastolic passive filling (E wave), reducing LV preload. This form of diastolic dysfunction occurs spontaneously during first-degree AV block, frequently accompanies LBBB, and is corrected by the short pAVIs necessary to achieve maximum evidence of ventricular fusion activation. An insufficiently short pAVI, particularly in the presence of significant first-degree AV block (long P-R interval) could also result in this form of diastolic dysfunction. This is commonly referred to as a pAVI that is “too long” relative to the intrinsic A-V interval (iAVI). A different form of diastolic dysfunction is induced when LA contraction occurs simultaneously, or immediately after LV contraction. Late diastolic filling (A-wave) is truncated by mitral valve closure and in the most extreme form results in atrial transport block. This reduces LV preload; causes increased LA pressure and pulmonary venous flow reversal, yielding a pattern of restrictive diastolic dysfunction; and can trigger counterphysiologic neurohormonal reflexes. This derangement never occurs spontaneously. However, these timing abnormalities can be inadvertently induced by a pAVI that is “too short” relative to the iAVI. Since early passive filling (E wave) is tied to the prior ventricular contraction, and late active filling (A wave) is independently timed by the sinus rate, the pAVI controls the timing relationship between A wave and ventricular contraction. These considerations frame the dominant clinical concern and challenge to CRT programming regarding AVI management. Because generation of maximum evidence of ventricular activation wavefront fusion requires that BiV paced activation replace native ventricular activation, pAVIs substantially shorter than the iAVI are applied, usually accompanied by sequential ventricular timing (e.g., LV

stimulation first, see later). Consequently, it is much less likely that pAVIs during CRT will be “too long.” It is much more likely that pAVIs sufficiently short to generate maximum evidence of ventricular activation fusion will inadvertently induce truncation or block of latediastolic active (A-wave) filling (e.g., pAVI “too short”). This is a particular concern when the baseline P-R interval (iAVI) is short (e.g., <200 msec). Conventional Echocardiography Left Ventricular Inflow Analysis.  Several methods to assess and tailor AV resynchronization using analysis of LV inflow velocities have been described. These methods involve real-time iterative manipulation of the pacemaker AVI and visual analysis of LV inflow patterns. The endpoint is the pAVI that times mitral valve closure coincident with the end of the untruncated A wave. The assumption is that the pAVI generated by this approach will (1) maximize LV preload (FrankStarling) and (2) maximize diastolic filling time. According to the method of Ritter et al.,108 optimal pacemaker AVI during atrial sensing (SAVI) can be stated algebraically as: SAVIoptimal = SAVIshort + d, where d = (SAVIlong + QAlong) − (SAVIshort + QAIshort), Q = ventricular pacing stimulus, and A = termination of A wave.109 This process is performed in three steps, as follows: 1. SAVIlong and QAlong are determined by programming a “long” sensed AVI (SAVIlong). SAVIlong is the longest AVI that results in (a) ventricular capture without fusion of native conduction and (b) spontaneous closure of the mitral valve before LV ejection (Fig. 31-56). QAlong is then measured as the time from the ventricular pacing stimulus to the end of the A wave. 2. SAVIshort and QAshort are determined by programming a “short” sensed AVI (SAVIshort). SAVIshort is the longest AVI that results in A-wave truncation (Fig. 31-57). QAshort is then measured as the time from the ventricular pacing stimulus to the end of the A wave.



31  Troubleshooting of Biventricular Devices SAVIlong

945

QAlong

Fused E&A

Fused E&A

Isovolumetric contraction

Isovolumetric relaxation

ao

Figure 31-56  Ritter method for atrioventricular resynchronization: step 1. Determination of optimal pacemaker atrioventricular interval during atrial sensing: SAVIlong and QAlong. AVI 160 msec is the longest AVI that yields full ventricular capture without A-wave truncation. The time from the ventricular pacing stimulus to the end of the A wave is QAlong.

3. The SAVIoptimal is then calculated from these values. AV optimization is confirmed by noting the return of normal E- and A-wave separation indicating improved diastolic filling time and optimized AV timing relationship (Figs. 31-58 and 31-59). Figure 31-60 summarizes an example of this approach. Meluzin et al.110 described a “simplified” two-step approach to the Ritter method. First, a “long” sensed AVI that results in (a) ventricular capture without fusion of native conduction and (b) spontaneous closure of the mitral valve before LV ejection is selected. The time between the end of the A wave (representing the end of the diastolic filling period) to the time of onset of high-velocity systolic mitral SAVIshort QAshort

regurgitation (representing the onset of ventricular contraction) is recorded. Second, the time from the end of the A wave to the onset of low-velocity diastolic mitral regurgitation is denoted as t1. The optimal AVI is then calculated as the “long” AVI-t1. This approach accurately predicted the optimal AVI based on simultaneous invasive hemodynamic measurements in 78% of patients. Similar limitations as the Ritter method apply; also, at least mild mitral regurgitation is required for timing measurements. The Ritter method is a tedious process. The value of quantification using the Ritter “formula” is unclear. A similar result could be achieved by simply manipulating the pAVI across a range of values while

1.0

VDD 50 m/s E

A

Isovolumetric contraction

E

ao

A

Isovolumetric relaxation

0.0

Figure 31-57  Ritter method for AV resynchronization: step 2. Determination of SAVIshort and QAshort. The SAVI is shortened until A-wave truncation is observed. This is SAVIshort. The time from the ventricular pacing stimulus to the end of the A wave is QAshort. AVshort QAshort

1.0 VDD 80 m/s

E

Isovolumetric contraction

A

E

ao

A

Isovolumetric relaxation

0.0

Figure 31-58  Ritter method for AV resynchronization: step 3. Calculation of SAVIoptimal. Note restoration of normal E-A wave separation.

946

SECTION 4  Follow-up and Programming

SAVI: 60 ms (short)

SAVI: 160 ms (long)

60

160

1.0 1.0

m/s

m/s VP → MV closure = 100 ms

VP → MV closure = 20 ms

Optimal AVI = 60 + [(160 + 20) – (60 + 100)] = 60 + 20 = 80 ms. Figure 31-59  Ritter method for AV resynchronization: summary 1. Left: SAVIshort = 60 msec and QAshort = 100 msec. Right: SAVIlong = 160 msec and QAlong = 20 msec. Optimal AVI = 60 + [(160 + 20) − (60 + 100)] = 60 + 20 = 80 msec.

examining the LV inflow velocity pattern until E-A wave separation unaccompanied by A-wave truncation is observed (see Fig. 31-58). Although many published clinical investigations cite the “Ritter method” for AV resynchronization, only visual analysis of the LV inflow pattern was likely performed (e.g., algebraic calculations were omitted). As with all methods for AV synchronization using visual analysis of LV inflow patterns, subjective error is common because the terminal portion of the A wave is often difficult to discern. The Ritter method was developed for AV resynchronization in complete AV block and during monochamber RV pacing. Ventricular conduction is entirely different during biventricular pacing. However, a potentially more serious problem with the Ritter and related methods is the fundamental assumption that timing ventricular contraction to the terminal portion of the A wave optimizes preload;

this appears to be physiologically incorrect in the setting of heart failure with low ejection fraction. Insights regarding optimal AV resynchronization in the failing ventricle are generated by invasive hemodynamic studies that use the acute response of aortic pulse pressure, or LV +dP/dtmax, which are useful indices because they correlate with stroke volume and global contractile function. These studies indicate that the maximum acute improvement in LV pump function occurs when the left-sided atrioventricular mechanical latency (AVL) time is closest to zero (Fig. 31-61). This corresponds to the time of peak velocity of the A wave. Timing the onset of LV contraction to the end of LA emptying (e.g., A-wave termination, Ritter method) results in delayed AVL time and reduced hemodynamic response. As mentioned previously, the Ritter method was developed in pacemaker patients with normal LV function and AV block, a situation where LV pressure and

Native AV conduction

SAVI = 60 ms

SAVI = 80 ms

SAVI = 100 ms

SAVI = 120 ms

SAVI = 140 ms

Figure 31-60  Ritter method for AV resynchronization: summary 2. Top, LV inflow velocity pattern during native AV conduction. Note E-A wave fusion from marked first-degree AV block. Bottom, Change in LV inflow velocity pattern across a range of SAVIs. SAVI = 60 msec results in A-wave truncation (too short). SAVI = 140 msec results in E-A wave fusion. SAVI = 80 msec results in E-A separation without A-wave truncation. Note diastolic filling pattern is now stage I (normal).



31  Troubleshooting of Biventricular Devices

(a) (b)

10

75 50 25 0 −25 −50

−200 −150 −100 −50 0

A

−5 −10 −15 −20 −200 −150−100−50 0

C

(c) 100 ms

(d)

Non-responders Percentage of patients

LS

Percentage of patients

10 mmHg

40 35 30 25 20 15 10 5 0 < −50−40 −20 0 20 40 60 80 >90

B

AVL (ms)

50 100 150 200

AVL (ms)

Responders

APLS

RA

5 0

−25

50 100 150 200

AVL (ms)

AVL

AP

Non-responders

100 Maximum PP change

Maximum PP change (%)

Responders

947

40 35 30 25 20 15 10 5 0 < −50−40−20 0 20 40 60 80 >90

D

AVL (ms)

Figure 31-61  Optimal AV resynchronization using invasive hemodynamic monitoring. Left graph, Example of LV pressure response during BiV pacing (a) and intrinsic ventricular conduction (b), accompanied by intrinsic LV electrogram (c) and intrinsic RA electrogram (d). AP indicates the small presystolic peak in LV pressure caused by atrial contraction, and LS indicates the onset of LV pressure development during isovolumetric contraction, taken as the first point with slope greater than 10% of maximum rate of increase of LV pressure. The time from the RA EGM to AP is the interatrial electromechanical delay. In the absence of pacing, the RA-LS time indicates the electromechanical AV delay. The interval (APLS) between AP and LS is the atrioventricular mechanical latency (AVL). AVL reflects the time between the end of LA contraction and the onset of LV contraction. Therefore, a positive AVL (LA precedes LV) indicates LA contraction contributes to LV filling, whereas a negative AVL (e.g., pAVI “too short”) indicates LV contraction precedes LA emptying (truncation, transport block). During BV pacing, the LV electromechanical activation is advanced and the LS point moves from right → left, indicated by a shift in LV pressure curve from a → b. The LV pressure curves are time-aligned against RA activation. Right panel, Acute hemodynamic changes in relation to different AVL values during manipulation of the pacemaker AVI. A and B, Responders (≥5% increase in pulse pressure) had maximum hemodynamic improvement at pAVI of about 40% to 50% of the intrinsic A-V interval (iAVI). Further shortening of the pAVI reduced hemodynamic response. For responders, the maximum hemodynamic improvement occurred when AVL ~ 0 msec, which occurs at a pAVI that did not decrease LVEDP. Hemodynamic response was reduced at positive AVL values (pAVI “too long”) and negative AVL values (pAVI “too short”). C and D, Nonresponders (<5% increase in pulse pressure) had no improvement at any pAVI and were made worse as the pAVI shortened. (From Auricchio A, et al: Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol 39:2026-2033, 2002.)

volumes are low and compliance is high. However, in the failing ventricle, LV pressures and volumes are high and compliance is low (see Fig. 31-45). Consequently, onset of LV contraction at the highest point of LA pressure generation may be necessary for maximum hemodynamic improvement. With techniques for AV optimization using invasive LV pressure monitoring, some evidence indicates that acute hemodynamic response to CRT predicts better outcomes.68,77,111 However, pulse pressure and LV +dP/dt can be confounded by changes in preload and afterload. Although this technique is useful for assessing the acute effects of manipulating critical pacing control parameters, ventricular stimulation sites, and ventricular sequencing on LV pump function, it is impractical for routine clinical care. Left Ventricular Outflow Analysis.  Measurement of the continuouswave Doppler aortic velocity time integral (VTI) provides an estimate of stroke volume (Figs. 31-62 and 31-63). Changes in loading conditions during manipulation of critical pacing control parameters can be registered as increases or decreases in stroke volume. This approach is often applied during manipulation of the pAVI. A range of pAVIs is scanned, and the optimal interval is the pAVI that generates the largest increase in aortic VTI (stroke volume).

The aortic VTI method is simple to perform, assuming an adequate echocardiographic window can be obtained. Data acquisition is generally rapid, which allows for screening a broad range of pacing control parameters in abbreviated time. However, VTI measurements are influenced by extraneous factors (e.g., respiratory phase, sympathetic tone). The accuracy of the method is degraded because of at least 10% variation between measurements, and it cannot reliably discriminate changes in VTI smaller than this inherent error. Noninvasive Hemodynamic Monitoring Finger photoplethysmography (FPPG) has been used as a surrogate to invasive hemodynamic monitoring for optimizing AV resynchronization (Fig. 31-64). FPPG accurately tracks beat-to-beat changes in arterial pulse pressure at rest and during exercise and therefore provides an attractive alternative to direct LV pressure recordings. At rest, FPPG correctly identified positive aortic pulse pressure responses with 71% sensitivity and 90% specificity compared to invasive aortic pressure recordings, and the magnitude of FPPG changes in response to manipulation of the pAVI during CRT was well correlated with positive aortic pulse pressure changes (R2 = 0.73; see Fig. 31-64).112 However, the correlation with negative aortic pressure changes was poor (R2 = 0.43). FPPG identified 78% of the patients having positive aortic

948

SECTION 4  Follow-up and Programming

increase in LV +dP/dt and maximum achievable % increase in LV +dP/ dt during conditions of atrial sensing (R2 = 0.99) and atrial pacing (R2 = 0.96)115 (Fig. 31-66). This strategy for programming pAVI was employed in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial116 and has been automated in one device-based application (SmartDelay, Boston Scientific; see later).

LV

Comparison of Methods for Optimizing AV Resynchronization

RV

LVOT VTI = 20 cm Apical 5 chamber view

Pulsed Doppler

Figure 31-62  Doppler aortic velocity time integral for estimating stroke volume during manipulation of the pacemaker AVI. Left, Signal acquisition is performed in the apical five-chamber view. Right, The aortic velocity time integral (AoVTI) envelope is outlined.

pulse pressure changes in response to manipulation of the pAVI and identified the single pAVI that yielded the maximum increase in pulse pressure in all patients. Maximum increase in systolic blood pressure using FPPG has been used to identity the optimal pAVI during rest and exercise and duplicates the parabolic relationship observed in acute hemodynamic studies.113 Electrogram Analysis The optimal pAVI for AV resynchronization can also be estimated using an EGM-based approach (Fig. 31-65). This is derived from timing observations made during invasive determination of the acute hemodynamic response (maximal positive change in LV +dP/dt) during manipulation of the pAVI. The single pAVI that generates the largest acute increase in LV +dP/dt is derived from the iAVI (time from local RA → local RV EGM) using two linear equations that incorporate baseline ventricular conduction delay (QRSd).114 If QRSd > 150 msec, the estimated optimal pAVI = 0.7*iAVI (msec) − 55 msec; if QRSd is 120 to 150 msec, the estimated optimal pAVI = 0.7*iAVI (msec). These regression formulas can be closely approximated by the following simple rules: the estimated pAVI for patients with QRSd > 150 msec is 50% of iAVI (P-R interval) and 75% for QRSd of 120 to 150 msec. These equations reflect the logical and necessary relationship between pAVI and ventricular conduction delay described earlier. This EGM method showed strong correlation (P <.0001) between maximum %

AV delay = 80 ms VTI = 16 cm

A direct comparison of the aortic VTI versus mitral inflow pattern method, using maximum increase in VTI as the endpoint, reported superiority of the aortic VTI method (58% greater relative increase, ~7% greater absolute increase in maximum LV stroke volume).117 The optimal pAVI predicted by the mitral inflow method was significantly shorter than the VTI method. A similar conclusion was reached in a comparison of the aortic VTI and mitral inflow methods using invasive hemodynamic measurements.118 In this study the maximum increase in LV +dP/dt showed good correlation with the mitral inflow (E-A) VTI (r = 0.96), poor correlation with the aortic VTI method (r = 0.54), and no correlation with the mitral inflow method (r = 0.35). It is argued that the aortic VTI method performs better than the mitral inflow method because it titrates a measure of LV ejection, whereas the mitral inflow method titrates a measure of LV filling. Using invasive hemodynamic monitoring, the EGM method was shown to yield the least difference between % LV +dP/dt and maximum achievable % LV +dP/dt during conditions of both atrial sensing and atrial pacing, compared with arbitrary pAVIs (100, 120, 140, 160 msec) or “best” pAVIs determined by the mitral inflow method or aortic VTI method.115 More importantly, no single method of AV resynchronization has demonstrated convincing clinical superiority, such as reduction in heart failure hospitalization or reductions in LV end-systolic volume (ESV) (reverse remodeling), although minimal prospective evaluation of any of these methods has been made. A randomized single-blind study of 40 patients compared the optimal pAVI determined by largest increase in aortic VTI against an empiric pAVI of 120 msec.80 A small improvement in ejection fraction, NYHA functional class, and quality of life scores were observed in the VTI-optimized group. These differences were probably spurious, because the mean-VTI optimized pAVI and the empiric pAVI were almost identical (119 vs. 120 msec, respectively). Individual patient variation may have accounted for the slight differences in outcomes between groups. Using variations on the mitral inflow method or invasive hemodynamic monitoring, the optimized pAVI is almost invariably in the range of 80 to 110 msec, regardless of other considerations.68,111,116,119,120 Therefore, some have argued empiric programming of the pAVI at about 100 msec. Further, the optimal pAVI varies with heart rate, loading conditions, and atrial pacing versus sinus rhythm.

AV delay = 150 ms VTI = 23 cm

Figure 31-63  Effect of change in pacemaker AVI on aortic VTI. Increase in pacemaker AVI from 80 to 150 msec increases aortic velocity time integral (AoVTI) from 16 to 23 cm. This is interpreted to indicate that pAVI 80 was “too short,” resulting in atrial truncation and reduced LV preload.



31  Troubleshooting of Biventricular Devices

949

50 Atrial sensing resting heart rate

30

Sensed-paced difference in AV optimum at resting rate = 73 ms

20 10

y = 1.1503x–0.8236 R2 = 0.73

0 0

10

20

30

40

50

% change finger

10

SBPml (mm Hg)

–10

Change AOP (%)

0

–1 –2 –3

0 –2 –4 –6 –8 –10 –12

B

50

100

150

AV delay (ms)

200

250

–14 0

50

100

150

200

250

AV delay (ms)

y = 1.1448x–0.8488 R2 = 0.43 –50 –40 –30 –20 –10

C

2

0

0

–30

–50

4

–5

–20

Optimal AVD 169 ms

6

–4

–10

–40

Optimal AVD 97 ms

2 1

–10

A

Atrial pacing just above resting rate

Resting rate

SBPml (mmHg)

Change AOP (%)

40

0

10

Change finger (%)

Figure 31-64  Optimizing AV resynchronization using acute changes in aortic pressure recorded by finger photoplethysmography (FPPG). A, Good correlation between positive changes in aortic pressure measured by FPPG compared to invasive measurement of aortic pressure (AOP). B, Optimal pacemaker AVI at rest and during atrial pacing just above sinus rate identified by maximum increase in systolic blood pressure using FPPG. C, Poor correlation between negative changes in AOP by FPPG as compared to invasive measurement of aortic pressure. (Modified from Whinnet ZI, et al: The atrioventricular delay of cardiac resynchronization can be optimized hemodynamically during exercise and predicted from resting measurements. Heart Rhythm 5:378-386, 2008.)

Although ventricular activation fusion (electrical resynchronization) clearly is the translational mechanism of improvement in LV pump function (reverse remodeling), the additional contribution of optimal AV resynchronization to clinical outcomes after maximal correction of LV conduction delay has not been demonstrated. Atrial Pacing/Pacemaker AVI Interaction: Loading Conditions and Diastolic/Systolic Function Atrial pacing disturbs left-sided AV electromechanical coupling because of (1) latency in atrial capture and sensing, (2) interatrial conduction delay, (3) latency in ventricular capture, and (4) interventricular conduction delay. The situation is made even more complex because all four elements are influenced by atrial and ventricular lead positions. Capture latency refers to the delay between emission of the right atrial (RA) pacing stimulus and atrial contraction. Sensing latency refers to the delay between the onset of atrial depolarization and the time at which the local endocardial signal is sensed. Because of latency in atrial capture and sensing, the optimal pAVI for sensed and paced P waves may differ. During sinus rhythm, the programmed pAVI begins when the native P wave is sensed but the physiologic A-V interval, which begins with atrial depolarization and the onset of mechanical contraction, may be delayed from sensing latency. The mean latency between the beginning of atrial depolarization and the time of atrial sensing is 30 to 50 msec. Thus, the physiologic A-V interval is longer than the programmed pAVI. The opposite situation occurs during atrial pacing. The programmed AV delay begins with emission of the atrial pacing stimulus, but the physiologic A-V interval begins with atrial depolarization and mechanical

contraction. The mean latency between atrial output and capture is reported to be 30-50 ms, however it may be greater than 300 msec. The physiologic A-V interval is therefore shorter than the programmed pAVI. The magnitude of atrial capture and sensing latencies varies among patients and is influenced by many factors, including lead design, sensing circuitry, amplitude and rate of stimulation, and characteristics of the local endocardial atrial electrogram. A further complication is the effect of autonomic innervation of the AV node during atrial pacing. Atrioventricular intervals during atrial pacing shorten during exercise and lengthen by as much as 150% in the standing or supine position.121 A mismatch between the lower pacing rate and autonomic balance may contribute to this situation. For example, patients with a relatively high lower rate programmed (70 or 80 bpm) often experience significant AVI extensions during atrial pacing while sleeping because of parasympathetic predominance.7 Additionally, significant interatrial conduction delays may result from cardiomyopathy and atrial enlargement, antiarrhythmic drugs, and other causes. Interatrial conduction delays are common during RA pacing and are influenced by pacing lead position. RA pacing from the regions of Bachmann’s bundle, fossa ovalis, and coronary sinus os results in less delayed left atrial (LA) activation compared to other common pacing sites, such as the RA appendage. The common consequence of these effects is that the pAVI is already in progress before LA contribution to ventricular filling has begun. In this situation, the optimized pAVI during sinus rhythm may be “too short” during atrial pacing resulting in diastolic dysfunction. This can be understood by analysis of atrial and ventricular activation times using the surface ECG and local electrograms (EGMs)

950

SECTION 4  Follow-up and Programming

A

B Figure 31-65  Optimal AV resynchronization using electrogram analysis. A, Surface ECG during intrinsic rhythm. P-R interval = 220 msec, QRSd (LBBB) = 170 msec. Note E-A fusion on mitral inflow caused by PR prolongation (e.g., iAVI is “too long”). B, Surface ECG during BiV pacing at estimated optimal pacemaker AVI = 100 msec, derived from timing of RA-RV EGM (200 msec) and QRSd 170 msec (see text for calculation). Note E-A separation and lack of A-wave truncation.

(Figs. 31-67 to 31-73). P-wave duration represents total atrial activation time (AAT) (see Fig. 31-67). The earliest deflection of the P wave indicates the onset of RA activation (A). It is assumed that the latest termination of the P wave represents the end of LA electrical activation (B). Therefore, the AAT is measured as time interval A → B. Interventricular conduction delay (bundle branch block, BBB) results in sequential ventricular electrical activation. This is typically registered on the surface ECG as a “split” or “notched” QRS complex. The notch indicates the transition point between sequential monoventricular electrical activation. The portion of the QRS that occurs before the notch is composed of the first chamber activated, whereas the portion

% LV dP/dt from the EGM method

50

of the QRS that occurs after the notch consists of the second (delayed) chamber activated. The earliest first upstroke of the LBBB QRS indicates the onset of RV activation (right bundle branch, RBB) conduction (C in Fig. 31-67). The earliest first notch in the QRS indicates the transition point between the end of RV activation and the onset of LV activation caused by LBBB (D). The latest return of the QRS complex to baseline in any ECG lead indicates the termination of delayed LV activation from LBBB (E).72 The time from P-wave onset to the first upstroke of the QRS (onset of RV activation from RBB conduction) indicates the right intrinsic AVI (iAVI) (A→C), which is the AV conduction time estimated by the

50

Atrial sensing y = 1.0221x–1.3581 R2 = 0.992

40

40

30

30

20

20

10

10 0

0 –10

A

0 –10

Atrial pacing y = 1.0298x–2.9187 R2 = 0.956

10

20

30

40

Max achievable % LV dP/dt

50

–10

B

0 –10

10

20

30

40

50

Max achievable % LV dP/dt

Figure 31-66  Atrial sensing (A) and pacing (B). Correlation between % LV +dP/dt using the electrogram (EGM) method and maximum achievable % LV +dP/dt. (Modified from Gold MR et al: A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy. J Cardiovasc Electrophysiol 18:490-496, 2007.)



31  Troubleshooting of Biventricular Devices

A

B

C

D

E

P-wave

A

T-wave

B

C

T-wave QRS

F: RA EGM A = Onset of (right) atrial activation B = Offset of (left) atrial activation C = Onset of RV activation (RBB conduction) D = Offset of RV activation (RBB conduction/onset of LV activation [LBB conduction]) E = Offset of LV activation (LBB conduction) Figure 31-67  Analysis of atrial and ventricular electrical activation times on surface ECG. See text for details.

P-R interval (see Fig. 31-68). The time from P-wave offset (LA activation offset) to the earliest notch in the QRS (LV activation onset) indicates the left iAVI (B→D). Time from QRS onset to first notch is RV activation time (RVAT, C→D); time from first notch to QRS offset is LV activation time (LVAT, D→E); time from QRS onset to offset is interventricular conduction time (C→E). The effects of capture and sensing latency on local EGM timing relative to onset of electrical activity on the surface ECG are shown in Figure 31-69. The time from the earliest deflection of the P wave (RA activation onset) to the time of local RA EGM during sinus rhythm (atrial pacing-inhibited) is the RA sensing latency time (A→F). The time from earliest upstroke of the QRS (RV activation onset due to RBB conduction) to the time of the local RV EGM is the RV sensing latency time (C→G). The time from the local RA EGM to the local RV EGM is the right sinus rhythm pAVI, which is the EGM-based surrogate of the minimum right sinus rhythm iAVI (A→C). Therefore, at the atrioventricular level, because of RA and RV sensing latency, the right sinus rhythm pAVI and the true right sinus rhythm iAVI (indicated by surface activation timing) are not the same. The right sinus rhythm pAVI may be longer or shorter than the true right sinus rhythm iAVI. Similarly, at the ventricular level, the local EGM surrogate of the total interventricular activation time (C→E) is the time from local RV EGM to the local LV EGM (G→H). This inaccurately estimates true interventricular activation time because of (1) RV sensing latency, (2) LV sensing latency, and (3) variable timing of LV EGM relative to QRS offset, as determined by LV lead position. Also, because current CRT systems do not directly measure the offset of LV activation or the onset

B

C

D

G: RV EGM

H: LV EGM

A→F = RA sensing latency F→G = RA EGM→RV EGM = Right sinus rhythm pAVI C→G = RV sensing latency RV EGM→LV EGM = Interventricular conduction time Figure 31-69  Atrial-ventricular activation time by surface ECG and local EGM timing during sinus rhythm.

of earliest LV activation, right-sided EGM timing does not accurately reflect left-sided electromechanical activation (see Fig. 31-70). These effects are important because device timing instructions are EGM based, and EGM timing may be dissociated from the true onset and offset of electromechanical activation in the chamber of interest. This introduces the possibility of cross-chamber and multichamber timing errors that could negatively influence pump function. The effects of right atrial pacing on multichamber timing can be understood with this framework (see Fig. 31-71). Atrial capture latency is the time from emission of the atrial pacing stimulus (AP) to the earliest deflection of the P wave (RA activation). Note the increase in AAT (A→B) during AP because of intra-atrial and interatrial conduction delay. The atrial paced pAVI is measured from the time the atrial pacing stimulus is emitted to the onset of native or paced ventricular activation. During native AV conduction, the RA paced AVI (pAVI) exceeds the true right AV conduction time by a factor equal to atrial capture latency and RV sensing latency. Note that the LA paced AVI (pAVI) is shorter than the left sensed iAVI (e.g., ↓B→D) because of the increased AAT during RA pacing, assuming no increase in AV conduction time (A→C). The consequence is that during RA pacing, the true right-sided AV electromechanical timing relationship is overestimated by local EGM timing, and the true left sided AV electromechanical timing relationship is unpredictably shortened. The effects of RA pacing on left-sided AV electromechanical timing during biventricular pacing are shown in Figure 31-72. In this situation, the timing of ventricular contraction is controlled by the pAVI. The pAVI must be shorter than the time from RA activation to earliest

E A

P-wave

E

P-wave

QRS

A

D

951

T-wave QRS

B

Figure 31-68  Calculation of intrinsic atrial-ventricular electrical activation times on surface ECG. See text for details.

D

P-wave

E

T-wave QRS

F: RA EGM A→C = Right sinus rhythm iAVI (AV conduction time, or PR interval) B→D = Left sinus rhythm iAVI C→D = RVAT D→E = LVAT or QRSd–RVAT C→E = Interventricular conduction time

C

G: RV EGM

H: LV EGM

B→D = Left sinus rhythm iAVI F→B = Time from RA EGM to LA offset G→D = Time from RV EGM to LV onset Figure 31-70  Differences in right-sided AV timing using local EGMs and left-sided AV electrical timing on surface ECG. See text for details.

952

SECTION 4  Follow-up and Programming

A

B

C

D

A

E

P-wave QRS G: RV EGM

H: LV EGM

C

AVC in progress P-wave

T-wave

AP

B

AP

D

QRS

G: RV EGM

E

T-wave H: LV EGM

Earliest BVP AP = Right atrial pacing stimulus AP→A = Atrial capture latency; note ↑ atrial activation time (AAT) during AP (↑A→Β) B→D = Left atrial paced AVI Figure 31-71  Effect of right atrial pacing on estimation of leftsided AV timing by local EGM timing. See text for details.

LV activation (A→D), to advance delayed LV activation. Therefore, AP→G is the longest pAVI that will advance LV activation, whereas AP→B is the shortest permissible pAVI to prevent A-wave truncation. However, the values of AP→A, A→B, and G→D are not known and not incorporated into the pAVI. Consequently, because of atrial capture latency and increased AAT, the true left-sided AV electromechanical time is significantly shorter than the pAVI. The consequence of these effects is an increased risk that the pAVI is “too short,” resulting in left-sided timing disruptions (e.g., A-wave truncation). If RA pacing is accompanied by an increase in AV conduction time (see Fig. 31-73), the same considerations apply, except that the “outer bound” for the longest pAVI that will advance LV activation (AP→G) is increased. This may be a more favorable situation because a short pAVI that sufficiently advances delayed LV activation is less likely to result in left-sided timing disruptions (e.g., A-wave truncation). The negative effect of atrial pacing on diastolic function during CRT is dramatic.122 The increase in AAT may result in severe diastolic dysfunction (A-wave truncation, E-A fusion) and reduced LV preload (Fig. 31-74). Typically, a pAVI offset (40-50 msec) is applied during atrial pacing to compensate for increased AAT by delaying ventricular contraction. In the absence of complete AV block, the increased pAVI results in progressive fusion with native ventricular conduction and withdrawal of ventricular resynchronization. The consequence of this unintended effect is a reduction in LV systolic pump function, indicated by increases in LV isovolumetric conduction time and ejection time. A sufficiently prolonged pAVI offset to prevent truncation of diastolic filling results in incomplete ventricular activation fusion. The probability of this scenario increases inversely with the P-R interval. At shorter P-R intervals during atrial pacing, pAVI extensions sufficient

A

B

C

AVC in progress P-wave AP

D

E

T-wave QRS

G: RV EGM

H: LV EGM

Earliest BVP Figure 31-72  Effect of right atrial pacing on left AV electromechanical timing during biventricular pacing (BVP). See text for details. AVC, Atrioventricular conduction.

Figure 31-73  Effect of right atrial pacing on left AV electromechanical timing during BVP. See text for details.

to eliminate A-wave truncation are more likely to result in loss of maximum LV preexcitation than at longer P-R intervals. A longer P-R interval provides greater leniency for allowing pAVI extensions to accommodate increased AAT without withdrawal of LV preexcitation. This problem is magnified by observations during invasive hemodynamic monitoring that indicate the maximum achievable increase in % LV dP/dt occurs at pAVI that is substantially longer during atrial pacing compared to atrial sensing (~mean 134 msec, range 69-262 msec vs. ~mean 208 msec, range 105-340 msec)115,123 (Figs. 31-75 and 31-76). This mean difference is substantially longer than the typical pAVI offset during atrial pacing in most CRT pacing systems (~40 to 60 msec). As noted, unless such patients have significantly prolonged P-R intervals, pAVIs in this range will result in incomplete LV resynchronization because of fusion between native ventricular conduction and paced activation wavefronts. For this reason, AV junction ablation has been advocated from patients with (1) relatively short P-R intervals, (2) requirement for atrial pacing, and (3) requirement for long pAVI during CRT to overcome atrial pacing–related diastolic dysfunction. If AV conduction is completely eliminated, the pAVI during CRT necessary to prevent compromise of LV preload during obligatory atrial pacing is not restrained by progressive loss of ventricular resynchronization due to fusion with native ventricular conduction. Atrial pacing should be minimized or avoided altogether if possible. Programming approaches include reducing the lower pacing rate, eliminating sensor-modulated pacing (if active), or choosing an atrialsynchronous ventricular pacing mode that does not provide atrial pacing (i.e., VDD at a low programmed rate). INTERVENTRICULAR TIMING CONSIDERATIONS The translational mechanism of CRT is ventricular activation wavefront fusion.12,72 Resynchronization of ventricular activation corrects part or all of the LBBB-related conduction delay. Replacement of LBBB activation with fusion activation instantaneously improves mechanics and initiates the processes leading to reverse volumetric remodeling. The best ventricular resynchronization occurs when the wavefronts from the RV pacing site (or originating from RBBc) and the LV pacing site collide halfway78 (see Fig. 31-10). Fusion of ventricular activation wavefronts is easily achieved and confirmed in animal models. However, this is not the case in the diseased, failing human ventricle because (1) the conduction times of activation wavefronts initiated on opposite sides of the left ventricle are difficult to measure, (2) timing between stimulation sites does not accurately reflect global activation, (3) a readily available measure of global activation for fusion evidence does not exist, and (4) propagation of paced activation wavefronts is unpredictably modified by conduction blocks and other factors (e.g., fiber orientation, capture latency). Ventricular conduction blocks are poorly understood but appear to be the primary barrier to achieving maximum ventricular activation



31  Troubleshooting of Biventricular Devices

R

R P

P T

E

A

ICT↑

T E

IVRT↑

A

87±48

137±75

371±94

E+A dur↓

309±48

ET↑

A

41±8%

59±8% R

R P

P T

E

953

A

ICT↓

T

IVRT↓

E

A

63±31*

103±35*

458±123*

E+A dur↑

281± 32*

ET↓

B

50±6%*

50±6%*

Figure 31-74  Effect of atrial pacing on diastolic function during CRT. Left, Timing periods of the cardiac electromechanical cycle (surface ECG, mitral inflow velocities, aortic outflow velocities). A, Atrial pacing during CRT in the DDD mode. Diastolic filling time is reduced because of A-wave truncation (indicated by ↓E-A duration). Isovolumetric contraction time (ICT) and ejection time (ET) are increased, indicating a reduction in systolic function. This is explained by unintentional partial withdrawal of ventricular resynchronization caused by the longer pacemaker AVI during atrial pacing intended to “offset” interatrial conduction delay. B, Improved diastolic and systolic performance in the VDD mode. Note ↑E-A duration and absence of A-wave truncation (resolution of diastolic dysfunction). Note ↓ICT and ↓ET caused by shorter pAVI, resulting in greater advancement of delayed LV activation and maximum ventricular resynchronization. Right, Diastolic function during different atrial pacing vs. sinus rhythm. A, DDD mode. Note E-A fusion caused by A-wave truncation despite longer pAVI “offset.” B, VDD mode. Note E-A separation in absence of right atrial pacing. (Modified from Bernheim A, et al: Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing. J Am Coll Cardiol 45:1482-1487, 2005.)

fusion. Conduction blocks may be fixed or functional. Fixed blocks are easiest to understand and are caused by ventricular scar. Functional blocks are more difficult to understand but can accompany LBBB in the absence of scar and also arise solely during LV pacing. A further complication is that conduction blocks may exist at different levels within the ventricular myocardium (e.g., epicardium vs. endocardium). Insight regarding ventricular conduction blocks has been generated by endocardial and epicardial activation mapping during LBBB and BiV pacing.

300

p <0.00001

10

Atrial sensing Atrial pacing

8 6 4

AVDmax (ms)

250

No. of patients

Figure 31-75  Optimal pAVIs during atrial sensing and atrial pacing using invasive hemodynamic monitoring (maximum increase % + LV dP/dt). (Modified from Gold MR, et al: A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy. J Cardiovasc Electrophysiol 18:490-496, 2007.)

Fixed conduction blocks are characterized by a boundary of activation delay that interrupts and redirects activation wavefront propagation. Sequential ventricular activation is consistently observed during LBBB (RV→LV) and posterobasal left ventricle (near mitral valve annulus) is invariably the latest activated region. However, the location, orientation, and extent of conduction blocks display significant interpatient variability, yielding distinct patterns of LV epicardial activation during similar activation patterns registered on the surface ECG (Fig. 31-77).

200 150 100 50

2 0

0 41– 80

81– 120

121– 161– 201– 241– 281– 321– 160 200 240 280 320 360

AS

AP

954

SECTION 4  Follow-up and Programming

20 AS: % LV dP/dtmax = 11.2% AVDmax = 140 ms

15 10

Atrial pacing Atrial sensing

5 0 0

50

100

150

200

250

300

350

400

450

AV delay (ms) Figure 31-76  Example of greater maximal increase in % LV dP/dt during atrial pacing vs. atrial sensing but requiring longer pAVI. Note that the pacemaker AVI (283 msec) that yields maximum increase in % LV dP/dt during atrial pacing is about twice the pAVI (140 msec) that yields the maximum increase in % LV dP/dt during sinus rhythm. (Modified from Gold MR, et al: Acute hemodynamic effects of atrial pacing with cardiac resynchronization therapy. J Cardiovasc Electrophysiol 20:894-900, 2009.)

Anterior

33 45 58 70 82 95 107120 132 144

Patient #7 se

32 LAD

172

QRSd 180ms

ms (Esyn: –113ms)

se

110 Apex

LV

36

ba

se

32 42 52 62 72 82 92 102112122 132 142152162

45

RVB 40 Apex

Front

(Esyn: –93ms)

QRSd 180ms

LAD

RV

ms

D. Anterior to inferior-posterior activation

se

D

83 LV

Apex

Ba

• Esyn = 0 indicates interventricular synchrony

153

RVB RV 31

Patient #3

C. Combined activation from apical, interior and superior LV

se

ba

Ba

se

ms (Esyn: –50ms) 34 44 55 65 75 85 96 106116127137 147 158168178 QRSd Patient #1 LAD 160ms 33 49 100

C

B. Inferior to anterolateral conduction

Ba

• Esyn = mean activation time difference between lateral RV and LV free walls

74

RVB 23

RV

B

134

A. Apical to lateral basal conduction

LV

26 36 46 56 66 75 85 95 105 115125135145155165

Patient #5

• Gray indicates MV area

101

Apex

A

base

• Line of block: >50 ms activation time difference

(Esyn: –73ms)

QRSd 140ms

se

RV

45

Posterior

ms

Ba

LAD RVB 31

39

ba

• Time 0 at onset of RV activation

Left lateral

2

25 % LV dP/dt

The physiologic basis of functional conduction blocks during LBBB is uncertain. The functional nature of such blocks is indicated by (1) absence of scar and (2) ability to shift the location of the line of block with pacing maneuvers (Figs. 31-78 and 31-79). These lines of functional block correlate with regional mechanical delay (Fig. 31-80). The implications of fixed and functional ventricular conduction blocks for CRT are significant. Because LV pacing usually targets the posterobasal left ventricle (latest activated region), conduction blocks usually reside between BiV pacing stimulation sites. This arrangement creates the opportunity for interference with the development of BiV pacing activation wavefront fusion. To reduce LV conduction delay maximally, LV stimulation must occur distal to the line of conduction block; LV paced activation wavefront must propagate out from the stimulation site; and R → L and L → R activation wavefronts must be properly timed to generate fusion (Figs. 31-81 and 31-82). Under some conditions, the emergence of a line of functional block during LV pacing may facilitate correction of LBBB conduction delay despite stimulation from a relatively early-activated site (Fig. 31-83). Alternately, LV pacing from an early-activated site proximal to a line of block may worsen LBBB conduction delay (Figs. 31-84 and 31-85). Fixed or functional lines of block may “jail” (electrically isolate) large regions of the left ventricle despite electrical resynchronization at the remote stimulation sites (Figs. 31-86 and 31-87).

AP: % LV dP/dtmax = 23.8% AVDmax = 283 ms

17

30

Left

173 LV

Back

Figure 31-77  Fixed ventricular conduction blocks caused by scar revealed by noninvasive ECG imaging of epicardial isochronal activation. Epicardial isochrone maps are shown during intrinsic activation (LBBB). Activation times relative to QRS onset are color-coded with red earliest and blue latest; framed numbers indicate earliest and latest activated sites. Note sequential ventricular activation (RV→LV): RV is activated earliest and latest activation occurs at posterobasal LV. Black lines indicate line/region of conduction block, which influences activation wavefront propagation. A, Line of block on anterior LV wall results in apical to lateral basal conduction. B, Line of block on anterior LV wall results in inferior to anterolateral conduction. C, Line of block on posterobasal LV wall results in combined activation from apical, inferior, and superior LV. D, Discrete line of block is absent. LV conduction is broadly slowed across the anterior and posterior walls. (Modified from Jia P et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006.)



31  Troubleshooting of Biventricular Devices

Line of block

Site of the line of block P

164 ± 29 2 (17)

139 ± 29 5 (63)

0.068 0.035

194 ± 32 61 ± 22 96 ± 18 127 ± 25 63 ± 10

156 ± 19 18 ± 21 95 ± 20 136 ± 23 84 ± 29

0.003 0.001 0.932 0.402 0.031

1 (8) 11 (92)

6 (75) 2 (25)

Time to LV breakthrough Time <20 ms, n (%) Time >40 ms, n (%)

Location of the line of block

Anterior

LAO 50°

Lateral

Measurements by NCM QRS duration (maximum), ms Time to LV breakthrough, ms Total LV activation time, ms Length of line of block, mm Distance from LV breakthrough site to line of block, mm

Lateral (n = 8)

Septum

Measurements by surface ECG (automatic recording) QRS duration (mean), ms QRS duration <150 ms, n (%)

Anterior (n = 12)

955

Inferior

0.002

NCM indicates non-contact mapping. Activation wavefront

Figure 31-78  Lines of functional block during LBBB activation. Endocardial LV activation times relative to QRS onset are color-coded with red earliest and blue latest. Activation is R → L and interrupted by a slow conduction zone on the midanterior LV wall (green line), which separates rapid early (red) and delayed late (blue) activation. Note that posterobasal LV is the latest activated region. Lines of functional block on the anterior wall were associated with greater QRSd (>150 msec), longer time to LV breakthrough (septum), and shorter distance from LV breakthrough, whereas lines of block on the lateral wall were associated with less prolonged QRSd (<150 msec), shorter breakthrough time, and greater distance from breakthrough. (Modified from Auricchio A, et al: Characterization of left ventricular activation in patients with heart failure and left bundle branch block. Circulation 109:1133-1139, 2004.)

120 ms

ISOCHRONES

100 ms

ISOCHRONES

80 ms

60 ms

80 ms 40 ms

60 ms 40 ms

20 ms 20 ms 0 ms

A

100 ms

0 ms

ISOCHRONES

80 ms

80 ms

60 ms

60 ms

40 ms

40 ms

20 ms

20 ms

0 ms

C

B

100 ms

0 ms

ISOCHRONES

D

Figure 31-79  Manipulation of line of functional block during biventricular pacing. Endocardial LV activation times relative to QRS onset are color-coded with red earliest and blue latest. A, Activation is R→L and interrupted by a slow conduction zone on the midanterior LV wall (green), which separates rapid early (red) and delayed late (blue) activation. Note that posterobasal left ventricle is the latest activated region. B, LV pacing from the posteral basal region shifts line of block L→R. Even earlier LV activation results in greater L→R shift of line of block, eliminating LV conduction delay caused by LBBB (C and D). (Courtesy Angelo Auricchio, MD.)

956

SECTION 4  Follow-up and Programming

LV activation map with NCM (unipolar recording)

SEPTAL-LATERAL DELAY IN PEAK SYSTOLIC MOVEMENT

Ts (ms)

300 250 200 150 100

BS BL BP BA MS ML MP MA AS AL AP AA

Earliest peak systolic movement at apical septum Figure 31-80  Correlation of line of functional block with regional mechanical delay. Top, Unipolar isopotential activation sequence (top) shows a U-shaped left ventricular (LV) activation wavefront that rotates around apex and activates lateral wall late; dashed circle indicates area of conduction block; NCM, noncontact mapping. Bottom left, Similar area of conduction block (black circle), however, LV activation wavefront splits and rotates around base and apex, merging on LV lateral wall. Bottom right, The earliest peak systolic movement (Ts) was located at the apical septal area (lower arrow) and significant delay between septal and lateral LV (upper arrows) resulting from zone of block. Ts, Time from onset of QRS complex to peak systolic velocity in each LV segment by tissue Doppler imaging; BS, basal septal; BL, basal lateral; BP, basal posterior; BA, basal anterior; MS, midseptal; ML, midlateral; MP, midposterior; MA, midanterior; AS, apical septal; AL, apical lateral; AP, apical posterior segment of LV wall; AA, apical anterior. (Modified from Fung JW et al: Variable left ventricular activation pattern in patients with heart failure and left bundle branch block. Heart 90:3-4, 2004.)

Late

Late

*

Early

*

Fusion

Figure 31-81  Schematic representation of interaction among anterior line of LV conduction block, LV stimulation site, and paced activation wavefront fusion. Anterior wall line of conduction block is indicated by dashed line. Purple arrow indicates rapid R→L conduction up to the line of block during LBBB. Jagged line indicates delayed R→L conduction across the line of block during LBBB. Asterisk indicates LV stimulation site. Curved arrows indicate BiV paced activation wavefronts. To generate paced activation wavefront fusion, LV stimulation must be delivered distal to the line of block (e.g., posterobasal left ventricle), and paced activation wavefronts must be properly timed to generate fusion.

Early

Fusion

Figure 31-82  Schematic of interaction among posterior line of LV conduction block, LV stimulation site, and paced activation wavefront fusion. Lateral wall line of conduction block is indicated by dashed line. Purple arrow indicates rapid R→L conduction up to the line of block during LBBB. Jagged line indicates delayed R→L conduction across the line of block during LBBB. Asterisk shows LV stimulation site. Curved arrows indicate BiV paced activation wavefronts. To generate paced activation wavefront fusion, LV stimulation must be delivered distal to the line of block (e.g., posterobasal left ventricle), and paced activation wavefronts must be properly timed to generate fusion.



31  Troubleshooting of Biventricular Devices Native rhythm (Esyn: –113 ms)

Patient #5

2

e

Bas e

LV stimulation from posterobasal free wall ended locally at basal free wall 110 ms after pacing

110 Apex

LV

RV

138 60 55*

Apex

se

110 LV

Posterior

Native rhythm (Esyn: –93 ms)

QRSd 180 ms LAD

LV stimulation from anterior LV.

se

Ba

Anterior line of fixed block present during SR and LV pacing. Latest activation occurred at anterior LV adjacent to line of block (138 ms)

Ba

45

Left lateral

* 45

se

Bas

e

89

QRSd 150 ms 99 LAD

Ba

RVB RV 40

Apex

173 LV

Ba

se

Biventricular pacing (Esyn: –45 ms)

46

RV

41

QRSd 120 ms LAD * 30

33 *

Apex

Activation pivots around anterolateral line of functional block and ends at posterobasal LV 117 ms later.

se Ba 17 1 5 10

160 151 142 133 124 115 106 97 88 79 70 61 52 43 34

172

Biventricular pacing (Esyn: 20 ms)

Anterior

ms

74

RV

Patient #3

B

LAD

RVB 23

s Ba

A

QRSd 180 ms 17

32

ms

166 156 146 136 126 116 106 96 86 76 66 56 46 36 26

957

LV

Figure 31-83  Hetergenous effects of conduction blocks and BV pacing on LV activation fusion. Same visual display as in Figure 31-77. A: Top, Activation during LBBB is R→L with latest activation at posterobasal LV. Activation propagates apically around anterior line of fixed block (present during LBBB activation and BV paced activation). Bottom, Stimulation from posterobasal LV corrects conduction delay; latest activation occurs on anterior wall (fusion). B: Top, Activation during LBBB is R→L with latest activation at posterobasal LV; no line of block. During stimulation from anterior LV (not the most delayed region) a line of functional block emerges on the anterior wall (black). Paced activation wavefront propagates around the line of functional block activating the posterobasal LV early, correcting LV conduction delay. (Modified from Jia P, et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006.)

Late

* Early

Figure 31-84  Schematic of interaction among anterior line of LV conduction block, LV stimulation site proximal to line of block, and failure to achieve paced activation wavefront fusion. Anterior wall line of conduction block is indicated by dashed line. Purple arrow indicates rapid R→L conduction up to the line of block during LBBB. Jagged line indicates delayed R→L conduction across the line of block during LBBB. Asterisk indicates LV stimulation site. Curved arrows indicated BiV paced activation wavefronts. LV stimulation proximal to anterior line of functional block displaces line of block further R→L, worsening LV conduction delay.

958

SECTION 4  Follow-up and Programming

Anterior

Left lateral Native rhythm

Patient 4

RVB RV

97

30

21 Apex

89

LV

Biventricular pacing QRSd (Esyn: –61ms) 200ms Ba s

e

LAD

e Bas

170 159 148 137 126 115 104 93 82 71 60 49 38 27

(Esyn: –71ms)

Ba s

e

LAD

QRSd 140ms

e Bas 130

ms

Posterior

* 47

187

120 RV

23 *

Apex

100

Fixed and functional blocks may also result in substantially different paced activation wavefront conduction times. Consequently, simultaneous BiV activation is dominated by, or duplicates, monochamber activation, usually favoring RV → LV (e.g., persistent R→L activation) (Figs. 31-88, 31-89, and 31-90). Persistent R→L activation, despite LV pacing from a late-activated site, can also be generated by LV capture latency (Fig. 31-91). In this situation, local activation delay (time from LV pacing stimulus to QRS onset) simulates differential paced activation wavefront conduction times. This is similarly overcome by sequential BiV stimulation in which LV pacing is advanced sufficiently to account for capture latency. Capture latency and differential paced activation wavefront

Late

*

Scar Early

Figure 31-86  Schematic of interaction among anterior zone of fixed block caused by scar, LV stimulation site, and paced activation wavefront fusion. Stimulation from late-activated posterobasal left ventricle results in activation wavefront fusion around a large zone of fixed conduction block on the anterior wall as a result of scar.

LV

Figure 31-85  Worsening of LV conduction delay by stimulation proximal to line of block. Same visual display as in Figures 31-77 and 31-83. Top, Activation during LBBB is R→L with latest activation at posterobasal left ventricle. Activation propagates apically around anterior line of fixed block. Bottom, Stimulation from anterior wall results in worsening LV conduction delay due to zone of slow conduction seen only during pacing (functional block). (Modified from Jia P, et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006.)

conduction times may coexist to yield persistent sequential (R→L) activation during BiV pacing (Fig. 31-92). Sequential BiV pacing (LV→RV) and increased LV voltage output (virtual electrode effect) are required to generate ventricular activation wavefront fusion (Fig. 31-93). An interesting related and counterintuitive observation is that equivalence of monochamber paced ventricular activation conduction times, measured between the RV and LV pacing sites, does not guarantee global activation wavefront fusion during simultaneous BiV pacing (Fig. 31-94). The most likely explanation for this is that the paced activation wavefront from the left ventricle is broadly delayed because of conduction blocks, even though the conduction path between the two stimulus sites yields simultaneous conduction times. This has significant implications for device-based automatic adjustment of BiV stimulation timing using local EGMs, since instructions based on simultaneous conduction times between pacing sites may not generate global activation fusion. Implications of Spontaneous and Pacing-Induced Conduction Blocks During Biventricular Pacing Ventricular conduction blocks present diverse and unpredictable challenges to generating ventricular activation wavefront fusion during CRT. Based on current limited understanding of the problem, the following conclusions can be made: 1. The LV posterior wall adjacent to the mitral annulus is almost always the latest electrically activated (most delayed) site during LBBB conduction and should be targeted for LV pacing. 2. Other unpredictable sites (anterior wall, apex) may be latest activated in some patients because of the effects of conduction blocks on wavefront propagation. Stimulation from these sites can effectively correct LV conduction delay and probably explains why some patients improve with non–LV posterior wall stimulation. 3. Any pacing site may induce or worsen conduction block unpredictably and degrade or abolish ventricular activation wavefront fusion. 4. Resynchronization of the most delayed LV region may be irrelevant if there is a large intervening zone of scar. 5. Selection of LV pacing sites based on interventricular timing recorded by local EGMs (RV, LV) may be misleading because simultaneous activation timing at widely spaced RV and LV sites may occur in LBBB and does not indicate absence of mechanical delay.



31  Troubleshooting of Biventricular Devices

Patient #8

Native rhythm (Esyn: –56 ms)

QRSd 130 ms

ms

e Bas

122

120

LAD

114

Base

130

959

RVB

106

25

98

RV

90

LV

Apex

82 74

Biventricular pacing

66 58

34 26

54

119

LAD 132

RVB

73

39 RV Anterior

49 70

* 52

Base

42

Bas e

50

(Esyn: –26 ms)

QRSd 140 ms

*

100 LV

Apex Left lateral

Posterior

Figure 31-87  Negative effect of conduction block caused by scar, despite electrical resynchronization at stimulation sites. Same visual display as in Figures 31-77, 31-83, and 31-85. Top, Activation during LBBB is R→L with latest activation at posterobasal left ventricle. Activation propagates apically around anterior line of fixed block. Bottom, Stimulation from posterobasal LV results in line of functional block that “jails” (electrically isolates) the entire anterior LV wall. The LV and RV stimulation sites are electrically synchronized, however the BiV paced activation wavefronts propagate around a large area of anterior wall delay. (Modified from Jia P, et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006.)

Late

*

200 ms LV>RV

Early

6. Equivalent conduction times between widely spaced RV and LV stimulation sites does not guarantee that simultaneous BiV pacing will generate global ventricular activation wavefront fusion. Against this background, a role of timed (sequential) ventricular stimulation exists. The ability to orchestrate ventricular chamber timing should theoretically provide additional leverage for overcoming functional and physiologic conduction barriers, to obtain maximum evidence of ventricular activation wavefront fusion. This is highlighted by the observation that simultaneous BiV pacing yields evidence of ventricular activation fusion, which is necessary for reverse volumetric remodeling, in only about 55% of cases.72 Implementation of Sequential Ventricular Timing in CRT Systems

100 ms LV>RV

Figure 31-88  Schematic representation of interaction between unequal BiV paced activation wavefront conduction times and paced activation wavefront fusion. Anterior wall line of conduction block is indicated by dashed line. Purple arrow indicates rapid R → L conduction up to the line of block during LBBB. Jagged line indicates delayed R→L conduction across the line of block during LBBB. Asterisk indicates LV stimulation site. Black arrows indicate BiV paced activation wavefronts. Conduction out of the LV stimulation site (L → R) is substantially delayed (200 ms) vs. conduction from the RV stimulation site (R→L, 100 msec). Consequently, paced activation wavefront fusion occurs distal to the anterior line of block and LV conduction delay persists.

The ability selectively to manipulate the timing of RV and LV stimulation appeared in third-generation CRT systems. This arrangement requires separately programmable RV and LV stimulation outputs and circuitry to permit timing delay between outputs by stimulation site (V-V timing). The goal of V-V timing is site-selective, sequential ventricular stimulation. Theoretically, V-V timing could be achieved with unipolar or dual cathodal electrode configurations. From a practical perspective, unipolar pacing is inapplicable in CRT-D, and anodal capture at high outputs with dual cathodal electrode configurations results in unintended BiV stimulation and could disrupt V-V timing. This is probably only relevant when RV stimulation precedes LV stimulation, because RV capture will render the local myocardium refractory, and anodal capture during high-output LV stimulation will not occur. Accordingly, the use of V-V timing, where RV precedes LV stimulation with dual cathodal electrode configurations, mandates exclusion of anodal capture by the 12-lead ECG at programmed

960

SECTION 4  Follow-up and Programming

Anterior

Left lateral

RV pacing

(Esyn: –76 ms)

Posterior ms

40 54 65 82 95 110 124 138 152 165 180 194 208 222 QRSd 160 ms

Ba s

*

99

36

85 se Ba

e

LAD 70

154

141

57 RV

122 Apex

89

A LV pacing

LV

134

(Esyn: 12 ms)

se Ba

130

167

RV

200

B BiV simultaneous

172

Apex

(Esyn: –72 ms) QRSd 160 ms

69

se Ba

*

158

57

149 93

BiV sequential LV-RV 80 ms

se

36

85

Ba

*

66

95

C

LV

223

LAD

RV

se

*

88

63

Ba

136

192

QRSd 240 ms

90

LAD

LV

132

Apex

(Esyn: –39 ms)

Ba

*

115

137 176 Front

91

169 211

RV

D

66

e

*

185

QRSd 230 ms

108

s Ba

se

LAD

RV

Apex Left

Back

Figure 31-89  Negative effect of unequal RV ↔ LV paced conduction times on electrical resynchronization. Same visual display as in preceding figures. A, LV activation during RV pacing is R → L with apical rotation around anterolateral line of block (black) and latest activation at posterolateral left ventricle adjacent to the line of block, 154 msec after RV stimulus. B, LV pacing from a posterobasal site. A large volume of the posterolateral and posterobasal left ventricle remains “jailed” (electrically delayed) because of conduction block. RV activation occurs 190 to 200 msec after LV stimulation. C, Simultaneous BiV pacing duplicates the R→L activation sequence of RV pacing because of uncompensated conduction time from the LV stimulation site. D, Sequential BiV pacing with LV preceding RV by 80 msec results in ventricular activation wavefront fusion, although a large volume of the posterior left ventricle remains electrically delayed. (Modified from Jia P, et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006.)

Time (ms)

0 0 200 400

26 36 47 57 67 78 88 98 108 119 129 139 150 160 ms Time (ms) 1 0 0 200 400

*

LAD

Potential (mV)

1

1

Time (ms)

0 0 200 400

961

Potential (mV)

31  Troubleshooting of Biventricular Devices

Potential (mV)



Anterior

Left lateral 1

Time (ms)

0 0 200 400

Potential (mV)

* Posterior

Figure 31-90  Sequential (R→L) ventricular activation despite simultaneous BiV pacing. Same visual display as in preceding figures. RV (apex) and LV (lateral wall) stimulation sites are indicated by asterisks and are the earliest activated regions during BiV pacing. Propagation away from the LV stimulation site is delayed because of conduction block (black); consequently a large volume of the posterior left ventricle is activated last (persistent R→L activation) despite stimulation from an immediately adjacent site. (Modified from Varma N, et al: Placebo CRT. J Cardiovasc Electrophysiol 19:878, 2008.)

RV

BiV

outputs (see earlier). Therefore, V-V timing is optimally delivered with true bipolar (RV and LV) electrode configurations. Figure 31-95 shows an example of interventricular timing operation. The key operating points of V-V timing are (1) the pacemaker A-V interval determines the timing of the first ventricular pacing stimulus, (2) the pacemaker V-A interval (atrial escape interval) is calculated based on the timing of the first ventricular pacing stimulus, and (3) the timing of the second ventricular pacing stimulus is determined by the selected V-V interval. Some interactions with other aspects of pacemaker timing exist. For example, ventricular safety pacing and Ventricular Sense Response (Medtronic; see later) are delivered at the nominal V-V (~simultaneous BiV) interval. Interlocks between inviolable blanking periods, pAVI, ventricular tachyarrhythmia (VTA) detection intervals, and the selected V-V interval often arise and force reconciliation, usually in the form of more lenient spacing of sequential ventricular stimulation.

LV

I II III aVR aVR aVF V1 V2

Clinical Experience with Sequential Ventricular Stimulation

V3 V4 V5 V6

97 ms

Figure 31-91  Sequential (R→L) ventricular activation despite simultaneous BiV pacing caused by LV capture latency. Simultaneous biventricular (BiV) pacing activation (middle column) duplicates monochamber right ventricular (RV) pacing activation (left column). Monochamber left ventricular (LV) pacing is complicated by marked capture latency (time from pacing stimulus to QRS onset 97 msec). (Modified from Herweg B et al: Latency during left ventricular pacing from the lateral cardiac veins: a cause of ineffectual biventricular pacing. Pacing and Clinical Electrophysiology 29:574-581, 2006.)

Despite the compelling rationale for timed ventricular stimulation during BiV pacing, the aggregate clinical experience has been a disappointment. Although acute studies demonstrated improvement in various metrics of LV systolic and diastolic performance during sequential versus simultaneous BiV pacing,84,124,125 no such benefit has been recorded in randomized clinical trials. The Resynchronization for the Hemodynamic Treatment for Heart Failure Management (RHYTHM II ICD) study randomized 121 CRT patients to either simultaneous or “optimized” BiV pacing, possibly including sequential ventricular stimulation pacing.82 Echocardiographic metrics were used to determine V-V timing parameters in the “optimized” group. Interestingly, 28% were assigned simultaneous BiV pacing, whereas the remaining 72% received sequential ventricular pacing (V-V interval up to 80 msec). There was no difference in the composite endpoint of

962

SECTION 4  Follow-up and Programming

Panel 1 Uncomplicated CRT

LV

BV activation time

BV activation time

Latency and slow conduction

Slow conduction

Latency

BV activation time

BV activation time

RV

Time

A

B

C

Panel 2

Increase LV output Latency

LV

D

Latency

LV

Latency

LV

BV activation time BV activation time BV activation Fusion time with spontaneous QRS Time

V-V delay RV

RV (Avoid RV anodal capture!)

A

B

C

Figure 31-92  Schematic of persistent sequential (R→L) ventricular activation despite simultaneous BiV pacing caused by LV capture latency and differential paced activation wavefront conduction times. Panel 1: A, Paced activation wavefront fusion during uncomplicated simultaneous biventricular (BiV) pacing. B to D, Worsening sequential (R→L) ventricular activation caused by LV capture latency and differential paced activation wavefront conduction times. Panel 2: A, Persistent sequential (RV→LV) activation caused by LV capture latency. B, The effect of LV capture delay is overcome by sequential (LV→RV) stimulation, and to a lesser extent, by increasing LV output (virtual electrode effect). C, In extreme situations, LV paced activation wavefront delay can only be overcome by eliminating RV pacing altogether. (Modified from Herweg B, et al: Latency during left ventricular pacing from the lateral cardiac veins: a cause of ineffectual biventricular pacing. Pacing and Clinical Electrophysiology 29:574-581, 2006.)



31  Troubleshooting of Biventricular Devices BiV pacing at 2.5 V @ 0.3 ms

963

BiV pacing at 6.0 V @ 1.6 ms

I II III aVR aVL aVF V1 V2 V3 V4 V5 V6 V-V

0 ms

20 ms

40 ms

60 ms

80 ms

0 ms

20 ms

40 ms

60 ms

80 ms

Figure 31-93  Sequential biventricular (BiV) pacing (LV→RV) and increased LV voltage output (virtual electrode effect) to generate ventricular activation wavefront fusion. Same patient as in Figure 31-91. Left, Progressively earlier LV stimulation generates evidence of ventricular activation wavefront fusion (lead V1 QS→R, lead I R→QS). Right, These effects are enhanced by increased LV pacing output. (Modified from Herweg B et al: Latency during left ventricular pacing from the lateral cardiac veins: a cause of ineffectual biventricular pacing. Pacing and Clinical Electrophysiology 29:574-581, 2006.)

freedom from CRT-related complications, NYHA functional class, distance covered in 6-minute hall walk, or standard measures of quality of life at 6 months (Fig. 31-96). Similar absence of benefit of sequential BiV pacing was observed in the FREEDOM trial (see later). The failure to demonstrate a clinical advantage of sequential versus simultaneous BiV pacing could be explained by two opposing but related possibilities. First, simultaneous BiV pacing is sufficiently adequate in a substantial majority of patients such that a benefit of sequential ventricular pacing can only be demonstrated in a very large study sample. Second, failure to properly apply sequential ventricular stimulation negated the leveraging advantage for generating maximum ventricular activation wavefront fusion in a substantial majority of patients. The latter possibility seems most likely given considerations discussed previously. Without exception, comparisons between simultaneous and sequential ventricular pacing have been made using various echocardiographic metrics for titration of cross-chamber timing (AV and interventricular level). None of these approaches provides evidence that ventricular activation wavefront fusion, the translational mechanism and primary target of CRT titration, has been achieved. As described, the primary leveraging advantage of sequential ventricular pacing is the ability to overcome asymmetrical conduction delays across the left ventricle. An exemplary failure of echocardiographically directed application of sequential ventricular pacing is a recommendation for RV→LV stimulation in LBBB (e.g., wrong ventricular chamber first). This arrangement could theoretically yield paradoxical activation fusion without maximal correction of LV conduction delay if LV→RV conduction time is substantially less than RV→LV conduction time, a situation that may exist but has not been reported. Methods for Automatic Adjustment of AV and V V Timing Recognition of the importance of proper four-chamber electromechanical timing for maximum pump function justified attempts automatically to orchestrate timing adjustments at the atrial-ventricular (pAVI) and ventricular (V-V timing) level. Such control systems have been implemented in CRT pacing platforms with the common strategy of exploiting intracardiac EGMs to measure and adjust chamber timing.

SmartDelay Optimization (Boston Scientific).  The latest iteration of SmartDelay optimization recommends AVI settings derived from an algorithm originally validated through semi-automatic EGM-based measurement of pAVI/iAVI and QRSd measured on the surface ECG (see Electrogram Analysis). QRSd has been replaced by EGM-based estimates of interventricular conduction time. This process requires up to 2.5 minutes but is usually completed much sooner. The approach was developed from the results of several acute hemodynamic studies of CRT,115,126 which indicated that the AVI yielding the maximum increase in LV dP/dt (optimal AVI, optAVI) can be estimated by simple linear regression: optAVI = K1 × QRSd + K2 × (iAVI or pAVI) + K3. The three coefficients (K1-K3) to be used are determined by LV lead location (anterior or free wall) and pacing chamber (LUV or BiV).115 This equation recites the necessary and logical relationship between AVI, which titrates the dose of LV electrical resynchronization,13 and the severity of LV conduction delay, which is positively correlated with QRSd.72 The greater the LV conduction delay (QRSd), the shorter is the AVI required to overcome that delay by replacing a greater extent of delayed activation with paced activation. In this manner, optimal ventricular resynchronization is prioritized, whereas AV resynchronization is a second-order target. The virtue of this approach is that it is derived from invasive hemodynamic measurements. Increases in LV dP/dt indicate improvement in global contractility and pumping efficiency and are associated with reduction in ventricular mechanical asynchrony. Increases in LV dP/dt during CRT occur without increasing myocardial oxygen consumption.127 Increases in LV dP/dt also correlate with increased aortic pulse pressure68 and stroke volume. SmartDelay Operating Specifics.  SmartDelay Optimization evaluates the timing of native RV (right iAVI) and LV (left iAVI) activation in response to atrial sensed and paced events to determine optAVI. Acquisition of these measurements requires that (1) the device is operating in an atrial tracking mode (e.g., VDD, DDD), (2) intrinsic AV conduction is present, and (3) sinus rhythm is present (e.g., AF results in test abort). The testing sequence is initiated by automatic switch to a unipolar LV sensing configuration (LV tip → CAN). This permits simultaneous measurement of atrial-biventricular monochamber timing (e.g., atrial-RV local EGM, atrial-LV tip EGM), rather than

964

SECTION 4  Follow-up and Programming

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

–


O

Figure 31-94  Persistent sequential (R→L) ventricular activation during simultaneous BiV pacing despite equal bidirectional monochamber ventricular conduction times. Top, Intrinsic LBBB conduction. Middle, Simultaneous BiV pacing. Paced QRS is visibly narrower (concealed fusion); however, global activation pattern is unchanged compared to LBBB conduction (e.g., persistent R in leads I, L; persistent QS in leads V1-V2). Activation remains R→L, A→P. Bidirectional (RV↔LV) monochamber conduction times, measured between stimulation sites using local EGM timing, are identical (160 msec). Bottom, Sequential BiV pacing (LV + 60 msec) yields evidence of ventricular activation wavefront fusion (lead I R→qR, lead V1 QS→RS, lead V2 QS→R, lead V3 QS→RS).

cross-chamber ventricular timing (e.g., LV ↔ RV conduction time). Earlier versions of SmartDelay did not switch to the LV unipolar configuration, and with a unipolar lead required the manual input of native QRSd. To collect the atrial sensed biventricular iAVI (AS-RVS, AS-LVS), the lower rate limit is reduced to 40 bpm (nominally) and the BiV pAVI is extended (up to 400 msec) to permit emergence of native AV and VV conduction. The intrinsic AVI is defined as the interval from an A sense (As) marker to first V sense (Vs) marker in each ventricular chamber. Once the atrial sensed test is completed, the algorithm automatically switches to the atrial paced portion of the test. The atrial paced BiV pAVI is similarly generated, except that the lower rate limit is increased to 80 bpm (nominally, or manually to at least 10-15 bpm above prevailing sinus rate, to force atrial pacing), and the pAVI is

extended to 450 msec. The longer pAVI during atrial pacing increases the probability that BiV sensing will occur, since AVIs increase with atrial pacing at higher rates.7 These pAVIs apply only during SmartDelay operation (e.g., longest programmable pAVI during normal operation is 300 msec). The pAVI is defined as the interval from an A pace (Ap) marker to first V sense (Vs) marker in each ventricular chamber. For each condition (atrial sensing vs. pacing), the test initiates with a brief waiting period to allow stabilization of instrinsic AV conduction. Thereafter, at least 15 cycles are collected, outliers (>1 SD) are discarded, and approximately 15 AVIs are averaged to yield single representative atrial sensed biventricular iAVI and atrial paced pAVI. After sufficient atrial sensed and paced BiV AVIs are collected, additional calculations are made to generate a recommended optAVI using the linear regression described. In an older version of EGM-based AV



31  Troubleshooting of Biventricular Devices

DDD S A

P

RV

P

P

LV P

P SAV

V-V pace delay

PAV

Figure 31-95  Interventricular (V-V) interval timing cycle operation. Atrial sensing is shown on the left, atrial pacing on the right. The pacemaker A-V interval (pAVI) is initiated by either sensing (S) of the local atrial EGM (sinus rhythm) or the emission of an atrial pacing stimulus (P). An atrial blanking period (black bar) follows the sensed atrial event or atrial pacing stimulus. When the sensed pAVI (SAV) or atrial paced pAVI (PAV) expires, the ventricular pacing stimulus (P) for the first chamber selected (e.g., RV or LV) is emitted. In this manner, the programmed SAV or PAV controls the AV timing relationship for the first ventricular chamber stimulated. The first ventricular pacing stimulus initiates (1) a ventricular blanking period (black bar) and (2) the pacemaker V-A interval (atrial escape interval). The ventricular pacing stimulus (P) for the second chamber selected is emitted according to the programmer selected V-V interval (~4 to 100 msec). The second ventricular pacing stimulus must be delivered within the ventricular blanking period. Note the deformation of the evoked QRS complex by the second (delayed) ventricular pacing stimulus. (Modified from Medtronic InSync CRT pacing system manual.)

optimization (Expert Ease Heart Failure, EEHF), QRSd (surface ECG) and LV lead position (anterior, lateral) were manually entered through the user interface. Manual entry of QRSd has been eliminated for SmartDelay. Instead, calculated interventricular conduction time during BiV sensing is applied as a QRSd surrogate in the regression equation. Relative timing of RV and LV sensing during BiV sensing is also used to recognize LBBB (RV sense first) or LBBB (LV sense first), which influences AVI recommendations. Likewise, if LV lead position (anterior, lateral) is manually entered into the pulse generator, the appropriate regression coefficient is applied. Unlike EEHF, if no information regarding LV lead position is provided, the algorithm uses the timing difference in monoventricular AVIs to generate this coefficient, based on the assumption that RVS-LVS time is greater for free wall versus anterior wall sites. The algorithm then generates a single optAVI for atrial sensing/pacing–synchronous BiV pacing. These optAVIs are truncated to be within the range of 50 msec, with 70% of those (iAVI or pAVI) determined by testing. The algorithm cannot recommend an AVI greater than 300 msec, which is the maximum permissible pAVI. In earlier versions of SmartDelay, the difference between the recommended atrial sensed optAVI and atrial paced optAVI was termed the “AVI offset”; this terminology has been eliminated in the current version. Operating Constraints of SmartDelay Optimization.  If atrial fibrillation (AF) or an insufficient number of intrinsic AV conducted events are recorded (e.g., AV block with obligatory ventricular pacing), SmartDelay will abort and a “test failed” message is delivered on the user interface with a recommendation for nominal settings (pAVI 180 msec, sAVI 120 msec, simultaneous BiV pacing). Also, excessive variability in AVI measurements, atrial rates exceeding the maximum tracking rate, VPDs, action potential durations (APDs), noise, and loss of telemetry may cause the test to fail. If SmartDelay recommends an

NYHA class

6-minute hall walk

Per-treatment actually received

Per-treatment actually received

77.8%

61.2%

965

67.5%

60.0%

24.4% 34.7%

27.5%

22.2% 4.1% Simultaneous (n = 45)

5.0%

Optimized (n = 49)

15.6% Optimized (n = 45)

Simultaneous (n = 40)

Quality of life

Improvement No change Worsening

Per-treatment actually received 93.2%

68.8% 10.4%

2.3% 4.9% Simultaneous (n = 44)

20.8% Optimized (n = 48)

Figure 31-96  Neutral effect of sequential vs. simultaneous BiV pacing. There was no improvement in New York Heart Association (NYHA) functional class, distance covered in 6-minute hall walk, or standard measures of quality of life between sequential vs. simultaneous BiV pacing in the RHYTHM II ICD study. (Modified from Boriani G, et al: Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. Am Heart J 151:1050-1058, 2006.)

966

SECTION 4  Follow-up and Programming

optAVI and LV offset that together exceed the maximum programmable pAVI of 300 msec, SmartDelay will suggest a reduced LV offset. SmartDelay does not measure BiV conduction times and does not make a recommendation for sequential ventricular stimulation. If sequential BiV pacing is desired, an LV offset must be manually entered. SmartDelay uses simple arithmetic to account for the programmed LV offset. For example, if the recommended paced optAVD is 150 msec and the programmed LV offset is 20 msec, the recommended paced optAVD is changed to 170 msec because AV timing instructions are prioritized by this algorithm. SmartDelay optimization is inhibited during a VTA episode, immediately after a VTA therapy, during AT/AF mode switch episodes, and when the LV electrode configuration indicates no LV lead. If LV offset is manually adjusted after running SmartDelay optimization, the optAVI must be adjusted either by re-running SmartDelay or by manually programming the AVI to compensate for the LV offset. Clinical Performance of SmartDelay.  During acute hemodynamic monitoring, the EGM optimization method used in SmartDelay showed strong correlation (P <.0001) between maximum % increase in LV +dP/dt and maximum achievable % increase in LV +dP/dt during conditions of atrial sensing (R2 = 0.99) and atrial pacing (R2 = 0.96) (see Fig. 31-66). This EGM method was shown to yield the least difference between % LV +dP/dt and maximum achievable % LV +dP/ dt during conditions of both atrial sensing and atrial pacing, compared with arbitrary pAVIs (100, 120, 140, 160 msec) or “best” pAVIs determined by the mitral inflow method or aortic VTI method.115 The SMART-AV Trial, a 1014-patient, randomized, multicenter, double-blind, three-armed comparison of CRT optimization techniques demonstrated no benefit of SMART-AV or echo-guided mitral inflow analysis as compared to a fixed AVD.128 Limitations of SmartDelay Approach.  The hemodynamic data that generated the regression equations which dictate AVI recommendations in SmartDelay was acquired only for patients with QRSd greater than 120 msec, sinus rhythm (not requiring atrial pacing), and intact AV conduction with iAVI of 100 to 400 msec. Improvements in LV dP/ dtmax are incremental (~1% of baseline value) and have not been shown to correlate with long-term clinical benefit, although this seems logical. Since the optAVI is calculated based on the iAVI and a surrogate measure of QRSd, SmartDelay ignores AV timing altogether. Therefore, SmartDelay offers no protection against atrial transport block in patients with significant interatrial conduction time (IACT) and relatively short iAVIs. The exact mechanism of the improvement in ventricular mechanics using the regression formula that forms the basis of SmartDelay is unclear. An interaction among pAVI, QRSd, and maximum hemodynamic improvement has been observed.126,129 For longer QRSd (>150 msec), the probability of improvement is greater than shorter QRSd (<150 msec) and occurs at shorter pAVIs (≈50% of iAVI, or P-R interval). For QRSd < 150 msec, the hemodynamic improvement occurs at longer pAVIs (≈75% of iAVI, or P-R), and worsens at shorter pAVIs. A logical but unproven interpretation of these observations is that greater LV conduction delay (longer QRSd) requires greater correction with paced activation, which is titrated by a shorter pAVI. Reciprocally, lesser LV conduction delay (shorter QRSd) requires less paced activation replacement (longer pAVI). However, in some patients the acute hemodynamic response derived by the regression formula may be caused by optimal AV timing, rather than ventricular resynchronization.126 A potentially significant weakness of SmartDelay is the application of simultaneous BiV pacing, which yields evidence of ventricular activation fusion (necessary for reverse remodeling) about 55% of the time.72 Therefore, many patients with an acute hemodynamic response to SmartDelay optAVI probably did not have electrical resynchronization. This likely explains, at least in part, the historical “paradox” that acute hemodynamic improvement is not always followed by long-term volumetric remodeling. On the other hand, if the acute hemodynamic improvement is caused by ventricular resynchronization primarily (and possibly optimal AV timing secondarily), long-term remodeling

should occur, assuming LV conduction delay is sufficiently present and LV scar volume is not prohibitive. In summary, a potential problem with SmartDelay is that it does not directly account for ventricular conduction times because the test is conducted at the AV level. An obvious enhancement would be to add ventricular conduction tests and appropriate recommendations for sequential ventricular pacing. QuickOpt (St. Jude Medical).  QuickOpt is an empirical EGM-based method that semi-automatically adjusts AV and VV timing. QuickOpt requires about 90 seconds to complete. Unlike SmartDelay, QuickOpt attempts to optimize LV filling (preload) by timing BiV stimulation to an EGM-based surrogate of IACT. This approach is substantially different from the SmartDelay, which uses the AVI to maximize LV global contractile function as measured by LV dP/dt. QuickOpt Operating Specifics.  QuickOpt has two adjustment stages: AV timing and VV timing. AV timing recommendations are made during forced atrial sensing on the basis of the time measured interval from RA sensed event (surrogate for P-wave onset) to the end of the far-field (RA tip to CAN) P wave, which is held to represent IACT (Fig. 31-97). The optimal iAVI and pAVI are then calculated according to the following formulas. When IACT > 100 msec, SAVQO = IACT + 30 msec; when IACT < 100 msec, SAVQO = IACT + 60 msec. These arbitrary offsets are intended to guarantee that ventricular pacing does not induce diastolic dysfunction (A-wave truncation, atrial transport block). The optimal pAVIQO is similarly composed, except that an additional 50 msec is arbitrarily added to account for “atrial capture latency.” Limited justification for these calculations was provided in an unpublished clinical study of nine patients that demonstrated “reasonable correlation” with echo-based determination of optimal AVIs.130 Sequential ventricular timing (VV) recommendations are made during forced BiV sensing and pacing. The intrinsic VV conduction time (RVs-LVs δ) is corrected for differences in paced VV conduction

1009 1009 P R 230 781 R. atrial signal

L. atrial signal

Intra atrial delay (IAD) IAD – 10 ms = optimal delay Figure 31-97  QuickOpt method for IACT estimate. Interatrial conduction time (IACT) = onset of local RA EGM → offset of far-field P wave (RA electrode to CAN).



31  Troubleshooting of Biventricular Devices

times. A correction factor ε is the difference in LV→RV conduction time (LVp-RVs) and RV→LV conduction time (RVp-LVs) determined during atrial-synchronous monochamber pacing at short pAVIs to guarantee 100% paced activation. The Optimal V-V interval is then calculated according to the following formula: VVQO = 0.5 × (RVs-LVs δ + ε), where ε = 0.5 × [(LVp-RVs) − (RVp-LVs)]. If VVQO = 0, simultaneous BiV pacing is delivered. If VVQO > 0, sequential LV → RV pacing is delivered, whereas if VVQO < 0, sequential RV → LV pacing is delivered. Clinical Performance of QuickOpt.  QuickOpt was evaluated in 58 patients using maximum aortic velocity time integral (AoVTI) as the surrogate hemodynamic endpoint131 (Fig. 31-98). High concordance was observed between maximum AoVTI determined by the echocardiogram method, compared with the AoVTI achieved at the EGMbased settings for optimal AVI (AVQO), and optimal V-V interval (VVQO). The conclusion of this acute surrogate hemodynamic study was that this EGM method for AV and VV timing adjustment was equivalent to an echocardiographic-based approach (AoVTI). The FREEDOM Trial (A Frequent Optimization Study using the QuickOpt Method) randomized 1647 patients to either periodic semiautomatic adjustment of AV and VV timing or standard of care-based optimization methods, including traditional echo-based optimization. Preliminary results, presented at the Heart Rhythm 2010 conference, demonstrated equivalent clinical outcomes between treatment arms,

using a primary endpoint of heart failure clinical composite score (neutral, improved, worsened). In the RESPONSE-HF (Response of Cardiac Resynchronization Therapy Optimization with V-V Timing in Heart Failure Patients) trial, a higher percentage of CRT nonresponders became responders when QuickOpt optimization was used rather than simultaneous BiV pacing. The ongoing OPTIMISE CRT (Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy) trial is testing the hypothesis that periodic semi-automatic adjustment of AV and VV timing will result in greater LV reverse remodeling than simultaneous BiV pacing. Limitations of QuickOpt.  Regarding the acute surrogate hemodynamic study of QuickOpt, the high concordance was calculated between the AoVTI at predicted optimal AVIs, not between the predicted optimal AVIs. This is expected given the relatively flat doseresponse relationship between AoVTI on AV/VV timing adjustments. The accuracy of estimating IACT with RA near-field to CAN EGM has not been validated. This measurement can be easily confounded by lack of a clear offset of atrial activation on the far-field EGM (e.g., low-amplitude P wave) and far-field R-waves. The arbitrary offsets to the sAVI and pAVI are not validated, and this approach provides no guarantee that atrial truncation (transport block) does not occur. The physiologic basis for VVQO equation is unknown. The purported goal of this approach is to generate ventricular activation wavefront fusion,

ACUTE IEGM AV AND PV STUDY Max echo VTI versus IEGM VTI 60

60

40 30 20 10

40 30 20 10

0

0 0

10

20

30

40

50

60

0

10

20

30

40

50

60

Aortic VTI at IEGM optimized PV delay (cm)

Aortic VTI at IEGM optimized PV delay (cm)

ACUTE IEGM AV AND PV STUDY Max echo VTI versus IEGM VTI

VV pace delays recommended by QuickOpt™ optimization

60

25

Number of patients

AV delay group (n = 56) CCC = 97.5 p <0.01

50 Max echo VTI (cm)

VV delay group (n = 54) CCC = 96.6 p <0.01

50 Max echo VTI (cm)

Max echo VTI (cm)

ACUTE IEGM CRT VV STUDY Max echo VTI versus IEGM VTI

PV delay group (n = 56) CCC = 96.1 p <0.01

50

967

40 30 20 10 0

20 15 10 5 0

0

10

20

30

40

50

60

Aortic VTI at IEGM optimized PV delay (cm)

RV RV RV SIM LV LV LV 35–45 25–30 10–20 15–20 25–30 35–45

Figure 31-98  Concordance between maximum aortic VTI by echocardiogram method vs. EGM-based method using QuickOpt. High concordance between maximal acute Doppler-derived and electrogram-derived aortic velocity time integral (AoVTI) during atrial sensed BiV pacing (top left), atrial paced BiV pacing (bottom left), and after VV optimization (top right).

968

SECTION 4  Follow-up and Programming

but no evidence supports this. A key implicit assumption is that when intrinsic VV conduction delay and bidirectional paced ventricular conduction times are both 0, simultaneous BiV pacing will yield activation wavefront fusion. Another assumption is that wavefront fusion occurs with equal contribution (50%) from RV and LV pacing. Neither of these assumptions has been validated. Equivalent conduction times between widely spaced RV and LV stimulation sites does not guarantee that simultaneous BiV pacing will generate global ventricular activation wavefront fusion. None of these approaches provides evidence that ventricular activation wavefront fusion, the translational mechanism and primary target of CRT titration, has been achieved. QuickOpt recommended RV → LV sequential BiV pacing in 25% of patients with LBBB (e.g., wrong ventricular chamber first).131 Summary of Methods for Semi-Automatic Adjustment of AV and VV Timing Semi-automated EGM-based adjustments to AV and VV timing are an expected evolution of CRT platforms. Such control systems are relatively easily implemented in devices systems at low overhead operating cost and have a natural clinical appeal. However, regardless of the specific technique, EGM-based control systems are immediately challenged by several critical shortcomings. The common flaw of all EGM-based approaches is the assumption that local electrical activation, timed by single-site EGMs, accurately depicts chamber level and cross-chamber level mechanical activation. There are a variety of explanations for this failure. Sensing and capture latencies can occur at all chamber levels. Consequently, mechanical activation may be underway before local activation exceeds the sensing threshold (sensing latency). Alternately, mechanical activation may be delayed after a pacing stimulus (capture latency). Both conditions result in timing errors in stimulation of a later-activated chamber. Right-sided pAVIs are flawed surrogates of left-sided electromechanical coupling because direct measurement of LA electrical activation is currently not feasible. Intra-atrial, interatrial, and interventricular conduction delays have unpredictable effects on left-sided AV electromechanical coupling. Despite these limitations, it is probably true that local EGM timing provides a reasonable working approximation of cross-chamber electromechanical level at the (right-sided) AV level. In contrast, relative timing of single-point ventricular EGMs, or conduction times between two cross-chamber ventricular EGMs, cannot be assumed to accurately characterize global ventricular activation. Because the translational mechanism of CRT is activation wavefront reversal, the inability to characterize global activation sequence with current EGM-based timing measures is a serious deficiency. None of the current control systems is fully automated; optimal AV and VV timing requirements are dynamic, may change substantially over time, and probably require adjustment on virtually every cardiac cycle. Finally, none of the EGMbased approaches has been shown to improve clinical outcomes by any measure. STRATEGIES FOR MAINTAINING CONTINUOUS CRT The primary goal of CRT programming is maximal and continuous correction of LV conduction delay; the secondary goal is maximal and continuous correction of AV timing. “Continuous” means on every cardiac cycle for the patient’s lifetime. This means that (BiV) LV pacing must occur on every cardiac cycle. In practical experience 100% BiV (LV) pacing is difficult to achieve. Transient interruptions to CRT occur in up to 36% of patients; permanent loss of CRT occurs in up to 5% of patients within 2 years. The diverse causes often relate to the complex interplay between spontaneous electrical activity (the patient) and inviolable elements of timing cycle operation (the device).132 Uninterrupted CRT can usually be restored by modification to critical pacing control parameters and correction of patient conditions that degrade CRT response independent of electrical operation.

Loss of CRT: Causes and Resolution PACING OPERATION–RELATED CAUSES Critical pacing control parameters during CRT should reflect the goal of guaranteeing biventricular pacing on every cardiac cycle. Therefore, any parameter choice that might reduce the frequency of ventricular pacing should be avoided. The most obvious example of a poor choice in critical control parameters is the use of pacing modes that do not synchronize ventricular pacing to normal atrial activity (e.g., DDI or VVI). Maximum leverage for maintaining continuous BiV pacing is applied by the pacemaker A-V interval (pAVI). The majority of patients who receive CRT have reliable AV conduction, and therefore programming choices that permit the emergence of native ventricular activation will interrupt continuous BiV pacing. Because generation of maximum evidence of ventricular activation wavefront fusion requires that BiV paced activation replace native ventricular activation, pAVIs substantially shorter than the intrinsic AVI are applied, usually accompanied by sequential ventricular timing (e.g., LV stimulation first). The result of this arrangement is that it is much less likely that pAVIs during CRT will be “too long.” Therefore, interruption of continuous BiV pacing due to emergence of native AV conduction is unlikely. However, fusion of native ventricular activation and BiV paced activation is more likely to occur when the iAVI (P-R interval) is relatively short and concerns regarding diastolic dysfunction constrain “short” pAVIs. In this situation, 100% BiV pacing may result in continuous but submaximal correction of LV conduction delay. The use of automatic AV interval extensions or any parameter that compromises continuous atrial tracking should be avoided. Absence of AV conduction renders loss of CRT from poor programming choices unlikely, because ventricular pacing cannot be inadvertently minimized by competition with native ventricular activation. Atrial Undersensing Atrial undersensing may result in loss of atrial-synchronous BiV pacing. Atrial undersensing has two forms: true undersensing and functional undersensing. True atrial undersensing results from a mismatch between endocardial signal amplitude and programmed sensitivity. This can usually be corrected by reprogramming of atrial sensitivity, but rarely requires surgical repositioning of the atrial lead. Functional atrial undersensing (“pseudo–atrial undersensing”) is caused by atrial events falling in refractory periods and is a much more common cause of transient loss of CRT. This is typically registered as a reduction in BiV pacing caused by loss of atrial tracking at high sinus rates. In this circumstance, high sinus rates and first-degree AV block, which are common in heart failure patients, displace the oncoming P wave into the postventricular atrial refractory period (PVARP) initiated by the BiV stimulus on the preceding cycle, resulting in simultaneous loss of atrial tracking and synchronous ventricular pacing. This situation is usually triggered by automatic PVARP extensions after a VPD or other circumstances intended to prevent pacemaker-mediated tachycardia.133 Spontaneous AV conduction emerges in the form of a preempted upper rate Wenckebach response (Fig. 31-99). Although not required for pseudo–atrial undersensing, doublecounting of the native ventricular EGM often participates in the initiation and maintenance of the phenomenon in nondedicated (Y adapters) or first-generation dual cathodal CRT systems where pacing and sensing from the right ventricle and left ventricle occurs simultaneously (Fig. 31-100). When spontaneous conduction with LBBB (or any form of ventricular conduction delay) emerges the LV EGM may be sensed sometime after detection of the RV EGM if the LV signal extends beyond the relatively short ventricular blanking period initiated by RV sensing. The LV signal continuously resets the PVARP resulting in an “implied total atrial refractory period” (iTARP) conflict and maintenance of pseudo–atrial undersensing. Failure to deliver CRT at high sinus rates can be corrected by minimizing the PVARP, increasing the upper tracking limit, and deactivating the VPD response in the DDD mode. Newer CRT systems minimize



969

31  Troubleshooting of Biventricular Devices

V1

M

1

2

3

p/RVcoil 0.5 mV/mm

A Channel R

A R

A R

V V V S S p/Airing 0.5 mV/mm S

A R

A R

V S

V S

A R

A R

V S

V S

A R

V S

A R

V S

A R

V S

A R

V P

A R

V P

V P

A R

V P

A R

V P

A R

V P

A R

V P

V P

Figure 31-99  Loss of CRT from pseudo–atrial undersensing. Top, Telemetry strip. Note sinus tachycardia with marked first-degree AV block (P-R interval, 400 msec) and loss of atrial synchronous biventricular (BiV) pacing on left. Note restoration of atrial synchronous BiV pacing after VPD on right. Bottom, Same patient. Sinus rate exceeds the programmed upper rate limit, displacing P waves into the PVARP (marked as AR). Spontaneous AV conduction occurs in the form of a preempted Wenckebach upper rate response. First VPD (arrow 1) resets PVARP and restores atrial tracking. Second VPD (arrow 2) occurs coincident with sinus event, which falls into the postventricular atrial blanking period (PVAB). Third VPD (arrow 3) resets PVARP and reinitiates pseudo–atrial undersensing. Atrial tracking is restored when sinus rate slows slightly at the end of the strip.

AS

AR SAV

iAV

IVCD

PVARP

PVARP

VP

VS

pTARP

VR

iTARP

Normal operation

Sensing operation VPD

AS

AS PVARP

VP SAV

AS PVARP

VP SAV

AR PVARP

VP SAV

AR

AR

AR

PVARP PVARP PVARP PVARP VR VR VR VR VR VS VS VS VS VS iAV iAV iAV iAV IVCD IVCD IVCD IVCD IVCD

Figure 31-100  Loss of CRT caused by pseudo–atrial undersensing and ventricular double-counting with implied total atrial refractory period. VPD is double-counted; second component resets the PVARP, which initiates pseudo–atrial sensing. Loss of CRT results in emergence of spontaneous AV conduction. Double-counting of the native ventricular electrogram continuously resets the PVARP, perpetuating pseudo–atrial sensing. Implied total atrial refractory period = SAV + PVARP + interventricular conduction delay.

970

DDD

SECTION 4  Follow-up and Programming

S A

S

R

R

Ventricular pacing: RV + LV First chamber paced: LV

R

RV P LV

S

S

S

R

S

R

P

Double senses without interventricular refractory period

Double senses with interventricular refractory period

DDD

S A

S

R

S

S Interventricular refractory period

RV LV

P

S

S

S R

P

P

P

P

P

ventricular double-counting by employing an interventricular ventricular refractory period (IVRP). Ventricular sensed events (e.g., LV sensing) during the IVRP do not reset the PVARP, eliminating the “implied TARP” conflict (Fig. 31-101). Another method to minimize loss of CRT caused by pseudo–atrial undersensing is Atrial Tracking Recovery (Medtronic; ATR) (Figs. 31-102 and 31-103). ATR operates in the DDD/R mode when a modeswitch episode is not in progress. Under certain conditions, ATR temporarily shortens PVARP to reduce the intrinsic TARP. ATR is initiated when eight consecutive pacing cycles satisfy the following conditions: (1) the current ventricular event is sensed, not paced; (2) the last ventricular interval contains exactly one refractory atrial event; (3) the last two atrial intervals vary from each other by less than 50 msec; (4) the last atrial interval is longer than the upper tracking rate (UTR) interval by at least 50 msec; (5) the last atrial interval is greater than current PAV plus current PVARP; (6) the last VS-AR interval (from previous ventricular event to atrial refractory event) is greater than 1

1

1

A R

A R

2

3

ECG

Figure 31-101  Role of interventricular refractory period to eliminate implied total atrial refractory period and reduce loss of CRT from pseudo–atrial undersensing.

postventricular atrial blanking (PVAB). To start or continue an ATR intervention, the device sets a temporary truncated PVARP equal to last VS-AR interval minus 50 msec (see Fig. 31-103). If this computed value is shorter than the programmed PVAB, the PVAB value is used. On subsequent pacing cycles during ATR intervention, the device recalculates the temporary PVARP. ATR intervention ends when a BiV paced event occurs at the scheduled PAV, or when the computed temporary PVARP is no longer shorter than the otherwise indicated PVARP. If the pacing pattern is interrupted, as by a ventricular sensed event, the intervention aborts. Atrial Tracking Preference (ATP) is a similar but less ornate approach than ATR that is used in Boston Scientific (St. Paul, Minn.) pulse generators (Fig. 31-104). ATP is designed to mitigate loss of AV resynchronization caused by pseudo–atrial undersensing at high sinus rates. If two consecutive cycles occur in which an RV sensed event is preceded by an atrial sensed event in the PVARP, the PVARP is shortened until continuous atrial tracking (AV resynchronization) is reestablished. ATP temporarily shortens the PVARP to reestablish AV synchronization at high sinus rate accompanied by delayed AV conduction (e.g., long iAVI). By programming ATP on, continuous CRT is delivered at rates below the maximum tracking rate (MTR), rates that otherwise might result in loss of AV resynchronization when the sum of PVARP and iAVI exceeds the MTR interval. Notably, ATP is disabled if the atrial rate interval is equal to or greater than the MTR interval. Atrial Oversensing

A P

A S

A S

A S

A S

Marker channel V S

V S

V S

B V

B V

B V

B V

AV interval PVARP 200 ms

Figure 31-102  Atrial tracking recovery. 1, Atrial events occur during PVARP and are not tracked. 2, After 8 qualifying AR-VS cycles, PVARP is automatically shortened. 3, Shortened PVARP is maintained until proper AV resynchronization at the programmed PAV is restored.

Automatic mode switching is intended to prevent undesirable rapid ventricular pacing caused by tracking of atrial tachyarrhythmias during DDD operation. Detection of atrial tachyarrhythmias results in reversion to a nontracking mode (DDI or VDI). Spurious mode switching is a common problem and can result in loss of atrialsynchronous ventricular pacing during CRT. The dominant cause of spurious mode switching is far-field R-wave (FFRW) oversensing.134-138 This can be recognized on stored marker channels or EGMs by an alternating pattern of atrial cycle lengths with one signal timed close to the ventricular EGM. Less common causes of spurious mode switching include “near-field” or “early” R-wave oversensing (atrial R-wave sensing before arrival of depolarization wavefront at ventricular pacing lead position) and oversensing of the paced atrial depolarization during the PAV.138,139 Spurious mode switching can usually be eliminated by the use of bipolar atrial pacing leads, extending the PVAB or



31  Troubleshooting of Biventricular Devices

971

RVEGM PVARP reset

AR-VS emerges

AEGM AS

AS

VP

AS

VP

AR

AR

AR

AR

AR

AR

TF FS

VS

VS

VS

VS

VS

AS

VP

VS

AR TF

AR VS

AR VS

AR VS

VS

PVARP shortened, atrial tracking restored AR

AR

VS

AR

VS

VS

AR VS

AR VS

AS VS

AS VP

AS VP

VP

AS

AS

VP

VP

AS VP

Figure 31-103  Atrial tracking recovery operation. Top, The first of 3 consecutive VPDs resets the PVARP. Pseudo–atrial undersensing emerges because of high sinus rates and delayed AV conducton, which displace atrial events into the programmed (“too long”) PVARP, resulting in loss of CRT (AR-VS pattern). Bottom, PVARP is automatically shortened, which restores AV synchronization at the PAV and continuous BiV pacing.

reducing atrial sensitivity so as to reject far-field signals without compromising atrial sensing. PREVENTION OF PACING ON T WAVE Theoretically, conduction delay could prevent an LV VPD from reaching the RV electrode (univentricular sensing) and inhibiting the scheduled atrial-synchronous BiV paced event. In this situation, lack of LV Pacing rate reaches MTR, ventricular Ventricular sense events are sensed

COMPETITION WITH NATIVE VENTRICULAR ACTIVATION

Rate

MTR

Ventricular pace

Ventricular pace

Pacing if tracking preference is on; no pacing if tracking preference is off.

P

PVARP PR MTR

R

P

PVARP PR

Any situation that permits competition between the delivery of continuous ventricular pacing and native ventricular activation will degrade CRT efficacy. This is far more likely to occur amongst patients with intact AV conduction. Atrial Tachyarrhythmias with Rapid Ventricular Conduction

Time R

sensing could result in competitive LV pacing outside the absolute myocardial refractory period. To prevent competitive pacing or LV pacing during the relative refractory period, some Boston Scientific CRT systems include a left ventricular protection period (LVPP). The LVPP is defined as the period after an LV event (paced or sensed) when LV pacing is inhibited (programmable at 300-500 msec). The LVPP reduces the maximum LV pacing rate and theoretically could disrupt CRT by preventing LV stimulation during sequential (RV→LV) BiV pacing, depending on the VV timing delay and the conduction time from the RV to LV electrode.

R

P

BVP

PAV Shortened PVARP

Figure 31-104  Atrial tracking preference. Two consecutive cycles are recorded where RV sensed event (R) is preceded by atrial sensed event (P) in the PVARP. The PVARP is automatically shortened on the next cycle, restoring atrial-synchronous BV pacing at the (shortened) PAV. MTR, Maximum tracking rate.

By far the most common cause of loss of CRT pacing is atrial tachycardia/fibrillation (AT/AF) with rapid AV conduction, accounting for 18% of all therapy interruptions in one study.132 This consequence is instantaneous and simultaneous loss of AV and ventricular resynchronization (total cardiac desynchronization) combined with rapid, irregular ventricular rates (Fig. 31-105). The importance of rate control and regularization of the ventricular response during AT/AF to maximize CRT response should not be underestimated. For example, the relatively neutral effect of BiV versus RVA pacing immediately after AV junction ablation among patients with systolic heart failure suggests that the benefits of rate control in AT/AF are so great that it conceals the effect of asynchronous ventricular activation.26

972

SECTION 4  Follow-up and Programming

CARDIAC COMPASS REPORT P = Program I = Interrogate AT/AF total hours/day

V. rate during AT/AF (bpm) VF FVT VT Max/day ↓ Avg/day

P

P

P

X

X

24 20 16 12 8 4 0 >200

AF onset

RVR

150 I

100 <50

Sep 2003

Nov 2003

Jan 2004

Mar 2004

Mo

CARDIAC COMPASS REPORT P = Program I = Interrogate % pacing/day Atrial Ventricular Avg V. rate (bpm)

P

P

P

X

X

100 75 50 25 0 >120

Loss of CRT

Pacing

Feb 19, 2004

Aug 14, 2003

AS-VS AS-VP AP-VS AP-VP

99.1% 0.7% <0.1% 0.2%

4.3% 95.6% <0.1% <0.1%

There is some evidence that lower lifetime effective BiV pacing caused by AT/AF is associated with reduced clinical response and increased risk of death. Higher cumulative percent BiV pacing (>93%100%) recorded by device event counters was associated with reduced risk of heart failure and death, whereas cumulative percent BiV pacing of less than 92% was associated with a 44% increase in relative risk. A lower cumulative percent BiV pacing (<92%) was more likely among patients with history of AT/AF140 (Fig. 31-106). Pacing event counters probably underestimate the true magnitude of the negative effect of AF with native AV conduction on effective BiV pacing delivery. Using 24-hour ambulatory ECG monitoring, only 47% of patients with permanent AT/AF had effective BV pacing (defined as >90% BiV pacing with complete ventricular capture) despite pacing event counters showing greater than 90% BiV pacing. The remaining patients had ineffective (pseudofusion, ~23% of all cycles) or incompletely effective (fusion, ~16% of all cycles) BiV pacing141 (Fig. 31-107). Ambulatory ECG evidence of ineffective or incompletely effective BiV pacing was associated with reduced clinical response to CRT. Also supporting the goal of 100% BiV pacing, retrospective analysis indicates that patients with permanent AF have similar improvement after CRT as patients with sinus rhythm, but only if ablation of the AV junction is performed, to guarantee 100% BiV pacing with full replacement of ventricular conduction (Fig. 31-108). Patients with permanent AF and more than 85% BiV pacing who did not undergo AV junction ablation had substantially less long-term improvement in LVEF, LVESV (reverse remodeling), and exercise capacity.142 Specific features of pacing operation may increase the percentage of BiV pacing during rapidly conducted AF and thereby prevent disruptions to CRT. Conducted AF Response (Medtronic) increases the ventricular pacing rate in alignment with the native conducted ventricular response (Figs. 31-109 and 31-110). The intent is to regularize the ventricular rate by increasing the overall percentage of ventricular

Figure 31-105  Instantaneous and total cardiac desynchronization caused by atrial fibrillation (AF). Onset of persistent AF is indicated by transition from 0 total atrial tachycardia (AT)/AF hours/day to 24 total AT/ AF hours/day (top). Average ventricular rate during AT/ AF is about 100 beats per minute (bpm) with frequent rate excursions to 160 bpm, extending into the VT detection zone (red line) and VF detection zone (blue line). Percent BiV pacing instantaneously declines from 100% to less than 0.1% at onset of AF with rapid ventricular response (bottom).

pacing while minimizing the increase in overall heart rate. This is achieved by adjusting the pacing escape interval after each ventricular event. The escape interval increases or decreases based on a contextual analysis of the preceding events. For example, a BiV-AR-VS sequence will increment the pacing rate by 1 bpm, whereas a BiV-BiV sequence will decrement the pacing rate by 1 bpm. The result is a higher percentage of ventricular pacing at an average rate that closely matches the patient’s own ventricular response. The maximum rate for Conducted AF Response pacing is programmable. The minimum rate derives from the otherwise indicated (sensor rate, mode switch, or lower rate) pacing interval. When the otherwise indicated pacing rate is faster than the programmed maximum rate, this feature is suspended, and the device operates at the otherwise indicated pacing rate. The use of Conducted AF Response necessitates interactions with other device operations. For example, in DDD and DDDR modes, Ventricular Rate Stabilization (VRS) and Conducted AF Response cannot operate at the same time. When both are enabled, VRS operates only when the device is not mode-switched. Conducted AF Response operates only in nontracking modes. Therefore, when DDD or DDDR mode is programmed, Conducted AF Response operates only during a mode switch. Conducted AF Response is suspended during automatic tachyarrhythmia therapies, arrhythmia inductions, manual therapies, and emergency fixed burst, cardioversion, and defibrillation. Ventricular Rate Regulation (VRR, Guidant) is designed to reduce VV cycle length variability during conducted atrial arrhythmias by moderating the ventricular pacing rate based on a previous VV average (Figs. 31-111 to 31-113). VRR provides ventricular regulation during conducted atrial arrhythmias, whereas Rate Smoothing (Guidant) is typically more useful for reducing pauses following premature ventricular complexes (PVCs). VRR operates in the DDD/R mode only during an AT/AF mode-switch episode, but is available all the time in the single-chamber VVI/R modes.



31  Troubleshooting of Biventricular Devices

Event free probability

1.0 0.9 0.8 0.7

1st quartile: 0%–92% N = 267 2nd quartile: 93%–97% N = 313 3rd quartile: 98%–99% N = 361 4th quartile: 100% N = 254

0.6 0.5 0

2

A

4

6

8

10

12

10

12

Months post-implant

Event free probability

1.0 0.9 0.8 0.7

1st quartile: 0%–92% N = 200 2nd quartile: 93%–97% N = 161 3rd quartile: 98%–99% N = 148 4th quartile: 100% N = 106

0.6 0.5 0

B

2

4

6

8

Months post-implant

Figure 31-106  Survival free from heart failure hospitalization and death in patients with AT/AF vs. no AT/AF. Event rates are plotted by quartiles of cumulative percent biventricular (BiV) pacing. A, Survival is highest for patients with 100% BiV pacing and lowest for patients with ≤92% BiV pacing. B, This relationship is enhanced by a history of AT/ AF. (Modified from Koplan BA, et al: Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J Am Coll Cardiol 53:355-360, 2009.)

Unlike rate smoothing, where changes are based on the most recent V-V interval, VRR uses a weighted ventricular average based on cycle lengths during the mode switch episode. This weighted average is made up of two parts: (1) the most recent V-V interval multiplied by 1.1 (if most recent ventricular event was sensed) or 1.2 (if event was paced); this calculation provides 6% of the next calculated VRR pacing rate value; and (2) the calculated VRR interval value just before the most recent V event; this calculation provides 94% of the next calculated VRR pacing rate value. Therefore, the next VRR pacing rate interval = .07 (recent V-V interval × 1.2 or 1.1) + 0.93 (previous VRR interval calculation). The calculated rates based on the weighted average yields a pacing rate that still adjusts on a cycle-by-cycle basis, but in much smaller increments than observed during rate smoothing. The frequency of VRR pacing is directly related to ventricular cycle length variability (e.g., pacing frequency increases with ventricular cycle length variability). The use of VRR necessitates interactions with other device operations. The maximum programmable VRR pacing rate is limited between 60 and 150 bpm. In dual-chamber modes, rate smoothing is temporarily disabled when VRR is active. Frequent Ventricular Premature Beats Frequent VPDs may disrupt CRT. Ventricular Sense Response (VSR, Medtronic) is intended to force BiV pacing in response to ventricular (RV) sensing. Each RV sensed event triggers a pace in one or both ventricles, as programmed (Fig. 31-114).

973

When VSR is enabled in a nontracking or single-chamber pacing mode, an RV sensed event triggers an immediate VP. VSR pacing is delivered in one or both ventricles, according to the programmed ventricular pacing pathway. When VSR is enabled in an atrial tracking mode, a sensed ventricular event during the pAVI triggers an immediate pacing output to both ventricles (Fig. 31-115). The triggered output is rendered ineffectual in the chamber where sensing occurred due to ventricular refractoriness. Therefore, the triggered output “resynchronizes” ventricular activation by stimulating the chamber opposite the sensed event. Some timing rules apply to prevent disruption of normal device operation. VSR pacing stimuli are delivered 1.25 msec after the ventricular sensed event only if the triggered pace does not violate the programmed VSR Maximum Rate. If the ventricular interval measured from the preceding ventricular event is shorter than the VSR Maximum Rate interval, no VSR pacing pulse is delivered. Ventricular sensing for VSR operation occurs through only the RV lead. The VRS operation necessitates interactions with other device operations. When both VSR and Ventricular Safety Pacing (VSP) are enabled, VSP operation takes precedence during the VSP interval. If a ventricular event is sensed during the VSP interval, the device performs a safety pace at the end of the VSP interval. After the VSP interval expires, VSR remains active for the remainder of the pAVI. VSR pacing pulses are not considered in interval calculations for arrhythmia detection or pacing. VSR pacing pulses also are not considered in the counts of consecutive sensed and paced events that define the beginning and end of ventricular sensing episodes storage. VSR operation is suspended during automatic tachyarrhythmia therapies, electrophysiologic study induction, manual therapies, and emergency fixed burst, cardioversion, and defibrillation. Conducted AF Response and VSR display some synergism in forcing BiV pacing during AF (Fig. 31-116). As noted previously, % BiV pacing derived from event counters likely underestimates % effective BiV pacing (full replacement of ventricular conduction) during AF with competitive AV conduction during CRT. There is no evidence that device-based strategies to force BiV pacing during AF or VPDs improve clinical outcomes.

100% 90%

7.7% 5.9%

80%

19.9% 13.3%

70% 60% 50% 40% 30%

86.4% 66.6%

20% 10% 0% Responders Non-responders Fully paced beats Fusion beats Pseudo-fusion beats Figure 31-107  Reduction in effective BiV pacing among clinical nonresponders during CRT for permanent AF. Data are derived from 24-hour ambulatory holters. Responders were defined as having ≥1 NYHA functional class improvement. Nonresponders had a significantly higher percentage of ineffective biventricular pacing resulting from fusion (P = .04) and pseudofusion (P = .02) beats. (Modified from Kamath GS, et al: The utility of 12-lead Holter monitoring in patients with permanent atrial fibrillation for the identification of nonresponders after cardiac resynchronization therapy. J Am Coll Cardiol 53:1050-1055, 2009.)

974

SECTION 4  Follow-up and Programming

60 Functional capacity score

Left ventricular ejection fraction (%)

60 50 40 30 20 10 0 12

A

24

36

48

Left ventricular end systolic volume change (%)

–60

30 20 10

Baseline 6

B

Months

C

40

0 Baseline 6

–15

50

12

24

36

48

Months SR AF + AVJ ablation AF no AVJ ablation

15 0 Total n. pts N. deaths

–30

D

673 Baseline

649 523 12 7 6 12 Months

365 13 24

233 7 36

127 5 48

–45

Figure 31-108  Comparison of several response measures to CRT during sinus rhythm. Atrial fibrillation (AF) with atrioventricular junction (AVJ) ablation and AF without AVJ ablation. Improvement in LVEF (A), functional capacity score (B), and LV reverse remodeling (C) are similar for sinus rhythm and AF with AVJ ablation and exceed outcomes observed in AF without AVJ ablation. D, Key and summary. (Modified from Gasparini M et al: Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 48:734-743, 2006.)

LOSS OF LEFT VENTRICULAR CAPTURE The principal limitation of the coronary venous approach to LV pacing is that the selection of sites for pacing is entirely dictated by navigable coronary venous anatomy. A common problem is that an apparently suitable target vein delivers the lead to a site where ventricular capture can be achieved only at very-high-output voltages, or not at all. This presumably relates to the presence of scar on the epicardial surface of the heart underlying the target vein, or inadequate contact with the epicardial surface, and cannot be anticipated by fluoroscopic examination. In some cases this can be overcome by mapping a more proximal or distal site within the same vein, but this may require an alternate lead design to achieve mechanical stability. These practical realities 1

2

3

ECG

A S

A R

A A A R S R

A S

A R

A A A S R S

A R

A S

A R

A S

A A R S

Marker channel B V

V S

B V

B V

V S

B V

B V

V S

Figure 31-109  Conducted atrial fibrillation response. 1, BV-AR-VS sequence causes pacing rate to increase by 1 beat/minute. 2, VS-BV sequence causes pacing rate to remain unchanged. 3, BV-BV sequence causes pacing rate to decrease by 1 bpm.

have forced acceptance of comparatively higher pacing thresholds in the left ventricle, compared with endocardial pacing in the right side of the heart. Infrequently, the inability to achieve stable LV capture from any coronary venous target mandates surgical placement of LV leads, which permits more detailed mapping of viable sites in the anatomic region of interest. Data on long-term pacing thresholds and retention of capture during LV pacing is not as robust as right-sided heart endocardial pacing. Documented loss of ventricular capture occurred in up to 10% of patients and was the second most common cause of interrupted CRT in one analysis.132 About 75% of these cases were caused by gross dislodgment of the LV lead; 23% were caused by chronic pacing threshold elevation, overcome by increasing voltage output in most cases. A comparison of thoracotomy and first-generation dedicated coronary venous lead systems found no significant differences in chronic thresholds with either approach, which on average were 1.5 to 2.0 V up to 30 months after implant. Similarly, there were no chronic threshold differences between different coronary venous lead designs (OTW vs. preformed shape).143 Similar results were more recently obtained with a third-generation active-fixation coronary venous LV pacing lead (Fig. 31-117). An interim progress report of the InSync Registry PostApproval Study in 903 patients showed similar range and stability of LV thresholds (mean, 1.88 ±1.44 V) with two preformed transvenous lead designs at 6 months retained at 36 months.144 In this same report, epicardial voltage thresholds were similarly stable, but slightly higher (2.42 ±0.74 V) at 12 months, although data were available on a much smaller number of patients. An analysis of 2078 patients enrolled in MIRACLE, MIRACLE ICD, and the InSync-III Study demonstrated that LV voltage pacing thresholds using second-generation transvenous leads were stable for at least 6 months of follow-up (1.65 ±1.23 V before discharge to 1.73 ±1.17 V at the 6-month follow-up).145 Complete loss of LV capture during follow-up was observed in only 21 of 2078 patients (1.01%).



975

31  Troubleshooting of Biventricular Devices

II 0.1 mV/mm

A A S S

A A A S S S

1p/RV ring

V S

AA A A A A A SS S S S S S

A S

V S

1 mV/mm

A S

A S

A S

V S

A A A A S S S S V S

A A AA A A A S S SS S S S

V S

Mode switch

V S

A A A A S S S S

V S

A S

A S

A S

V S

V S

A F

A A A A A A R R S RR R

A A S S

A S

A A A S S S V S

conducted AF response ON

ECG lead II 0.1 mV/mm

AA A A SS S S

A S

A S

A AA A S SS S

A A AA R R SS

V V S S EGM2: RVtip/RV ring 1 mV/mm

V S

A A S R

B V

A A A A R S R R

B V

A S

A R

B V

A S

A R

B V

A A R R

B V

B V

B V

A AA R RS

A S

B V

Figure 31-110  Effect of conducted atrial fibrillation (AF) response on biventricular (BiV) pacing delivery. Top, Programmed mode is VVI 30 bpm. Note AF with intact AV conduction and absence of ventricular pacing. Bottom, Programmed mode is DDD 30 bpm with Conducted AF Response “on.” Note modest increase in ventricular pacing rate immediately after mode switch (MS marker) occurs, which initiates Conducted AF Response operation.

VRR OFF

↑↑

AS

VP

↑↑ ↑

AS

AS

↑

AS

↑

AS

VS

↑↑ ↑

AS

AS

↑ ↑ ↑↑

AS

VP

↑

↑

↑↑ ↑

↑↑ ↑ ↑ ↑↑ ↑ ↑↑

↑↑↑

↑↑ ↑

↑↑ ↑

↑

↑

↑ ↑↑ ↑ ↑

↑

↑ ↑↑

↑

AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS (VS) VS VS VS VS (VS) VS VP VS VS VS VS

VRR ON

↑

↑↑ ↑

↑

↑

↑

↑↑ ↑

AS AS AS AS AS AS AS VP VP

↑

↑

AS

↑

VP

↑

AS

↑

↑↑ ↑

↑↑

↑

↑↑

↑

↑

↑

↑

↑

AS AS AS AS AS AS AS AS AS AS VP VP

↑

↑

AS

↑

↑

AS

↑

↑

AS

↑

VP

Figure 31-111  Ventricular Rate Regularization (VRR, Boston Scientific). Top, VRR “off.” Mean ventricular rate 167 ±49 bpm. Note wide ventricular interval variation (red horizontal bars). Bottom, VRR “on.” Mean ventricular rate 138 ±37 bpm. Note increase in ventricular pacing and reduction in ventricular interval variation (red horizontal bars).

976

SECTION 4  Follow-up and Programming

160

400

120

300

80

200

40

100 0

0 1

0

2 3 Time (minutes)

Rate

4

R-R interval difference (msec)

Rate (ppm)

VRR OFF

5

Interval difference

160

400

120

300

80

200

40

100

0

0 0

1

2

3 4 Time (minutes)

Rate

5

6

7

R-R interval difference (msec)

Rate (ppm)

VRR ON

Interval difference

Figure 31-112  Ventricular Rate Regularization. Note reduction in ventricular interval variation but increase in pacing rate during VRR operation “on” (bottom) vs. VRR operation “off” (top).

It is not unusual to record a modest rise in chronic LV pacing thresholds using coronary venous leads, unaccompanied by any radiographic evidence of lead displacement. This likely relates to micro-dislodgment of the lead tip, reducing contact of the cathode and/or anode(s) with the epimyocardium. This complication is best addressed with implantation technique. Probably of most importance is an optimal match between the diameter of the LV lead and the luminal diameter of the target vein. Support at multiple (>2-3) positions increases mechanical stability. Larger leads with preformed shapes should be advanced sufficiently within the target vein to unfold completely. In the case of the smallest-diameter, purely over-the-wire (OTW) leads, it is useful to position the tip in a tertiary branch to achieve support at more than one position and increase mechanical stability. A particularly difficult problem with chronic epicardial leads is exit block, which in some patients results in voltage thresholds that exceed pulse generator output and permanent loss of CRT. Although infrequent, this is a devastating problem for the patient because the epicardial approach is usually taken only when the transvenous approach fails. Contributing factors relate to lead design and surgical technique. The most frequently used epicardial pacing lead is a fixed helix mechanism without steroid, and chronic doubling of the implant threshold is common. Furthermore, this situation worsens with multiple applications of the helix and incautious use of suturing, which increase local tissue trauma and the inflammatory response. Phrenic Nerve Stimulation Another frustratingly common problem is that the target vein delivers the lead to a site resulting in phrenic nerve stimulation. Careful examination of cadaver hearts demonstrates that the phrenic nerve passes over the lateral coronary veins in ∼80% of specimens and over the anterior interventricular vein in the remaining 20%.146 This presents a high probability of anatomic conflict between the optimal site for LV

stimulation and unacceptable phrenic nerve stimulation. Phrenic stimulation can be difficult to demonstrate during implantation when the patient is supine and sedated but may be immediately evident when the patient is later active and changes body positions, even in the absence of lead dislodgment. It is important to recognize that once phrenic nerve stimulation is observed acutely (during implantation), it is almost invariably encountered during follow-up despite manipulation of output voltages, and therefore alternative site LV pacing is sought. As with high LV capture thresholds, phrenic nerve stimulation can often be overcome by repositioning the LV lead more proximally within the target vein. Occasionally, if there is a significant differential in the capture thresholds for phrenic nerve stimulation versus LV capture, this can be overcome by manipulation of LV voltage output in devices that permit separate RV and LV outputs. More recently, some LV leads have two or more electrodes that permit selection of specific LV sites for dual cathodal biventricular stimulation, BiV stimulation with true bipolar LV stimulation, or true bipolar LV-only univentricular stimulation. It has not been convincingly demonstrated that true bipolar LV stimulation reliably overcomes phrenic stimulation compared to dual cathodal or unipolar LV pacing. On the other hand, selecting alternate LV electrodes for dual cathodal BiV stimulation may occasionally overcome phrenic stimulation by altering the LV-RV pacing vector. This can be achieved noninvasively using some pulse generators and is referred to as “electronic repositioning.”147 Another noninvasive strategy for dealing with phrenic stimulation exploits algorithms for automatically adjusting LV output voltage based on periodic threshold testing. This provides the possibility of overcoming phrenic stimulation when the voltage differential between phrenic nerve capture (higher) and LV capture (lower) is sufficiently differentiated. In this situation, LV output voltage can be automatically “capped” beneath the phrenic nerve capture voltage without compromising LV capture. In any case, the problem of phrenic nerve stimulation is more reliably addressed by LV lead repositioning at implant. If phrenic stimulation during attempted transvenous LV pacing cannot be overcome by any means, surgical placement of LV leads should be considered. Phrenic stimulation can occur with surgically placed epicardial leads if careful visualization of the course of the nerve sheath is not performed prior to fixation. Chronic development of phrenic nerve stimulation results in permanent loss of CRT in about 1% to 2% of patients.132

Complications of CRT PACING OPERATION–RELATED PROBLEMS A myriad of unusual pacemaker behaviors and interactions between timing cycle operation and ambient cardiac electrical activity have been reported. Most of these are end cases that will not be observed or recognized by the average practitioner. For example, the additional timing cycle complexities of nondedicated and dedicated CRT systems have introduced new forms of pacemaker-mediated tachycardia (PMT). Barold and Byrd148 described a “cross-ventricular” endless-loop tachycardia (ELT) in a conventional dual-chamber pacemaker pulse generator used for CRT during permanent AF with the RV lead in the ventricular port and the LV lead in the atrial port. In the VVIR mode, T-wave oversensing on the LV lead (atrial channel) triggered ventricular pacing on the RV lead (ventricular channel). This could be overcome by reducing atrial channel (LV) sensitivity or by using the DVIR mode that excludes the possibility of LV sensing (atrial channel). Berruezo et al.149 described an unusual form of PMT in a CRT system without an atrial lead because of “permanent” AF. This was explained by the serendipitous occurrence of spontaneous termination of AF and dislodgment of the LV lead into the coronary sinus, resulting in simultaneous LA and LV capture. Since AV conduction was intact, LA capture resulted in a RV sensed event, which triggered the VSR feature (see earlier), resulting in emission of a BiV pacing stimulus, which perpetuated the phenomenon.



31  Troubleshooting of Biventricular Devices

977

VRR OFF Histograms – Since last reset

Histograms with VRR OFF ATR

25%

0 30 50 70 90 110 130 150 170 190 210 220 250

Atrial Paced

Sensed

25%

Right ventricular Ventricular tachy detections Right paced Tracked Device determined Right sensed

60% 63% 37% 40%

0 780K 491K 289K 520K

67% 65% 35% 33%

771K 501K 270K 380K

83% 66% 34% 17%

0 605.9K 399.9K 206.0K 124.1K

85% 67% 33% 15%

552.5K 370.2K 182.3K 97.5K

Left ventricular Left paced Tracked Device determined Left sensed

0 30 50 70 90 110 130 150 170 190 210 230 250

Rate (bpm) Ventricular RV LV

Paced Sensed VRR ON Histograms – Since last reset

Histograms with VRR ON ATR

25%

0 30 50 70 90 110 130 150 170 190 210 230 250

Right ventricular Ventricular tachy detections Right paced Tracked Device determined Right sensed Left ventricular

Atrial Paced

Sensed

25%

Left paced Tracked Device determined Left sensed

0 30 50 70 90 110 130 150 170 190 210 230 250

Rate (bpm) Ventricular RV LV

Paced Sensed Figure 31-113  Increase in biventricular pacing during AT/AF caused by VRR. Ventricular Rate Regularization (VRR) results in significantly higher frequency of ventricular pacing during AT/AF with rapid ventricular conduction (BiV pacing percentage ~60% → ~80%).

978

SECTION 4  Follow-up and Programming

ECG A S

A S

A S

A S

A S

Marker channel V S

V S

V S

V S

V S

VSR maximum rate interval 200 ms

Each VS event (first downward line on marker channel) triggers an immediate BiV paced event (second downward line; annotation not shown due to space limitations).

Figure 31-114  Ventricular Sense Response (VSR).

In all these situations, sensed events in the left and right ventricles are “merged” into a single recording channel in parallel, dual cathodal systems. The degree of temporal displacement between sensed RV and LV events depends on the interventricular conduction time and lead position. If the interventricular conduction time during LBBB exceeds the relatively short ventricular blanking period initiated by sensing, a single ventricular depolarization may be counted twice. This yields a characteristically oscillating interval plot resulting from cycle-to-cycle variation in the ventricular cycle length. In CRT-P systems, this can result in inhibition BiV pacing and spurious high-rate ventricular episodes (Fig. 31-118). In CRT-D systems, this may result in inhibition of ventricular pacing and spurious ventricular therapies for sinus tachycardia, rapidly conducted AT/AT below the programmed ventricular tachycardia (VT) detection interval because the ventricular doublecounting interval exceeds the VT detection interval (Fig. 31-119). Similarly, the rate of true VT may be overestimated, resulting in misclassification as ventricular fibrillation (VF) and treated with shocks rather than rate-appropriate antitachycardia pacing,152 and nonsustained VT may satisfy VF detection criteria, resulting in aborted or delivered shocks. Pacing inhibition and inappropriate therapies caused by far-field sensing of LA activity by the LV lead have also been reported.153-155 In this situation, ventricular double-counting is caused by sensing of the far-field atrial and near-field ventricular signals. Ventricular triplecounting can also occur when the far-field atrial signal and both components of the prolonged native VEGM are sensed (Fig. 31-120).

Ventricular Oversensing Ventricular oversensing is common in ICD platforms, including those that deliver CRT. Oversensing is a cause of inappropriate ventricular detection and therapy in common ICDs and loss of BiV pacing in CRT systems (see previous discussion). Ventricular oversensing was a much greater problem when the single ventricular output channel of conventional pacemaker and ICD generators was Y-adapted to serve two ventricular pacing leads. The divided single ventricular output provided simultaneous stimulation of the right and left ventricles (dual cathodal system with parallel outputs). First-generation dedicated multisite pacing pulse generators similarly provided a single ventricular output for simultaneous RV and LV stimulation, although two separate ventricular channels internally connect in parallel. This connection is made for both the lead tip and the ring connections and eliminates the need for a Y adapter. However, this configuration still provides simultaneous RV and LV sensing with associated limitations. The common consequence of simultaneous RV and LV sensing is double-counting of the prolonged native ventricular electrogram (VEGM)150,151. During pacing, RV and LV depolarization is synchronized and refractory periods are prolonged, preventing doublecounting. Any situation that inhibits ventricular pacing and permits emergence of the prolonged native VEGM (e.g., ventricular premature beats, loss of atrial tracking during sinus tachycardia, rapidly conducted AF, nonsustained or sustained VTA) may cause ventricular oversensing caused by double-counting.

I

aVR

V1

V4

II

aVL

V2

V5

III

aVF

V3

V6

VI

Figure 31-115  Ventricular Sense Response (VSR) operation. Third QRS complex (arrow) is a left ventricular VPD (note QS in lead I) that triggers VSR pacing. Note ventricular pacing stimulus is delivered almost 100 msec after onset of QRS.



979

31  Troubleshooting of Biventricular Devices

A S

A A A S S S

AA A SS S

V S

A A S R

A S

A R

A R

A S

A S

V S

V S

A A R S

V S

A A A A S S S S

V S

V S

V S

A R

B V

A A S R

A AM R SS

B V

B V

A A S R

B V

A A S R

A A A A R R S R

A S

B V

A A A S S S

V S

V S

A R

A A R S

B V

A S

A S

A R

A A A A R R S R

B V

B V

B V

A A S S

A S

V S

A A A A A A A A R S R R R R R R

B V

A S

V S

B V

A A R S

B V

A A A A S S S S

A A A R S R

B B V V conducted AF response ON

A A S R

B V

A A AA S S SS

V S

A A S R

B V

Mode switch

A R

A A A A S S S S

A A A A A A A A S R R S R R S R

V S

A S

A S

A S

A R

B V

A A A R S R

B V

A A A A A R R S R R

B V

Figure 31-116  Combined effects of VSR and Conducted AF Response on ventricular pacing during AF with intact AV conduction. Top, Programmed mode is VVI 30 bpm. Note AF with intact AV conduction and absence of ventricular pacing. Middle, Programmed mode is VVI 30 bpm with Ventricular Sense Response (VSR) “on.” Note delivery of biventricular pacing without any increase in ventricular rate. Bottom, Programmed mode is DDD 30 bpm with VSR and Conducted AF Response “on.” Note increase in ventricular pacing rate immediately after mode switch (MS marker) occurs, which initiates Conducted AF Response operation and VSR pacing during PVC (5th complex from left).

Far-field sensing of atrial activity is more likely when the LV lead is close to the AV groove, caused by either coronary venous anatomy or lead displacement from a more distal position within a venous branch. Rarely, atrial oversensing from a nondisplaced integrated bipolar RV lead may cause inhibition of ventricular pacing and double-counting.156 The options for eliminating ventricular double-counting in nondedicated CRT-P and CRT-D systems that achieve parallel dual cathodal sensing with a Y adapter are limited and mostly unsatisfactory. In one small series, 36% of patients had one or more inappropriate shocks (range, 1-64 per patient) caused by double-counting, over a mean follow-up of 13 ±7 months.96 With the exception of misclassification of true VT as VF, double-counting of the native VEGM during conducted supraventricular rhythms caused all inappropriate therapies. This could be overcome only by interrupting AV conduction with catheter ablation or disconnection of the Y-adapted LV lead, since CRT-D pulse generators with dedicated univentricular sensing were unavailable. Theoretically, manipulation of the ventricular blanking period could reduce ventricular double-counting in some situations with nondedicated CRT-P/D systems. Manufacturer-specific differences in programmable postventricular sense blanking periods in conventional ICDs may be useful in this regard, but a common concern is true VT/VF detection failure due to pseudo–ventricular undersensing when the blanking period is maximally extended. In some cases, decreasing the programmed ventricular sensitivity may reduce ventricular doublecounting if the later of the RV and LV electrograms has significantly

lower amplitude than the earlier EGM. This approach mandates validation of VF sensing and detection at the reduced ventricular sensitivity and is generally undesirable. Second- and third-generation dedicated CRT-P and CRT-D generators have independent ventricular ports for differential pacing output and timing, but restrict ventricular sensing to the RV or LV lead alone, depending on programmability. Removing the Y adapter and replacing the generator with one that uses single-site (typically RV) sensing exclusively eliminates the potential complications of BiV sensing. Fortunately, these systems are no longer in place, and this problem is mostly of historical interest. In dedicated CRT systems, double-counting of the prolonged native VEGM is eliminated by univentricular sensing, which is either hardwired (RV) or programmable (RV or LV). Accordingly, an interventricular refractory period is not necessary, although it is provided in some dedicated CRT-P/D systems that permit selection of BiV sensing. However, double-counting of the far-field atrial and near-field ventricular EGM can still occur during (univentricular) LV sensing when the LV lead is close to the AV groove because of displacement or coronary venous anatomy. In this situation, reprogramming univentricular RV sensing resolves the double-counting problem but does not address LV lead displacement as the cause. Newer bipolar or dual cathodal LV leads will probably not reduce the likelihood of far-field atrial oversensing in nondisplaced leads because the proximal electrode is closer to the AV groove. The incidence of LV lead dislodgment is considerably higher than right-sided endocardial leads and has a reported incidence of 5% to

980

SECTION 4  Follow-up and Programming

Capture threshold (V)

3.5 3 2.5 2 1.5 1 0.5 0 1

5

10

15

20

25

30

35

Months after implantation 35

2 1.6 1.4 1.2

30 377 347 371 345 356

334

253

177

154

97

25 20

1 15

0.8 0.6

R wave (mV)

Stimulation threshold (volts)

1.8

10

0.4

Stimulation threshold R wave

0.2 0 0

200

400

600

800

1000

5 0 1200

Days Figure 31-117  Chronic thresholds with different LV lead designs. Top, Comparison of chronic LV capture thresholds for surgical epicardial, stylet-driven (shaped) coronary venous, and over-the-wire (OTW) first-generation coronary venous leads. Bottom, Chronic LV capture thresholds and local LV EGM amplitude using a third-generation activefixation coronary venous LV pacing lead. (Top modified from Daoud E, et al: Implantation techniques and chronic lead parameters of biventricular pacing dual-chamber defibrillators. J Cardiovasc Electrophysiol 13:964-970, 2002; bottom modified from Crossley GH et al: Chronic performance of an active fixation coronary sinus lead. Heart Rhythm 7:472-478, 2010.)

10% in larger studies.116,119,157 Typically, RA leads dislodge onto the floor of the right atrium and RV leads dislodge toward the inflow of the right ventricle. LV leads typically dislodge into the main body of the coronary sinus, and less often into the right atrium. Ineffectual LV pacing stimuli may cause RV oversensing and inhibit pacing output, causing syncope in pacemaker-dependent patients. NON–PACING OPERATION–RELATED COMPLICATIONS Ventricular Proarrhythmia During Left Ventricular Pacing Small studies suggest that CRT might reduce the likelihood of inducible or spontaneous ventricular arrhythmia in susceptible patients.158,159 The VENTAK CHF study dubiously reported a reduction in spontaneous ventricular arrhythmias during 3 months of CRT on versus off in 32 patients who served as their own controls.160 The short duration of follow-up, small number of patients, and stochastic nature of arrhythmia recurrence render these data inconclusive. The magnitude of the reduction in sudden death with CRT-P alone in the CARE-HF Trial was similar to that recorded in primary prevention ICD trials and

implies that the positive effects of CRT reduced the risk of lifethreatening VTA.161 This concept has not been confirmed in large, randomized controlled trials (RCTs) of CRT-D where no significant difference in the incidence or frequency of adjudicated VTA between patients randomized to CRT on or CRT off was observed.116,157,162 For example, in the VENTAK CHF/CONTAK CD study, 15% of patients randomized to CRT received appropriate VTA therapies versus 16% of patients randomized to no CRT.162 When excluding patients who had no VTA episodes, those patients randomized to CRT had a median of 2.5 episodes while those randomized to “no CRT” had a median of two episodes during the therapy evaluation phase. During the 6-month randomization period in MIRACLE ICD, 26% of patients in the control group versus 22% in the CRT group had at least one spontaneous episode of VTA (P = 0.47).157 In patients with spontaneous VTA, those randomized to CRT had 0.39 VT/VF episodes per month, versus 0.41 episodes per month in those randomized to no CRT. Additional analysis of MIRACLE ICD reinforced these observations with regard to overall detected VTA.163 There was no difference by randomization in the proportion of patients experiencing episodes or the cycle lengths of the episodes during the randomization period. For primary prevention patients, 18% of those randomized to CRT off had at least one appropriately detected VTA episode, versus 14% with CRT on, with average cycle lengths of 285 msec and 291 msec, respectively. For secondary prevention patients, 28% of those randomized to CRT off had at least one episode compared to 27% with CRT on, with average cycle lengths of 352 msec and 361 msec, respectively. Nonetheless, an important question is whether pacing site-specific changes in ventricular activation might facilitate reentry and initiation of VTA under certain conditions. Initiation of VT by LV pacing but not RV pacing, or from one LV pacing site but not another, implies that local tissue anisotropy might affect the ability of site-specific stimulation wavefronts to interact with the reentrant VT circuit164,165 (Figs. 31-121 and 31-122). Additionally, the sudden alteration in LV activation sequence from endocardial to epicardial and reversal of wavefront direction from left to right might affect arrhythmogenesis. Stimulator model: InSync 8040

Serial number: PIN633204

Jul 12, 2002 09:45

Rate (ppm)

Thoracotomy OTW Shaped

4

High rate epis-V. data 102 seconds

>300 250 200 150 100 50 0

DR

–4 –2

0

2

22 24 26 28

212 214 216 218

Beats Sensed event Paced event V. EGM 2.35 seconds of EGM Figure 31-118  Ventricular double-counting of nonsustained VT in nondedicated CRT-D system. Spurious high-rate ventricular episode with stored EGM caused by loss of CRT and ventricular double-counting of the native ventricular BiV EGM. Note two components of ventricular EGM (first deflection is RV activation, second deflection is LV activation). Note characteristic W appearance resulting from oscillation of cycle lengths caused by sensing of both components of the prolonged biventricular EGM.



981

31  Troubleshooting of Biventricular Devices

II III

IV

720 A P

7 2 0

720 V P

6 7 0

A P

A R

1060

FF SS 1 3 0

5 3 0

FF SS 1 3 0

4 6 0

A R

1000 FF SS 1 3 0

3 6 0

FF SS 1 3 0

A R

1120

3 4 0

FF SS 1 3 0

3 6 0

FF SS 1 3 0

3 6 0

A R

850 FF FF SS SS 1 3 0

2 9 0

1 2 0

3 3 0

A R

820

FF FF FF SS SS SS 1 3 0

1 3 0

2 9 0

3 7 0

A R

850

1 3 0

3 2 0

FF SS 1 3 0

3 1 0

A R

840

FF FV SS DS 1 2 1 3 6 2 0 0 0

3 2 0

A R

830

A R

830

VV VV VV VV SS SS SS SS 1 2 1 2 3 4 2 6 0 0 0 0

1 2 2 8 0 0

1 2 0

3 2 0

A R

840

VV VV V SS SS S 1 3 0

2 7 0

1 2 0

2 8 0

1 2 0

Detection Figure 31-119  Ventricular double-counting during VT on stored EGM in nondedicated CRT-D system. Top, Telemetry strip of nonsustained interrupting biventricular pacing. Bottom, Corresponding stored single-channel EGM and marker channel for the same event. Note only atrial EGM is stored. Double-counting of each VT event (marked as VS-FS or FS-FS) results in misclassification and detection as VF.

Recent studies have shown that pacing-site–dependent changes in ventricular activation sequence can alter ventricular repolarization and refractoriness.166,167 Medina-Ravell et al.166 demonstrated that LV epicardial and BiV pacing caused significant increases in the JT and QTc intervals (Fig. 31-123), and LV pacing increased transmural dispersion of repolarization in humans with systolic heart failure. In a small number of patients, QT prolongation and spontaneous polymorphic VT (torsades de pointes) occur within hours of initiating BiV pacing (Figs. 31-124 and 31-125), and were completely suppressed by RV-only endocardial pacing. In animal experiments, electrical heterogeneity within the LV wall is amplified when the normal direction of activation is reversed (e.g., switching from endocardial to epicardial pacing). The longest action potential durations (APDs) occur in the midepicardial (M) cells, which are responsible for transmural dispersion of repolarization (TDR). The TDR can be measured as the time difference from T-wave peak to

Figure 31-120  Ventricular triple-counting in nondedicated CRT-P system. Simultaneous recordings of (top to bottom) surface ECG, marker channel, and real-time atrial EGM. The spontaneous rhythm is 2 : 1 AV block. The nondisplaced LV lead senses the late portion of the P wave because of its proximity to the AV groove (note VS and AS are nearly merged) resulting in ventricular pacing inhibition. Alternating P waves conduct resulting in emergence of the prolonged native ventricular EGM and ventricular double-counting. Thus, there are three ventricular sensed events marked for each conducted sinus event: the first (VS) is the farfield atrial signal, the second (VR) and third (VR) are the two components of the “split” ventricular EGM. (From Lipchenca I et al: Inhibition of biventricular pacemakers by oversensing of far-field atrial depolarization. Pacing Clin Electrophysiol 25:365-367, 2002.)

T-wave end on the surface ECG. Epicardial activation increases the TDR because the epicardial APD activates and repolarizes earlier, whereas the M-cells with longest APD repolarize later compared with endocardial activation, probably related to directional differences in tissue resistivity. Delayed activation and repolarization of M cells, coupled with earlier activation and repolarization of epicardial cells, results in QT prolongation, increased TDR, and genesis of torsades de pointes.167 The clinical characteristics of VTA-proarrhythmia during CRT are somewhat defined. Onset is generally rapid, within minutes (polymorphic VT/VF) to days (monomorphic VT) after initiating BiV pacing.164,165,168,169 There is a tendency to VTA storm, which occurred in 4% of patients after a mean 16 days of BiV pacing in one series. Without exception, VTA-proarrhythmia during CRT is characteristically unresponsive to antiarrhythmic drugs, ceases with deactivation of LV pacing, and in some patients has been successfully treated with catheter ablation to maintain CRT safely.169

[ 0.1 mV/mm

A S

NNEL

mV/mm

A S

VVV SRR

A.EGM

A S

V S

A S

VVV SRR

A S

V S

A S

VVV SRR

0.2 mV/mm

V S

982

SECTION 4  Follow-up and Programming

I II III aVR aVL aVF I II III aVR aVL aVF Figure 31-121  Site-specific effects of LV and RV pacing on VT initiation and termination. Top panel, Reproducible initiation of monomorphic VT during LV, but not RV or BV pacing threshold determination. Bottom panel, Reproducible overdrive pacing termination of induced monomorphic VT by RV, but not LV pacing. (Modified from Guerra J, Wu J, Miller JM, Groh WJ: Increase in ventricular tachycardia frequency after biventricular implantable-cardioverter defibrillator upgrade. J Cardiovasc Electrophysiol 14:1245-1124, 2003.)

A

Initial LV lead in AIV. No VT for >1 year

B

LV lead dislodgment, heart failure exacerbation

C

New LV lead placed in lateral vein. Incessant MMVT 72 hours later

II

III

aVR Figure 31-122  Site-specific initiation of VT during BV pacing. A, Initial left ventricular (LV) lead in proximal anterior interventricular vein. No ventricular tachycardia (VT) was recorded for more than 1 year after implant. B, Late LV lead dislodgement. C, New LV lead in lateral vein. Incessant monomorphic VT (bottom) emerged 72 hours later. VT was eliminated by deactivating LV pacing. (Modified from Shukla G, et al: Potential proarrhythmic effect of biventricular pacing: fact or myth? Heart Rhythm 2:951-956, 2005.)



31  Troubleshooting of Biventricular Devices

983

700

JTc and QTc (msec)

600

QTc JTc

500 400 300 200 100 Baseline

RVEndoP

BiVP

LVEpiP

Figure 31-123  Effect of biventricular (BiV) and left ventricular (LV) pacing on ventricular repolarization (QTc interval). Increase in QTc is greatest during LV-only epicardial pacing (LVEpiP). (From Medina-Ravell VA, et al: Effect of epicardial or biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization. Circulation 107:740-746, 2003.)

RVEndoP QT = 485 msec

LVEpiP QT = 580 msec

A

1

2

3

4

48

49

50

51

Continue LVEpiP

B

39

40

41

42

43

44

45

46

47

Continue LVEpiP

C

53

54

55 RVEndoP QT = 485 msec

BIVP QT = 540 msec

D Figure 31-124  Polymorphic VT (torsades de pointes) during BV pacing. Note QT is 585 msec during LV pacing vs. 485 msec during RV pacing. Polymorphic ventricular tachycardia is initiated by short-long-short sequence during LV pacing. (From Medina-Ravell VA, et al: Effect of epicardial or biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization. Circulation 107:740-746, 2003.)

984

SECTION 4  Follow-up and Programming

ICD shock II III 2v

Short-long-short onset II III 2v

II III 2v Figure 31-125  Ventricular tachycardia (VT). Repetitive polymorphic VT 6 hours after initiation of BiV pacing in a woman with dilated cardiomyopathy, LBBB, but no history of VTA or syncope. The two sustained events (top and middle tracings) occurred within 6 seconds of one another and were terminated by shocks. Polymorphic VT is initiated by a short-long-short sequence (middle tracing). Note VPD salvos in the bottom tracing. No further events have occurred over the subsequent 7 years despite uninterrupted CRT.

REFERENCES 1. Sakamoto SI, Nitta T, Ishii Y, et al: Interatrial electrical connections: the precise location and preferential conduction. J Cardiovasc Electrophysiol 16:1077-1086, 2005. 2. Bailin SJ, Adler S, Giudici M: Prevention of chronic atrial fibrillation by pacing in the region of Bachmann’s bundle: results of a multicenter randomized trial. J Cardiovasc Electrophysiol 12:912-917, 2001. 3. Hettrick DA, Mittelstadt JR, Kehl F, et al: Atrial pacing lead location alters the hemodynamic effects of atrial-ventricular delay in dogs with pacing induced cardiomyopathy. Pacing Clin Electrophysiol 26:853-861, 2003. 4. Mabo P, Pouillot C, Kermarrec A, et al: Lack of physiological adaptation of the atrioventricular interval to heart rate in patients chronically paced in the AAIR mode. Pacing Clin Electrophysiol 14:2133-2142, 1991. 5. Grant SC, Bennett DH: Atrial latency in a dual-chambered pacing system causing inappropriate sequence of cardiac chamber activation. Pacing Clin Electrophysiol 15:116-118, 1992. 6. Chirife R, Ortega DF, Salazar AI: Nonphysiological left heart AV intervals as a result of DDD and AAI “physiological” pacing. Pacing Clin Electrophysiol 14:1752-1756, 1991. 7. Sweeney MO, Ellenbogen KA, Tang ASL, et al: Severe atrioventricular decoupling, uncoupling and ventriculoatrial coupling during enhanced atrial pacing: incidence, mechanisms and implications for minimizing right ventricular pacing in ICD patients. J Cardiovasc Electrophysiol 19:1175-1180, 2008. 8. Durrer D, Van Dam RT, Freud GE, et al: Total excitation of the isolated human heart. Circulation 41:899-912, 1970. 9. Wyman BT, Hunter WC, Prinzen FW, et al: Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction. Am J Physiol 282:H372-H379, 2002. 10. Wiggers C: The muscular reactions of the mammalian ventricles to artificial surface stimuli. Am J Physiol 73:346-378, 1925. 11. Prinzen FW, Peschar M: Relation between the pacing induced sequence of activation and left ventricular pump function in animals. Pacing Clin Electrophysiol 25:484-498, 2002. 12. Verbeek XA, Vernooy K, Peschar M: Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block. J Am Coll Cardiol 42:558567, 2003. 13. Vernooy K, Verbeek XA, Cornelussen RN, et al: Calculation of effective VV interval facilitates optimization of AV delay and VV interval in cardiac resynchronization therapy. Heart Rhythm 4:75-82, 2006. 14. Vassallo JA, Cassidy DM, Miller JM, et al: Left ventricular endocardial activation during right ventricular pacing: effect of underlying heart disease. J Am Coll Cardiol 7:1228-1233, 1986.

15. Vassallo JA, Cassidy DM, Machlinski FE, et al: Endocardial activation of left bundle branch block. Circulation 69:914-923, 1984. 16. Rodriguez LM, Timmermans C, Nabar A, et al: Variable patterns of septal activation in patients with left bundle branch block. J Cardiovasc Electrophysiol 14:135-141, 2003. 17. Lambiase PD, Rinaldi A, Hauck J, et al: Non-contact left ventricular endocardial mapping in cardiac resynchronisation therapy. Heart 90:44-51, 2004. 18. Auricchio A, Fantoni C, Regoli F, et al: Characterization of left ventricular activation in patients with heart failure and left bundle branch block. Circulation 109:1133-1139, 2004. 19. Fung JW, Yu CM, Yip G, et al: Variable left ventricular activation pattern in patients with heart failure and left bundle branch block. Heart 90:3-4, 2004. 20. Jia P, Ramanathan C, Ghanem RN, et al: Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 3:296-310, 2006. 21. Bax JJ, Ansalone G, Breithardt OA, et al: Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical use? A critical appraisal. J Am Coll Cardiol 44:1-9, 2004. 22. Grines CL, Boshore TW, Boudoulas H, et al: Functional abnormalities in isolated left bundle branch block: the effect of interventricular asynchrony. Circulation 79:845-853, 1989. 23. Varma N: Left ventricular conduction delays induced by right ventricular apical pacing: effect of left ventricular dysfunction and bundle branch block. J Cardiovasc Electrophysiol 19:114-122, 2008. 24. Kanzaki H, Bazaz R, Schwartzman D, et al: A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy: insights from mechanical activation strain mapping. J Am Coll Cardiol 44:1619-1625, 2004. 25. Ypenburg C, Lancellotti P, Tops LF, et al: Acute effects of initiation and withdrawal of cardiac resynchronization therapy on papillary muscle dyssynchrony and mitral regurgitation. J Am Coll Cardiol 50:2071-2077, 2007. 26. Leclercq C, Faris O, Runin R, et al: Systolic improvement and mechanical resynchronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block. Circulation 106:1760-1763, 2002. 27. Lardo AC, Abraham TP, Kass DA: Magnetic resonance imaging assessment of ventricular dyssynchrony: current and emerging concepts. J Am Coll Cardiol 46:2223-2228, 2005. 28. Wyman BT, Hunter WC, Prinzen FW, McVeigh ER: Mapping propagation of mechanical activation in the paced heart with MRI tagging. Am J Physiol 276:H881-H891, 1999.

29. Prinzen FW, Hunter WC, Wyman BT, McVeigh E: Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol 33:1735-1742, 1999. 30. Baller D, Wolpers HG, Zipfers J, et al: Comparison of the effects of right atrial, right ventricular apex, and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency: a laboratory investigation. Pacing Clin Electrophysiol 11:394-403, 1988. 31. Nahlawi M, Waligora M, Spies SM, et al: Left ventricular function during and after right ventricular pacing. J Am Coll Cardiol 44:1883-1888, 2004. 32. Zile M, Blaustein A, Shimizu G, et al: Right ventricular pacing reduces the rate of left ventricular relaxation and filling. J Am Coll Cardiol 10:702-709, 1987. 33. Zhou Q, Henein M, Coats A, Gibson D: Different effects of abnormal activation and myocardial disease on left ventricular ejection and filling times. Heart 84:272-276, 2000. 34. Prinzen FW, Augustijn CH, Arts T, et al: Redistribution of myocardial fiber strain and blood flow by asynchronous activation. Am J Physiol (259):H300-H308, 1990. 35. Delhaas T, Arts T, Prinzen FW, Reneman RS: Regional fiber stress–fiber strain as estimate of regional oxygen demand in the canine heart. J Physiol (Lond) 477:481-496, 1994. 36. Vernooy K, Verbeek XA, Peschar M, et al: Left bundle branch block induces ventricular remodeling and functional septal hypoperfusion. Eur Heart J 26:91-98, 2005. 37. Nowak B, Sinha AM, Schaefer WM, et al: Cardiac resynchronization therapy homogenizes myocardial glucose metabolism and perfusion in dilated cardiomyopathy and left bundle branch block. J Am Coll Cardiol 41:1523-1528, 2003. 38. Tse H-F, Lau CP: Long-term effect of right ventricular pacing on myocardial perfusion and function. J Am Coll Cardiol 29:744749, 1997. 39. Nielsen JC, Bottcher M, Nielsen TT, et al: Regional myocardial blood flow in patients with sick sinus syndrome randomized to long-term single chamber or dual chamber pacing: effect of pacing mode and rate. J Am Coll Cardiol 35:1453-1461, 2000. 40. Tse HF, Yu C, Wong KK, et al: Functional abnormalities in patients with permanent right ventricular pacing: the effect of sites of electrical stimulation. J Am Coll Cardiol 40:1451-1458, 2002. 41. Ten Cate TJF, Visser FC, Panhuyzen-Goedkoop NM, et al: Pacemaker-related myocardial perfusion defects worsen during higher pacing rate and coronary flow augmentation. Heart Rhythm 2:1058-1063, 2005.



31  Troubleshooting of Biventricular Devices 42. Vernooy K, Cornelussen RN, Verbeek XA, et al: Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts. Eur Heart J 28:2148-2155, 2007. 43. Lee MA, Dae MW, Langberg JL, et al: Effects of long-term right ventricular pacing on left ventricular perfusion, innervation, function and histology. J Am coll Cardiol 24:225-232, 1994. 44. Van Oosterhout MFM, Prinzen FW, Arts T, et al: Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall. Circulation 98:588-595, 1998. 45. Spragg DD, Akar FG, Helm RH, et al: Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts. Cardiovasc Res 67:77-86, 2005. 46. Spragg DD, Leclercq C, Loghmani M, et al: Regional alterations in protein expression in the dyssynchronous failing heart. Circulation 108:929-932, 2003. 47. Karpawhich PP, Justice CD, Cavitt DK, Chang CH: Developmental sequelae of fixed rate ventricular pacing in the immature canine heart: an electrophysiologic, hemodynamic and histopathologic evaluation. Am Heart J 119:1077-1083, 1990. 48. Wecke L, Rubulis A, Lundahl G, et al: Right ventricular pacinginduced electrophysiologic remodeling in the human heart and its relationship to cardiac memory. Heart Rhythm 4:1477-1486, 2007. 49. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al: Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 23:2932-2937, 2003. 50. Sweeney MO, Bank AJ, Nsah E, et al: Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 357:1000-1008, 2007. 51. DAVID Trial Investigators: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. 52. Steinberg JS, Fischer A, Wang P, et al: The clinical implications of cumulative right ventricular pacing in the Multicenter Automatic Defibrillator Trial II. J Cardiovasc Electrophysiol 16:359365, 2005. 53. Nielsen JC, Kristensen L, Andersen HR, et al: A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 42:614-623, 2003. 54. Goldenberg I, Moss AJ, Hall WJ, et al; Causes and consequences of heart failure after prophylactic implantation of a defibrillator in the Multicenter Automatic Defibrillator Implantation Trial II. MADIT-II Investigators. Circulation 113:2810-2817, 2006. 55. Hayes JJ, Sharma AD, Love JC, et al: Abnormal conduction increases risk of adverse outcomes from right ventricular pacing. DAVID Investigators. J Am Coll Cardiol 48:1628-1633, 2006. 56. Smit MD, Van Dessel PF, Nieuwland W, et al: Right ventricular pacing and the risk of heart failure in implantable cardioverterdefibrillator patients. Heart Rhythm 3:1397-1403, 2006. 57. Zannad F, Huvelle E, Dickstein K, et al: Left bundle branch block as a risk factor for progression to heart failure. Eur J Heart Fail 9:7-14, 2007. 58. Chen L, Hodge D, Jahangir A, et al: Preserved left ventricular ejection fraction following atrioventricular junction ablation and pacing for atrial fibrillation. J Cardiovasc Electrophysiol 19:19-27, 2008. 59. Breithardt OA, Sinha AM, Schwammenthal E, et al: Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol 203:765-770, 2003. 60. Kanzaki H, Bazaz R, Schwartzman D, et al: A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy: insights from mechanical activation strain mapping. J Am Coll Cardiol 44:1619-1625, 2004. 61. Otsuji Y, Gilon D, Jiang L, et al: Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering. J Am Coll Cardiol 32:398404, 1998. 62. Nof E, Glickson M, Bar-Lev D, et al: Mechanism of diastolic mitral regurgitation in candidates for cardiac resynchronization therapy. Am J Cardiol 97:1611-1614, 2006. 63. Lee SJ, McCullouch C, Mangat I, et al: Isolated bundle branch block and left ventricular dysfunction. J Card Fail 9:87-92, 2003. 64. Blanc JJ, Fatemi M, Bertault V, et al: Evaluation of left bundle branch block as a reversible cause of non-ischaemic dilated cardiomyopathy with severe heart failure: a new concept of left ventricular dyssynchrony-induced cardiomyopathy. Europace 7:604-610, 2005. 65. Castellant P, Fatemi M, Bertault-Valls V, et al: Cardiac resynchronization therapy: “nonresponders” and “hyperresponders.” Heart Rhythm 5:193-197, 2008. 66. Stenestrand U, Tabrizi F, Lindback J, et al: Comorbidity and myocardial dysfunction are the main explanations for the higher 1-year mortality in acute myocardial infarction with left bundlebranch block. Circulation 110:1896-1902, 2004. 67. Kass DA, Chen CH, Curry C, et al: Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 99:1567-1573, 1999. 68. Auricchio A, Stellbrink C, Block M, et al: Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing

Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group. Circulation 99:2993-3001, 1999. 69. Nelson GS, Berger RD, Fetics BJ, et al: Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle branch block. Circulation 105:3053-3059, 2000. 70. Breithardt OA, Stellbrink C, Kramer AP, et al: Path-Chf Study Group. Echocardiographic quantification of left ventricular asynchrony predicts an acute hemodynamic benefit of cardiac resynchronization therapy. J Am Coll Cardiol 40(3):536-545, 2002. 71. Leclercq C, Walker S, Linde C, et al: Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J 23:1780-1787, 2002. 72. Sweeney MO, van Bommel RJ, Schalij MJ, et al: Analysis of ventricular activation using surface electrocardiography to predict left ventricular reverse volumetric remodeling during cardiac resynchronization therapy. Circulation 121:626-634, 2010. 73. Steendijk P, Tulner SA, Bax JJ, et al: Hemodynamic effects of long-term cardiac resynchronization therapy: analysis by pressure-volume loops. Circulation 113:1295-1304, 2006. 74. Yu CM, Chau E, Sanderson EJ, et al: Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneous delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 105:438-445, 2002. 75. Van Gelder BM, Bracke FA, et al: Morphology of the RV electrogram during LV pacing is related to the hemodynamic effect in cardiac resynchronization therapy. Pacing Clin Electrophysiol 30:1381-1387, 2007. 76. Van Gelder BM, Bracke FA, Van Der Voort PH, Meijer A: Optimal sensed atrioventricular interval determined by paced QRS morphology. Pacing Clin Electrophysiol 30:476-481, 2007. 77. Nelson GS, Curry CW, Wyman BT, et al: Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation 101:2703-2709, 2000. 78. Verbeek XA, Auricchio A, Yu Y, et al: Tailoring cardiac resynchronization therapy using interventricular asynchrony. Validation of a simple model. Am J Physiol Heart Circ Physiol 290:H968H977, 2006. 79. Van Gelder BM, Bracke FA, Meijer A, Pijls NHJ: The hemodynamic effect of intrinsic conduction during left ventricular pacing as compared to biventricular pacing. J Am Coll Cardiol 46:2305-2310, 2005. 80. Sawhney NS, Waggoner AD, Garhwal S, et al: Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy. Heart Rhythm 1:562-567, 2004. 81. Leon AR, Abraham WT, Brozena S, et al: Cardiac resynchronization with sequential biventricular pacing for the treatment of moderate-to-severe heart failure. InSync III CSI. J Am Coll Cardiol 46:2298-2304, 2005. 82. Boriani G, Muller C, Seidl K, et al: Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. The Resynchronization for the Hemodynamic Treatment for Heart Failure Management II Implantable Cardioverter Defibrillator (RHYTHM II ICD) study. Am Heart J 151:1050-1058, 2006. 83. St John Sutton MG, Plappert T, Abraham WT, et al: Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. MIRACLE Study Group. Circulation 105:1985-1990, 2003. 84. Sogaard P, Egeblad H, Kim W, et al: Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during cardiac resynchronization therapy. J Am Coll Cardiol 40:723-730, 2002. 85. Lau CP, Yu CM, Chau E, et al: Reversal of left ventricular remodeling by synchronous biventricular pacing in heart failure. Pacing Clin Electrophysiol 23:1722-1725, 2000. 86. Pitzalis MD, Iacoviello M, Romito R, et al: Ventricular asynchrony predicts a better outcome in patients with chronic heart failure receiving cardiac resynchronization therapy. J Am Coll Cardiol 45:65-69, 2005. 87. Saxon LA, De Marco T, Schafer J, et al: Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling. Circulation 105:1304-1310, 2002. 88. Yu CM, Fung JWH, Chan CK, et al: Comparison of efficacy of reverse remodeling and clinical improvement for relatively narrow and wide QRS complexes after cardiac resynchronization therapy for heart failure. J Cardiovasc Electrophysiol 15:10581065, 2004. 89. Yu CM, Gorscan J, Bleeker GB, et al: Usefulness of tissue Doppler velocity and strain dyssynchrony for predicting left ventricular reverse remodeling response after cardiac resynchronization therapy. Am J Cardiol 100:1274-1281, 2007. 90. Bleeker GB, Mollema SA, Holman ER, et al: Left ventricular resynchronization is mandatory for response to cardiac resynchronization therapy: analysis in patients with echocardiographic evidence of left ventricular dyssynchrony at baseline. Circulation 116:1440-1448, 2007. 91. Bax JJ, Bleeker GB, Marwick TH, et al: Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 44:1834-1840, 2004.

985

92. Yu C-M, Bleeker GB, Fung JW-H, et al: Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 112:1580-1586, 2005. 93. Ypenburg C, van Bommel RJ, Borleffs CJW, et al: Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. J Am Coll Cardiol 53:483-490, 2009. 94. Penicka M, Bartunek J, De Bruyne B, et al: Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography. Circulation 109:978-983, 2004. 95. Fantoni C, Raffa S, Regoli F, et al: Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure. J Am Coll Cardiol 46:1875-1882, 2005. 96. Kanagaratnam L, Pavia S, Schweikert R, et al: Matching approved “nondedicated” hardware to obtain biventricular pacing and defibrillation: feasibility and troubleshooting. Pacing Clin Electrophysiol 25:1066-1071, 2002. 97. Bulava A, Ansalone G, Ricci R, et al: Triple-site pacing in patients with biventricular device-incidence of the phenomenon and cardiac resynchronization benefit. J Interv Card Electrophysiol 10:37-45, 2004. 98. Crossley GH, Mead H, Kleckner K, et al: Automated left ventricular capture management. Pacing Clin Electrophysiol 30: 1190-1200, 2007. 99. Ho R, Mark GE, Rhim ES, Shorrock SM: Pseudo crosstalk behavior in a patient with atrio-ventricular block and implanted biventricular defibrillator. Pacing Clin Electrophysiol 30:15551557, 2007. 100. Sweeney MO, Ruetz LL, Belk P, et al: Bradycardia pacing induced short-long-short sequences at the onset of ventricular tachyarrhythmias: a possible mechanism of proarrhythmia? J Am Coll Cardiol 50:614-622, 2007. 101. St John Sutton MG, Plappert T, Hilpisch KE, et al: Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circulation 113:266-272, 2006. 102. Vernooy K, Cornelussen RNM, Verbeek XA, et al: Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts. Eur Heart J 28:2148-2155, 2007. 103. Das MK, Suradi H, Maskoun W, et al: Fragmented wide QRS on a 12-lead ECG: a sign of myocardial scar and poor prognosis. Circ Arrhythmia Electrophysiol 1:258-268, 2008. 104. Ypenburg C, Roes SD, Bleeker GB, et al: Effect of total scar burden on contrast-enhanced magnetic resonance imaging on response to cardiac resynchronization therapy. Am J Cardiol 99:657-660, 2007. 105. Strauss DG, Selvester RH, Lima JAC, et al: ECG quantification of myocardial scar in cardiomyopathy patients with or without conduction defects: correlation with cardiac magnetic resonance and arrhythmogenesis. Circ Arrhythmia Electrophysiol 1:327-336, 2008. 106. Strauss DG, Selvester RH, The QRS complex—a biomarker that “images” the heart: QRS scores to quantify myocardial scar in the presence of normal and abnormal ventricular conduction. J Electrocardiol 42:85-96, 2009. 107. Giudici MC, Tigrett DW, Carlson JI, et al: Electrocardiographic patterns during pacing the great cardiac and middle cardiac veins. Pacing Clin Electrophysiol 30:1376-1380, 2007. 108. Ritter P, Padeletti L, Gillio-Meina L, et al: Determination of the optimal atrioventricular delay in DDD pacing: comparison between echo and peak endocardial acceleration measurements. Europace 1:126-130, 1999. 109. Kindermann M, Frölig G, Doerr T, Schieffer H: Optimizing the AV delay in DDD pacemaker patients with high degree AV block: mitral valve Doppler versus impedance cardiography. Pacing Clin Electrophysiol 20:2453-2462, 1997. 110. Meluzin J, Novak M, Mullerova J, et al: A fast and simple echocardiographic determination of the optimal atrioventricular delay in patients after biventricular stimulation. Pacing Clin Electrophysiol 27:58-64, 2004. 111. Auricchio A, Stellbrink C, Sack S, et al: Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Pacing Therapies in Congestive Heart Failure (PATHCHF) Study Group. J Am Coll Cardiol 39:2026-2033, 2002. 112. Butter C, Stellbrink C, Belalcazar A, et al: Cardiac resynchronization therapy optimization by finger plethysmography. Heart Rhythm 1:568-578, 2005. 113. Whinnet ZI, Briscoe C, Davies JER, et al: The atrioventricular delay of cardiac resynchronization can be optimized hemodynamically during exercise and predicted from resting measurements. Heart Rhythm 5:378-386, 2008. 114. Auricchio A, Kramer A, Spinelli J, et al: Can the optimum dosage of resynchronization therapy be derived from the intracardiac electrogram? J Am Coll Cardiol 39:124, 2002. 115. Gold MR, Niazi I, Giudici M, et al: A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy. J Cardiovasc Electrophysiol 18:490-496, 2007. 116. Bristow MR, Saxon LA, Boehmer J, et al: Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. Comparison of

986

SECTION 4  Follow-up and Programming

Medical Therapy Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. N Engl J Med 350:2140-2150, 2004. 117. Kerlan JE, Sawhney NS, Waggoner AD, et al: Prospective comparison of echocardiographic atrioventricular delay optimization methods for cardiac resynchronization therapy. Heart Rhythm 3:148-154, 2006. 118. Jansen AH, Bracke FA, van Dantzig JM, et al: Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 97:552-557, 2006. 119. Abraham WT, Fisher WG, Smith AL, et al: Cardiac resynchronization in chronic heart failure. MIRACLE Study Group. N Eng J Med 346:1845-1853, 2002. 120. Cazeau S, Leclercq C, Lavergne T, et al: Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. The Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. N Engl J Med 344:873-880, 2001. 121. Brandt J, Fahraeus T, Ogawa T, Schuller H: Practical aspects of rate adaptive atrial (AAI,R) pacing: clinical experiences in 44 patients. Pacing Clin Electrophysiol 14:1258-1264, 1991. 122. Bernheim A, Ammann P, Sticherling C, et al: Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing. J Am Coll Cardiol 45:1482-1487, 2005. 123. Gold MR, Niazi I, Giudici M, et al: Acute hemodynamic effects of atrial pacing with cardiac resynchronization therapy. J Cardiovasc Electrophysiol 20:894-900, 2009. 124. Bordachar P, LaFitte S, Reuter S, et al: Biventricular pacing and left ventricular pacing in heart failure: Similar hemodynamic improvement despite marked electromechanical differences. J Cardiovasc Electrophysiol 15:1342-1347, 2004. 125. Whinnett ZI, Davies JE, Willson K, et al: Haemodynamic effects of changes in AV and VV delay in cardiac resynchronisation therapy show a consistent pattern: Analysis of shape, magnitude and relative importance of AV and VV delay. Heart 92:16281634, 2006. 126. Auricchio A, Stellbrink C, Sack S, et al: Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Group PTiCHFP-CS. J Am Coll Cardiol 39:2026-2033, 2002. 127. Nelson GS, Berger RD, Fetics BJ, et al: Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundlebranch block. Circulation 102:3053-3059, 2000. 128. Ellenbogen KA, Gold MR, Meyer TE, et al: Primary results from the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial/Clinical perspective: a randomized trial comparing empirical, echocardiography-guided, and algorithmic atrioventricular delay programming in cardiac resynchronization therapy. Circulation 122(25):2660-2668, 2010. 129. Auricchio A, Stellbrink C, Sack S, et al: The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study. Am J Cardiol 83:130D-135D, 1999. 130. Meine M, Min X, Kordmann M, et al: EGM-based method for estimating optimal AV delay in cardiac resynchronization therapy. J Card Fail 10(suppl 4):74(206), 2004. 131. Baker JH, McKenzie J, Beau S, et al: Acute evaluation of programmer-guided AV/PV and VV delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dualchamber ICD implants. J Cardiovasc Electrophysiol 18:185-191, 2007 132. Knight BP, Desai A, Coman J, et al: Long-term retention of cardiac resynchronization therapy. J Am Coll Cardiol 44:72-77, 2004.

133. Richardson K, Cook K, Wang PJ, Al-Ahmad A: Loss of biventricular pacing: what is the cause? Heart Rhythm 2:110-111, 2005. 134. Brandt J, Fahraeus T, Schuller H: Far-field QRS complex sensing via the atrial pacemaker lead. I. Mechanism, consequences, differential diagnosis and countermeasures in AAI and VDD/DDD pacing. Pacing Clin Electrophysiol 11:1432-1438, 1988. 135. Brandt J, Fahraeus T, Schuller H: Far-field QRS complex sensing via the atrial pacemaker lead. II. Prevalence, clinical significance and possibility of intraoperative prediction in DDD pacing. Pacing Clin Electrophysiol 11:1540-1544, 1988. 136. Brandt J, Worzewski W: Far-field QRS complex sensing: prevalence and timing with bipolar atrial leads. Pacing Clin Electrophysiol 23:315-320, 2000. 137. Weretka S, Becker R, Hilbel T, et al: Far-field R wave oversensing in new dual-chamber ICDs: incidence, predisposing factors and clinical implications [abstract]. Pacing Clin Electrophysiol 23:571, 2000. 138. Johnson WB, Bailin SJ, Solinger B, et al: Frequency of inappropriate automatic pacemaker mode switching as assessed 6 to 8 weeks post implantation [abstract]. Pacing Clin Electrophysiol 19:720, 1996. 139. Frohlig G, Kinderman M, Heisel A, et al: Mode switch without atrial tachyarrhythmias [abstract]. Pacing Clin Electrophysiol 19:592, 1996. 140. Koplan BA, Kaplan AJ, Weiner S, et al: Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J Am Coll Cardiol 53:355-360, 2009. 141. Kamath GS, Cotiga D, Koneru JN, et al: The utility of 12-lead Holter monitoring in patients with permanent atrial fibrillation for the identification of nonresponders after cardiac resynchronization therapy. J Am Coll Cardiol 53:1050-1055, 2009. 142. Gasparini M, Auricchio A, Regoli F, et al: Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 48:734-743, 2006. 143. Daoud E, Kalbfleisch FJ, Hummel JD, et al: Implantation techniques and chronic lead parameters of biventricular pacing dual-chamber defibrillators. J Cardiovasc Electrophysiol 13:964970, 2002. 144. Storm C, Harsch M, DeBus B: InSync Registry: post market study. Progress Report No 7. Minneapolis, 2005, Medtronic. 145. Leon AR, Abraham WT, Curtis AB, et al: Safety of transvenous cardiac resynchronization system implantation in patients with chronic heart failure: combined results of over 2,000 patients from a multicenter study program. MIRACLE Study Program. J Am Coll Cardiol 46:2348-2356, 2005. 146. Sanchez-Quintana D, Cabrera JA, Climent V, et al: How close are the phrenic nerves to cardiac structures? Implications for cardiac interventionalists. J Cardiovasc Electrophysiol 16:309-313, 2005. 147. Gurevitz O, Nof E, Carasso S, et al: Programmable multiple pacing configurations help to overcome high left ventricular pacing thresholds and avoid phrenic nerve stimulation. Pacing Clin Electrophysiol 28:1255-1259, 2005. 148. Barold SS, Byrd CL: Cross-ventricular endless loop tachycardia during biventricular pacing. Pacing Clin Electrophysiol 24:18211823, 2001. 149. Berruezo A, Mont L, Scalise A, Brugada J: Orthodromic pacemaker-mediated tachycardia in a biventricular system without an atrial electrode. J Cardiovasc Electrophysiol 15:11001102, 2004. 150. Barold SS, Herweg B, Gallardo I: Double counting of the ventricular electrogram in biventricular pacemakers and ICDs. Pacing Clin Electrophysiol 26:1645-1648, 2003. 151. Garcia-Moran E, Mont L, Brugada J: Inappropriate tachycardia detection by a biventricular implantable cardioverter defibrillator. Pacing Clin Electrophysiol 25:123-124, 2002.

152. Schreieck J, Zrenner B, Kolb C, et al: Inappropriate shock delivery due to ventricular double detection with a biventricular pacing implantable cardioverter defibrillator. Pacing Clin Electrophysiol 24:1154-1157, 2001. 153. Lipchenca I, Garrigue S, Glikson M, et al: Inhibition of biventricular pacemakers by oversensing of far-field atrial depolarization. Pacing Clin Electrophysiol 25:365-367, 2002. 154. Taieb J, Benchaa T, Foltzer E, et al: Atrioventricular cross-talk in biventricular pacing: a potential cause of ventricular standstill. Pacing Clin Electrophysiol 25:929-935, 2002. 155. Oguz E, Akyol A, Okmen E: Inhibition of biventricular pacing by far-field left atrial activity sensing: case report. Pacing Clin Electrophysiol 25:1517-1519, 2002. 156. Vollmann D, Luthje L, Gortler G, Unterberg C: Inhibition of bradycardia pacing and detection of ventricular fibrillation due to far-field atrial sensing in a triple chamber implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 25:15131516, 2002. 157. Young JB, Abraham WT, Smith AL, et al: Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure. Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. JAMA 289:2685-2394, 2003. 158. Zagrodzky JD, Ramaswamy K, Page RL, et al: Biventricular pacing decreases the inducibility of ventricular tachycardia in patients with ischemic cardiomyopathy. Am J Cardiol 87:12081210, 2001. 159. Walker S, Levy T, Rex S, et al: Usefulness of suppression of ventricular arrhythmia by biventricular pacing in severe congestive cardiac failure. Am J Cardiol 86:231-233, 2000. 160. Higgins SL, Yong P, Scheck D, et al. Biventricular pacing diminishes the need for implantable cardioverter defibrillator therapy. J Am Coll Cardiol 36:824-827, 2000. 161. Cleland JGF, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. Cardiac Resynchronization—Heart Failure (CARE-HF) Study Investigators. N Engl J Med 352:1539-1549, 2005. 162. Higgins SL, Hummel JD, Niazi IK, et al: Cardiac resynchronization therapy for the treatment of heart failure and intraventricular conduction delay and malignant ventricular tachyarrhythmia. J Am Coll Cardiol 42:1454-1459, 2003. 163. Wilkoff B, Hess M, Young JD, Abraham WT: Differences in tachyarrhythmia detection and implantable cardioverterdefibrillator therapy by primary or secondary prevention indication in cardiac resynchronization therapy patients. J Cardiovasc Electrophysiol 15:1002-1009, 2004. 164. Guerra J, Wu J, Miller JM, Groh WJ: Increase in ventricular tachycardia frequency after biventricular implantablecardioverter defibrillator upgrade. J Cardiovasc Electrophysiol 14:1245-1247, 2003. 165. Shukla G, Chaudry M, Orlov M, et al: Potential proarrhythmic effect of biventricular pacing: fact or myth? Heart Rhythm 2:951956, 2005. 166. Medina-Ravell VA, Lankipalli RS, Yan GX, et al: Effect of epicardial or biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization. Circulation 107:740746, 2003. 167. Fish JM, Di Diego JM, Nesterenko V, Antzelevitch C: Epicardial activation of left ventricular wall prolongs QT interval and transmural dispersion of repolarization: implications for biventricular pacing. Circulation 109:2136-2142, 2004. 168. Medina-Ravell VA, Lankipalli RS, Yan G-X, et al: Effect of epicardial or biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization: does resynchronization therapy pose a risk for patients predisposed to long QT or torsade de pointes? Circulation 107:740-746, 2003. 169. Nayak HM, Verdino RJ, Russo AM, et al: Ventricular tachycardia storm after initiating biventricular pacing: incidence, clinical characteristics, management, and outcome. J Cardiovasc Electrophysiol 19:708-715, 2008.

32  32

Follow-up Monitoring of Cardiac Implantable Electronic Devices NIRAJ VARMA

C

ardiovascular implantable electronic devices (CIEDs) include cardiac pacemakers, implantable cardioverter-defibrillators (ICDs), and leadless devices such as implantable loop recorders and cardiovascular monitors. Implantation is indicated for treatment, diagnosis, and monitoring of bradycardia, tachycardia, and most recently, heart failure.1 Since their inception in 1958, the function of CIEDs and monitoring of patients have become more complex. Functional roles may overlap, and capabilities for ventricular tachyarrhythmia therapy, biventricular stimulation, and collection of heart failure monitoring data may be contained in a single device. Positive results from recent trials for prophylactic ICDs and cardiac resynchronization therapy (CRT) devices have driven an expansion of indications and spurred an exponential increase in CIED use. An estimated 1 million devices were implanted in 2007, and this number will increase as their range and versatility increase.2 Current CIEDs have a sophisticated capacity to identify, quantify, and present diagnostic data regarding their own performance as well as the patient’s condition (e.g., arrhythmias, hemodynamic parameters). Concomitantly, improved CIED monitoring mechanisms are needed for timely retrieval of important diagnostic data and rigorous assessment of system performance to ensure patient safety. However, CIED follow-up has not been standardized. Collective experience has led to the evolution of specialized CIED follow-up clinics staffed by trained physicians and device specialists. Recently, data to guide postimplant follow-up have emerged from prospective trials testing conventional follow-up as well as the value of remote monitoring mechanisms.

Purpose of CIED Monitoring A guiding principle of medical therapy is the requirement for monitoring both the action of the therapy and the condition of the patient. Extension of this to CIED therapy implies implementation of careful postimplant monitoring and timely response to any changing need. Despite this, physician and patient interest has generally focused on the acute implant itself. The aims of monitoring are to (1) establish and maintain appropriate CIED function, (2) optimize its programming, (3) identify risks in implanted device (e.g., impending lead failure) or from changes in patient condition (e.g., advent of AF), (4) monitor response to therapy, and (5) provide a communication channel for systematic data review. Current practice generally follows an in-clinic follow-up protocol by physicians and specially trained staff with retrieval of stored diagnostic data. For ICDs and CRT devices, this is performed at short intervals because of safety concerns (e.g., 3 monthly), although optimal frequency has not been tested.2 Significant challenges are increasing volume of patients, complexity of both CIED and patient, maintaining continuous surveillance, capability of prompt problem detection, and management of retrieved data.3,4 These place increasing demands on the health care system.

In-Person Monitoring In-person monitoring with a physician or allied professional in a clinic or medical institution has been the conventional standard for device follow-up. Face-to-face evaluation permits history taking, physical

examination, electrocardiography, and radiography as indicated. Interrogation of the device is performed using a programmer for bidirectional communication with the CIED. This has been traditionally wand-based but more recently, with wireless telemetry using a programmer located within 10 feet (3 m). Device function, including capture and sensing thresholds, may be reviewed (Table 32-1). Response to medical therapy may be disclosed, such as for atrial fibrillation (AF). Programmed settings and functions may be reprogrammed if necessary to optimize device operation and individualize parameters according to patient need (“actionable” encounters). The frequency of this may depend on the indication for the encounter; a routine scheduled check differs from unscheduled encounters to follow a particular condition or specific symptoms (Box 32-1). In-person evaluation is required after implantation and before hospital discharge, for wound checks within 2 weeks, and then again at 6 to 12 weeks to set chronic parameters for pacemakers, ICDs and CRT devices. This period is significant because system-related problems (e.g., threshold increase, perforation, need for revision) tend to cluster in the early postoperative period.5,6 Subsequent follow-up schedules vary according to facility, physician preference, and available resources. Therefore, guidelines based on consensus opinion were issued by the Heart Rhythm Society (HRS) and European Heart Rhythm Association (EHRA). This consensus advocated a minimal recommended schedule of device follow-up of 3 to 6 monthly clinic checks for ICDs and 6 to 12 monthly checks for pacemakers, but with increased frequency (e.g., monthly) in response to product advisories and recalls.2 Such scheduled checks represent an estimated 4 million encounters in the United States alone. Problem discovery rates with this protocol have been unknown until recently.7 The incidence of unscheduled checks occurring with this schedule—an added burden to already-saturated device clinics—is also undetermined. The occurrence of significant cardiac or arrhythmic symptoms (e.g., shock therapy, palpitations) or detection of a CIED alert (e.g., audible alert) traditionally has required emergent clinic attendance and CIED interrogation. In the mid-2000s, a succession of advisories demanding higher frequency of follow-up overwhelmed clinic follow-up capacity, motivating the development and application of remote monitoring technologies.3

Remote Monitoring TECHNOLOGIC ADVANCES Remote monitoring may be defined as a method for communication of information contained in the patient’s CIED (usually from home) and the physician and/or allied professional responsible for follow-up. This technology has the capability to maintain constant surveillance of a large volume of patients, with early notification in the minority who develop problems. This is especially important for asymptomatic conditions. Remote monitoring may improve clinic efficiency by reducing unnecessary health care utilization while allowing rapid patient evaluation when necessary. It should provide almost identical information to a conventional, in-person interrogation. Automatic transmission technology independent of patient or physician interaction may be preferred. Automatic databasing of retrieved data may aid assessment of system performance and patient condition. Several

987

988

TABLE

32-1 

SECTION 4  Follow-up and Programming

Modern Systems

Scheduled Device Evaluations (In Person or Remote)

Review Frequency Battery voltage Lead impedance (RA, RV, and LV) Sensing: P and R wave; sample electrogram Pacing threshold (RA, RV, and LV) and dependency Alerts % Pacing in each chamber (RA, RV, and LV) Arrhythmia history (AF/VT) Therapy history (AF/VT) Shock impedance Charge time Hemodynamics

Pacemakers 6-12 monthly + +

ICDs 3-6 monthly + +

CRT 3-6 monthly + +

+

+

+

+

+

+

+ +

+ +

+ +

+

+ + + + +

+ + + + +

AF/VT, Atrial fibrillation/ventricular tachycardia; CRT, cardiac resynchronization therapy; ICDs, implantable cardioverter-defibrillators; LV, left ventricular; RA, right atrial, RV, right ventricular.

remote monitoring technologies are available, but not all offer these options. Transtelephonic Monitoring Without Interrogation Historically, remote monitoring of pacemakers has occurred for decades using transtelephonic monitors with modem technology. This system converts electrocardiographic information into sound to communicate over telephone lines to a decoding machine, which changes the sound back into the “rhythm strip.” This was introduced in the early 1970s to monitor the longevity of pacemakers8 and implemented for remote surveillance of sensing and capture as well as lead and device malfunction. It permitted frequent monitoring of pacing rate, determination of the underlying rhythm, and timely detection of battery depletion. Although extensively used, transtelephonic monitoring (TTM) was restricted to pacemakers, depended on active patient participation (and thus vulnerable to adherence issues), and delivered only a “snapshot” of the cardiac rhythm that was likely to miss intermittent problems. Indeed, in a recent trial, only 3 of 190 events were found on TTM, with discovery of the remainder requiring (delayed) inpatient assessment.9

Box 32-1 

UNSCHEDULED EVALUATIONS (IN PERSON OR REMOTE) Patient Initiated Shocks: appropriate/inappropriate; multiple, phantom Patient or family concerns Emergency room visits for cardiovascular problems (e.g., syncope, acute heart failure decompensation) Physician Initiated Assess response to changed CIED parameters (e.g., % pacing). Follow rising threshold Follow CIED function (e.g., lead parameter drift, approaching ERI, advisories). Assess response to medical therapy (e.g., for arrhythmia, heart failure). Assess influence on CIED function (e.g., DFTs, VT detection zones) Plan surgeries or medical interventions CIED, Cardiac implantable electronic device; DFTs, defibrillation thresholds; ERI, elective replacement indicator; VT, ventricular tachycardia.

Remote monitoring systems permit access to the extensive data recorded in diagnostic memory of current-generation CIEDs. Each system is proprietary and works only with compatible devices from the same manufacturer: Home Monitoring (HM; Biotronik, Berlin), CareLink Network (Medtronic, Minneapolis), Latitude Patient Management System (Boston Scientific, St. Paul, Minn.), and HouseCall Plus (St. Jude Medical, Sylmar, Calif.). Their characteristics are summarized in Table 32-2. All technologies from a single manufacturer may not be available in all countries. CareLink may employ wand-operated or wireless transmitters. HM has been most extensively studied,5,10,11 in contrast to CareLink, although this is widely used. Latitude and Merlin (St. Jude Medical) have no published data regarding their technical or clinical utility. Mode of operation and level of patient involvement during transmission vary among monitoring systems. Operating differences pertain to the frequency of data transmission and report generation, type of reports generated, sensor technologies, and degree of patient involvement required for successful transmissions. For example, a high level of patient interaction is required by wand-based systems (e.g., CareLink), but virtually none by automatic systems (e.g., HM). Most remote monitoring systems transmit data via standard telephone lines, whereas HM uses a fully mobile, wandless, cellular-network transmitter that can be worn on the belt or carried in a purse to deliver automatic, daily device interrogations and alert reports (Fig. 32-1). All remote monitoring systems require a small external device to communicate programmed parameters and diagnostic data stored in the CIED memory, either with active patient participation (via a wand) or automatically (wandless). These may be preset at intervals of variable frequency (e.g., 3 monthly) with patient-activated systems, or more frequently with automatic remote monitoring (e.g., every 21 days with wireless CareLink, daily with HM). Once transferred from the CIED to the patient device, encrypted data are uploaded via telephone landlines, or cellular transmissions, to a secure central database or data-processing facility organized by the manufacturer. Details are posted on a secure website for review by authorized personnel. Generally, the transmitted parameters of different remote monitoring systems are programmable according to individual needs. Alert messages may be communicated to physicians via e-mail, text messaging, fax, or telephone call, according to the clinical urgency of the event. The customization of alerts for individual patients may be web-based with HM (obviating the need for patient attendance) or may require the use of a programmer during an ambulatory visit (e.g., CareLink). In some systems, patients may be informed of alert messages by an audible signal (beep) or vibration from the CIED. Remote monitoring reports are typically generated and sent with different alert levels, enabling the caregiver to respond according to the relative urgency. For example, Latitude delivers event notifications to the physician or clinic either as “red alerts,” signifying conditions that might leave the patient without appropriate device therapy, or “yellow alerts” of lesser urgency, regarding patient and device functions. A unique feature of the Latitude system is the ability of ambulatory patients to connect weight scales and blood pressure cuffs to allow the remote identification of sudden changes in heart failure status. An important potential of remote monitoring systems is the ability to perform early detection, especially of asymptomatic events, although systems vary in this ability. Clinically important events may be considerably delayed with systems relying on patient activation but, in contrast, can be notified within minutes by HM.12 However, remote manual testing or reprogramming of devices, although possible from an engineering perspective, is not available because of safety and security concerns. Actionable events, even if straightforward and easily resolved with simple reprogramming, demand in-person assessment. Patient-Activated Remote Monitoring These versions require patient-driven communication, whereby wandderived data are relayed via telephone connections to following facilities (see Fig. 32-1). This requires the patient at home to manipulate a



32  Follow-up Monitoring of Cardiac Implantable Electronic Devices

TABLE

32-2 

989

Remote Monitoring Resources from Selected Manufacturers

Characteristic Operation

Biotronik Home monitoring (HM) 2001 Replace device interrogation during in-office follow-ups Early detection of silent asymptomatic arrhythmias Portable (wearable) Automatic

Products permitting remote monitoring

ICD, PPM, CRT-P, CRT-D (All wireless)

Long-range telemetry

Cellular (4-band GSM) and/ or landline Daily periodic; automatic event messaging Low

Popular name FDA approval: technology FDA approval: clinical utility

Transmission Impact of daily transmission on battery longevity Event notification Early detection IEGM/Holter transmission Alert programming Patient notification mechanism Heart failure sensor Data archive

Website; fax; e-mail; SMS <24 hr Automatic periodic real-time and event-triggered IEGM Remote Callback light on transceiver Heart rate variability Long term (>25 yr)

Medtronic Carelink 2005 —

Boston Scientific Latitude 2006 —

St. Jude Medical Merlin 2007 —

Stationary Patient initiated and automatic ICD, CRT (PPMs and ILRs require wanded download) Landline

Stationary Patient initiated and automatic ICD, CRT (no PPM) Wand-operated/wireless

Stationary Automatic and patient initiated ICD, PPM, CRT-P, CRT-D (All wireless)

Landline

Landline/cellular

Scheduled; patient-initiated event messaging High

Scheduled; patient-initiated event messaging High

Daily alert check Scheduled; patient initiated Low

Website; e-mail; phone; SMS <24 hr (some event types) Pacemaker Holter; 10-sec IEGM strip on request Requires patient presence Phone call from clinic to patient OptiVol Long term

Website; fax; phone <24 hr (some event types) Automatic periodic real-time and event-triggered IEGM Remote Phone call from clinic to patient Weight; blood pressure Long term

Website; fax; phone; SMS <24 hr (event based) Real-time IEGM Requires patient presence Device vibration and/or transceiver light Heart rate variability Long term

CRT, Cardiac resynchronization therapy; D, defibrillator; GSM, Global System for Mobile communications; ICD, implantable cardioverter-defibrillator; IEGM, intracardiac electrogram; ILRs, implantable loop recorders; P, pacemaker; PPM, permanent pacemaker; SMS, Short Message Service. Data from Biotronik: http://www.biotronik-healthservices.com; Medtronic: http://www.medtronic.com/carelink; Boston Scientific: http://www.aboutlatitude.com/how-latitude-works/ patient-management.html; http://www.bostonscientific.com/cardiac-rhythm-resources/products.html#productDetailPage(10124672); St. Jude Medical: http://www.sjmprofessional.com/ Products/US/CRT-Systems/Merlin-net-Patient-Care-Network.aspx; http://www.sjm.com/devices/device.aspx?name=Merlin%26%23153%3B.net+Patient+Care+Network&location=us&t ype=38.

programmer and coordinate with clinic personnel to ensure communication and transmission, typically on a formal, calendar-based schedule. Early data from these systems reported technical feasibility and patient acceptance.13,14 Data transfer was similar to in-person interrogation. Nevertheless, these systems are cumbersome to use (patients reported difficulty in manipulating the wand,14 raising compliance issues) and time-consuming. As a tool, they essentially substituted for scheduled calendar-based in-person encounters, with the lack of monitoring in interim periods risking overlook of interim asymptomatic events. Therefore, although superior to TTM,9 patientactivated systems may not provide an efficient method of follow up. Automatic Remote Monitoring Current-generation remote monitoring systems implement an automatic transmission mechanism fully independent of patient or physician interaction. This relies on a CIED-initiated remote transmission using a Medical Implant Communication Service (402-405 MHz) or Industrial, Scientific and Medical (902-928 MHz) radiofrequency band allocated for implanted medical devices. An encrypted telemetric signal is sent from the CIED to a transceiver. The only requirement is that the patient be within a distance of approximately 6 feet (~2 m) from the transceiver. The transceiver (which may be a mobile unit with HM) uses telephone links, which may be landline and/or cellular based (see Fig. 32-1). The system can be programmed to download data at specific times and dates, usually when the patient is sleeping adjacent to the base unit. The transceiver automatically connects the phone link for data transfer. The treating physician can manually access the information and preprogram a customized set of alerts for each patient according to need (Fig. 32-2). If triggered, these alerts are transmitted promptly for physician review (color-coded according to urgency), enabling prompt clinical intervention if necessary. The amount and quality of transmitted information, including real-time intracardiac

data, continue to improve and have reached the level of an in-office interrogation. Automatic remote monitoring was pioneered by Biotronik (Home Monitoring, HM) and has been used in more than 50 countries (U.S. FDA approval in 200215). Other manufacturers are following (Table 32-2). This technology allows for automatic, patient-independent, wireless transmission of diagnostic ICD, CRT, and pacemaker data (see Fig. 32-1). Published data for technical efficacy for automatic remote monitoring are available only for the HM system.12,16 Reliability and early notification ability of this communication system were excellent. The wireless transmission ability is especially useful since almost 20% of U.S. households are currently estimated to have no landline facility.17 Greater than 90% of transmissions were received in less than 5 minutes (Fig. 32-3), and data integrity was 100% preserved.5,10,16,18 HM system operation is not energy costly and not susceptible to electromagnetic interference. The HM transceiver is a fully-mobile cellular unit. The novel quad-band transceiver is compatible with all major Global System for Mobile (GSM) cellular networks worldwide. It permits a unique callback function so that the medical professional can contact the patient worldwide via the transceiver, which is especially useful for travelers. Thus, automatic HM has the ability to maintain surveillance and rapidly bring to attention significant data, enabling clinically appropriate intervention. TRUST Trial The current variety of follow-up practices, with or without the assistance of different remote technologies, contrasts with a paucity of data to support any particular method or schedule. Although guidelines advocate 3 to 6 monthly clinic checks, the efficacy of this schedule with regard to patient safety, adherence, incidence of unscheduled encounters, and rate of problem detection remain untested. The TRUST (Lumos-T Safely Reduces Routine Office Device Follow-up) trial was

990

SECTION 4  Follow-up and Programming

Wand-based remote monitoring

Automatic remote monitoring

Figure 32-1  Contrasting remote monitoring technologies. Top, Patient-activated system from home. Bottom, Example of automatic remote home monitoring by Biotronik Home Monitoring (HM). HM transmits data daily at a preset time, and immediately in response to a critical event. Transmission steps are as follows. A very-low-power radiofrequency transmitter circuitry is integrated within the pulse generator. The implanted device wirelessly transmits stored data on a daily basis to a mobile transceiver (typically placed at bedside at night). The transceiver automatically and silently accepts patient data from the implant and transfers this digital information using a cellular short-messaging system. The data are relayed wirelessly or via landline (automatically seeking first path available) to a dedicated service center. The service center generates a customized summary with informative trends, charts, parameters, electrograms, and graphs, available to the physician online via secure Internet access. Thus, daily patient monitoring may occur between scheduled office device interrogations providing trended information (e.g., battery status, lead impedance, sensing function). Service center processing and data upload on the HM webpage is automatic, bypassing potential delays (and errors) associated with manual processing. Data are stored in service center repository and analyzed and disseminated electronically. Critical and clinically relevant status changes data may be transmitted immediately without the need for patient interaction and flagged for attention on the HM webpage (see Fig. 32-2). Automatic alerts occur for silent but potentially dangerous events (e.g., device/lead failure, onset of asymptomatic AF). Event details include transmission of intracardiac electrograms similar to those available during office device interrogations. Physicians may be notified of alert conditions via e-mail or fax, if required. Useful information about the most important device or patient status changes can be delivered to the physician as quickly as a few minutes after the event. HM uses a triple-band and a quad-band exterior wireless transceiver connected to available worldwide cellular telephone networks (>55 countries). (Modified from Varma N: Rationale and design of a prospective study of the efficacy of a remote monitoring system used in implantable cardioverter defibrillator follow-up: the Lumos-T Reduces Routine Office Device Follow-Up Study (TRUST). Am Heart J 154:1029-1034, 2007.)

undertaken to resolve some of these outstanding questions in a heart failure population receiving ICDs.19 TRUST has been the only prospective multicenter clinical study to assess and compare conventional follow-up and remote monitoring. The automatic remote monitoring mechanism tested was Biotronik Home Monitoring (HM). Representing U.S. implant recipient demographics, 1516 patients enrolled at 105 U.S. sites in a predominantly community-based setting. Patients were randomized to conventional care (HM off) or to remote monitoring (HM on) groups (Fig. 32-4). Eligible patients were enrolled from 0 to 45 days after successful device implantation and then randomly assigned in a 2 : 1 ratio to HM or conventional groups,

respectively. All patients had scheduled postimplant follow-ups at 3, 6, 9, 12, and 15 months, with unscheduled (interim) evaluations as needed. Patients assigned to conventional care were evaluated in-clinic only. In the HM arm, patients had HM checks followed by office visits at 3 and 15 months. At 6, 9, and 12 months and for interim visits, cumulated transmission files were remotely retrieved from the secure website and evaluated. Thus, both groups adhered to 3-month follow-up. Investigators were permitted to evaluate patients additionally in-office following HM checks during the study. Between these periodic checks, early notification could automatically occur for compromised system integrity (battery, lead parameters, high-voltage



991

32  Follow-up Monitoring of Cardiac Implantable Electronic Devices ICD: EVENT TRIGGERS

HOME MONITORING: TRANSMISSION TIME >90% of messages received within <4 minutes 100

90.7

Percent

100

76.7

80

A

97.4

94.3

60 40 20

21.8

0 <1 min

<2 min

<4 min

<10 min <60 min

<10 h

Data based on 22,356 transmissions Figure 32-3  Transmission time with automatic remote monitoring. Current Home Monitoring (HM) units are able to provide transmission speeds of less than 30 seconds. (From Varma N, Stambler B, Chun S: Detection of atrial fibrillation by implanted devices with wireless data transmission capability. Pacing Clin Electrophysiol 28(suppl 1):133-136, 2005.)

circuitry) or arrhythmia occurrence (e.g., AF, ventricular arrhythmia). These were evaluated online and patients brought in for office visits if deemed necessary by the investigator. Scheduled and unscheduled clinic visits (including responses to HM event notifications) were tracked for each individual in both study arms. Unscheduled interrogations in interim periods resulted from physician or patient initiation. TRUST’s primary objectives were to compare total in-hospital device evaluations in HM compared to conventional care and to assess the safety of the remote follow-up method. Home monitoring reduced total (scheduled and unscheduled) hospital encounters for device interrogation by 45% (Fig. 32-5).20 The number of in person encounters occurring at scheduled 3-month intervals was reduced by 60%. This was not a 75% reduction, expected if all 6-, 9-, and 12-month checks were performed online, because the protocol permitted reviewing physicians to follow online check with in-person evaluations if deemed necessary. However, the small number of such cases indicated physicians’ confidence in the extent and quality of transmitted data, even at a stage of gaining familiarity with a new technology. Thus, more than 85% of all HM-group 6-, 9-, and 12-month follow-ups were performed using HM only, indicating that HM provided sufficient assessment in these patients. HM maintained

B

Onset

A RV Detection VF

FF A RV

Predetection –6 –5

A RV

–4

Time (seconds) –3

–2

–1

TRUST study design In-office follow-up Remote follow-up

0

mV

Conventional (RM disabled)

FF A

C

RV

Figure 32-2  Example of HM event notification. A, Event notifications are programmable on line with Biotronik Home Monitoring (HM) and may be customized to each patient. B, The review list for any individual displays the history and event notifications for that patient. Accessing any one will permit review of details, such as for event date June 23 (C), when appropriate pacing therapy was delivered for ventricular arrhythmia detected in the ventricular fibrillation (VF) zone.

Randomization 1:2

Remote monitoring (RM)

Enrollment 0–45 days after implant

3m

6m

9m

Figure 32-4  TRUST study design.

12 m

15 m

992

SECTION 4  Follow-up and Programming

Office visits per patient

4 HM Conventional

3

p <0.001

2

1

0 0

60

120

180

240

300

360

Enrollment time (days) 100

Cumulative survival (%)

95 90 85 80

frequent hospital evaluations. Detection was advanced by more than 30 days compared to conventional care20 (Fig. 32-6). (With 6 monthly scheduled conventional visits, HM would provide a correspondingly greater advance notification of at least 3-4 months.) Notably, this was not a test of transmission time (a technologic feature) but of “time to physician evaluation” (i.e., of clinical practice). Another study, Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT), applied a separate automatic technology from a different manufacturer to a similar patient group.21 It reported broadly similar effects on total in-person evaluations, endorsing the results of TRUST. A significant shortening of hospital length of stay was observed as well, possibly because of a positive impact on patients’ health. Overall hospital costs were reduced by use of remote technology. However, only a minority of attempted alerts were transmitted successfully, severely limiting the utility of this proprietary technology for early detection. In summary, TRUST demonstrated significant limitations of previously untested “conventional care” while, in contrast, showing the safety, efficacy, and early-warning capability of automatic remote monitoring. Automatic HM ensured follow-up continuity of a large patient volume, avoiding unnecessary in-hospital patient evaluation (thus reducing clinic load by almost 50%), but maintained near-continuous surveillance to rapidly identify problems. The trial results promote a paradigm shift in current clinical practice to exception-based hospital care.22 IMPLEMENTATION OF REMOTE MONITORING

75 70 65 60 55 50 0

60

120

180

240

300

360

333 741

282 630

Enrollment time (days) Conventional: 431 HM: 908

425 880

406 848

380 803

358 774

Figure 32-5  TRUST results. Top, Cumulative hospital-based encounters for ICD evaluations. There is progressive divergence of curves. In Home Monitoring (HM), the slow rise in the curve reflects unscheduled visits after the first common 3-month device clinic check. Bottom, Safety, a composite adverse event rate comprising death, strokes, and events requiring surgical interventions (e.g., device explants or lead revision), was preserved with remote monitoring. (Compiled from Varma N, Epstein A, Irimpen A, et al: Efficacy and safety of automatic remote monitoring for ICD follow-up: the TRUST Trial. Circulation 122:325-332, 2010.)

better continuity of follow-up compared with traditional methods. A small proportion of the total number of in-person evaluations also resulted from unscheduled encounters. This is an important observation: a concern exists in the implanting community that an automatic remote monitoring system that self-screens daily would result in an increased presentation of patients to the hospital. However, this did not occur. Extension of face-to-face encounters to yearly in remote monitoring was not accompanied by loss of safety (see Fig. 32-5). The incidence of death and stroke trended toward improvement with use of HM. TRUST’s secondary endpoint assessed the early-detection capability of HM, defined by time elapsed from event onset to physician evaluation. Evaluation in HM occurred on receipt of event notifications in response to detection of preprogrammed events or in-office interrogation (scheduled or unscheduled). In conventional care, event detection occurred at in-office interrogation (scheduled or unscheduled). HM enhanced problem discovery (even if asymptomatic) despite less

Patients receiving CIEDs span a wide spectrum: young versus old, sedentary versus competitive athletes, working versus retired, and those who may be completely healthy versus those with extensive comorbidities. Before implant, patients must receive education regarding the indications for the device and expected postimplant restrictions. Some may have limited access to telephone landlines or to transportation (e.g., remote areas) or may be physically limited, affecting choice of remote technology. Automatic remote monitoring may have particular utility in young children, who are susceptible to higher rates of lead or pulse generator failure than adults but are unable to describe specific symptoms.23 Inquiries about occupation and environment may yield important information regarding potential sources of electromagnetic interference. In-person monitoring is required after implantation before hospital discharge. Complications such as hematoma, lead dislocation, and perforation are generally seen within 24 hours after implantation. This assessment should document appropriate CIED function, establish patient-specific programming, document initial telemetry values, ensure the absence of operative complications, educate and emotionally support the patient and family, and provide a CIED identification card to the patient. Device Clinic The use of remote monitoring has important implications for device clinics, which have increasing patient volume but limited trained health care professionals.24 However, in-person follow-up at 2 to 12 weeks after implant as an outpatient is important.2 It permits assessment of wound healing and determination of chronic thresholds as well as setting of final pacing parameters.5,6 Problems such as lead perforations or system errors requiring revision and symptomatic reactions to implantation (e.g., pacemaker syndrome, diaphragmatic pacing, pocket infection) cluster in this early postimplant period and occur more frequently with dual-chamber or resynchronization units.5,6,25 At the 3-month encounter, the need for continuation of postimplant follow-up is emphasized. The patient and family need to become familiar with remote monitoring and understand the patient’s responsibility in adhering to the follow-up schedule. Patients receiving implantable loop recorders (ILRs, implanted on a temporary basis) may have follow-up scheduled on basis of symptoms. ILRs store limited recordings of heart rhythm, triggered for prespecified boundaries to diagnose syncope, bradycardia, or arrhythmia



32  Follow-up Monitoring of Cardiac Implantable Electronic Devices

180

p <0.001

p <0.001

p <0.001

993

p <0.001

160

Onset to evaluation (days)

140 120 100 80 60 40 20 0 n = 82

n = 33

n = 159

n = 62 VT

AF

n = 105 VF

HM 180

n = 257

p <0.001

n = 108

n = 41 SVT

Conventional p <0.001

160

Onset to evaluation (days)

140 120 100 80 60 40 20 0 n = 606

n = 241 All

n = 271

n = 114 Silent

Figure 32-6  Early detection with home monitoring (TRUST secondary endpoints). HM secured earlier physician evaluation of arrhythmias (top) and of silent events (bottom). (Compiled from Varma N, Epstein A, Irimpen A, et al: Efficacy and safety of automatic remote monitoring for ICD follow-up: the TRUST Trial. Circulation 122:325-332, 2010.)

burden. In contrast, ensuing monitoring of ICDs and CRT devices demands careful surveillance. These are complex devices implanted in patients with significant clinical comorbidities. The TRUST scheme for device follow-up incorporating remote monitoring has been adopted by several large-volume centers in the manner described here. After the in-person 3-month postimplant assessment, face-to-face checks may be scheduled once yearly with three interim monthly checks via remote monitoring, according to current guidelines.2 These checks mainly involve collection of routine measurements only (e.g., battery status, lead impedance, sensing function), which require no programming or device changes, or alteration of antiarrhythmic medications (see Table 32-1). Current-generation devices have automatic threshold

assessment, which permits monitoring of threshold changes. If an actionable (or questionable) event is detected, the patient may be contacted to report for formal assessment. However, these represent a minority, because TRUST demonstrated that approximately 90% of these three monthly checks were “nonactionable.” Evaluation of interim unscheduled checks is important. These may be patient or physician initiated. Remote technology may be used to triage patient inquiries, such as perceived device discharges. Currently, most patients call their physician/clinic immediately after perceiving a received shock, often prompting an emergency room (ER) or clinic visit. With remote monitoring, shock data and online electrogram (EGM) are available and may be used to determine optimal patient management confidently. An appropriate shock may require reassurance only,

994

SECTION 4  Follow-up and Programming

without the need for hospital visit. In contrast, a series of inappropriate shocks may be rapidly evaluated online and the patient asked to report to the hospital promptly. Using conventional monitoring methods, increased frequency of visits were mandated for generators approaching the elective replacement indicator (ERI), deviations in lead behavior (impedance, sensing, or threshold), and ICD components under

advisory, which tend also to manifest with battery, high-voltage (HV) circuitry, or lead failure.26 In contrast, physicians following such patients with automatic remote monitoring may perform accelerated follow-up online and wait for affected devices to self-declare an issue rapidly, thus avoiding overloading device clinics with non-actionable inpatient encounters (Figs. 32-7 to 32-9). This “wait-and-see” management

A RV LV A RV LV

A

–6 –5 Predetection

–4

–3 Time (seconds)

–2

–1

0

Mean ventricular heart rate (bpm)

100

75

50 Mode switch./day Mode switch. duration (%) 60 45 30 15 0 4

B

18

25

100 90 80 70 60 50 40 30 20 10 0

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Patient number

24 h/day >18 h/day >12 h/day >6 h/day

Days

# Days

C

11

Figure 32-7  Atrial fibrillation (AF). A, Home monitoring (HM) notification for AF with confirmatory automatically transmitted intracardiac electrogram (EGM). B, Patient trends may be reviewed online for atrial fibrillation (AF) paroxysms and associated ventricular rates. C, Automatic databasing permits epidemiologic analysis; 276 consecutive patients implanted with pacemakers with automatic daily remote monitoring home (HM) capability were followed for 12 ± 2 months; 29 patients experienced at least 1 day with AF. In each patient, days in which AF was recorded were classed by mode-switch duration (regardless of mode-switch number) according to >6, >12, >18, and >24 hours per day. AF burden differed significantly among and within individual patients. For example, patient 22 had only 1 day of AF, versus 93 days in patient 15, in whom 81 of the 93 days were associated with >18 hours of AF (i.e., AF burden was heavy when it occurred). In contrast, patient 20 had 7 AF days, but none of these exceeded 18 hours in duration on any single day. (B compiled from and C generated from central HM service center data. A from Varma N, Stambler B, Chun S: Detection of atrial fibrillation by implanted devices with wireless data transmission capability. Pacing Clin Electrophysiol 28(suppl 1):133-136, 2005.)

mV

995

VF VF 94

VF VF 78

V

Vs 703

32  Follow-up Monitoring of Cardiac Implantable Electronic Devices

Vs VF 78 VF 156 VF 141 VF 125



VF detected

+4 V –4 –3

–2

–1

0

Time (seconds)

A

>3,000

Pacing imp. (ohm)

3,000 2,600 2,200 1,800 1,400 1,000 600 200 <200

B

12/30/07

12/28/07

12/26/07

12/24/07

12/22/07

12/20/07

12/18/07

12/16/07

12/14/07

12/12/07

12/10/07

12/08/07

12/06/07

12/04/07

12/02/07

11/30/07

FU

Time (days)

Figure 32-8  Lead fracture (Fidelis lead under advisory): two event notifications transmitted immediately on lead fracture. In this patient, events occurred silently during sleep at 4:43 AM, 6 weeks after last clinic follow-up on Nov. 14. A, Two occurrences of detection in VF zone are noted (top) and flagged (exclamation mark). The accompanying wirelessly transmitted electrogram (EGM) demonstrated irregular sensed events. Marker channels indicated coupling intervals as short as 78 msec. The transmission terminated with VF detection (marked). The summary below shows that no therapy was delivered, indicating that this VF sensed event terminated spontaneously. B, The second event report shows a separate notification in response to the same event, indicating a lead impedance alert. Lead impedance trend was stable below 600 ohms in prior weeks, but then suddenly increased >500 ohms, triggering an event notification (red), although this absolute value was still within specifications. The resolution of the illustrated intracardial EGM transmission is 1/64 second in this first-generation device with wireless EGM transmission (Lumos). Internally, the device works with a resolution of 1 msec. The signal is compressed by means of a pattern-like analysis to make the EGM data fit into one SMS. In this case, the overall image together with markers provided sufficient information to enable a clinical decision, although EGM definition was modest. Current-generation devices transmit EGMs with improved resolution (1/128 second) and longer duration, including postdetection sequences. These devices use lossless compression; i.e., EGM is identical to the view on the programming device (e.g., in Fig. 32-11). (Modified from Varma N: Remote monitoring for advisories: automatic early detection of silent lead failure. Pacing Clin Electrophysiol 32:525-527, 2009.)

996

SECTION 4  Follow-up and Programming

Status - Implant: Battery Status Voltage [V] Voltage measured on

ERI 6.20 Nov 20, 2006

Transmitter xxxxxxxx Nov 20, 2006 10:50:41 AM event triggered

Transmitter SN Last transmission received on Message type

A

EOS

ERI

MOL2

MOL1

390

Ven. shocks Shocks started

300 Shocks

BOL

Shocks aborted

Shocks successful

200

100

0

B

Oct. 20 21 2006

B FU

24

27

30

Nov

05

08

11

14

17

Nov 20

Time (days)

Status - Lead: RV lead

C

Pacing impedance [ohm] Shock lead Impedance of last delivered shock [ohm]

Measured on 420

Nov 20, 2006

<25

Nov 20, 2006

Figure 32-9  Generator malfunction. Event notifications of A, elective replacement indicator (ERI), B, shock history, and C, disintegration of highvoltage (HV) circuitry. Event notifications were transmitted for delivered and aborted VF therapies, shock impedance <25 ohms, and ERI (EOS, end of service). Notification showed 381 shocks started, 82 aborted, and 250 ineffective maximum-energy shocks that contributed to battery depletion. These occurred in a short span leading to the near-vertical ascent in the cumulative shock score. Lead dislodgment and fracture due to “twiddling” was the cause. (Compiled from Varma N, Michalski J, Epstein A, Schweikert R: Automatic remote monitoring of ICD lead and generator performance: the TRUST trial. Circ Arrhythm Electrophysiol 3:428-36, 2010.)

strategy emphasizes a monitoring philosophy of exception-based care. Problem discovery during unscheduled visits is significantly higher than with routine evaluations.6 In TRUST, patients evaluated in person on basis of physician- or patient- initiated encounters, or called in because of event notification requiring further assessment, had an actionability rate greater than 30%; that is, problem discovery rates were approximately threefold those for scheduled checks.7 Automatic remote monitoring with daily screening may generate increased alert transmissions that may augment unscheduled office visits. This concern was assessed in TRUST. The number of patients generating an event notification was less than 50% at 12 months. Less than 2% of 350,000 potential “opportunity” days to trigger an event notification were used.27 These data are consistent with previous reports.11,28 Therefore, even though an event notification may be potentially triggered every day, in practice such messages occurred infrequently, resulting in a very low transmission load, indicative of the strong filtering exerted by a programmable messaging system. A significant advantage of the HM remote monitoring systems is that alerts may be customized online according to changing needs, without demanding patients to report for in-person reprogramming. For

example, the physician may want to be alerted for ventricular tachycardia (VT) during adjustments of antiarrhythmic drug therapy, but not in all ICD recipients, or may need to eliminate AF notifications in a patient in whom attempts at restoration of sinus rhythm have been abandoned. Thus, diagnostic event messages may be tailored for each patient at the physician’s discretion (Figs. 32-10 and 32-11; see also Fig. 32-2). As implanted devices from all manufacturers begin to incorporate automatic remote monitoring mechanisms, follow-up routines in device clinics may become more uniform. Several major institutions already depend on remote monitoring as an essential instrument for managing large patient volumes. TRUST demonstrated that almost 90% of scheduled checks, whether in person or remote, were nonactionable, indicating that most of the three routine monthly checks may be accomplished online safely. However, implementation requires a change in clinic and physician workflow patterns, with daily attention to remote websites to evaluate event notifications, and a structured approach to maintain consistent scheduled device interrogations. Website review may be conducted rapidly compared to in-person follow-up, which improves clinic efficiency and delivers prompt



32  Follow-up Monitoring of Cardiac Implantable Electronic Devices

997

Detection VF

Abort

–4 –3 –2 Predetection Time (seconds)

–1

0 Time (seconds) Pretermination

HISTOGRAM OF 1392 PATIENTS WITH ONE OR MORE ABORTED SHOCKS 1200

1120 Count

1000

Figure 32-10  Example of remote monitoring surveillance. An ICD population was monitored for silent, nonsustained detections in  the ventricular arrhythmia zone (VF, ventricular fibrillation). A significant percentage of patients had high (>15) event rates, risking premature battery depletion. (Modified from Varma N, Johnson MA: Prevalence of cancelled shock therapy and relationship to shock delivery in recipients of implantable cardioverterdefibrillators assessed by remote monitoring. Pacing Clin Electrophysiol 32[suppl 1]:42-46, 2009.)

# patients

800

600

400

200

130 49

30

19

44

11 to 15

16 to 20

21 to 25

26 or greater

0 1 to 5

communication to patients when necessary. This is especially valuable for potentially dangerous asymptomatic events. Remote CIED monitoring systems have improved presentation as well as capacity of data retrieval. For example, reports graphically display trended parameters of atrial and ventricular pacing, heart rate, AF events, and patient activity or sensor-derived data (e.g., OptiVol). The rapid presentation of salient data facilitates prompt interpretation. Thus, in one HM study, a nurse expert in cardiac pacing consulted the website daily and reviewed problematic transmissions with a physician. During a mean follow-up of 227 ±128 days, 23,545 daily messages and 1665 alert events were received. The nurse and physician spent on average, respectively, 1 and 0.2 hr/week analyzing the data. The mean

6 to 10

Number of aborted shocks

connection time per patient was 2 minutes and had decreased to 1.65 min/patient for the last 50 connections. The nurse submitted 133 transmissions from 56 patients to the physician. The authors concluded that automatic remote monitoring optimized medical treatment and device programming, at low cost for the health care system.16 Device clinics using remote monitoring were found to reduce physician time compared with conventional care (8 vs. 26 minutes) and also patient time (7 minutes vs. 3 hours).29 Thus, application of the TRUST follow-up protocol, which gained U.S. Food and Drug Administration (FDA) approval in May 2009,30 is likely to require fewer hospital personnel while improving patient surveillance.

SECTION 4  Follow-up and Programming

>150 150 125 100 75 50

A RV

DSImp

Onset

LV

Detection VF

A RV

25 <25

A

01/29/08

01/27/08

01/25/08

01/23/08

01/21/08

01/19/08

01/17/08

01/15/08

01/13/08

01/11/08

01/09/08

01/07/08

01/05/08

01/03/08

01/01/08

FU 12/30/07

Shock impedance (ohm)

998

LV –6 –5 Predetection

–4

–3 –2 Time (seconds)

–1

0

B

Time (days) A RV

ATR onset | ATR post-trigger EGM displayed at 25 mm per second ATR onset ATR onset

Detection VF

FF A

A

RV –6 –5 A Predetection RV 60405498 mV

–3 Time (seconds)

–2

–1

V

FF A RV

C

0

0

Termination

SN: Episode: 7 ATP in VT/VF: 0 ATP One Shot: NO Shocks: 0

–4

10 11 Pretermination

12 13 Time (seconds)

ATR onset

14

15

Shock AS

AF VP

D

ATR↓ ATR↑

AS

AF VP

ATR↓ ATR↑

AS AF AF AF AF AF AF AF AFAF

(AS) AF AF (AS)

VP VP VP ATR↑ ATR↑ ATR↑ ATR↑ ATR↑ ATR↑ ATR↑ ATR•Out ATR↓ ATR↑

VP

AS

(AS)

AP

VP ATR ATR↓

Figure 32-11  Monitoring lead function. A, High-voltage impedance alert. B, T-wave oversensing triggering an event notification. This silent problem was corrected the following day with reprogramming before inappropriate therapy was delivered. C, Nonphysiologic signals. In this case, electromagnetic interference triggered an event notification. The patient was informed within 24 hours. Asymptomatic detections meeting ventricular fibrillation (VF) detection criteria resulted in immediate event notifications. Wireless electrogram transmission automatically accompany detections in VF zone, even if shock therapy is aborted.43 D, Atrial lead noise (Latitude) triggering an alert. (Compiled from Varma N, Michalski J, Epstein A, Schweikert R: Automatic remote monitoring of ICD lead and generator performance: the TRUST trial. Circ Arrhythm Electrophysiol 3:428-36, 2010.)

Patient Aspects Ideally, remote CIED monitoring should have a positive impact on the quality of medical care and patients’ quality of life, by reducing the cost and workload imposed by uncomplicated, clinically stable patients; by early detection of abnormalities or changes in clinical status before scheduled follow-ups; and by providing patients with the highest level of assurance that the implanted device functions properly, with the advantage of fewer regular, uneventful clinical visits. TRUST demonstrated several of these aspects. Automatic remote home monitoring enabled routine follow-up evaluations without face-to-face encounters, but also permitted in-person assessment when required, and sooner. (In contrast, patientactivated remote systems failed to reduce cardiac-related resource utilization).31 This shift to exception-based assessment has key advantages for patients who, to maintain in-person follow up, have to take time off work, or need an accompanying person, or for whom access is limited (e.g., nursing home residents, geographically remote patients). Patients who travel extensively (including internationally) may benefit from the versatility of cellular service. Home monitoring enabled physician evaluation within 24 hours, including detection of asymptomatic events (vs. ≥5 months with patient-activated systems9). This ability for rapid self-declaration of fault detection enabling preemptive clinical action may be potentially lifesaving, especially for clinically silent problems, such as lead fracture, device dysfunction,32,33 and

arrhythmias (see Figs 32-7 and 32-8). Current systems provide an opportunity for patient notification via the receiver (callback function, third-party arrhythmia service, live interaction) that may be reassuring for patients during remote follow-up. Concerns that remote follow-up would promote a loss of contact between patient and physician have not been borne out when tested. Earlier remote monitoring versions demonstrated a high level of satisfaction among patients, who found their physicians to be just as available when required.13 TRUST demonstrated that scheduled evaluations were better maintained with remote technology compared to in-person interactions (which demonstrated a significant loss of adherence). This occurred without increase in ER utilization or number of patient-initiated evaluations, indicative of patient confidence in relying on remote monitoring for their follow-up. On trial conclusion, 98% of patients assigned to remote follow-up mode elected to retain it.34 Similarly, in a separate study, almost 99% of patients expressed complete or high satisfaction with remote interrogation.35 The follow-up scheme described is directed to device management only and is not intended to replace patient consultations with internists, cardiologists, or heart failure specialists, which may otherwise occur. The established follow-up framework may require interim adjustments according to individual situations (e.g., stability of patient’s medical condition) (see Box 32-1). CIEDs may need to be temporarily reprogrammed before and after a medical investigation or



32  Follow-up Monitoring of Cardiac Implantable Electronic Devices

surgical procedure, to prevent potential damage (e.g., from cautery). The frequency of system checking may need to be temporarily increased for recurrence of arrhythmic events, assessment of response to treatment, or recently modified parameters for sensing, pacing, or therapy. This may need to be accompanied by in-person follow-up. For example, more frequent monitoring of arrhythmias may be accomplished by remote checks, but treatment of heart failure decompensation may require inpatient assessment. In either case, when the clinical condition has stabilized, the monitoring schedule may revert to protocol. Patients who are terminally ill may opt for deactivation of their CIED.

Special Situations ARRHYTHMIAS The most common event notifications received during automatic remote surveillance are for AF and nonsustained ventricular arrhythmias27 (see Figs. 32-7 and 32-10). These may drive important clinical decisions. Atrial fibrillation in heart failure patients may be associated with increased morbidity and mortality.36,37 This is likely to be multifactorial, involving increased risk of heart failure by adversely affecting ventricular hemodynamics as well as stroke and facilitation of ventricular arrhythmias.38 Detection is important; a first episode of AF in a patient with risk factors prompts anticoagulation initiation, and AF conducting with rapid ventricular rates may elicit inappropriate shock therapy. However, diagnosis is challenging because of the evanescent and largely asymptomatic nature of this arrhythmia. Automatic remote monitoring in patients with CIEDs may resolve this problem and aid diagnosis and response to treatment.12,39 In the future, analysis of automatically archived data may enable accurate arrhythmia characterization, to provide insights into AF patterns, including absolute AF burden, degree of temporal dispersion, and progression to persistent arrhythmia (see Fig. 32-7, bottom). This characterization may aid understanding of risks posed and responses to treatment. For example, AF presence and duration (0 vs. >5 minutes or 24 hours) detected by continuous AF monitoring combined with CHADS-2 score–enhanced thromboembolic risk assessment.40 Early detection of asymptomatic AF by HM allows prompt clinical reaction, including antiarrhythmic therapy, cardioversion, and timely introduction of anticoagulation therapy. Computer modeling studies suggest that this could reduce potential stroke risk by 9% in patients with long-lasting episodes compared to standard follow-up.41 Ongoing large-scale prospective trials are examining these questions further. The principal reason for ICD implantation is to treat ventricular arrhythmia. However, inappropriate shocks occur with appreciable frequency, especially in the current era, when more ICDs are implanted prophylactically than for secondary prevention.42 Remote monitoring has an important role in this problem by early identification of atrial arrhythmias or hardware/sensing problems, to enable intervention to minimize inappropriate shocks and maximize appropriate therapy (see Fig. 32-11). Recurrent nonsustained ventricular arrhythmias occur in a sizable minority of the ICD population. These are significant because they may contribute to early battery depletion and may also presage delivered shocks43 (see Fig. 32-10). Emerging data indicate that shock therapy may have deleterious long-term consequences.44,45 Early recognition by remote monitoring of nonsustained events may provide an opportunity for preemptive intervention and improve patient outcomes. HEART FAILURE Recipients of ICD therapy typically have heart failure, which is a dynamic condition. Hospitalizations for acute decompensated heart failure (ADHF) continue to increase46 and are associated with increased 1-year mortality47,48 and significant expense for health care services. ADHF development is complex, involving several processes, which may include hemodynamic, neurohumoral, electrophysiologic, and vascular abnormalities that converge to manifest with fluid congestion.

999

Therapeutic strategies aimed at interrupting this train of events are potentially valuable. Symptoms are unreliable as early warning signs in this cascade. Implantable devices, including leadless automatic physiologic monitors, may serve this purpose.49 Some of the upstream factors triggering heart failure deterioration may include atrial and ventricular arrhythmias, occurrence of right ventricular (RV) pacing,50 or lack of biventricular pacing in patients with implantable devices. These data are routinely quantified in device diagnostics. Figure 32-12 illustrates several asymptomatic parameters tracked over time to monitor the progress of clinical deterioration: AF, loss of CRT pacing, and fluid accumulation. These parameters also show the time taken from an inciting event (likely AF in this case) to clinical presentation. CRT’s mortality benefit51 diminishes when it drops to less than 92% because of AF or significant ventricular ectopy.52 Thus, AF with rapid ventricular rates may have promoted loss of CRT pacing, a possible contributor to ultimate decompensation. Figure 32-12 also demonstrates a positive detection of excess fluid, derived by decreased electrical impedance between the RV lead and generator. This measure correlated inversely with pulmonary capillary wedge pressures in hospitalized patients in one study,53 and it began decreasing approximately 2 weeks before hospitalization for ADHF. However, assessment in recent large scale trials (e.g., SENSE-HF) has indicated that this has an indifferent predictive value. Impedance vectors employing a left ventricular (LV) lead may improve this yield.54 Direct hemodynamic assessments (e.g., pulmonary artery or left atrial pressure) may reduce heart failure hospitalizations.55-57 Data from these studies applied to remote follow-up may propel development of leadless stand-alone devices acting as automatic physiologic monitors. Other derived features include heart rate variability (HRV), calculated by continuous measurement of atrial-to-atrial depolarization intervals during predominant sinus rhythm. Both the absolute value and its change over time are important markers of clinical stability.58 A decrease in HRV preceded clinical decompensation by 16 days in one large study.59 These analyses may be performed best by data collected remotely. Therefore, device-based physiologic information and diagnostics support the concept that several interdependent cardiovascular factors may change several days to weeks before patients present with volume overload necessitating hospitalization. All the features reported merit testing in clinical trials.60 To be effective, features need to be specific and have a high predictive value for ADHF requiring hospitalization and enable implementation of a treatment algorithm that may prevent hospitalization. In this regard, preliminary data are modest. For example, fluid sensors demonstrated 60% sensitivity with 60% positive predictive value for detecting hospitalization. The false-positive rate was 38%.61 However, early discovery of out-of-bounds parameters may enable earlier and more effective intervention. In this regard, remote monitoring such as HM, which automatically establishes trends with prompt notification of deviations, has considerable value.62 Remote care strategies require prospective evaluation of change-detection algorithms, as in ongoing trials.63

Lead and Device Performance The last several years have witnessed a series of well-publicized problems associated with CIED performance, which continue. Although the absolute incidence usually has been low, the issues have highlighted the lack of a robust monitoring mechanism. Assessing system performance is challenging in view of increasing volume and device complexity, but it is an important responsibility for both physician and industry, recognized by recent position statements.2-4 The Fidelis lead advisory illustrates that innovative designs may degrade rather than enhance performance32,33 (see Fig. 32-8). Critical system problems cluster around battery depletion, HV circuitry failure, and lead failure.26 These are often clinically asymptomatic and could present with sudden death in the event of lack of appropriate therapy, as with lead failure in a pacemaker-dependent patient or undersensing of ventricular arrhythmias in an ICD patient. Alternatively, problems could present with

1000

SECTION 4  Follow-up and Programming

Resynchronization therapy

>120 100 80 60 <40

Atrial Ventricular

Day

Lbs

>8 6 4 2 0 Jun 2009

Aug 2009

120 80

C

40 0

Thoracic impedance (ohms)

A

Jun 2009

Aug 2009

Jun 2009

Aug 2009

>100 90 80

Daily Reference

70 60 50 40 Apr 2009

158 154 150 146

Weight

04/26/04

04/24/04

04/22/04

04/20/04

04/18/04

04/16/04

04/14/04

04/12/04

04/10/04

04/08/04

HEALTH TRENDS

Dec 2009

mm Hg

160

Apr 2009

04/06/04

Most recent measurement Measure 156.38 lbs 07 Feb 2010 Weight Weight gain of at least 5 lb. in a week or at least 2 lb. average ! over a two or more day period 117/70 mm Hg 07 Feb 2010 Blood pressure bpm 07 Feb 2010 Mean heart rate 1.82% of day 07 Feb 2010 Activity level % 07 Feb 2010 HRV footprint ms SDANN 07 Feb 2010 Autonomic balance monitor

>200

Fluid

04/04/04

HEALTH SUMMARY

Night

Apr 2009

04/02/04

B

03/31/04

100 75 50 25 0

FU

03/29/04

100 <50

100 90 80 70 60 50 40 30 20 10 0 03/27/04

Ven. paces (%)

CRT – % ventricular pacing (%)

150

Patient activity hours/day

Avg. V. rate (bpm)

24 20 16 12 8 4 0

2009 OptiVol fluid index

REMOTE MONITORING

>200

% pacing/day

V. rate during AT/AF (bpm) max/day, avg/day

AT/AF total hours/day

IN CLINIC INTERROGATION

140 124 108 92 76 60

3 MONTHS

Jan 2010

Feb 2010

Jan 2010

Feb 2010

Blood pressure

Systolic Diastolic

Dec 2009



32  Follow-up Monitoring of Cardiac Implantable Electronic Devices

1001

Figure 32-12  Heart failure diagnostics. A, This middle-aged male had a long-standing history of ischemic cardiomyopathy and left bundle branch block (LBBB) treated with a CRT-D device without remote monitoring capability. The patient felt lassitude and worsening shortness of breath and presented when fluid congestion started to occur. At outpatient evaluation, he was found to be in atrial fibrillation and congestive heart failure and was admitted for treatment with diuretics. Device interrogation revealed several notable features. Illustrated is the cardiac compass report from the Medtronic CareLink Network system, with graphic display of trended parameters (e.g., atrial fibrillation events, ventricular pacing, and patient activity. The report incorporates OptiVol as a pulmonary fluid accumulation sensor. The patient had developed AF prior to development of heart failure symptoms. Rapid ventricular conduction during AF sometimes led to loss of biventricular pacing. Device retrieved data recorded reduced patient activity and progressive fluid accumulation. B, Remote monitoring (HM) triggering an immediate event notification for loss of CRT pacing function. The patient was treated and the problem rectified rapidly. C, Blood pressure and weight profile in a patient with decompensation in heart failure status (Boston Scientific Latitude). (A modified from Varma N: Automatic remote monitoring of implantable cardiac devices in heart failure: the TRUST trial. J Innov Card Rhythm Manage 1:22-29, 2010.)

extreme patient morbidity, as with lead failure causing multiple inappropriate ICD therapy from oversensing of noise. Premature battery failure may be catastrophic (see Fig. 32-9). Early detection of these complications is desirable to ensure patient safety. The demand for stringent performance evaluation contrasts with the techniques employed to date. Methods based on voluntary return of products are vulnerable to reporting bias, resulting in incomplete and nonvalidated data.64 ICD generator malfunction is acknowledged to be low (0.003 per patient-year was reported from a meta-analysis of device registries), but this is still an order of magnitude higher than for pacemakers, emphasizing the need for monitoring.65 Lead malfunction is more frequent, but rates reported vary sharply among independent studies: 0.6% at 1 year66 and 2.5% to 15% at 5 years.67,68 Malfunction rates reported vary even for a single component in different studies.69 This likely reflects inconsistent methods of data collection and lack of uniform definitions of normal performance versus malfunction. Thus, in one study, problems were discovered during routine face-to-face follow-up, and reprogramming changes without surgical intervention were included in the “failure” rate.67 In contrast, in another study, 76% of lead malfunction came to clinical attention because of inappropriate ICD therapies, and the need for surgical revision defined failure.68 Both reports may underestimate the true incidence of lead failure if malfunctions are asymptomatic or intermittent or result in death (only a minority of devices are interrogated postmortem). Automatic remote monitoring resolves many of these problems. In TRUST the detection method (HM) for system performance was independent of symptoms, follow-up schedule, or patient in-clinic attendance. Additionally, TRUST used a uniform definition for out-of-range behavior and prespecified the recording of clinical actions requiring surgical intervention. The results demonstrated very high system reliability of the ICD system used. Malfunction, when it occurred, was often asymptomatic but could be handled with reprogramming (see Fig. 32-11) and required system revision infrequently. Importantly, remote monitoring detected more patients with device-related issues than calendar-based in-person interrogations.70 Thus, conventional follow-up may underreport device malfunctions, although monitoring guidelines indicate that patients may be followed either in person or remotely.2 HM permitted prompt evaluation of life-threatening problems, including disintegration of HV circuitry and battery or lead failure persisting asymptomatically33,71,72 (see Figs. 32-8, 32-9, and 32-11). Transient asymptomatic sensing issues (e.g., nonphysiologic electrical signals) could be diagnosed rapidly and managed conservatively by reprogramming, thus avoiding inappropriate therapies.70,73 The study creates a device management model in which nearcontinuous surveillance is combined with an automatic ability for self-declaration of system problems. The timeliness and quality of transmitted information enable it to be used as a rigorous mechanism for monitoring system performance, directing prompt therapeutic interventions when required. Automatic archiving of longitudinally collected data with high temporal (24-hour) definition and detection of sudden parameter deviations from baseline trends facilitates assessment of system performance. These features meet the Heart Rhythm

Society’s call for a technology providing continuous surveillance, rapid problem identification and notification, and system performance monitoring.3,4

Economic and Regulatory Considerations Organizational costs may be reduced by preventing unnecessary hospital utilization by nonactionable scheduled or unscheduled visits (e.g., ER attendance due to phantom shocks). Cost benefits are favorable for patients living at greater distances and for facilities that use remote monitoring for large proportions of their patients, and these accrue with time.16,74,75 Although physicians regard prompt notification of life-threatening events as valuable, it remains to be proven whether early diagnosis and timely intervention of serious medical events via remote monitoring reduces hospital admissions and associated costs. However, attaching a value to the economic benefits of remote monitoring also depends on health care models. For example, the cost savings observed in some countries may not be easily transferable to other countries, or indeed within a single country from one health care system to another. Reimbursement tends to spur adoption and implementation of new technologies. Reimbursement guidelines for remote interrogation and in-person programming evaluations were established in January 2009 in the United States (http://www.ama-assn.org/) with CPT (current procedural terminology) codes for monitoring and technical support (which need not be permanent). A single fee is provided for all remote interrogations performed within a 90-day period even if some individual patients may generate several transmissions. However, remote interrogations that prompt in-person programming evaluations may be billed as well. The programming evaluation, which can also be done at least yearly, includes an interrogation of capture, sensing, sensor, rhythms, and overall function through the programmer. Permanent alteration of programmed parameters is not necessary to qualify the in-person evaluation as a programming evaluation. DATABASES Current remote monitoring databases are proprietary and maintained by manufacturers. Information can only be accessed by designated providers through a password system. Integration of remote monitoring data into electronic medical records may facilitate accessibility to diagnostic data and device status. This is a process in evolution. An open-architecture design will expand compatibility and enable data transfer to other repositories. INTEGRATION OF SERVICES Device data retrieved by remote monitoring may be of potential value to several health care providers involved with a patient’s care. This may variously be the implanting or referring physician or heart failure specialist. A communication system is necessary to direct appropriate data to the responsible physician to enable this process.

1002

SECTION 4  Follow-up and Programming

Multidisciplinary efforts aid patient care when applied to a CRT optimization clinic.76 Access to Internet-based information systems may provide a framework for such collaborative models, such as electrophysiologists monitoring device function (arrhythmias, paced burden) and heart failure experts assessing hemodynamic parameters. This may be facilitated by remote monitoring interfacing with electronic medical records, thus immediately placing all relevant data in a single, central database accessible by all treating physicians. REGULATIONS In the United States there is a legal requirement for postmarket registration and tracking of CIEDs.77 Data registration and maintenance are responsibilities shared among implanting physician, center, and manufacturer. These mandates necessitate documentation of model and serial numbers of CIED components as well as patient demographics and communication details. CIED revisions and replacements need to be similarly tracked. Access to these data becomes critical if a patient presents emergently or when a field safety corrective action is issued by regulatory agencies. A database that directly communicates with the registration system would automatically state the CIED follow-up physician and update patient demographics and contact information. Repositories such as the National Cardiovascular Device Registry (NCDR) are important to permit analysis of utilization, programming, and monitoring of system performance and to enhance understanding of treatment effects in different subgroups and disease processes.78 Automatic remote monitoring has a critical role. The ability to collect detailed device and patient data, with component function and clinical parameters assessed daily and automatically, sets a precedent for longitudinal evaluation to follow patient condition and establish norms for lead and generator performance. Automatic data upload and trending reduce the margin of error associated with manual data entry in an era of advancing complexity. These analyses are important not only to practicing physicians but also to private and public insurance agencies, regulatory agencies, professional bodies, and ministries of health that enable provision of these services.

MEDICOLEGAL ISSUES Several medicolegal issues must be addressed. Foremost, technologies can now deliver important information within seconds,33 but response from medical teams may take longer. This may create issues regarding delayed response to a spontaneous transmission of a life-threatening event. Responsibilities of all the parties involved in remote monitoring for specific aspects of the process have been outlined in a recent expert consensus document.2 Patients need to be informed of the purpose, use, and limitations of the technology, and that although the incoming data are verified regularly, remote monitoring is not an emergency information system. Patient inclusion in the responsibility of acquisition, management, and therapy implementation of remotely acquired data may be an appropriate step. Transmitted data, especially with systems providing worldwide cellular links, permit medical decisions to be made across state and international boundaries. Issues of confidentiality and medical responsibility will require further definition. (See Chapter 35 for ethical issues involving CIEDs.)

Conclusion The objective of a CIED implant is to provide ongoing therapy to improve longevity and quality of patients’ life. The clinical indication for implant is itself a dynamic and complex process. Postimplant monitoring is important and requires a structured management protocol. Therefore, adoption of remote monitoring, with its attendant advantages, is increasing and likely to become the standard of care. It allows near-continuous monitoring, automatically declaring parameter deviations, and provision of rapid preemptive clinical interventions when required. This is important in view of the expanding group of heart failure patients who are vulnerable to decompensation. This exceptionbased care model reduces utilization of hospital resources for the physician but permits rapid attention to actionable events. Patient safety and convenience are improved. Automatic data archiving provides a resource for monitoring system performance, advisories, and disease progression. Remote monitoring represents a paradigm shift in the management of patients with CIEDs.

REFERENCES 1. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 51:e1-e62, 2008. 2. Wilkoff BL, Auricchio A, Brugada J, et al: HRS/EHRA expert consensus on the monitoring of cardiovascular implantable electronic devices (CIEDs): description of techniques, indications, personnel, frequency and ethical considerations. Heart Rhythm 5:907-925, 2008. 3. Carlson MD, Wilkoff BL, Maisel WH, et al: Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm 3:12501273, 2006. 4. Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines: developed in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 6:869-885, 2009. 5. Brugada P: What evidence do we have to replace in-hospital implantable cardioverter defibrillator follow-up? Clin Res Cardiol 95(suppl 3):3-9, 2006. 6. Senges-Becker JC, Klostermann M, Becker R et al: What is the “optimal” follow-up schedule for ICD patients? Europace 7:319326, 2005. 7. Varma N, TRUST Investigators: Problem discovery rates of scheduled vs unscheduled and in-patient vs remote evaluations during post-implant ICD monitoring: actionability vs futility in the TRUST Trial. Heart Rhythm 7:S301, 2010. 8. Furman S, Escher DJ: Transtelephone pacemaker monitoring: five years later. Ann Thorac Surg 20:326-338, 1975.

9. Crossley GH, Chen J, Choucair W, et al: Clinical benefits of remote versus transtelephonic monitoring of implanted pacemakers. J Am Coll Cardiol 54:2012-2019, 2009. 10. Lazarus A: Remote, wireless, ambulatory monitoring of implantable pacemakers, cardioverter defibrillators, and cardiac resynchronization therapy systems: analysis of a worldwide database. Pacing Clin Electrophysiol 30(suppl 1):2-12, 2007. 11. Nielsen JC, Kottkamp H, Zabel M, et al: Automatic home monitoring of implantable cardioverter defibrillators. Europace 10: 729-735, 2008. 12. Varma N, Stambler B, Chun S: Detection of atrial fibrillation by implanted devices with wireless data transmission capability. Pacing Clin Electrophysiol 28(suppl 1):133-136, 2005. 13. Joseph GK, Wilkoff BL, Dresing T, et al: Remote interrogation and monitoring of implantable cardioverter defibrillators. J Interv Card Electrophysiol 11:161-166, 2004. 14. Schoenfeld MH, Compton SJ, Mead RH, et al: Remote monitoring of implantable cardioverter defibrillators: a prospective analysis. Pacing Clin Electrophysiol 27:757-763, 2004. 15. US Food and Drug Administration (FDA): Home Monitoring approval, 2001. http://www.fda.gov/MedicalDevices/Products andMedicalProcedures/DeviceApprovalsandClearances/PMA Approvals/ucm113561.htm. 16. Ricci RP, Morichelli L, Santini M: Home monitoring remote control of pacemaker and implantable cardioverter defibrillator patients in clinical practice: impact on medical management and health-care resource utilization. Europace 10:164-170, 2008. 17. Blumber S, Luje J: Wireless substitution: early release of estimates from the National Health Interview Survey (NHIS). National Center for Health Statistics. http://www.cdc.gov/nchs/ nhis.htm. 18. Heidbuchel H, Lioen P, Foulon S, et al: Potential role of remote monitoring for scheduled and unscheduled evaluations of patients with an implantable defibrillator. Europace 10:351-357, 2008. 19. Varma N: Rationale and design of a prospective study of the efficacy of a remote monitoring system used in implantable cardioverter defibrillator follow-up: the Lumos-T Reduces Routine

Office Device Follow-Up Study (TRUST). Am Heart J 154:10291034, 2007. 20. Varma N, Epstein A, Irimpen A, et al: Efficacy and safety of automatic remote monitoring for ICD follow-up: the TRUST trial. Circulation 122:325-332, 2010. 21. Crossley G, Boyle A, Vitense H, et al: The Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT) trial: the value of wireless remote monitoring with automatic clinician alerts. J Am Coll Cardiol 57:1181-1189, 2011. 22. Varma N: Automatic remote monitoring of implantable cardiac devices in heart failure: the TRUST trial. J Innov Card Rhythm Manage 1:22-29, 2010. 23. Zartner P, Handke R, Photiadis J, et al: Performance of an autonomous telemonitoring system in children and young adults with congenital heart diseases. Pacing Clin Electrophysiol 31:1291-1299, 2008. 24. Fye WB: Cardiology workforce: there’s already a shortage, and it’s getting worse! J Am Coll Cardiol 39:2077-2079, 2002. 25. Lee DS, Krahn AD, Healey JS, et al: Evaluation of early complications related to de novo cardioverter-defibrillator implantation: insights from the Ontario ICD database. J Am Coll Cardiol 55: 774-782, 2010. 26. Hauser RG, Kallinen L: Deaths associated with implantable cardioverter-defibrillator failure and deactivation reported in the United States Food and Drug Administration Manufacturer and User Facility Device Experience Database. Heart Rhythm 1:399405, 2004. 27. Varma N, Epstein A, Irimpen A, et al: Event notifications by remote monitoring systems performing automatic daily checks: load, characteristics and clinical utility. Eur Heart J 30:1909, 2009. 28. Theuns DA, Rivero-Ayerza M, Knops P, et al: Analysis of 57,148 transmissions by remote monitoring of implantable cardioverter defibrillators. Pacing Clin Electrophysiol 32(suppl 1):63-65, 2009. 29. Raatikainen MJ, Uusimaa P, van Ginneken MM, et al: Remote monitoring of implantable cardioverter defibrillator patients: a safe, time-saving, and cost-effective means for follow-up. Europace 10:1145-1151, 2008. 30. US Food and Drug Administration (FDA): Home Monitoring approval, 2009. P050023/S020. http://www.fda.gov/



MedicalDevices/ProductsandMedicalProcedures/Device ApprovalsandClearances/PMAApprovals/ucm166550.htm. 31. Al-Khatib SM, Piccini JP, Knight D, et al: Remote monitoring of implantable cardioverter defibrillators versus quarterly device interrogations in clinic: results from a randomized pilot clinical trial. J Cardiovasc Electrophysiol 21:545-550, 2010. 32. Medtronic: Physician advisory letter: Urgent medical device information, Sprint Fidelis lead, patient management recommendations, 2007. http://www.medtronic.com/product-advisories/ physician/sprint-fidelis/PROD-ADV-PHYS-OCT.htm. 33. Varma N: Remote monitoring for advisories: automatic early detection of silent lead failure. Pacing Clin Electrophysiol 32:525527, 2009. 34. Varma N, Stambler BS: Patient aspects of remote monitoring. Circulation 123(7):e247, 2011. 35. Ricci RP, Morichelli L, Quarta L, et al: Long-term patient acceptance of and satisfaction with implanted device remote monitoring. Europace 12:674-679, 2010. 36. Ehrlich JR, Hohnloser SH: Milestones in the management of atrial fibrillation. Heart Rhythm 6:S62-S67, 2009. 37. Bunch TJ, Day JD, Olshansky B, et al: Newly detected atrial fibrillation in patients with an implantable cardioverter-defibrillator is a strong risk marker of increased mortality. Heart Rhythm 6:2-8, 2009. 38. Stein KM, Euler DE, Mehra R, et al: Do atrial tachyarrhythmias beget ventricular tachyarrhythmias in defibrillator recipients? J Am Coll Cardiol 40:335-340, 2002. 39. Ricci RP, Morichelli L, Santini M: Remote control of implanted devices through home monitoring technology improves detection and clinical management of atrial fibrillation. Europace 11:54-61, 2009. 40. Botto GL, Padeletti L, Santini M, et al: Presence and duration of atrial fibrillation detected by continuous monitoring: crucial implications for the risk of thromboembolic events. J Cardiovasc Electrophysiol 20:241-248, 2009. 41. Ricci RP, Morichelli L, Gargaro A, et al: Home monitoring in patients with implantable cardiac devices: is there a potential reduction of stroke risk? Results from a computer model tested through monte carlo simulations. J Cardiovasc Electrophysiol 20:1244-1251, 2009. 42. Kadish A, Dyer A, Daubert JP, et al: Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 350:2151-2158, 2004. 43. Varma N, Johnson MA: Prevalence of cancelled shock therapy and relationship to shock delivery in recipients of implantable cardioverter-defibrillators assessed by remote monitoring. Pacing Clin Electrophysiol 32(suppl 1):42-46, 2009. 44. Poole JE, Johnson GW, Hellkamp AS, et al: Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 359:1009-1017, 2008. 45. Sweeney MO, Sherfesee L, Degroot PJ, et al: Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients. Heart Rhythm 7:353-360, 2010. 46. Rosamond W, Flegal K, Friday G, et al: Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115:e69-e171, 2007.

32  Follow-up Monitoring of Cardiac Implantable Electronic Devices 47. Pulignano G, Del Sindaco D, Tavazzi L, et al: Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF Registry). Am Heart J 143:45-55, 2002. 48. Blackledge HM, Tomlinson J, Squire IB: Prognosis for patients newly admitted to hospital with heart failure: survival trends in 12,220 index admissions in Leicestershire 1993-2001. Heart 89:615-620, 2003. 49. Varma N, Wilkoff BL: Device features for heart failure. Heart Fail Clin North Am 7, 2011. 50. Wilkoff BL, Cook JR, Epstein AE, et al: Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 288:3115-3123, 2002. 51. Cleland JG, Daubert JC, Erdmann E, et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539-1549, 2005. 52. Koplan BA, Kaplan AJ, Weiner S, et al: Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J Am Coll Cardiol 53:355-360, 2009. 53. Yu CM, Wang L, Chau E, et al: Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization. Circulation 112:841-848, 2005. 54. Khoury DS, Naware M, Siou J, et al: Ambulatory monitoring of congestive heart failure by multiple bioelectric impedance vectors. J Am Coll Cardiol 53:1075-1081, 2009. 55. Bourge RC, Abraham WT, Adamson PB, et al: Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 51:1073-1079, 2008. 56. Hoppe UC, Vanderheyden M, Sievert H, et al: Chronic monitoring of pulmonary artery pressure in patients with severe heart failure: multicentre experience of the monitoring Pulmonary Artery Pressure by Implantable device Responding to Ultrasonic Signal (PAPIRUS) II study. Heart 95:1091-1097, 2009. 57. Ritzema J, Melton IC, Richards AM, et al: Direct left atrial pressure monitoring in ambulatory heart failure patients: initial experience with a new permanent implantable device. Circulation 116:2952-2959, 2007. 58. Adamson PB, Kleckner KJ, VanHout WL, et al: Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. Circulation 108:266-269, 2003. 59. Adamson PB, Smith AL, Abraham WT, et al: Continuous autonomic assessment in patients with symptomatic heart failure: prognostic value of heart rate variability measured by an implanted cardiac resynchronization device. Circulation 110:2389-2394, 2004. 60. Adamson PB, Conti JB, Smith AL, et al: Reducing Events in Patients with Chronic Heart Failure (ReduceHF) study design: continuous hemodynamic monitoring with an implantable defibrillator. Clin Cardiol 30:567-575, 2007. 61. Vollmann D, Nagele H, Schauerte P, et al: Clinical utility of intrathoracic impedance monitoring to alert patients with an implanted device of deteriorating chronic heart failure. Eur Heart J 28:1835-1840, 2007.

1003

62. Ellery S, Pakrashi T, Paul V, Sack S: Predicting mortality and rehospitalization in heart failure patients with home monitoring: the Home CARE pilot study. Clin Res Cardiol 95(suppl 3):29-35, 2006. 63. Arya A, Block M, Kautzner J, et al: Influence of home monitoring on the clinical status of heart failure patients: design and rationale of the IN-TIME study. Eur J Heart Fail 10:1143-1148, 2008. 64. Hauser RG, Hayes DL, Epstein AE, et al: Multicenter experience with failed and recalled implantable cardioverter-defibrillator pulse generators. Heart Rhythm 3:640-644, 2006. 65. Maisel WH: Pacemaker and ICD generator reliability: metaanalysis of device registries. JAMA 295:1929-1934, 2006. 66. Borleffs CJ, van Erven L, van Bommel RJ, et al: Risk of failure of transvenous implantable cardioverter-defibrillator leads. Circ Arrhythm Electrophysiol 2:411-416, 2009. 67. Kleemann T, Becker T, Doenges K, et al: Annual rate of transvenous defibrillation lead defects in implantable cardioverterdefibrillators over a period of >10 years. Circulation 115:2474-2480, 2007. 68. Eckstein J, Koller MT, Zabel M, et al: Necessity for surgical revision of defibrillator leads implanted long-term: causes and management. Circulation 117:2727-2733, 2008. 69. Hauser RG, Hayes DL: Increasing hazard of Sprint Fidelis implantable cardioverter-defibrillator lead failure. Heart Rhythm 6:605-610, 2009. 70. Varma N, Michalski J, Epstein A, Schweikert R: Automatic remote monitoring of ICD lead and generator performance: the TRUST trial. Circ Arrhythm Electrophysiol 3:428-436, 2010. 71. Varma N, Cunningham D, Falk R: Central venous access resulting in selective failure of ICD defibrillation capacity. Pacing Clin Electrophysiol 24:394-395, 2001. 72. Hauser RG, Hayes DL, Almquist AK, et al: Unexpected ICD pulse generator failure due to electronic circuit damage caused by electrical overstress. Pacing Clin Electrophysiol 24:1046-1054, 2001. 73. Spencker S, Coban N, Koch L, et al: Potential role of home monitoring to reduce inappropriate shocks in implantable cardioverterdefibrillator patients due to lead failure. Europace 11:483-488, 2009. 74. Elsner CH, Sommer P, Piorkowski C, et al: A prospective multicenter comparison trial of home monitoring against regular follow-up in MADIT II patients: additional visits and cost impact. Comput Cardiol 33:241-244, 2006. 75. Fauchier L, Sadoul N, Kouakam C, et al: Potential cost savings by telemedicine-assisted long-term care of implantable cardioverter defibrillator recipients. Pacing Clin Electrophysiol 28(suppl 1):255259, 2005. 76. Mullens W, Grimm RA, Verga T, et al: Insights from a cardiac resynchronization optimization clinic as part of a heart failure disease management program. J Am Coll Cardiol 53:765-773, 2009. 77. Furman S: Safe Medical Devices Act of 1990. Pacing Clin Electrophysiol 14:387-388, 1991. 78. Hammill SC, Kremers MS, Kadish AH, et al: Review of the ICD Registry’s third year, expansion to include lead data and pediatric ICD procedures, and role for measuring performance. Heart Rhythm 6:1397-1401, 2009.

1004

SECTION 4  Follow-up and Programming

33  33

Electromagnetic Interference and CIEDs KAROLY KASZALA  |  SAMAN NAZARIAN  |  HENRY HALPERIN

Sensing of intrinsic cardiac electrical activity is essential for the

function of pacemakers and implantable cardioverter-defibrillators (ICDs). Device function may be severely compromised if extraneous, nonphysiologic signals are erroneously identified as cardiac signals, termed oversensing. The nonphysiologic signals usually originate from electromagnetic energy sources and present as electromagnetic interference (EMI), defined as an electromagnetic phenomenon that degrades the performance or function of a system. Since the inception of cardiac implantable electronic devices (CIEDs), technology continued to evolve to minimize EMI by using hermetic shielding, improved filtering, and application of interference rejection circuits. These efforts, together with a preference for bipolar sensing, made contemporary pacemakers and ICDs relatively immune to electromagnetic energy sources in homes and workplaces, and interactions remained predictable or avoidable in the medical environment. Management of EMI continues to be an important consideration during the evolution of CIEDs as new technologies within and outside of the field of medicine use more of the electromagnetic spectrum. Increasing presence of wireless telephones, personal electronics, and electronic article surveillance (EAS) devices and increased use of radiofrequency identification have rekindled interest in EMI risks for patients with CIEDs, because adverse interactions have been documented. It is hoped that with collaboration among industry, physicians, regulatory agencies, and consumer groups, full compatibility will be achieved between CIEDs and other technologies.

Electromagnetic Compatibility Sources and types of EMI have exponentially increased over the last two decades, parallel to the increased number of implanted pacemakers and ICDs. Wireless technology is increasingly used to transmit data and is now routinely used during device testing in the operating room (OR) and outpatient clinic. More importantly, semi-automated home monitoring systems are now used for device follow-up. Safe operation of these systems, along with other communication and electronic devices, is a key to maintaining adequate safety. Electro­ magnetic compatibility is defined as adequate device function in an accepted electromagnetic environment without interference with other devices. To achieve compatibility, several preventive steps are warranted. Transmission of electromagnetic waves should be limited to mitigate the risk of interaction, and pacemakers or ICDs should be equipped with protective mechanisms to guard against potential interference. International standards have been developed establishing the upper limit of permissible field intensities and protocols established to test CIEDs against possible interference. Regulatory agencies in the United States established recommendations to test for EMI in CIEDs.1 Draft recommendations are also available for guidance in the use of wireless technology.2

Sources of Electromagnetic Interference Sources of EMI can be classified according to type and spectral frequency of energy emitted, as well as the environment in which the source is encountered (Box 33-1). For clinical purposes, it is useful to recognize radiated and conducted sources of EMI.

1004

RADIATED EMI Radiated EMI can result from energy emitted for communication purposes or as an unintended effect of other electrical activity (e.g., motor operation in an electric razor). Electromagnetic fields have both an electric field, measured in volts per meter (V/m), and a magnetic field. The magnetic flux density is measured in milliteslas (mT). Another common way to characterize an electromagnetic field is by the power density, or power per unit area. Power density can be expressed in milliwatts (mW) or microwatts (µW) per square centimeter (cm2). The unit used to measure how much radiofrequency (RF) energy is actually absorbed by the body is the specific absorption rate (SAR); it is usually expressed in watts per kilogram (W/kg) or milliwatts per gram (mW/g). Electromagnetic sources, for the purpose of examining medical device interactions, may be broadly divided into RF waves, with frequencies between 0 Hz and 450 MHz (e.g., electric power, radio/television transmitters, electrosurgical units, EAS systems), and microwaves, between 450 MHz and 12 GHz (e.g., radar transmitters, cellular telephones, two-way phones, microwave ovens) (Fig. 33-1). The frequency of the EMI determines the efficiency of energy coupling to the device and the resulting effect. The signal may be modulated in amplitude or frequency, and it may occur in bursts or single, long pulses. An RF carrier with amplitude modulation may induce voltages in the signal processing and detection circuitry of a CIED that can be misinterpreted as intracardiac signals.3 In other words, if the amplitude modulation has frequency components in the device’s physiologic passband, significant interference occurs. Electromagnetic fields may also cause interference with RF telemetry. Programming requires access codes to establish the telemetry link, parity checks of transmitted messages, and often simultaneous magnetic reed-switch closure by a steady magnetic field. Although the chance of modifying programmable parameters in a CIED is unlikely with current systems, integrity of the wirelessly transferred data may be affected.4 Another form of radiated EMI may be the result of static magnetic fields, as seen in magnetic resonance imaging (MRI). Static magnetic field is measured in units of tesla (1 T = 10,000 gauss, G). CONDUCTED EMI Directly conducted galvanic currents (measured in amperes per square meter [A-m2]) are most often introduced into the body therapeutically, as by transcutaneous electrical nerve stimulation (TENS) but can also result from physical contact with improperly grounded electrical equipment. A wide range of frequencies may affect implanted devices, including the power frequencies of 50 Hz (Europe), 60 Hz (United States), and 400 Hz (aircraft). Pacemakers and ICDs can react to galvanic currents below the perception threshold (~1 mA/cm2 for moist skin). Clinically, this may result in oversensing in the channel where sensing is occurring. OTHER SOURCES OF RADIATED EMI Ionizing radiation is found in the environment and may be generated by medical imaging or therapeutic equipment. Therapeutic sources would rarely affect CIEDs, but therapeutic radiation used in oncology can damage the oxide layers of complementary metal oxide semiconductor-integrated (CMOS) circuits in ICDs and pacemakers, and the effects are cumulative. The ionizing radiation dose is the



33  Electromagnetic Interference and CIEDs

amount of energy absorbed per unit mass of material, with units of joules per kilogram (J/kg), or gray (Gy). Acoustic radiation from lithotripsy machines is used to disintegrate kidney and gallbladder stones. About 1500 discharges from a 20-kV spark gap generate pressure shock waves that typically measure 45 megapascals (MPa) at the 12-mm diameter focal area. If pressure waves of this magnitude were applied directly to a pacemaker or ICD, the electronic circuits could be damaged.

Box 33-1 

DOCUMENTED SOURCES OF ELECTROMAGNETIC INTERFERENCE (EMI) Electromagnetic Fields Daily life: Cellular telephones, electronic article surveillance devices, metal detectors, some home appliances (e.g., electric razors), toy remote controls, improperly grounded appliances held in close contact to the body, slot machines Work and industrial environment: High-voltage power lines, transformers, welders, electric motors, induction furnaces, degaussing coils Medical environment: MRI scanners, electrosurgery, defibrillation, neurostimulators, TENS units, radiofrequency catheter ablation, therapeutic diathermy

Sources of Knowledge Regarding Electromagnetic Interference Knowledge of EMI effects on implanted devices arises from several sources. Anecdotal reports highlight the possibility of interactions but provide little information regarding overall risk. The interaction may have depended on idiosyncratic programming or device malfunction. In the United States, the Center for Devices and Radiological Health of the Food and Drug Administration (FDA) maintains a database of reported incidents of deleterious interactions (MAUDE) that is searchable online.5 However, reporting is largely voluntary, and documentation is uneven. Case reports published in peer-reviewed journals

Ionizing Radiation Medical environment: Radiotherapy, diagnostic radiology Acoustic Radiation Medical environment: Lithotripsy MRI, Magnetic resonance imaging; TENS, transcutaneous electrical nerve stimulation.

Static Power field line

AM radio

106

104

FM Microwave radio TV oven

102

1

1005

102

Heat lamp

104

Tanning booth

106

108

Medical x-rays

1010

1012

Wavelength (meters) Frequency (Hz) 102

104

ELF

106

108

Radio (RF)

1010

1012

Microwave (M/V)

Non-Ionizing Nonthermal

Thermal

300 m

Optical

VHF-TV

AM radio 3000 m

1014 1016 1018 1020 V i X-ray Infrared s Ultraviolet (IR) i (UV) b l Ionizing e

UHF-TV

FM radio

Microwave oven

30 m

3m

30 cm

3 cm

10 MHz

100 MHz

1000 MHz

10 GHz

Wavelength (meters) Frequency (Hz) 100 kHz

1000 kHz

CB telephones

Cordless telephones

Cellular PCS telephones telephones

Figure 33-1  Electromagnetic spectrum. Frequencies used for communications in the radio and microwave ranges, 100 kHz to 10 GHz (detailed in the lower bar), can interact with implanted cardiac devices. (Modified from Moulder JP: Cellular phone antennas and health. http://www.mcw.edu/ gcrc/cop/cell-phone-health-FAQ/toc.html.)

1006

SECTION 4  Follow-up and Programming

Figure 33-2  Electromagnetic interference (EMI) with electronic article surveillance (EAS) system in patient with dual-chamber ICD. Patient has received several ICD therapies (ATP only); a representative device printout is shown. There is high-frequency, nonphysiologic signal present in all three electrograms (A, atrial; V, right ventricular; Shock, far-field EGM). There is atrial oversensing with ventricular tracking (*). Atrial (AN) and ventricular (VN) noise is identified by the device. Subsequently, ventricular tachycardia (VT) is diagnosed with intermittent ventricular oversensing and antitachycardia pacing (ATP) delivered. ICD shock is aborted due to termination of EMI. Several episodes were identified in the device memory. Further questioning of the patient revealed that all the episodes occurred at work. He was a greeter at a major retail store. With the support of the local device company representative, the workplace was evaluated. EMI was identified as a result of an EAS system, which was next to the chair where the patient frequently rested, usually leaning over the EAS system security gates. No further EMI was noted after the patient was instructed to avoid proximity to the gates.

(especially if they include a re-challenge in a controlled environment) can be most valuable. Prospective studies can be performed in vitro (i.e., bench testing) or in vivo, using laboratory animals or patient volunteers. In vitro studies are performed with the implantable device submerged in a saline-filled tank (to emulate electrical properties of tissue) and the source of radiated EMI in close proximity. A multichamber heart/trunk simulator allows more realistic in vitro testing of devices.6 Anatomically based electromagnetic models of the human body allow the use of numerical modeling to quantify the relationship between an external electromagnetic field and the voltage induced in the leads of a CIED.7 Such modeling can greatly strengthen the clinical relevance of in vitro simulation studies. These investigations allow expeditious study of interactions among various EMI sources and devices. Multiple iterations of the experiment permit examination of the effects of distance, position, field strength, and device programming on the frequency and severity of the interaction. Although simulation studies predict interference in vivo, they do not match clinical exposures identically. Discrepancies may be related to the inability to replicate the strength and path of induced body fields, differences in body position and movements, modifications from shielding effects, and specific absorption rate of the body. The orientation of the air gap between the source and the saline tank (i.e., perpendicular vs. parallel) significantly influences the distance threshold for interaction.8 In a few high-risk circumstances (e.g., MRI), in vivo testing is first conducted in laboratory animals implanted with a pacemaker system. More frequently, in vivo simulation studies require controlled patient exposure to potential sources of EMI while the cardiac rhythm is monitored. Patient exposure studies clarify the clinical significance of in vitro interactions. However, because of the time and effort involved, the number of assessed permutations is, by necessity, limited. To avoid inadvertent bias, it is important to recruit patients who are representative of the general population with implanted devices. In vivo studies are complicated by many sources of EMI also interfering with real-time or Holter electrocardiogram (ECG) recordings. Bipolar asynchronous pacing pulses that do not elicit a QRS complex are particularly difficult to ascertain. Special recording techniques are often necessary. Furthermore, real-time telemetry between the implanted device and the programmer is often compromised by EMI, even when device function remains otherwise normal. Critical review of the literature suggests that some purported instances of EMI have resulted from this inconsequential phenomenon.9 Furthermore, the programmer wand placed directly over the device can act as an artificial shield. Analysis of annotated stored electrograms (EGMs), if available, is the ideal method to

evaluate device behavior during exposure to potential sources of EMI (Fig. 33-2). Protocols for testing of implantable cardiac devices to interactions with sources of EMI were updated by the American National Standards Institute and the Association for the Advancement of Medical Instrumentation in 2007.1 This voluntary standard addresses electromagnetic compatibility of pacemakers and ICDs and provides guidance for device testing. Increased traveling, the globalization and advancement of technology in addition to a rapid increase of the number of implanted devices also warrant a global, international approach for the management of device interactions. International standards for electromagnetic compliance are issued by the International Electrotechnical Commission (IEC) and by the European Committee for Electrotechnical Standardization (CENELEC).10,11

Diagnosis of Electromagnetic Interference In clinical practice, it may be difficult to differentiate EMI from other sources of interference (e.g., myopotentials, lead malfunction, faulty connections) in stored EGMs. EMI typically results in very-highfrequency signals of constant amplitude that can be continuous or pulsatile, depending on the source, and tend to occupy the entire cardiac cycle. EMI is often present in more than one channel; in ICDs, its amplitude is higher in the far-field than in the near-field EGM. Careful history taking usually can retrospectively identify the source of EMI. Diaphragmatic myopotentials typically change in amplitude with the respiratory cycle, and their amplitude is higher in the near-field than in the far-field EGM. Lead fracture or faulty connections inscribe transient, high-amplitude, random signals that saturate the amplifier and occupy only a small fraction of the cardiac cycle. During clinic testing, myopotentials can usually be reproduced by isometric muscle contraction, deep breathing, or the Valsalva maneuver. Oversensing of make-break signals can often be reproduced by device manipulation in the pocket. Lead impedances are often abnormal in cases of lead failure or faulty connection.

Pacemaker and ICD Responses to Electromagnetic Interference The most frequent responses to EMI are inappropriate inhibition or triggering of pacemaker stimuli, reversion to asynchronous pacing, and spurious ICD tachyarrhythmia detection. Reprogramming of



1007

33  Electromagnetic Interference and CIEDs 25 mm/s

VP VP

VS (VS)

VS (VS) (VS) VS VS

VS

(VS) VS (VS)

VS

VS

(VS) (VS)

VS

VS VP

Figure 33-3  Oversensing of electromagnetic interference. Patient had a permanent pacemaker for complete heart block presenting with recurrent syncope. Further inquiry revealed that the EMI had occurred during a radiofrequency catheter ablation procedure for atrial tachycardia and could not account for the clinical episodes. Extensive testing (including prolonged monitoring in an epilepsy unit) established malingering and not true episodes of loss of consciousness.

operating parameters and permanent damage to the device circuitry or the electrode-tissue interface are much less common. PACING INHIBITION Sustained pacing inhibition can be catastrophic in pacemakerdependent patients (Fig. 33-3). Depending on the duration of inhibition and the emergence of escape rhythms, lightheadedness, syncope, or death could result. In pacemakers, protective algorithms make prolonged inhibition uncommon. Patients who are dependent on their ICD for bradycardia pacing may be more vulnerable to prolonged pacing inhibition from EMI. In ICDs, automatic adjustment of either the gain or the sensing threshold, according to the amplitude of the intrinsic R wave, ensures sensing of low-amplitude ventricular depolarization signals during ventricular fibrillation (VF) without oversensing of T waves and extracardiac signals. In the absence of sensed complexes, two potentially life-threatening diagnoses must be considered: asystole (requiring pacing) and fine VF (requiring amplifier gain adjustments for proper detection). To ensure the detection of VF, pacing onset triggers an increase in sensitivity in most devices. These very-high-sensitivity levels can promote oversensing of extracardiac

signals. Oversensing perpetuates, because the absence of spontaneous large-amplitude escape beats maintains the high operating sensitivity. Asynchronous pacing may not occur in the absence of reliable ICD noise-reversion modes. Therefore, EMI-induced prolonged inhibition and spurious tachyarrhythmia detection become likely (see later discussion). Simulation studies of the interactions between sources of EMI and ICDs require creation of a “worst-case scenario” (inducing maximum sensitivity during continuous pacing). TRIGGERING OF RAPID OR PREMATURE PACING Oversensing of EMI by the atrial channel of a pacemaker or ICD programmed to a tracking mode (DDD, VDD) can trigger ventricular pacing at or near the upper tracking rate limit. Alternatively, automatic mode switching may occur if this function is enabled (Fig. 33-4). In some pacemakers, detection of noise in the atrial channel can trigger a noise-reversion mode. Preferential detection of EMI does occur, because atrial sensitivity is usually programmed higher (more sensitive) than ventricular sensitivity. It is possible to observe rapid pacing caused by atrial oversensing as a patient approaches an electromagnetic field, followed by a period of ventricular oversensing (inhibition or

A

NF

FF

AS 508

AS (AS) (AS) AF AF AF AS 318 620 340 173 295 85 520 AS (AS) AF AF AS [AS] AF AP 325 600 100 223 318 133 273 VS VS VS VS VP-Sr VF 630 518 590 798 850 265 VF VF VF VS VS 168 293 200 670 468

AP-SR 928 VS 785

AP-Sr 840 VS 860

AP-SR 840 VS 845

AP-Sr 840 VS 843

AS 900

AS 628 VP-MT 800

VP-MT 800

AS 956 VP-FB 800

Figure 33-4  Spurious mode switch caused by atrial oversensing of EMI in patient with dual-chamber Guidant ICD. Stored atrial (A), nearfield (NF), and far-field (FF) electrograms in a patient who presented for routine ICD follow-up. Nonphysiologic, high-frequency pulsed activity is seen in the three channels, although with higher amplitude in the A and FF traces. Very little ventricular oversensing occurs, so ventricular fibrillation (VF) is not detected. However, atrial oversensing results in transient mode switching. The patient could not recall a potential source of EMI.

1008

SECTION 4  Follow-up and Programming

mode reversion) as the field becomes stronger. If sustained, inappropriate pacemaker acceleration induced by atrial oversensing can cause palpitations, hypotension, or angina. Less frequently, EMI can induce rapid pacing through other mechanisms. For example, some sources of EMI can trigger rapid pacing (up to the sensor-triggered upper rate limit) by activating the sensor in minute ventilation (MV) pacemakers. The signal emitted by acoustomagnetic EAS systems is at the same frequency as the pulses used by some MV pacemakers to measure transthoracic impedance. MV pacemakers may also erroneously interpret the signals generated by certain monitoring and diagnostic equipment, including cardiac monitors, echocardiography equipment, apnea monitors, and respiration monitors, which also use bioelectric impedance measurements.12-14 Very strong electromagnetic fields could induce enough voltage in the lead or leads to directly capture the myocardium. For example, 58-kHz acoustomagnetic EAS systems are capable of inducing 3.7 V in pacemaker leads.15 Isolated premature paced beats (but no sustained rapid pacing) have been observed in patients. In vitro and in vivo animal studies16 have shown that application of 64-MHz RF power, required to produce MRI scans, can result in rapid pacing at pulsing periods between 200 and 1000 msec. Rapid pacing requires an intact lead connected to a pacemaker. Apparently, energy is coupled to the pacemaker defibrillation protection diodes or to the output circuit, bypassing the runaway protection mechanisms. Very rapid pacing could induce VF. Irregular rapid pacing at a rate of approximately 100 beats per minute (bpm) temporarily related to RF pulses during magnetic resonance imaging (MRI) was observed in a patient with a VVI pacemaker programmed at subthreshold output.17 SPURIOUS TACHYARRHYTHMIA DETECTION Electromagnetic interference signals can satisfy ICD tachyarrhythmia detection criteria and lead to spurious ICD discharges (Fig. 33-5). As noted, pacemaker-dependent patients can have concomitant inhibition of pacing. In a follow-up study of 341 ICD patients who received education regarding avoidance of sources of EMI, spurious tachyarrhythmia caused by EMI occurred five times in four patients.18 The incidence was 0.75% per patient-year of follow-up. In a study of 200 chronically implanted Medtronic ICDs with detection of VF, oversensing of EMI was the cause in three patients.19 Intermittent EMI can result in shock delivery if tachycardia detection fails to terminate between the self-limited EMI episodes.

TABLE

33-1 

Pacemakers incorporate protective algorithms against prolonged inhibition from spurious signals (Table 33-1). A common response is transient reversion to asynchronous pacing. These algorithms are based on the fact that rapid frequencies are unlikely to represent myocardial activation. In most pacemakers, a noise-sampling or noise-interrogation window (also known as a relative refractory period) occupies the second part of the ventricular refractory period. Pacemakers do not respond to signals during the initial portion of the ventricular refractory period (i.e., ventricular blanking), which may or may not be programmable, and in some devices is adjusted automatically by the generator based on the strength and duration of the ventricular event. Signals recognized during the noise-sampling window cannot reset the lower rate timer, thus preventing inhibition, but they do affect other timing intervals, most importantly the ventricular refractory period. In some models, a noise-sampling period exists in both the atrial and the ventricular channel. Signals sensed in the noise-sampling period results in resetting of the noise-sampling window and extension of the blanking period. Repetitive triggering of the noise-sampling period eventually leads to asynchronous pacing. During simulation studies, a variable but narrow window of inappropriate pacing or inhibition is frequently observed at field or current strengths just below the reversion thresholds, because of intermittent oversensing. This phenomenon has little clinical significance during real-life EMI exposure. Occasional inhibition over a range of external field strengths is possible because EMI-induced body currents can fluctuate widely with changes in posture, respiratory phase, and other natural circumstances.20 Although transient asynchronous pacing is generally safe, it is not completely innocuous. Symptoms secondary to loss of atrioventricular (AV) synchrony and an irregular heartbeat can occur. Competition with the spontaneous rhythm can induce ventricular tachyarrhythmias if the pacing stimulus captures the ventricle during its vulnerable period. This is extremely uncommon in pacemaker patients, as attested to by the routine use of a magnet during clinic or transtelephonic pacemaker checks. Implementation of noise-protection algorithms is more difficult in ICDs (Table 33-2). By design, these devices must be able to recognize the rapid rates of VF. Therefore, long refractory periods after sensed events are not feasible. Furthermore, asynchronous pacing is undesirable in patients who are vulnerable to reentrant ventricular arrhythmias.21 Newer Boston Scientific devices (Teligen, Cognis) utilize a Dynamic Noise Algorithm (DNA), which adjusts automatic gain

Noise-Reversion and Electrical Reset Responses of Dual-Chamber Pacemakers Programmed DDDR

Manufacturer Biotronik

Model Evia Cylos Phylos II

Boston Scientific

Insignia Altrua

Sorin Group

Symphony Rhapsody Esprit, Reply Sensia Versa Adapta Accent Zephyr

Medtronic St. Jude

NOISE-REVERSION MODE

Magnet Response Automatic*: DOO at 90 bpm (80 bpm at ERI) for 10 beats then DDD at programmed rate ERI: DOO at 80 bpm for 10 beats, then DDD at 89% of programmed rate Asynchronous: DOO at 90 bpm ERI: DOO at 80 bpm Synchronous: Battery good: no effect on pacing rate/mode DDD at 89% of basic rate ERI: DDD at 89% of basic rate Asynchronous*: DOO at 100 bpm if battery is good; 85 bpm if ERI Third beat at 50% programmed pulse width OFF: No change, magnet is ignored EGM mode: No change in pacing mode; magnet application initiates data collection DOO at 96 bpm, gradually declining to 80 bpm at ERI

Full Reset DDI/VVI 70 bpm, 4.8 V at 1 msec

Three beats at 100 bpm, amplitude reduced by 20% on last beat, then DOO at 85 bpm if battery is good; VOO 65 bpm if ERI

VVI 65 bpm, 5 V at 0.4 msec detected polarity

Battery test: DOO at 100 bpm, gradually down to 85 bpm at ERI OFF: No change in pacing Battery test: DOO at 98.6 bpm, gradually down to 86.3 bpm at ERI OFF: No change in pacing

VVI 67 bpm, 5 V at 0.6 msec unipolar VVI 67.5 bpm, 4 V at 0.6 msec unipolar

*Nominal. †Dedicated bipolar” model reverts to bipolar. EGM, Electrogram; ERI, elective replacement indicator.

VVI 65 bpm, 5 V at 1 msec detected polarity Magnet response is OFF VVI 70 bpm, unipolar† Output: 5 V/0.5 msec



33  Electromagnetic Interference and CIEDs

––

1009

–– 221

–– –– –– –– –– –– AS AS 88 455 100 365 129 90 184 531 AS –– –– –– –– –– –– 88 559 188 154 125 133 115 –– –– –– –– – – VT VF VF 512 168 398 225 320 191 174 –– –– –– –– – – VF VF 164 158 449 463 137 273 277

AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS 393 172 340 90 102 221 166 123 213 150 170 523 256 262 348 129 191 AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS AS 162 158 328 354 510 242 352 125 355 479 314 168 365 189 252 514 152 VF VF VF VF VF VF VF VF VF VF VF VF VT VT VF VF VF VF VF VF VF 162 164 188 221 141 240 270 223 279 223 184 158 340 244 180 164 268 150 305 210 615 VF VF VS VF VF VF VF VF VF VF VF VF VF VF VF VF VF VF – – VF 297 164 357 154 250 285 178 139 145 143 221 156 291 227 137 137 230 145 151 137

AS AS AS 533 135 145 AS AS 170 158 VF – – VF 383 135 221 VF VF 158 281

AS 1160 VF 191 VS 930

AS 1088

VS 1025

AS 916 VS 938

AS 836

VS 842

AS 813 VS 824

AS 793

VS 797

AS 785 VS 787

AS 771

VS 773

Figure 33-5  Spurious ICD shock caused by EMI of unknown cause at home. Stored electrogram was retrieved from the memory of a dualchamber ICD during a routine checkup in a 60-year-old man. There is simultaneous sudden onset of electrical noise in the three channels (top to bottom, atrial, near field, far field), which is spuriously detected as ventricular fibrillation (VF). There is immediate disappearance of the noise on shock delivery. The episode had occurred several weeks earlier. Similar, shorter episodes with aborted shocks had been stored weeks before. The patient denied having received a shock. Specific questioning did not disclose any potential cause. The patient had not been subjected to any medical procedure known to induce EMI. The source of the interference remained uncertain. We suspected that the patient had received the shock while using some electrical device at home but did not want to share the information with the medical team. (The immediate disappearance of the interference after the shock suggests that the patient released the device.) Spurious shocks never recurred.

control (AGC) settings in the presence of noise. Sorin devices (Ovatio, Paradym) also decrease sensitivity if noise is detected (signals sensed over 16 Hz). ICDs from Boston Scientific, Sorin, and St. Jude Medical provide programmable noise-reversion modes, but their performance against common sources of EMI is not well documented. Medtronic ICDs lack noise-reversion capabilities. ELECTRIC (POWER-ON) RESET Momentarily strong EMI, by inducing very high voltage within device circuits or triggering special microprocessor timers, may reset pacemakers and ICDs to operate in a mode different from the programmed mode. Electrosurgery and external or internal defibrillation are

common causes of the reset phenomenon. In the reset mode, the pulse generator functions only with the basic factory-preset instructions (pacing mode and parameters) that are stored in the nonvolatile readonly memory (ROM), because communication between the micro­ processor and the random-access memory (RAM), which contains the programmable settings, has been interrupted. Most DDD(R) pacemakers reset to the VVI mode (see Table 33-1). The reset mode does not revert back when EMI is discontinued. Resolution of the problem requires a specific programmer command. In some pulse generators, there is no response to magnet application in the reset mode. In some pacemakers, the pacing mode and rate are similar during electrical reset and elective replacement indicator (ERI). In other pacemakers (e.g., older St. Jude Medical devices), strong EMI can trigger a reset

1010

TABLE

33-2 

SECTION 4  Follow-up and Programming

Noise Reversion, Asynchronous Pacing, and Electrical Reset Responses of Contemporary Implantable Cardioverter-Defibrillators

Manufacturer Biotrinik

Model Lumax

Boston Scientific

Teligen

Sorin Group

Ovatio Paradym Virtuoso Virtuoso II Maximo II Secura

If Sensing > 16 Hz VOO at basic rate while sensing noise None

Fortify Current Plus Current Accel

Programmable: VOO, DOO, or OFF* Fixed rate of 50 bpm

Medtronic

St. Jude Medical

Noise Reversion Non-programmable VOO/DOO pacing when noise exceeds interference rate Programmable: AOO, DOO, VOO, Inhibit

Asynchronous Pacing No

Electrical Reset VVI 70 bpm, 7.5 V at 1.5 msec VR: 150 bpm, 40 J x 8 shocks

AOO, VOO, DOO (requires continuous telemetry link) Electrocautery mode: AOO/VOO/ DOO and Tachy therapy OFF Programmable: V pacing on noise

VVI 72.5 bpm, 5 V at 1 msec unipolar VF: 165 bpm, 41-J committed shocks

Programmable: DOO, VOO with Tachy therapy OFF

Programmable: DOO, VOO, OFF

VVI 60 bpm, 5 V at 0.35 msec VF Detect: 316 msec, 42 J × 4 shocks Partial reset: No change in programmed parameters Full reset: VVI 65 bpm, 6 V at 1.5 msec VF: 320 msec, 35 J × 6 shocks High-urgency alert sounds every 20 hours until cleared “Severe” reset: tachyarrhythmia therapy OFF, VVI 65 bpm, 6 V at 1.5 msec High-urgency alert sounds every 9 hours Software reset: VVI 67 bpm, 5 V at 0.6 msec Defib Only, 36 J × 6 shocks Alert: 2 vibratory stimulus 6 seconds long, 16 seconds apart, every 10 hours

*Nominal setting.

mode or ERI. In those cases, clearing the ERI message with the programmer restores normal function. In Medtronic pacemakers, two levels of electrical reset exist: partial and full. Partial reset tends to occur with less intense interference, preserving the programmed pacing mode and rates. Electrical reset can be differentiated from battery depletion by telemetric assessment of battery voltage and impedance. If reset was caused by EMI, the battery voltage should be normal (~2.8 V), and the battery impedance should be either normal or slightly raised according to battery age. In ICDs, electrical reset generally results in a “shock box” configuration, with VVI pacing and maximum energy shocks (see Table 33-2). A special type of reset (called “hard reset” by St. Jude Medical, “cold reset” or “safety core mode” by Boston Scientific) can occur if there is damage to the ICD microprocessor or memory (e.g., from radio­ therapy). This type of reset is irreversible and cannot be reverted by a programmer command. Prompt generator replacement is usually required. CLOSURE OF THE REED SWITCH Most pacemakers and some ICDs contain a magnetic reed switch that is closed by a 7 mT (Boston Scientific) to 1 mT (Medtronic) static magnetic field. This generally results in temporary asynchronous pacing in pacemakers and temporary suspension of tachyarrhythmia detection and therapy in most ICDs. Normal function returns as soon as the magnetic field dissipates. Older Guidant ICDs were deactivated by continuous application of a magnetic field for 30 seconds or longer. Reactivation required reapplication of the magnet for 30 seconds or longer or a programmer command. Guidant ICDs have been inadvertently deactivated by items that generate inconspicuous strong magnetic fields, such as magnetized screws,22 stereo speakers,22 and bingo wands,23 as well as by unadvised magnet application in health care settings.24 In later devices, this function was programmable and nominally disabled, and it is no longer available in the latest generation of Boston Scientific ICDs. In most contemporary ICDs, magnetic reed switch and its function has been largely replaced by other technologies (integrated solid-state detection, Boston Scientific; Hall effect sensor, Medtronic; telemetry coil, Sorin Group; GMR circuit, St. Jude Medical). Transient suspension of antitachycardia pacing caused by reedswitch closure had been shown to occur frequently with oldergeneration ICDs. In a study of 46 patients with St. Jude ICDs (which keep a log of magnet reversions), nine unexplained inactivations occurred outside the medical environment (10% per patient-year of follow-up).25

Response to magnet application is also programmable in various devices to trigger specific behaviors, including storage of EGMs and event markers or replay of alert tones. Exposure to a strong magnetic field when these functions are activated can result in eccentric (but clinically inconsequential) device behavior.26 However, inadvertent asystole can occur when magnet application does not result in asynchronous pacing in pacemakers during electrosurgery. DAMAGE TO GENERATOR OR ELECTRODEMYOCARDIUM INTERFACE In almost all cases, the effects of EMI are temporary, lasting only as long as the device is within range of the source. However, very strong EMI (e.g., electrosurgery, external defibrillation) can cause permanent damage to an implanted device. Circuitry damage can result in output failure, pacemaker runaway, and other malfunctions, requiring generator replacement (at times emergently). Increases in pacing thresholds secondary to local heat-related injury at the lead-myocardium interface are also possible. Current devices incorporate elements (Zener diodes, thyristors) that protect the pacing output circuitry and sensing amplifiers by shunting excess energy away from the device. The Zener diode behaves as a short circuit as soon as the voltage exceeds a certain value, such as 10 to 15 V, that is substantially above the output voltage of the pulse generator. Other circuit designs can also limit the current flowing up the lead, but at the expense of inhibition of pacing output during the reception of large voltages.27 INTERACTIONS WITH TELEMETRY FUNCTION Communication between the CIED and programmer is achieved by RF transmission via a wand. Once the “handshake” is complete and connection established with the programmer, further communication may be accomplished via wireless communication with certain devices. Wireless communication has also been increasingly used for home monitoring of device function and clinical status.28,29 Communication may be inhibited or greatly degraded if interference from external sources is present. These interactions may occur during device testing in the OR or clinic as well as potentially in the home. DETERMINANTS OF ELECTROMAGNETIC INTERFERENCE The effects of EMI on pacemakers and ICDs depend on the intensity of the electromagnetic field, the frequency spectrum of the signal, the



33  Electromagnetic Interference and CIEDs

Box 33-2 

FACTORS INFLUENCING EMI Intensity of the field Signal spectrum Duration of exposure Nonprogrammable device characteristics Lead configuration Programmed parameters Sensitivity Mode (baseline, noise reversion) Committed versus noncommitted (ICDs) Patient characteristics Distance and position of the patient Pacemaker dependency Susceptibility to asynchronous pacing Susceptibility to rapid pacing rates ICDs, Implantable cardioverter-defibrillators.

distance and positioning (angle) of the device relative to the source, the electrode configuration (unipolar or bipolar), nonprogrammable device characteristics, programmed settings, and patient characteristics (Box 33-2). Electrical and magnetic fields decrease inversely with the square of the distance from the source. Devices from different manufacturers differ in susceptibility to various sources of EMI, depending on circuitry design. EMI from digital cellular telephones has largely been suppressed by incorporation of simple RF feedthrough filters to the circuitry. Interference is most likely when the antenna is placed over the device header. Neither the sensing electrodes near the distal tips of the leads, nor the coated lead body, is susceptible. A higher-programmed sensitivity level increases device susceptibility to EMI. Unipolar pacemakers are more vulnerable to EMI from sources in the lower range of the frequency spectrum, such as power lines.30 Left-sided unipolar CIEDs are particularly susceptible because of the larger loop for voltage induction between the lead and the generator. Sensing configuration loses importance at longer radiation wavelengths. The extent of pacemaker dependency and presence of an ICD are the main determinants of the clinical sequelae of EMI. Prolonged pacing inhibition does not cause symptoms in a patient with a good escape rhythm, but could result in catastrophic asystole in a pacemakerdependent patient, or it may trigger ICD therapies.

Sources of Electromagnetic Interference DAILY LIFE Cellular Telephones, Wireless Communication Devices, Personal Media Players By the end of 2010, subscribers to mobile cellular phone services are expected to reach 5 billion worldwide. Although cell phones continue to be the most popular wireless communications devices, personal digital assistants (PDAs), laptop computers, wireless Internet connections, portable digital media players, and other appliances are being increasingly used for wireless voice, data, music, and video transmission. Assessment of the effects of cell phones on CIEDs has been complicated by the wide variety of technologies in use.31 Almost all current wireless telephones operate with digital technologies, although many can fall back to analog operation if their digital mode is not available. The Global System for Mobile (GSM) communications has become the predominant digital platform worldwide. Other digital technologies in use in the United States and elsewhere include North American Digital Cellular (NADC), also known as Time Division Multiple Access (TDMA-50 Hz); Code Division Multiple Access (CDMA); integrated Dispatch Enhanced Network (iDEN), a cell phone system that also serves as a walkie-talkie platform; and Personal Communication System (PCS). New third- and

1011

fourth-generation (3-G, 4-G) networks with increased speed for data transmission are being deployed. Wireless networks operate in the 800- to 960-MHz or the 1.8- to 2.5-GHz band. The power level used by a wireless telephone (and the consequent emitted electromagnetic field) fluctuates throughout the call, according to distance from the base station and the number of devices being used on the system at the same time. The maximal power of handheld phones is limited to 0.6 W in the United States and 2 W in Europe. Vehicle-mounted units can transmit at higher powers (up to 8 W), but they are not in common use by the general public. Although isolated case reports have suggested the potential for severe interactions,32 most research indicates that deleterious interactions are unlikely to happen with normal cell phone use. Large-scale bench-testing studies of the effects of wireless telephones on pacemakers and ICDs have been conducted at the FDA’s Center for Devices and Radiological Health,33,34 the Medical Devices Bureau of Canada,35 and the University of Oklahoma’s Wireless Electromagnetic Compatibility Center.36,37 These studies encompassed several thousands of runs of telephone-device combinations and provided consistent results. Interference was nonexistent with the now-outdated analog telephones. The pulsed component of the transmission in digital cell phones was detectable by pacemaker sensing circuitry if the field was strong enough. PCS and similar technologies produced interactions in less than 1% of tests, whereas other digital technologies (GSM, TDMA) produced inter­ ference in 0% to 25% of tests. In all studies, just a few models were responsible for a disproportionately large number of interactions, and other models were largely immune. An older version of TDMA-11 technology (used only for specialized business applications such as trucking, delivery, and construction in the United States) accounted for most interactions with ICDs. Titanium casing and introduction of feedthrough filters, now common in modern pacemakers, made devices virtually immune to interference. Almost all interactions occurred at distances of less than 10 cm. Devices always reverted to normal operation when the phone was turned off. Systematic investigations of the effects of cell phones in patients with pacemakers and ICDs have documented that severe interactions are improbable with most technologies during regular phone use. In a comprehensive multicenter study, Hayes et al.38 tested 980 patients with implanted pacemakers for potential interference with five types of telephones (one analog and four digital: NADC, TDMA-11, PCS, and CDMA). Telephones were tested in a simulated worst-case scenario; in addition, NADC telephones were tested during transmission to simulate actual use. Patients were monitored while the phones were held at the ipsilateral ear and in a series of maneuvers directly over the pacemaker. The incidence of any type of interference was 20% in the 5533 tests. Tracking of interference sensed in the atrial channel, asynchronous pacing, and ventricular inhibition were the most common reactions observed (14%, 7%, and 6%, respectively). Interference was least frequent with analog (2.5%) and PCS (1.2%) systems. Clinically significant EMI was observed in 7% of tests and was considered severe in 1.7%. There were no clinically significant EMI episodes when the telephone was placed in the normal position over the ear. The presence of feedthrough filters in the pacemakers almost abolished the risk of EMI (from 29% to 56% down to <1%). In a study of 39 pacemakers, EMI was more common with portable 8-W GSM telephones than with handheld 2-W models (7% vs. 3% of tests); oversensing was more frequent at maximal than at nominal sensitivity (6% vs. 2% of tests).39 In a recent study of 100 patients with pacemakers from five manufacturers equipped with feedthrough filters testing a GSM cell phone with maximum power of 2 W in the standby, dialing, and operating mode, only two instances of ventricular inhibition were observed with the phone held directly over the pocket and the ventricular sensitivity programmed unipolar at 0.5 mV or less. Reprogramming of the sensitivity to 1 mV abolished the interaction in both cases.40 In another European study, 158 patients with pacemakers from one of seven manufacturers were tested for EMI using a GSM and PCS phone (max power 2 W vs. 1 W, operating frequency 900 MHz vs. 1800 MHz, respectively).41 The

1012

SECTION 4  Follow-up and Programming

phones were placed over the device (as if carried in breast pocket), and EMI was evaluated while the device received a call (highest power emission). Device interaction was very rare and only occurred in four older devices with less advanced filters. The GSM telephones did not induce inappropriate rapid pacing in patients with MV pacemakers42 or atrial oversensing in single-lead VDD pacemakers programmed at maximum atrial sensitivity.43 In a study of 95 children with a variety of pacemakers programmed to a worst-case scenario, GSM telephones did not induce significant interference.44 Clinical worst-case scenario testing has not disclosed significant interactions between ICDs and wireless digital telephones.44-47 Digital cell phones do not interfere with the detection of induced VF in the electrophysiology laboratory.47 Inconsequential intermittent loss of telemetered EGMs and surface ECGs and inscription of erroneous event markers (i.e., “pseudo-oversensing”) recorded via the programmer are common. Although this may have limited significance during a clinic visit, implications may be different if interaction occurred during the use of a remote home monitoring system. Effect of GSM phones were tested in vitro (three-chamber heart stimulator) as well as in vivo in a study to evaluate possible interactions with Biotronik pacemaker/ICD home monitoring system. A proprietary telemetry is used in these devices transmitting in the 402 to 405–MHz band with maximum power of 25 µW to communicate with the base unit within a 10-foot (3-m) distance. The base unit in turn transmits data via GSM cellular network to the monitoring center. No interactions were observed during in vitro testing, and there was 93% success in transmissions in vivo.48 Delay or loss of transmission was seen as result of EMI. Similar home monitoring systems are also available from several other manufacturers. Portable media players, especially iPODs (Apple, Cupertino, Calif.) have been increasingly used (>270 million units sold worldwide). Because these units are frequently carried in the shirt pocket and close to the CIED, several studies addressed possible device interactions. While reproducible programmer telemetry interactions were common, these were clinically nonsignificant, and no other serious interaction was seen with modern pacemakers.49-52 Clinically significant device interaction caused by strong magnetic field may occur, however, if portable headphones are held close to a CIED.53 Telemetry interactions may have important implications in the use of home monitoring systems, and these need to be addressed in the future. Although cell phones can potentially interfere with the function of implanted devices, this interference does not pose a health risk when telephones are placed over the ear. Maintaining an activated cell phone at least 6 inches (15 cm) from the device prevents interactions. The FDA has issued simple recommendations to minimize the risks. Patients should avoid carrying their activated cell phone or iPOD in a breast or shirt pocket overlying a CIED. A wireless telephone in use should be held to the ear opposite the side where the device is implanted. A survey of 1567 Japanese patients with implanted pacemakers revealed that, although 94% were right-handed, 41% used the left hand preferentially to hold a wireless telephone.54 Not-so-obvious reasons for choosing one hand versus the other to hold the phone included hearing loss on one side (10%) and use of the opposite hand for dialing or writing memos (22%). At least in some patients, apparently the hand preferentially used to hold the wireless telephone should be considered when selecting the site for pacemaker implantation. Limited in vitro and in vivo testing has suggested that 3-W GSM telephones do not interfere with the function of an implantable ECG loop recorder.55 A single case report suggested interference between an ILR and the handheld activator if an iPOD is operating in proximity to the devices.56 In an in vitro study, PDAs connected to a hospital wireless local area network (WLAN) using the 802.11b protocol did not interfere with a variety of pacemakers and ICDs manufactured by Guidant, Medtronic, or St. Jude Medical.57 As other wireless communication devices become prevalent, their effects on CIEDs should be carefully scrutinized.

Electronic Article Surveillance Devices Also known as antitheft devices or “antishoplifting gates,” EAS devices are ubiquitous in retail stores, libraries, and office buildings. More than 1 million systems have been installed worldwide. The transmitter in these devices emits an electromagnetic field that is designed to interact with a “tag” in an unpurchased item. As a result of the interaction, the tag emits a signal that is detected by the receiver. Customers are exposed to an electromagnetic field as they walk through the gate, which typically consists of a pair of transmitter and receiver pedestals. EAS systems differ greatly in the frequency and strength of their emitted fields. Available technologies include high-frequency systems (operating beyond 900 MHz), swept RF systems (operating at 2 to 10 MHz), low-frequency acoustomagnetic systems (30-132 kHz), and electromagnetic systems (20 Hz to 18 kHz). These technologies serve different retailers’ needs in terms of area covered, cost, detection, and “false alarm” rate, and they are not strictly interchangeable. The general consumer cannot differentiate these systems by their external appearance. Electromagnetic fields from these devices have the potential to induce interference signals in the sensing circuit of implanted cardiac devices. A sentinel report described a patient with complete heart block and a Ventak (CPI/Guidant) AV ICD in an abdominal pocket who developed multiple shocks and near-fatal inhibition of pacing on exposure to an acoustomagnetic EAS system.58 Provocative testing with similar equipment in a controlled environment reproduced the interaction. The maximum distance at which ventricular oversensing occurred was 30 cm. When sensitivity was reprogrammed from “nominal” to “least sensitive,” the interaction occurred only at closer proximity. Prospective studies have clarified the incidence, severity, and risk factors for EMI from EAS systems. An in vitro study showed that 20 of 21 pacemaker models reacted to the field of an acoustomagnetic EAS system, and 10 reacted to an electromagnetic system.59 Responses included inhibition and noise reversion. Interference occurred when the simulator was within 33 cm of the transmission panel for the acoustomagnetic system, or 18 cm for the electromagnetic system. Mugica et al.60 exposed 204 patients with pacemakers to two different EAS systems (acoustomagnetic at 58 kHz and electromagnetic at 73 Hz) for up to 30 seconds. Interference occurred in 17% of patients and was twice as likely with the acoustomagnetic system. Atrial tracking, asynchronous pacing, and single-beat inhibition were observed. All the interactions were transient and deemed benign. McIvor et al.15 studied the effects of six EAS devices of three types (magnetic audiofrequency, swept radiofrequency, acoustomagnetic) in 50 patients with pacemakers and 25 patients with ICDs from seven different manufacturers. One exposure protocol mimicked the most common real-life situation, walking at a normal pace midway between the gates. A “worst-case scenario” protocol required the patients to lean against the transmitter gate with the body parallel and then perpendicular to the transmitter. Interactions occurred with 48 pacemakers, almost exclusively with acoustomagnetic systems. No pacemaker reacted to the swept RF systems. Only two patients had transient asynchronous pacing while exposed to an electromagnetic system. The frequency of interactions with the acoustomagnetic system increased with the duration and closeness of the exposure: 16% when walking through the gates and 96% when leaning against the pedestal. Transient asynchronous pacing was the most common response, followed by atrial oversensing with tracking, ventricular oversensing with inhibition, and “voltage-induced” paced beats. Changing the sensing configuration from unipolar to bipolar, or programming a lower sensitivity setting, did not abolish the interactions but limited them to closer distances from the center of the gate. There were no instances of false tachyarrhythmia detection, but the ICDs were not programmed to pace during the testing. Groh et al.61 studied the interaction between ICDs and two electromagnetic and one acoustomagnetic EAS devices in 169 patients. No spurious detections occurred during a 10- to 15-second walk through the gates. False VF detection occurred in three patients during a



2-minute exposure to the acoustomagnetic system. When the 2-minute exposure was repeated during continuous pacing in 126 patients, oversensing was observed in 19 (15%). Oversensing was severe (complete or prolonged pacing inhibition) in 7 patients (6%), including 3 patients who had had spurious tachyarrhythmia detection at baseline and 4 additional patients with Ventritex ICDs who had oversensing during exposure to an electromagnetic system. All the patients with serious interactions had an abdominal implant; however, by multivariate analysis, diminished R-wave amplitude and a Ventritex ICD were the only predictors of interactions. In summary, severe interactions between EAS systems and CIEDs are unlikely when patients walk through the gates at a normal pace. On the other hand, dangerous interactions are likely with prolonged, close exposure to acoustomagnetic or electromagnetic systems. Patients should be instructed not to linger in proximity or lean against theftdeterrent gates. Retailers should avoid placing systems where people are required to linger, such as at checkout counters. Merchandise or information (e.g., store floor plans) should not be displayed close to antitheft systems. The FDA recommends that all manufacturers of electronic antitheft systems develop labeling or signage to post on or near all new and currently installed systems, indicating that an electronic antitheft system is in use. The labeling or signage should be positioned so that it is visible before an individual enters the monitored area.62 Metal Detectors Handheld and walk-through metal detectors are used for security applications. They function by sensing disturbances in electromagnetic fields. Handheld metal detectors typically operate at a frequency of 10 to 100 kHz and produce weak fields (≤4 A/m at a distance of 1 inch). Weapons are detected only within 1 to 4 inches. Walk-through metal detectors have coils on one or both sides of the equipment. They operate in a continuous wave (5-10 kHz) or in pulsed mode (200400 Hz). Magnetic fields measured at the chest level inside the arch are less than 2 G.63 Typically, a person walking through is exposed for 3 seconds. Kolb et al.64 monitored 200 patients with pacemakers and 148 patients with ICDs from a variety of manufacturers for interactions with a standard airport metal detector gate. Pacemakers were reprogrammed to force ventricular pacing and ICDs to maximum sensitivity. Testing included normal walking through the gate and a worst-case scenario in which the chest was as close as possible to the gate and a 360-degree torsion was performed around the body axis. There were no interactions with any system. The FDA has received one report of a spurious ICD shock triggered by a handheld metal detector in an airport. In several other instances, older-model Guidant ICDs reverted to “monitor-only” mode after being exposed to metal detectors.5 Current FDA recommendations state that it is safe for patients with implanted cardiac devices to walk through a metal detector gate, although the alarm may be triggered by the generator case. If scanning with a handheld metal detector is needed, patients should ask the security personnel not to hold the detector close to the implanted device longer than is absolutely necessary. A manual personal search can also be requested.65 Electric Power Electromagnetic interference from electric power sources can occur if patients come in proximity to high-voltage overhead power lines (accidentally or by occupation). EMI also may be caused by electrical appliances that are held close or in direct contact with the chest. Implanted devices are susceptible to interference signals of 50 to 60 Hz, frequencies that lie within the bandwidth sampled for detection of intracardiac signals. Detrimental effects from incidental exposure to high-voltage lines are unlikely. Even at a distance of 40 m from a 400-kV line, the electric and magnetic field strength is very low. Numerical studies suggested that the thresholds for EMI from magnetic fields at power line

33  Electromagnetic Interference and CIEDs

1013

frequencies under the worst-case scenario for unipolar pacemakers are 40 µT in the atrium and 140 µT in the ventricle.66 In vivo studies disclosed that all types of response (inhibition, triggering, noise reversion) could occur, depending on the strength of the field, the generator model, the sensing configuration, and the programmed sensitivity.30 Trigano et al.67 exposed 250 pacemaker patients to a 50-Hz magnetic field with a flux density of 100 µT (the maximum allowed public exposure by European activities). There were no effects in devices programmed to bipolar sensing. Three patients with unipolar devices had noise-reversion to asynchronous mode; in one, symptomatic pacing inhibition followed. The studies suggest that bipolar sensing protects from EMI in all but the most extreme environmental conditions, such as power-generating stations. With unipolar sensing, inappropriate pacemaker behavior can occur during routine daily exposures. The EMI from household appliances results almost exclusively from improper grounding. Washing machines appear to be a frequent offender.68-70 Anecdotal reports have incriminated slot machines,71 power drills operated in a wet environment,70,72 a current leak from a water boiler (occurring when the hot-water faucet was opened),73 and vibrators.18 A patient with a normally functioning ICD received spurious shocks caused by 60-Hz interference while entering and exiting a public swimming pool; the current leak was otherwise undetectable.74 Household induction ovens are safe in patients with pacemakers75 or ICDs.76 Two case reports describing patients with spurious ICD discharges from low-level alternating-current leak are especially illuminating. In a man with spurious ICD discharges caused by use of an electric razor, provocative testing confirmed oversensing of 50-Hz power with the patient’s razor and a new similar unit. At operative revision, an insulation break was discovered at the ventricular coil of the “integrated” bipolar Endotak (Guidant) lead.77 A boy with a single-chamber Medtronic ICD with an “integrated” bipolar Sprint lead had spurious detection of VF caused by oversensing of 60-Hz current while swimming in a pool and taking a shower powered by an electrical generator. The proximal and distal coils had been inverted in the device header. Because of the hardwiring in the lead and device header, the generator may become part of the sensing circuit.78 Both systems were operating “de facto” in a unipolar sensing mode. Neuromuscular incapacitation devices have been increasingly used by law enforcement officers and by the general public. The Taser device (Taser International, Scottsdale, Ariz.) shoots darts that are wired to the device and deliver up to 50,000 V over 5 seconds to the victim, causing painful tetany. Oversensing with spurious detection of VF has been described after application of a shot from a Taser device.79 Lakkireddy et al.80 analyzed the effects of Taser shots in animals implanted with an ICD. No permanent device damage was seen, but oversensing was common with Taser application. Alternative Medicine Devices A variety of “therapeutic magnets” are commercially available for the treatment of arthritis and other musculoskeletal ailments. Despite manufacturers’ claims of very strong magnetic field strengths (up to 30,000 G), in vitro testing showed that the magnets were able to close the reed switch only when placed at a distance less than 1 inch from the generator.81 Spurious ICD shocks have been reported with unsupervised use of popular battery-operated muscular stimulators for abdominal training.82 Acupuncture entailing delivery of current to needles inserted in the anterior chest has triggered spurious ICD shocks.83 The “Zapper” is a battery-powered alternative medicine device that delivers a square-wave output at a constant frequency of 33.3 kHz.84 These electronic pulse frequencies are applied to both hands. It is marketed to enhance immune function and eliminate chronic illnesses, parasites, and germs. Vendors advise against the use of these devices in patients with pacemakers. Symptomatic pacemaker inhibition from oversensing has been documented in a patient with heart block during use of the Zapper.84

1014

SECTION 4  Follow-up and Programming

WORKING ENVIRONMENT Industrial Equipment The return of the CIED patient to a work environment suspected of high-level EMI can be challenging. Among the myriad potential EMI sources, arc or spot welders, industrial welding machines, degaussing coils, and electrical motors are frequent causes of concern. Not only do these sources emit energy in the RF spectrum, but their associated magnetic fields could potentially cause magnet response in pacemakers and ICDs. Static magnetic fields strong enough to close the reed switch are unlikely to be present in industrial environments. For example, in a petroleum refinery, peak fields of almost 2 mT were measured close to large compressors and in power distribution centers. However, the fields dropped off to less than 0.1 mT at a distance of 4 feet.85 High levels of electromagnetic radiation exist in the cockpits of general aviation aircraft. However, in vitro testing of five modern pacemakers programmed in a unipolar configuration during flight conditions in single-engine fixed-wing aircraft did not demonstrate EMI.86 There are no current guidelines regarding certification of air pilots with implanted cardiac rhythm management devices. Each patient should be evaluated individually for recommendations to manage EMI at the workplace, although a few generalizations can be made. Bipolar sensing systems with close-coupled (≤1 cm) electrodes should be used preferentially in patients who may be exposed to high levels of EMI at work. The sensitivity should not be programmed very high in relation to the intrinsic EGM amplitude. Implant testing of VF detection at the least sensitive setting allows estimation of the sensing “safety margin” and appropriate reduction in the chronically programmed sensitivity. It is useful to ask a technical consultant from the device manufacturer to conduct a comprehensive EMI test at the patient’s worksite. However, this service may not be generally available because of liability issues. There is no professional reimbursement provided for an on-site visit by clinic staff. Testing should include measurement of magnetic fields at various distances from the source and review of telemetered and stored EGMs and event markers while the patient is operating the equipment. (ICDs should be programmed “monitor only” to avoid spurious shocks).87 In pacemaker-dependent patients, testing of a device identical to the one implanted coupled to a heart simulator represents a safe, sensitive preliminary step.88 In patients with Guidant ICDs, a simple screening strategy consisting of listening to QRS-synchronous beep tones (a programmable feature) after extending the detection duration while the patient routinely operates the equipment is safe and effective.89 This feature is not available in the newer Boston Scientific models (Cognis/Teligen). In patients with ICDs from St. Jude Medical or Boston Scientific that are exposed to intense magnetic fields at work, inhibition of tachyarrhythmia therapy in response to magnet application may be programmed off. Additional general precautions include ensuring appropriate grounding of the equipment and avoiding close contact with the EMI source. Arc welders, for example, should wear nonconductive gloves and should not carry the cables on their shoulder.90 Accidental grasping of a 60V/30A alternating-current power line by a television cable line installer with an ICD triggered a spurious shock due to detection of 60-Hz electrical noise.91 Patients should be instructed that, if they experience lightheadedness or an ICD shock (see Fig. 33-5), they should stop operating the equipment and contact their physician. Many patients could return to work with these precautions. Following these general guidelines in everyday situations is challenging because of inadequate resources to carry out these tests and potential medicolegal considerations for the provider as well as the employer. Furthermore, changing work environments need to be constantly reassessed. MEDICAL ENVIRONMENT Patients with implanted cardiac devices (who typically are of advanced age and with severe cardiovascular disease) often require diagnostic and therapeutic procedures that involve strong sources of EMI. Most

of these procedures can be performed safely with appropriate planning. Consultation regarding exposure to EMI in the medical environment constitutes a common clinical practice issue for physicians and nurses who are caring for patients with pacemakers and ICDs. The routine use of preprocedural checklists to identify CIED patients in advance is strongly recommended.92 Likewise, all institutions (especially those with dedicated staff and clinics) should have written policies regarding evaluation and management of patients before, during, and after procedures involving sources of EMI. Continuous education of patients and colleagues in other specialties and avoidance of improvisation will minimize unexpected outcomes and reduce legal liability. Magnetic Resonance Imaging Compared with x-ray–based diagnostic techniques, MRI has many advantages, including lack of ionizing radiation, superior soft tissue resolution, and multiplanar imaging capabilities. In properly operating MRI systems, hazardous interactions between electromagnetic fields and the human body are negligible.93 However, deleterious interactions between electromagnetic fields of MRI and CIEDs may occur. The FDA database contains several reports of deaths in pacemaker patients during or immediately after MRI.94 These reports are poorly characterized in terms of type of pacemaker and programming, patients’ pacemaker-dependency status, field strength of the MRI unit, imaging sequence, and cardiac rhythm at death. Six deaths during MRI in patients with pacemakers have been reported from Germany; none of these patients was pacemaker dependent. The scans were performed in private radiology practices for orthopedic or neurologic reasons, with 0.5- to 1.5-T scanners and without monitoring. In three cases, VF was documented.95 Earlier literature regarding interactions between implanted devices and MRI has become obsolete because of the continuous evolution in device construction and function and improved MRI protocols. However, at most institutions, the presence of an implantable device has remained an absolute contraindication to MRI, precluding a substantial and growing number of patients from the advantages of this imaging modality. Three types of electromagnetic fields are present in the MRI environment: an “always-on” static magnetic field (with its spatial gradient), a rapidly changing magnetic gradient field, and an RF field (Box 33-3). The last two are pulsed during imaging.96 Exposure to the static magnetic field (0.2 to 3 T at the center of the magnet bore in current commercially available systems) occurs on entry into the MRI suite. This results in activation of the reed switch with asynchronous pacing in pacemakers and suspension of tachyarrhythmia detection in most ICDs. Paradoxically, when the MRI static field is perpendicular to the reed-switch axis (i.e., when patient inside gantry of scanner), the reed switch may not be activated, and demand pacing (as programmed) may persist.97,98 The static magnetic field can also impart translational Box 33-3 

POTENTIAL EFFECTS OF MRI ON CIEDS Static Magnetic Field Reed-switch closure/magnet response Generator displacement Radiofrequency Field Alterations of pacing rate (inhibition or triggering) Spurious tachyarrhythmia detection Heating Electrical reset Time-varying magnetic gradient field Induction voltage (resulting in pacing) Heating Reed-switch closure/magnet response CIEDs, Cardiac implantable electronic devices; MRI, magnetic resonance imaging.



and rotational (torque) forces to a generator containing sufficient ferromagnetic material, which may theoretically result in pain and tissue damage. No magnetic force is measured at the isocenter of the magnet, but it increases rapidly toward the portal of the scanner. On the other hand, magnetic torque is highest at the isocenter of the magnet. In vitro studies have shown that translational attraction and torque levels are mild (i.e., acceleration lower than the gravity of the Earth) with current pacemaker and ICD generators exposed at 1.5 T.99-101 However, limited tests suggest that even modern pacemakers can be subjected to potentially dangerous translational attraction with 3.0-T scanners.100 The metallic parts of the leads are usually composed of MP35N, an alloy of nickel, cobalt, chromium, and molybdenum that is nonferromagnetic. Therefore, leads will not move or dislodge as a result of magnetic attraction.102 The RF fields can induce EMI in device circuitry, with resulting inhibition, tachyarrhythmia detection,103 reset,104 or rapid pacing. Several mechanisms for rapid pacing have been proposed. Rapid pacing up to the upper track limit can occur in dual-chamber devices if EMI is sensed in the atrial channel. Inhibition in pacemakerdependent patients may be avoided by programming asynchronous modes, whereas tracking may be avoided by programming inhibited modes. “Runaway” pacing synchronized to the RF pulses (attributed to interference with pacemaker electronics) is the most severe potential complication. Rates up to 300 bpm have been observed in animal studies.16 Additionally, the time-varying magnetic fields pulsed during imaging may induce voltage in leads that can pace the heart or interfere with sensing. This could occur even when the device is in OOO mode or when it is programmed to deliver subthreshold pulses.17 Tandri et al.105 assessed the magnitude of MRI-induced current using a current recorder connected in series to single-chamber permanent pacemakers programmed to subthreshold asynchronous output during unipolar and bipolar pacing. Under conventional implant conditions (without additional lead loops), the magnitude of induced current was less than 0.5 mA. The addition of five lead loops allowed current induction at greater than 30 mA and resulted in myocardial capture. Additionally, breaking the return pathway by electrically isolating the pulse generator case from the circuit abolished low-frequency–induced current. High-level RF fields can also produce reversible or permanent damage to the device circuitry or memory. MRI has been reported to reprogram103 or permanently damage ICDs and pacemakers.101 Certain older-generation devices (e.g., Ventak Mini III ICD) are prone to complete loss of programmability if exposed to MRI.101,106 Generally, ICDs manufactured before 2000 are irreversibly damaged by in vivo and in vitro tests, whereas more current ones are not affected. In 15 dogs with chronically implanted ICDs manufactured after 2000, 3- to 4-hour MRI scans did not result in device dysfunction, although spurious detection of ventricular tachyarrhythmia was common.101 Recently, device reset to a backup pacing mode was described in a modern device at 3 T, resulting in transient asystole in a pacemaker-dependent patient.107 Therefore, further testing will be needed to assess device safety at 3 T. The RF field in an MRI scanner has sufficient energy to cause local heating of long conductive wires, such as pacemaker leads, which could damage the adjacent myocardial tissue. Such thermal changes may theoretically result in increased thresholds, or even myocardial perforation. Bench studies have provided varying estimates of the heating at the lead tip, because the cooling effect of circulating blood is difficult to simulate.101,108 In open-chest dogs with right ventricular (RV) pacing or defibrillation leads connected to temperature probes, the maximum recorded heating was only 0.2° C, even during nonclinical high-SAR (up to 4 W/kg) imaging protocols.101 In swine experiments using chronically implanted pacing leads modified by the addition of a thermocouple sensor at the tip, increases in temperature of up to 20° C were measured during MRI of the heart at 1.5 T and high SAR.109 Heating peaked within seconds and appeared to depend strongly on the position of the pacing lead within the body coil of the MRI unit. Maximal heating was observed when the pacemaker and the whole lead were inside the RF field-transmitting body coil. A significant increase

33  Electromagnetic Interference and CIEDs

1015

in lead impedance was measured immediately and 2-weeks after scanning. Changes in capture threshold were minor, although one RV apical lead showed an acute increase in capture threshold of 2 V that returned to baseline within 2 weeks. There was no release of troponin. Pathologic analysis could not clearly demonstrate heat-induced damage around the lead attachment.109 In the in vivo studies of Roguin et al.,101 one of 15 dogs with chronically implanted ICD, subjected to a 4-hour MRI scan, revealed immediate failure to capture at maximum output, which resolved after 12 hours. There were no acute or chronic changes in capture threshold in the other animals. Histopathologic analysis revealed no or very limited necrosis or fibrosis around the tip of the lead, similar to findings in control animals. Importantly, most undesirable clinical events have occurred in patients who were inadvertently subjected to scanning without appropriate device programming or monitoring. On the other hand, there have been no major complications in clinical series of planned MRI in patients. Vahlhaus et al.97 performed 34 MRI examinations with a 0.5-T system in 32 nondependent patients with pacemakers reprogrammed to pace asynchronously above the intrinsic rate. In almost one half of the patients, temporary deactivation of the reed switch (activated on entering the MRI suite) occurred when the patient was positioned in the gantry of the scanner at the center of the magnetic field. No instance of rapid pacing was seen. Lead impedance and pacing and sensing thresholds did not change. Battery voltage decreased immediately after MRI and recovered within 3 months, without changes in projected longevity. Programmed data and the ability to interrogate, program, or use telemetry were not affected. The authors concluded that MRI at 0.5 T is feasible in select patients with pace­ makers, and that it does not affect the devices irreversibly. Martin et al.110 reported results of 62 clinically indicated MRI examinations at 1.5 T in 54 nondependent pacemaker patients. No specific programming was followed. All pacemakers were interrogated immediately before and after MRI scanning. No adverse events occurred. ECG changes and patient symptoms were minor and did not require cessation of MRI. There were significant threshold changes in 10 leads (9.4%). Only 2 (1.9%) of the 107 leads required a change in programmed output. Threshold changes were unrelated to cardiac chamber, anatomic location, peak SAR, or time from lead implantation to the MRI examination. MRI at 2 T was uneventful in 13 nondependent patients with St. Jude Affinity bipolar pacemakers.111 Gimbel et al.112 reported safe MRI of the head and neck in 10 pacemaker-dependent patients. The pacemakers (St. Jude Medical or Medtronic) were reprogrammed DOO or VOO, and MRI pulse sequences were modified to limit the whole-body SAR. There was no significant change in threshold immediately after imaging or 3 months later. There are no clinical series describing the results of MRI in pacemaker-dependent ICD patients. In another study, Gimbel et al.113 described eight MRI scans (7 cranial, 1 lumbar spine) at 1.5 T in seven patients with ICDs (all but one from Medtronic). Detection was programmed off, and pacing was set to a subthreshold output during the scan. After MRI, all devices demonstrated no changes in pacing, sensing, impedance, charge time, or battery status. The ICD exposed to the lumbar spine scan reverted to the “power-on-reset” mode, without permanent damage. MR scanning was safe in 10 patients with Medtronic Reveal implantable loop recorders. In the majority of patients, postscanning device interrogation disclosed artifacts mimicking tachycardia. There was no permanent damage to the devices.114 Based on in vitro and in vivo analyses,101 a protocol has been developed at the Johns Hopkins Hospital, including (1) device selection based on previous testing, (2) device programming to minimize inappropriate activation or inhibition of brady/tachyarrhythmia therapies, and (3) limitation of the SAR of MRI sequences (<2.0 W/kg).115 To perform MRI in patients with CIEDs, it was recommended that device generators prone to EMI be excluded (generally, older devices not on the tested devices list in the protocol, Fig. 33-6). Despite the low risk for lead and generator movement, patients were excluded who were judged to have higher risk of lead movement. Therefore, MRI was avoided in new CIED patients (<6 weeks) or patients with no fixation

1016

SECTION 4  Follow-up and Programming

Device with satisfactory previous MRI testing?

Pacemakers with satisfactory previous MRI testing

Yes

No

Device implant >6 weeks prior to MRI?

No

Alternative tests

Yes

Guidant Vigor (1232) Discovery (1272) Insignia (1194, 1290)

Absence of non-transvenous epicardial, No abandoned, and no-fixation leads? Yes Check device parameters: lead impedance and threshold, P/R wave amplitude, and battery voltage

ICD

Monitoring and tachyarrhythmia therapies (antitachycardia pacing/defibrillation)—off

Pacemaker dependent?

Pacemaker dependent?

No

VOO/DOO

No

Yes

St. Jude Photon (V-194, V-230, V-232) Atlas (V-240) Epic (V-197, V-235, V-239) Guidant Prizm (1850, 1851, 1850, 1860, 1861) Contak (1823, H119, H170, H175) Vitality (T125, T135)

VVI/DDI

Medtronic Maximo (7232) Gem-II (7273) Gem-II (7275) Marquis (7274) InSync (7272)

Magnet, rate, PVC, noise, ventricular sense, conducted atrial fibrillation response—off

Estimated SAR of sequence >2.0 W/kg

Medtronic EnPulse (AT-500, E2SRO1, E2DRO1) Kappa (701, 901) Prodigy (7860) In Sync BiV (8040, 8042) ICDs with satisfactory previous MRI testing

Pacemaker

Yes

St. Jude Pacesetter AFP (262) Trilogy (2360) Entity (5326) Affinity (5130, 5330) Integrity (5142, 5342, 5346) Identity (5172, 5370, 5376, 5380, 5386)

Yes

No Monitor blood pressure, ECG, oxygen saturation, and symptoms during MRI

Limit SAR by increasing repetition time or field of view, and/or reducing flip angle or the acquisition bandwidth

Recheck device parameters: lead impedance and threshold, P/R wave amplitude, and battery voltage Figure 33-6  Protocol used at the Johns Hopkins Hospital for magnetic resonance imaging (MRI) studies in patients with cardiac implantable electronic devices (CIEDs).

(superior vena cava coils) leads. Using the Hopkins Protocol, patients with mature active- and passive-fixation endocardial (and coronary sinus) leads of any diameter could safely undergo MR scans. MRI is avoided when device leads prone to heating are present, such as nontransvenous epicardial and abandoned (capped) leads. To reduce the risk of inappropriate inhibition of pacing caused by detection of RF pulses, devices are programmed to an asynchronous, dedicated pacing mode in pacemaker-dependent patients. Also, given the lack of asynchronous pacing programming capability and transient

loss of pacing capture after worst-case scenario (SAR 3.5 W/kg for 3 hours) with in vivo testing of 1 of 15 animals implanted with an ICD,101 we recommend excluding pacemaker-dependent patients with ICDs. To avoid inappropriate activation of pacing caused by tracking of RF pulses, we suggest device programming in patients without pacemaker dependence to a nontracking ventricular or dual-chamber inhibited pacing mode. We also recommend deactivation of rate response, premature ventricular contraction response, ventricular sense response, and conducted atrial fibrillation response to ensure that sensing of



33  Electromagnetic Interference and CIEDs

Generator susceptibility artifact

Left atrium

1017

initial study, we successfully limited the system-estimated whole-body average SAR to 2.0 W/kg in more than 99% of sequences while maintaining the diagnostic capability of MRI. Almost all clinical experience has been obtained with 1.5-T magnets. Susceptibility lead and generator artifacts are observed on MR images and are most pronounced on steady-state free-precession images (Fig. 33-7). Selecting imaging planes perpendicular to the plane of the device generator, shortening the echo time, and using spin-echo and fast spin-echo sequences reduces the qualitative extent of artifact. Bright artifact areas on delayed enhancement images can mimic areas of scar. However, areas with true late gadolinium enhancement can be identified by selection of appropriate image planes and correlation to functional images (Fig. 33-8). Diagnostic questions were answered in 100% of nonthoracic and 93% of thoracic studies. Clinical findings included diagnosis of vascular abnormalities (9 patients), diagnosis or staging of malignancy (9 patients), and assessment of cardiac viability before surgical ventricular reconstruction (13 patients).115 As long as manufacturers do not claim their devices to be “MR safe” or “MR compatible,” wide use of MRI in CIED patients is unlikely to be implemented.116 Future developments in lead and device design and technology may reduce MRI-induced heating and other forms of interference and make MRI safer.117,118 Shielding strategies include special coating (i.e., nanomagnetic) and low-pass filtering. A fiber-optic pacing lead (Biophan Technologies, Rochester, N.Y.) has been developed and appears safe in the MR environment.119 Most recently, a new pacemaker system (Medtronic EnRhythm MRI SureScan and CapSureFix MR leads) has been designed and tested for safe use in the MR environment. The new system includes hardware and software changes

Lead susceptibility artifact

Figure 33-7  Steady-state free-precession vertical long-axis magnetic resonance (MR) image of the left ventricle in a patient with an implantable defibrillator. The right ventricular lead susceptibility artifact is noted in the inferoapical portion of the left ventricle.

vibrations or RF pulses does not lead to unwarranted pacing. Although asynchronous pacing for short periods is typically well tolerated, we prefer to reduce the already-minimal chance of inducing arrhythmia or causing AV dyssynchrony by minimizing asynchronous pacing in patients without pacemaker dependence through deactivation of the magnet mode when possible. We typically deactivate tachyarrhythmia monitoring to avoid battery drainage that results from recording of multiple RF pulse sequences as arrhythmic episodes. Reed-switch activation in ICD systems disables tachyarrhythmia therapies. However, reed-switch function in the periphery versus the bore of the magnet is unpredictable; therefore, therapies should be disabled to avoid unwarranted antitachycardia pacing or shocks. Also, to reduce the risk of thermal injury and changes in lead threshold and impedance, we recommend limiting the estimated whole-body averaged SAR of MRI sequences (<2.0 W/kg when possible). Blood pressure, ECG, pulse oximetry, and symptoms should be monitored for the duration of the examination. We also favor the presence of a radiologist and cardiac electrophysiologist, or advanced cardiac life support–trained individual familiar with device programming and troubleshooting, during all scans.115 At the end of the examination, all device parameters are checked and programming restored to pre-MRI settings. Using this protocol we have now safely performed MRI on more than 400 CIED patients. Our initial report of safety included 31 patients with permanent pacemakers (22% of whom were pacemaker dependent) and 24 patients with ICDs.115 No episodes of inappropriate inhibition or activation of pacing were observed, and there were no significant differences between baseline and immediate or long-term sensing amplitudes, lead impedances, or pacing thresholds. In this

Left ventricle

Left atrium

Lead susceptibility artifact

Apical delayed enhancement

Figure 33-8  Postcontrast inversion-recovery prepared-gradient recalled-echo horizontal long-axis cardiac MR image. Lead susceptibility artifacts are noted in the right atrium and ventricle. An apical area of late gadolinium enhancement is also visible.

1018

SECTION 4  Follow-up and Programming

to ensure reliable operation during MRI and lead changes to reduce lead tip heating from RF energy. The EnRhythm MRI study, a prospective randomized controlled trial (RCT), was designed to test the safety of this new MRI-compatible pacing system.120 The results have favorable FDA review and suggest that a dual-chamber pacing system can be designed that is not affected by MR scanning. Until fully MRI-compatible systems are clinically available, the decision to perform MRI in patients with potential contraindications is frequently made by considering the potential benefit of MRI relative to the attendant risks. The reader is encouraged to consult other resources, such as the recent American Heart Association Scientific Statement,121 and websites that provide more specific information regarding individual devices (e.g., www.mrisafety.com) for specific device testing details. Neurostimulators Case reports suggest that deep-brain stimulators (used to treat Parkinson’s disease and other movement disorders) are compatible with pacemakers or ICDs. Two scenarios are possible: the need to implant a cardiac device in a patient with a preexisting neurostimulator122-124 and the decision to implant neurostimulators in a CIED patient.125 Testing protocols and surgical approaches vary accordingly. If possible, testing for interactions should be performed preoperatively with a simulation screener device, intraoperatively, before discharge, and at each programming session. True bipolar sensing should be preferred. Unipolar deep-brain stimulation has not resulted in oversensing by pacemakers or ICDs.123-125 High-energy ICD shocks can reset neurostimulators to the off mode.124 The programmer wand for Medtronic neurostimulators contains a magnet that will close the reed switch of a pacemaker or ICD if moved close to the pocket. Transtelephonic monitoring (TTM) of the pacemaker may require that the neurostimulators be turned off transiently.125 Spinal cord stimulation has been used to treat peripheral vascular disease, intractable pain, and refractory angina pectoris. Concomitant use of pacemakers or ICDs and spinal cord stimulators is feasible, but testing is needed to avoid interactions.126,127 Oversensing of the output of a spinal cord stimulator programmed in a unipolar configuration can result in pacemaker inhibition or noise-reversion. Therefore, only bipolar spinal cord stimulation should be used. If a cardiac device is implanted after a spinal cord stimulator has been placed, bipolar sensing should be preferred. Ekre et  al.128 reported on 18 consecutive patients treated with concomitant spinal cord stimulators for refractory angina and permanent pacemakers. Postimplantation testing consisted of ECG monitoring after programming of the pacemaker to a worst-case scenario (unipolar sensing and high sensitivity) while increasing the bipolar spinal cord stimulator output to the maximally tolerated level. There was no interference during acute testing. During long-term follow-up, there was no clinical evidence of pacemaker malfunction. No published experience is available on the concomitant use of CIEDs and other stimulators used to treat epilepsy (vagus nerve), fecal incontinence, or neurogenic bladder, but similar testing for interactions appears indicated. Stimulators in which the power source is not implanted but instead is RF-coupled (e.g., Medtronic Mattrix) are contraindicated in patients with pacemakers or ICDs. Peripheral Nerve and Muscular Stimulation Peripheral nerve stimulators are used to assess the extent of neuromuscular blockade intraoperatively or in the intensive care unit (ICU) and to locate nerves for blocks. Frequencies of less than 4 Hz (240 bpm) are unlikely to invoke noise-reversion modes. Reproducible inhibition of a unipolar right-sided VVI pacemaker during intraoperative left facial nerve stimulation with the standard train-of-four mode at 2 Hz has been reported.129 Peripheral nerve stimulators can inhibit the display of pacemaker pulses in modern digital monitors and make the diagnosis of EMI difficult.130 Diagnostic nerve conduction studies with needle electrodes introduced at or distal to elbows or knees are safe in pacemaker patients.131 Although guidelines suggest that

electrodiagnostic studies are safe in patients with ICDs, provided special precautions are taken regarding the duration and frequency of stimulation pulses,132 experts recommend that tachyarrhythmia detection be turned off during such studies.133 This topic deserves further study. Transcutaneous electrical nerve stimulation (TENS) and interferential electric current therapy are methods for the relief of acute and chronic musculoskeletal pain. A TENS unit consists of electrodes that are placed on the skin and connected to a generator that applies 20-µsec rectangular pulses of up to 60 mA at a frequency of 20 to 110 Hz. Output and frequency are adjusted to provide maximum pain relief. Early studies in patients with unipolar pacemakers reported inhibition by TENS, which at times could be eliminated by increasing the sensing threshold.134 In a study of the effects of TENS (at four sites, in 51 patients with 20 different pacemaker models), there were no instances of interference, inhibition, or reprogramming.135 It appears that TENS can be used safely in patients with modern implanted bipolar pacemakers and in patients with unipolar pacemakers if sensitivity is reduced. TENS electrodes should not be placed parallel to the lead vector; electrodes should be placed close to each other and as far as possible from the generator/lead system. There is anecdotal experience with the use of TENS in patients with ICDs. Spurious shocks triggered by TENS application in patients with a variety of lead configurations and sensing algorithms have been documented.136-138 Ambulatory TENS has triggered ICD shocks in patients in whom acute provocative testing did not show interactions.139 Therefore, TENS should be avoided in patients with ICDs. Chronic low-frequency stimulation of thigh muscles with biphasic symmetrical pulses of approximately 0.5 msec at frequencies of 15 to 63 Hz is useful in patients with chronic congestive heart failure and muscular weakness, many of whom have pacemakers or ICDs.140 In a pilot acute study, electrical stimulation of the neck and shoulder and of the thighs induced oversensing in three of eight patients with bipolar ICD systems.141 In select patients with pacemakers or ICDs in whom acute testing did not demonstrate interaction, long-term stimulation of thigh muscles with two different protocols was safe.142,143 Electroconvulsive Therapy Electroconvulsive therapy (ECT) is useful in major depressive illness, especially in elderly and medically frail patients. Potential concerns are EMI from the ECT shock itself, oversensing of myopotentials during succinylcholine-induced fasciculations or from incomplete muscular paralysis during the induced seizure, and detection of the common but generally benign tachyarrhythmias that occur during the seizure. There are isolated case reports of uncomplicated ECT in patients with pacemakers. The Mayo Clinic has reported on ECT in 26 patients with pacemakers and three patients with ICDs, who received a total of 493 treatments.144 In patients with ICDs, tachyarrhythmia detection was disabled during the procedure. There were no instances of deleterious EMI. The authors concluded that ECT was safe in patients with implantable devices; they recommended a consultation and device interrogation before the beginning and at the end of treatment, as well as proper attention to grounding. No special programming appears to be necessary in patients with pacemakers. A nondepolarizing muscle relaxant can be used for patients who demonstrate oversensing of fasciculations. In patients with ICDs, tachyarrhythmia therapy should be disabled before the procedure and re-enabled as soon as the seizure is over. Electrosurgery Several electrosurgical techniques can generate EMI. The nomenclature of these techniques can be confusing. In Europe, “surgical diathermy” is often used to describe electrosurgical techniques, whereas in the United States, diathermy refers to the therapeutic application of current directly to the skin and is used for musculoskeletal ailments. Application of diathermy in heating or nonheating modes can result in excessive heating of tissue around leads and irreversible damage. RF



33  Electromagnetic Interference and CIEDs

1019

A V S

––

–– –– 246 213 –– 162 –– 297 –– –– 424 189

–– 410

–– 418 –– –– 430 527 –– –– 629 393 –– 236

–– 324

–– 602

–– VT 211 297 –– 191

AS 1412 VF 172

VS 373

AS 352

VS 484

AF 270 VF 266

AS AS 553 363 AF 143 VS 574 VF VF 283 201

Figure 33-9  Spurious ventricular fibrillation detection due to electrosurgical equipment. Stored atrial (A), ventricular (V), and shocking lead (S) EGMs in a patient with a Ventak atrioventricular Mini III ICD who underwent placement of a Hickman catheter contralateral to the ICD pocket. Nonphysiologic signals are seen in both sensing channels. Tachyarrhythmia therapy was disabled before surgery. The atrial sensitivity was nominal; the ventricular sensitivity was programmed to “less.” The device logged in seven detections during the surgical procedure. (From Pinski SL, Trohman RG: Interference in implanted devices. Part II. Pacing Clin Electrophsyiol 25:1496-1509, 2002.)

(short-wave) or microwave diathermy is absolutely contraindicated in patients with pacemakers or ICDs.145 Although “electrocautery” is often used when referring to electrosurgery, in its strict sense, electrocautery describes a technique that promotes hemostasis by heating a metal instrument. Because no current is passed in the body, there is little or no risk of EMI. Batteryoperated electrocautery is often used during pacemaker implantation. Electrofulguration and electrodessication are monoterminal techniques that destroy only superficial tissues; these are used mostly in dermatologic surgery. Because there is no dispersive ground electrode, minimal current is generated in the body away from the lesion being treated. The most common electrosurgery modalities, electrosection (electrocutting) and electrocoagulation, involve passing current through tissue. Coagulation or cutting current is usually delivered in monopolar configuration. Current begins at the active electrode located on the surgical instrument and, after traveling through the body, returns to the electrosurgical generator through a dispersing ground pad. Both cutting and coagulation use high-voltage, low-amperage current with high-frequency radio wave oscillations greater than 100,000 Hz. Pure cutting is generated by a continuous signal, rarely in excess of 2000 V. It creates high temperatures, causing cell explosion and evaporation. Coagulation is produced by a higher-amplitude signal (up to 10,000 V) that has a very short dwell time. The short, intermittent bursts produce heat within the tissue to control bleeding by thermally sealing the end of a blood vessel. Coagulation current is more likely than cutting current to cause interference.146 A blended current (e.g., 50% of the time on and 50% off) is used most frequently. Few surgeons use pure cutting current unless specifically asked. In true bipolar electrocoagulation, the current flow is localized across the two poles of an instrument (e.g., coagulation forceps). Because current flow outside the surgical site is minimal and less power is used, it is unlikely to induce EMI. However, it is useful only for delicate surgical procedures and small vessels. Both monopolar and bipolar configurations are used during therapeutic endoscopic procedures (e.g., polypectomy, bleeding vessel cauterization).147 A recent study reported the prevalence of EMI during 52 gastrointestinal endoscopy procedures in 41 ICD patients, 10 of which required electrocautery. The ICD was programmed to monitor only for VT detection. No instances of EMI or tachycardia detection were noted, but the study has limited immediate clinical impact because of the small number of patients.148 Alternative surgical tools that will not produce EMI include the Shaw scalpel149 (Oximetrix, Mountain View, Calif.), laser scalpels,150,151 and ultrasound scalpels (Harmonic Scalpel, UltraCision,

Smithfield, R.I.).152 Extensive in vitro testing of a microwave thermotherapeutic device for transurethral ablation of benign prostatic hyperplasia (BPH) suggests that it does not interact with pacemakers or ICDs.153 During electrosurgery in monopolar modes, the electric current spreads out and penetrates the entire body of the patient. This stray current may be interpreted by an implanted device as an intracardiac signal. Pacing inhibition, pacing triggering, automatic mode switching, noise reversion, or spurious tachyarrhythmia detection can occur,154 depending on the type of device, the programmed settings, the duration of EMI, and the channel in which the current is oversensed (Fig. 33-9; see also Fig. 33-2). Although some investigators have suggested that electrosurgery is safe in patients with activated ICDs,155 the risk of spurious tachyarrhythmia detection is clearly present. Electrosurgery can also induce sensor-mediated pacing at the upper rate limit in MV pacemakers.156 A more recent study was conducted in 92 patients with contemporary pacemaker or ICD who underwent electrocautery. The investigators identified only minor, temporary effects (brief atrial oversensing). Ventricular oversensing occurred rarely and only in pacemaker patients if electrocautery was less than 8 cm from the pulse generator. No ICD interactions were observed while VT detection was programmed on.157 Other types of interaction are more common during electrosurgery than with other sources of EMI. In one study, up to 20% of older pacemakers reverted to the power-on reset mode, especially when the surgical wound was close to the pacemaker pocket.158 In a more recent, prospective study of 45 patients, electrosurgery triggered electrical reset in 7% of the patients.159 Myocardial electrical burns may occur if there is conductivity between the pacing electrode and the indifferent (return) electrode of the electrosurgical unit. This may be facilitated by a pacing electrode with a small surface area and a higher current density. Furthermore, protective circuitry (i.e., Zener diodes, thyristors) that shunt current away from the device may also contribute to the development of myocardial burns and subsequent elevation in pacing thresholds. Severe damage (and even VF) can occur if the dispersive electrode is disconnected from the circuit, because the pacing electrode becomes the return electrode in the circuit and delivers current to the heart directly.160 Irreversible generator failure caused by damage to internal circuitry can occur, especially when current is applied close to the device pocket. Permanent loss of output or runaway syndrome161 can be life threatening. Voltage control oscillator lockout has been identified as a mechanism of sudden output failure after electrosurgery current.162,163 Irreversible loss of output has been

1020

SECTION 4  Follow-up and Programming

reported after an initial application of electrocoagulation current far away from the pacemaker system (i.e., during hip replacement).164 Although late recovery of function can occur,163 the device should not be trusted after initial failure. Under special circumstances, an interaction may be documented between the self-check system of an electrosurgical generator and the high-voltage (HV) impedance test of Teligen ICD (Boston Scientific). Impedance of the patient return electrode patch in this particular electrosurgical generator model (Force FX, Valleylab, Boulder, Colo.) is constantly measured to ensure adequate skin contact and prevent skin injury during electrosurgical generator activation. Infused current is similar to that used for noninvasive testing of HV lead impedance in Teligen devices, and erroneous HV impedance measurements may occur. Other manufacturers (Medtronic and St. Jude were tested) use higher current for the same measurement and were immune to this form of interference.165 Guidelines exist for the management of CIED patients undergoing electrosurgery166,167 (Box 33-4). Short notice and scarcity of specialized personnel make compliance with such guidelines difficult, even in a large hospital with a well-staffed pacemaker clinic. Preoperative evaluation should routinely include a procedure for implantable device management in case electrocautery or other procedure is expected that may result in EMI. Ideally, the patient should be evaluated before surgery to determine pacemaker dependency and to document pacing Box 33-4 

MANAGEMENT OF CIED PATIENTS UNDERGOING ELECTROSURGERY Preoperative Consider alternative tools (scalpel and ligatures, ultrasonic scalpel, laser scalpel). Identify device and determine “reset” mode. Check device (programming, telemetry, thresholds, battery status). Develop a contingency plan in case arrhythmias or device malfunction occur during the procedure. In the Operating Room Disable tachyarrhythmia therapies (by programming or magnet application). Deactivate rate-responsive features. If the patient is pacemaker dependent, reprogram device to asynchronous or triggered mode (with long refractory period). Remember that asynchronous pacing is not available in some ICDs. In these cases: Decrease the maximum sensitivity. If available, program the noise-reversion mode to asynchronous. Apply external transthoracic pacing system. Consider insertion of separate transvenous pacing wire. Monitor peripheral pulse or oximeter (ECG is obscured by artifact). Position the ground pad to keep the active-to-dispersive current pathways as far as possible and perpendicular from the pulse generator-to-electrode pathway. The current should flow away from the pulse generator. Use true electrocautery or bipolar electrocoagulation whenever possible. Limit cutting current to short bursts interrupted by pauses of at least 10 seconds. Use the lowest effective cutting or coagulation power output. Do not use probe near device. Reprogram if reset mode is hemodynamically unfavorable. Postoperative Reactivate ICD tachyarrhythmia therapy. Check device (programming, telemetry, thresholds, battery status). Reprogram if necessary. Replace generator if circuit damage documented. Replace lead or leads if pacing threshold is too high.

and sensing thresholds, although chart review may suffice if the device was tested within 3 to 6 months in a chronic implant. Rate-response and tachyarrhythmia detection should be disabled just before surgery. In patients who are not pacemaker dependent, it is best not to change the programmed mode. Pacemaker-dependent patients should be reprogrammed to an asynchronous mode (DOO, VOO, AOO) above the intrinsic rate. Magnet application over the device may also be considered. In some pacemakers, magnet application does not result in asynchronous pacing, and in ICDs, magnet application suspends detection but does not trigger asynchronous pacing. Asynchronous pacing modes are not available in many ICDs. Current from the electrosurgical unit distorts the ECG, and it may be impossible to determine whether pacemaker inhibition occurs. Pulse oximeter plethysmography and invasive arterial pressure monitoring are invaluable in this situation. The dispersive pad should be placed as close as possible to the operating site and as far as possible from the pulse generator and leads, so that the electrical pathway is directed away from the pacing system. For example, during transurethral resection of the prostate, the grounding pad should be on the buttocks or lower leg. Good contact of the pad is mandatory, because with poor contact the pulse generator becomes the anode for the applied current. The patient’s body should not come in contact with any grounded electrical device that might provide an alternative pathway for current flow. Proper grounding of all electronic equipment used near the patient is essential. The monopolar probe should not be used within 15 cm of the pulse generator or lead. Cutting or coagulation time should be as short as possible, using the lowest feasible energy level. If electrosurgery causes inhibition of an implanted pacemaker, it should be used in short bursts so as to produce only short pauses at a time. If there is no underlying rhythm, current should be applied for less than 1 second at a time, followed by 5- to 10-second periods free from current to allow resumption of rhythm and normal hemodynamics. Communication with the OR personnel, including nurses, anesthesiologists, and surgeons, is very important. Ideally, a trained physician and the corresponding programmer should be available within the hospital whenever a CIED patient undergoes electrosurgery. Education, training, and certification of anesthesiologists in perioperative cardiac pacing appear necessary.168 Because damage to the pacing system may occur, the capability of instituting emergency pacing must be present. An external transcutaneous pulse generator and defibrillator should be available. In case of inadvertent reprogramming that is not hemodynamically tolerated, the pulse generator must be reprogrammed as soon as possible. Magnet application can be attempted as an interim measure (the magnet rate usually varies from 60 to 100 bpm) but is unlikely to help in these cases. A damaged pulse generator should be replaced expeditiously, especially if runaway syndrome occurs. All devices must be carefully tested after the procedure because malfunction may be inapparent, especially if the spontaneous rhythm is faster than the lower rate of the pulse generator. Ideally, testing should be performed immediately after surgery and repeated 24 to 48 hours later. Endocardial burns should be suspected if the capture and sensing thresholds have increased. Follow-up is then required until stability can be demonstrated. Occasionally, a rise in threshold requires placement of a new pacing lead. As more surgical procedures are performed outside the hospital (in physicians’ offices or freestanding ambulatory surgery centers), these recommendations become difficult to implement. Although industryemployed allied professionals often participate in the perioperative management of CIED patients in these settings, current guidelines suggest that they should perform technical support tasks only with an appropriately trained and experienced physician nearby (i.e., accessible to attend to the patient within a few minutes).169 It is not clear what precautionary practices are standard in the community. In a survey of 166 cutaneous surgeons performing electrosurgery of epitheliomas in the office setting, many had encountered instances of EMI with pacemakers or ICDs, but very few routinely checked or reprogrammed devices before or after surgery.170 Most of them restricted current



bursts to less than 5 seconds, used minimal power, and avoided electrosurgery around a pacemaker or ICD. The estimated overall incidence of complications was low (0.8 cases per 100 years of surgical practice). The types of interference reported included pacemaker reprogramming, ICD firing, asystole, bradycardia, and premature pacemaker battery depletion. Use of bipolar forceps was not associated with interference. More clinical evidence must be gathered on the incidence and severity of EMI with current implantable devices related to various electrosurgical techniques and operations. Current “blanket” recommendations may need to be revised to accommodate different degrees of risk and to allow efficient, cost-effective, high-quality perioperative management in the electrosurgical setting.167 Radiofrequency Identification Technology Radiofrequency identification (RFID) systems have been extensively used in nonmedical environments, including retail stores for real-time tracking and highway toll systems for automatic pay. Unlike bar-code reader systems, RFID tags may be used to store larger amounts of data and allow better tracking. The technology has the potential to improve both the safety and the efficacy of care and utilization in hospital (and nonhospital) environments and will likely dramatically increase in the near future. The RFID tags are attached to the monitored entity, and stored data are read by a handheld or fixed device. RFID tags may be passive (powered by the reader) or active (powered by intrinsic power source). The FDA performed in vitro, worst-case scenario testing to identify interactions with pacemakers and ICDs when RFID readers were operated in close proximity. Pacemakers (15) and ICDs (15) were exposed to RFID readers at three frequency bands (134 kHz, 13.56 MHz, 915 MHz). Significant device interactions were present and were most common with modulated, low-frequency systems.171,172 To date, no clinical reports have described similar EMI.

33  Electromagnetic Interference and CIEDs

1021

radiation. These results cannot be extrapolated to other devices from the same or other manufacturers, but similar interactions should be expected. Diagnostic radiation may affect the coating (polyvenylidene fluoride; PVDF or Kynar) of a pacemaker accelerator, as recently documented in a single-chamber, rate-modulated Zephyr pacemaker (St. Jude Medical) during cardiac catheterization.176 The PVDF surface is altered by movement but also by radiation, and a voltage is generated because of its piezoelectric properties, mimicking activity.177 Temporarily increased pacing rate may occur during cineangiography (Fig. 33-10). Pacemaker sensors operating on the principles of intrathoracic impedance changes may be affected by monitoring equipment or diagnostic studies and may result in iatrogenic device-mediated tachycardia. Rate modulation feature should be programmed off during hospitalization, especially in the ICU. Video Capsule Endoscopy

Left ventricular assist devices (LVADs) are being increasingly used for the treatment of refractory heart failure, and many candidates for this therapy have already received an ICD or pacemaker. Device interactions were reported with older-generation St. Jude ICDs (Atlas, Epic) and an LVAD (HeartMate II, Thoratec, Pleasanton, Calif.).173 These ICDs use 8-kHz communication frequency with the programmer wand. The HeartMate II uses a pulse-width modulator that operates at constant 7.2-kHz frequency and results in EMI that blocks proper wand communication of the affected ICD, while the ICD function otherwise remains normal. Although a cumbersome barrier method may be used to regain communication (large cast-iron pans placed over both devices for shielding),174 long-term management is optimized if the ICD generator is exchanged to an unaffected model. Newer models use different communication frequencies and appear to be immune to this problem.

Video capsule endoscopy (PillCam, Given Imaging, Norcross, Ga., previously marketed as M2A) is useful in the investigation of obscure gastrointestinal bleeding and small-bowel pathology. A miniature camera, equipped with near-focus lenses, acquires video images that are telemetered to a waist belt–mounted receiver at a rate of 2 frames/ sec at 434 MHz. Once the images have been stored, 8 hours of conti­ nuously recorded information is downloaded to a workstation for analysis. The FDA and the device manufacturer consider the presence of a pacemaker or other CIED a contraindication to video capsule endoscopy. However, case reports and small series suggest that the procedure can be safe in such patients. Five pacemaker patients admitted to the hospital and continuously monitored during capsule endoscopy had no instances of interference with pacemaker function, and the quality of the images was good.178 Dubner et al.179 challenged 100 patients who had a variety of pacemakers with an external video capsule simulator transmitting at the same frequency. In four devices (2 St. Jude, 2 Biotronik), there was noise-reversion operation when the simulator capsule was positioned within 10 cm of the body, close to the generator. The interaction occurred within 10 seconds after capsule activation and was reproducible a week later. During clinical practice, the interaction is likely to occur only during the period when the capsule descends through the esophagus. The authors recommend that patients with pacemakers undergo initial testing with the external simulator to exclude significant EMI before undergoing the actual procedure with the video capsule system. In an in vitro study, six ICD models from different manufacturers were exposed to the same external video capsule simulator, for a total of 864 test runs.180 There was consistent oversensing that resulted in false detection of VF in the Biotronik Belos ICD. Other devices (Medtronic GEM III, Guidant Vitality, St. Jude Profile) were affected neither during the in vitro tests nor in vivo in a limited number of patients. Until more information becomes available, it appears prudent to recommend that patients with CIEDs undergo capsule endoscopy only as inpatients and with tachyarrhythmia therapy disabled.

Diagnostic Radiation

Direct-Current Cardioversion and Defibrillation

Diagnostic radiation has been thought to affect pacemakers or ICDs only rarely. More recent case reports suggest that EMI may occur during diagnostic computed tomography (CT) studies. This was confirmed in an in vitro study using the Irnich human body model.175 Five pacemaker/lead models (Thera SR, Kappa DR, EnRhythm, and Adapta by Medtronic; Synchrony II by St. Jude Medical) were tested in a CT scanner at maximum radiation level. Evidence of EMI was demonstrated by documentation of temporary pacing inhibition in all studied modern pacemakers, which are equipped with advanced CMOS circuits (all Medtronic models). EMI occurred when the CMOS was directly radiated. It was proposed that internal photoelectric effect from x-radiation affected the ECG amplifier and induced false sensing. The older pacemaker generator (Synchrony II) was not affected by

Direct-current (DC) external cardioversion and defibrillation with paddles (or disposable electrodes) can apply several thousand volts and tens of amperes of current to a CIED system. Of all sources of EMI, this represents the highest amount of energy delivered in the vicinity of such a device, and it has potential to damage the pulse generator as well as the myocardial tissue in contact with the lead or leads. At times, the backup (reset) mode is activated by the countershock. However, if the protection mechanism is overwhelmed by high-energy input, permanent pulse generator circuitry damage may ensue. Additionally, capacitative coupling or shunting in the pacemaker circuit may induce currents in pacemaker or defibrillator leads sufficient to cause thermal damage (burn) to the electrode-tissue interface, resulting in chronic threshold elevation. In dual-chamber pacemakers, cardioversion

INTERFERENCE WITH MISCELLANEOUS MEDICAL EQUIPMENT Left Ventricular Assist Devices

1022

SECTION 4  Follow-up and Programming

Baseline rhythm Marker

RV bipolar

Marker

Initiation of cineangiography

RV bipolar

Figure 33-10  Radiation-induced spurious activation of accelerometer and pacing at upper sensor rate. Patient was undergoing diagnostic heart catheterization, and intermittent tachycardia was noted during cineangiography. See text for details.

energy may be preferentially shunted to the ventricular lead.181 Even with modern pacemakers, acute exit block can occur. A mild, acute initial rise in capture threshold can be followed by exit block a few weeks later.182 The risk of damage to the implanted device depends on the amount of energy applied, the characteristics of the device and lead, and the distance between the paddles or pads and the pulse generator and leads. Box 33-5 lists recommendations for external cardioversion in patients with CIEDs. In elective situations, the minimum energy that is likely to be successful should be delivered. External cardioversion or defibrillation with a biphasic waveform is more efficient (i.e., requires less energy) than the conventional damped sine-wave monophasic shocks and should be preferred in patients with implanted devices. Unipolar pacing systems are more susceptible to damage than bipolar systems. Whenever possible, an anteroposterior configuration of the shocking electrodes should be employed, because it maximizes the distance between the source and the implanted generator. If an anteroapical position must be used, the electrodes should be at least 10 cm from the pulse generator. However, this may be impossible with devices implanted in a right pectoral pocket, because the anterior paddle will lie directly on top of it. Transient elevations in capture threshold are common after DC shocks and should be anticipated. The threshold rise is usually temporary, lasting up to a few minutes, but occasionally the threshold remains elevated permanently and necessitate lead replacement. Preprocedural and postprocedural interrogation and device testing for proper function should follow external DC shocks to all implantable devices. Internal cardioversion may be attempted in patients who fail external cardioversion of atrial fibrillation (AF). There is limited published experience with this procedure in patients with pacemakers. There were no instances of pacemaker malfunction in seven patients who underwent internal cardioversion of AF, with electrodes in the right atrium and in the coronary sinus or left pulmonary artery, with biphasic shocks of up to 20 J.183 However, when high-energy endocavitary shocks were used for ablation purposes, pacemaker failure was common.184

Radiofrequency Ablation Radiofrequency catheter ablation (RFA) is first-line therapy for a variety of supraventricular and ventricular arrhythmias. Interactions between RF current and implantable devices have been studied most

Box 33-5 

MANAGEMENT OF CIED PATIENTS UNDERGOING EXTERNAL CARDIOVERSION OR DEFIBRILLATION Before Cardioversion In patients with ICDs, choose internal cardioversion via the device with commanded shock. Have pacemaker programmer available in the room. Determine (if possible) degree of pacemaker dependency. Program a higher-voltage output. Have transcutaneous external pacemaker available. During Cardioversion Use self-adhesive patches or paddles in an anteroposterior configuration. Keep patches or paddles as far from generator and leads as possible. Use lowest possible energy. Use a biphasic waveform. Respect a time interval of at least 5 minutes between successive shocks to allow cooling of protective diodes. After Cardioversion Repeat determination of pacing and sensing thresholds immediately, and again 24 hours later. Consider monitoring for 24 hours. Consider a higher output for 4 to 6 weeks (especially in pacemaker-dependent patients). Recheck pacemaker in 4 to 6 weeks (sooner if there is an acute increase in capture threshold).



thoroughly during RFA of the AV junction for drug-refractory AF and of monomorphic ventricular tachycardia in patients with ICDs. Radiofrequency current, delivered as an unmodulated sine wave at 500 to 1000 kHz, can interact unpredictably with CIEDs. Energy delivery may result in asynchronous pacing, rapid tracking, spurious tachyarrhythmia detection, and electrical reset. Different interactions may be seen (in the same patient) during consecutive energy applications. Interactions are generally transient and terminate with cessation of energy delivery. In vitro and in vivo studies have examined the incidence, mechanisms, and risk factors for these interactions. Dick et al.185 investigated the effects of RF current (55 W; tip temperature 65°-70° C) applied to four different pacing or defibrillation leads in a tissue bath model. Photographic and microscopic examination after energy delivery revealed no damage to the target lead. No malfunction occurred in the attached pulse generators. The magnitude of induced current measured at the target tip lead was inversely proportional to the distance. Significant current was detected only when the ablation catheter was less than 1 cm from the target lead tip. Chin et al.186 studied 19 pulse generators implanted in 12 dogs and found that interactions depended on the proximity of current application to the pacing leads. Interactions were common at 1 cm and absent at more than 4 cm. The most dangerous interaction was runaway pacing with possible VF induction. The clinical incidence of acute interaction between RF current application and permanent pacemakers has ranged widely. The incidence and severity of EMI depend in part on the protective circuits of the implanted device.187 The combined incidence of acute pacemaker malfunction during RF current application in three relatively large series involving a total of 125 patients with assorted pacemakers was 44%.188,189 The most common interaction was asynchronous pacing caused by noise reversion, followed by oversensing resulting in refractory period extension and “functional undersensing,” pacemaker inhibition, or antitachycardia pacing in special pacemakers. Electrical reset, RF-induced pacemaker tachycardia, erratic behavior, and transient loss of capture were less common. In contrast, Proclemer et al.190 did not observe transient or permanent pacemaker dysfunction in 70 consecutive patients with Medtronic Thera and Kappa single- and dual-chamber pacemakers with unipolar leads who underwent AV junction RFA. The pacemakers were implanted before RFA in a single-session procedure and were transiently programmed to VVI mode at 30 bpm. The long-term effects of RF application on permanent pacing systems have been less well studied. Exit block (possibly caused by scar at the lead-tissue interface), lead damage, and chronic generator malfunction (requiring replacement) have been reported.187,189,191 In two series of patients with pacemakers, changes in lead impedance and pacing and sensing thresholds did not appear clinically significant.187,190 In a study of 59 patients with preexisting pacemaker (46) or defibrillator leads (13) undergoing AV junction RFA, a significant increase in pacing threshold was present immediately after ablation and further increased 24 hours later.192 A twofold increase in pacing threshold was much more likely to occur in patients with defibrillator leads. Two of the ICD patients (15%) and two of the pacemaker patients (4%) had a progressive rise in pacing threshold requiring lead revision. The mechanism of the increased vulnerability of the ICD leads was not clear. A few simple precautions can minimize adverse outcomes with RFA. Complete pacemaker inhibition is dangerous in patients who are without an escape rhythm during AV junction RFA. Rate responsiveness should be disabled. Pacing at the upper rate limit may occur when MV pacemakers that measure transthoracic impedance misinterpret RF current.193 Tachyarrhythmia detection should be disabled in patients with ICDs to prevent spurious therapies. Older pacemakers should not be trusted to provide backup pacing, because loss of output or capture could occur despite programming an asynchronous mode. Pacemakers and ICDs should be checked carefully after RF catheter ablation. Also, RF energy can be used for ablation of other tissues. Uneventful percutaneous RF trigeminal rhizotomy194 and intrahepatic RFA of liver

33  Electromagnetic Interference and CIEDs

1023

neoplasms195 in patients with pacemakers have been reported. With extracardiac RFA, the current return pad should be placed as close as possible to the delivery electrodes.196 Lithotripsy Acoustic radiation, from extracorporeal shock wave lithotripsy (ESWL) machines, provides a noninvasive means to disintegrate renal, ureteral, gallbladder, and biliary calculi. With the original device (Dornier HM3, Dornier Medical System, Marietta, Ga.), the patient lies in a water bath and multiple (~1500) hydraulic shocks are generated from an underwater 20-kV spark gap and focused on the calculi by an ellipsoid metal reflector. The shock wave can produce ventricular extrasystoles, so it is synchronized to the R wave. Implanted devices could be subject to electrical interference from the spark gap and mechanical damage from the hydraulic shock wave. Newer units (e.g., Dornier Compact Delta) use an enclosed water cushion for shock wave coupling. Other units use electromagnetic (e.g., Lithostar, Siemens Medical Systems, Iselin, N.J.) or piezoelectric (e.g., Wolf Piezolith, Richard Eolf GmbH, Knittlingen, Gemany) shock wave generators.197 Most information regarding interactions with CIEDs has been collected with the Dornier HM3 unit. Several investigators have studied the effects of ESWL on pacemakers in vitro.198-200 Pacemaker output was not inhibited by properly synchronous shocks, but asynchronous shocks caused inhibition in both unipolar and bipolar devices. During AV sequential pacing, a shock inappropriately synchronized to the atrial pacing pulse was often sensed by the ventricular channel, with the potential to cause inhibition of the ventricular output. Intermittent reversion to magnet mode can occur because of transient closure of the reed switch from the high-energy vibration. Other responses noted during in vitro testing included an increase in pacing rate secondary to tracking of EMI in the atrial channel, noise reversion, spurious tachyarrhythmia detection,201 and malfunction of the reed switch. Activity-sensing pacemakers increased their pacing rate to the upper limit within 1 minute after the shock. ESWL caused no physical damage to the hermetic seal or internal components of the pacemakers tested, except that piezoelectric crystals shattered when an activity-sensing pacemaker was placed at the focal point of the ESWL.198 In vitro testing of two ICDs with a new-generation lithotripter did not disclose any adverse interactions (even with generator placed within focus of lithotripter), provided that the shock waves were applied synchronized to the R wave.196 Case reports and clinical series suggest that ESWL is safe to use with CIEDs as long as the device and target are at least 6 cm apart. Adverse events have been rare and mild, occurring mostly with older devices.202205 Activity-sensing rate-adaptive devices implanted in the thorax can undergo lithotripsy safely, but the procedure should be avoided if the device is located in the abdomen. Synchronization of the shocks to the R wave is crucial. Activity sensors and tachyarrhythmia detection should be temporarily disabled in all cases. Reprogramming of dualchamber pacemakers to VVI or VOO (if the patient is pacemaker dependent) avoids ventricular inhibition caused by shocks synchronized to the atrial output, irregular pacing rate, tracking of induced supraventricular tachycardia, and triggering of the ventricular output by EMI. Careful follow-up should be performed over the next several months to ensure appropriate function of the reed switch. The piezoelectric shock wave generator does not induce ventricular extrasystoles, and therefore synchronization to the QRS complex is not required. This unit appears especially safe to use in CIED patients. Dental Equipment Multiple potential sources of EMI are present in the dental office, including sonic and ultrasonic scalers, amalgamators, composite light curing units, x-ray units and view boxes, dental chairs and lights, electronic apex locators, and ultrasonic bath cleaners. Research in this area has been of suboptimal quality. The paucity of reports of severe interactions between modern CIEDs and dental equipment suggests that this is not a clinical problem. Magnetic fields in the dental office are not strong enough to close the reed switch.206 Earlier reports described

1024

SECTION 4  Follow-up and Programming

pacemaker EMI with magnetorestrictive ultrasonic scalers, but not with piezoelectric ultrasonic scalers.207 An in vitro study reported pacemaker inhibition by magnetorestrictive ultrasonic scalers up to distances of 37.5 cm.9 However, review of the published telemetry strips suggests that these were not instances of true pacemaker inhibition, but instead represented interference with the telemetry link. Until further tests are conducted, it is prudent to avoid magnetorestrictive ultrasonic scalers in CIED patients.207 Manufacturers of electronic apex locators warn against the use of these devices in patients with pacemakers. In bench testing, four of five electronic apex locators did not interfere with a Biotronik pacemaker.208 Safe use of an electronic apex locator in a patient with a pacemaker has been reported.209 Prosthetic dental minimagnets can activate the reed switch only if placed very close (1 cm) to the pacemaker and therefore do not represent a risk to patients with a pacemaker.210 Radiotherapy Radiotherapy can induce various responses in implanted devices. EMI produced by the radiotherapy machine can result in pacing inhibition, tracking, noise reversion, or inappropriate ICD discharges. Most important is the risk of permanent generator damage caused by ionizing radiation.211 Current devices incorporating CMOS technology may incur damage during radiation therapy. Ionizing therapeutic radiation acts on the silicone and silicone oxide insulators within the semiconductors. Two potential mechanisms of damage have been described. Cumulative radiation can result in damage to circuit components, altering transistor parameters or creating electrical shorts that result in premature battery depletion. Failure may manifest as changes in sensitivity, amplitude, or pulse width; loss of telemetry; output failure; or runaway rates. This is uncommon unless the device is directly irradiated. More difficult to predict and avoid is random damage to the device’s memory caused by scatter radiation.212 Modern pacemakers and ICDs include memory error detection and correction schemes in their software programs. As a normal part of daily self-diagnostics, devices locate and correct affected memory locations. However, if the degree of memory alteration is beyond the capability of self-correcting algorithms, the device may invoke a ROM-based operating mode, referred to as “safety mode.” This ensures that the patient is protected with basic pacing and shock therapy. Physicians should be advised of this possibility and should carefully monitor device operation during and after radiation therapy. Previously, a total absorbed dose of up to 2 Gy was considered safe in permanent pacemakers.211 Later studies suggested that pacemaker susceptibility to radiotherapy is highly variable and that severe malfunction can occur at even lower doses. Mouton et al.213 irradiated 96 pacemakers in vitro with a high-energy photon beam. One pacemaker had severe malfunction at a cumulative dose of 0.15 Gy; at 2 Gy, 6% of pacemakers developed severe malfunction. The dose rate also affected the likelihood of failure, and the authors recommended using dose rates lower than the standard of 2 Gy/min. Hurkmans et al.214 performed in vitro testing during which 7 of 19 current pacemakers lost output at 120 Gy. Eight pacemakers showed inhibition during irradiation in the direct beam, whereas five pacemakers showed no malfunction. They also evaluated the effect of radiotherapy on ICDs. In their study, 11 modern ICDs were irradiated with a 6-megavolt photon beam with a cumulative dose of 120 Gy. Electromagnetic noise caused inappropriate sensing in all ICDs and would have resulted in inappropriate shocks in four devices. At the end of the 4- to 5-day consecutive irradiation schedule planned in the study, all devices had failed. The majority of the ICDs reached complete loss of function at dose levels between 0.5 and 1.5 Gy.215 Kapa et al.216 studied the effects of scatter radiation on ICD and cardiac resynchronization therapy (CRT) devices. The authors exposed 12 ICD and 8 CRT-ICDs to 400 cGy of scatter radiation from a 6-MV photon beam. No evidence of reset or malfunction was noted during or after radiation. The authors also performed a retrospective review of 12 patients with ICDs undergoing radiotherapy at their institution. The device was outside the

radiation field in all cases. No episodes of device reset, inappropriate sensing or therapy, or changes in programmed parameters were found in any of the 12 patients. Radiation oncology centers should have protocols for patients with implantable antiarrhythmic devices,217 but a recent survey reveals wide variations among facilities regarding patient management precautions.218 Manufacturers offer widely differing guidelines for patient management during radiotherapy, reflecting discrepancies in the perceived mechanism of damage. Vendors agree that the pulse generator should not be situated directly within the radiation field. If that is the case, the generator should be removed and reimplanted away from the field. Manufacturers also vary as to the total radiation exposure to the generator that should be allowed. For example, Medtronic recommends a limitation of 5 Gy or less for its pacemakers and 1 Gy or less to 5 Gy or less for its ICDs, depending on the model. In contrast, St. Jude Medical recommends a maximal cumulative dose to its pacemakers of 20 to 30 Gy. Boston Scientific offers no guidelines regarding dose limitation, emphasizing the random nature of memory damage by radiation scatter. Boston Scientific recommends maximizing shielding at the machine head but specifically discourages placing a lead apron over the pulse generator during treatment, because of its potential for increasing scatter. In contrast, St. Jude Medical and Sorin recommend shielding of the pacemaker with a piece of lead apron. The manufacturers also differ in their recommendations regarding the extent and frequency of patient monitoring during and after radiotherapy. It is difficult to provide universal guidelines for the management of patients with pacemakers or ICDs who are undergoing radiotherapy. The mode and site of radiation therapy, as well as the clinical characteristics of the patient (presence of pacemaker or ICD, pacemaker dependency) need to be considered.217 Monitoring should be tailored according to risk with device failure. In high-risk cases, device interrogation after each session may be required. In other cases, weekly evaluation may be appropriate.167 Box 33-6 proposes streamlined precautions to consider before, during, and after radiotherapy in patients with cardiac implantable electronic devices.

Box 33-6 

MANAGEMENT OF CIED PATIENTS UNDERGOING RADIOTHERAPY Before Treatments Avoid betatron. Evaluate device and pacemaker dependency before therapy. Plan radiotherapy to minimize total dose (including scatter) received by generator. Avoid direct radiation. Consider moving the pulse generator away from the field if the estimated dose is >2 Gy for a pacemaker or >1 Gy for an ICD. During Treatments Disable tachyarrhythmia detection and therapy in ICD patients. Measure actual dose received by the generator during the first treatment, using a thermoluminescent dosimeter or diode to confirm that the planned dose will not be exceeded. Institute appropriate level of monitoring: • All patients should be observed by therapists during all treatments and should have their pulse and blood pressure measured before and after each treatment. • Pacemaker-dependent patients and patients with deactivated ICDs should undergo continuous ECG monitoring during all treatments. • Pacemaker-dependent and ICD patients should have weekly device checks. After Treatments All patients should undergo full device check. Consider generator replacement at the earliest evidence of circuitry damage.



33  Electromagnetic Interference and CIEDs

1025

REFERENCES 1. American National Standards Institute, Association for the Advancement of Medical Instrumentation: Active implantable medical devices: electromagnetic compatibility. EMC test protocols for implantable cardiac pacemakers and implantable cardioverter-defibrillators. ANSI/AAMI PC69:2007. Washington, DC, 2007, ANSI. 2. Radiofrequency wireless technology in medical devices. Accessed January 2011. http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ucm 077210.htm. 3. Barbaro V, Bartolini P, Calcagnini G, et al: On the mechanisms of interference between mobile phones and pacemakers: parasitic demodulation of GSM signal by the sensing amplifier. Phys Med Biol 48:1661-1671, 2003. 4. Matthews JC, Betley D, Morady F, et al: Adverse interaction between a left ventricular assist device and an implantable cardioverter-defibrillator. J Cardiovasc Electrophysiol 18:11071108, 2007. 5. Center for Devices and Radiological Health: Medical Device Reporting. US Food and Drug Administration. http:// www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/ search.CFM. 6. Angeloni A, Barbaro V, Bartolini P, et al: A novel heart/trunk simulator for the study of electromagnetic interference with active implantable devices. Med Biol Eng Comput 41:550-555, 2003. 7. Dawson TW, Stuchly MA, Caputa K, et al: Pacemaker interference and low-frequency electric induction in humans by external fields and electrodes. IEEE Trans Biomed Eng 47:1211-1218, 2000. 8. Grant FH, Schlegel RE: Effects of an increased air gap on the in vitro interaction of wireless phones with cardiac pacemakers. Bioelectromagnetics 21:485-490, 2000. 9. Miller CS, Leonelli FM, Latham E: Selective interference with pacemaker activity by electrical dental devices. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:33-36, 1998. 10. CENELEC: Active implantable medical devices. Part 2-1. Particular requirements for active implantable medical devices intended to treat bradyarrhythmia (cardiac pacemakers). Bruxelles, 2003, Comité Européen de Normalisation Electrotechnique. 11. CENELEC: Active implantable medical devices. Part 2-2. Particular requirements for active implantable medical devices intended to treat tachyarrhythmia (includes implantable defibrillators). Bruxelles, 2006, Comité Européen de Normalisation Electrotechnique. 12. Southorn PA, Kamath GS, Vasdev GM, et al: Monitoring equipment induced tachycardia in patients with minute ventilation rate-responsive pacemakers. Br J Anaesth 84:508-509, 2000. 13. Chew EW, Troughear RH, Kuchar DL, et al: Inappropriate rate change in minute ventilation rate responsive pacemakers due to interference by cardiac monitors. Pacing Clin Electrophysiol 20:276-282, 1997. 14. Khunnawat C, Mukerji S, Sankaran S, et al: Echocardiography induced tachycardia in a patient with a minute ventilation rate responsive pacemaker. J Interv Card Electrophysiol 14:51-53, 2005. 15. McIvor ME, Reddinger J, Floden E, et al: Study of Pacemaker and Implantable Cardioverter Defibrillator Triggering by Electronic Article Surveillance Devices (SPICED TEAS). Pacing Clin Elec­ trophysiol 21:1847-1861, 1998. 16. Hayes DL, Holmes DR, Jr, Gray JE: Effect of 1.5 tesla nuclear magnetic resonance imaging scanner on implanted permanent pacemakers. J Am Coll Cardiol 10:782-786, 1987. 17. Fontaine JM, Mohamed FB, Gottlieb C, et al: Rapid ventricular pacing in a pacemaker patient undergoing magnetic resonance imaging. Pacing Clin Electrophysiol 21:1336-1339, 1998. 18. Kolb C, Zrenner B, Schmitt C: Incidence of electromagnetic interference in implantable cardioverter defibrillators. Pacing Clin Electrophysiol 24:465-468, 2001. 19. Gunderson BD, Gillberg JM, Swerdlow CD: Importance of oversensing in inappropriate detection of ventricular fibrillation by chronically implanted ICDs. Heart Rhythm 1:S244, 2005. 20. Butrous GS, Male JC, Webber RS, et al: The effect of power frequency high intensity electric fields on implanted cardiac pacemakers. Pacing Clin Electrophysiol 6:1282-1292, 1983. 21. Saeed M, Link MS, Mahapatra S, et al: Analysis of intracardiac electrograms showing monomorphic ventricular tachycardia in patients with implantable cardioverter-defibrillators. Am J Cardiol 85:580-587, 2000. 22. Schmitt C, Brachmann J, Waldecker B, et al: Implantable cardioverter-defibrillator: possible hazards of electromagnetic interference. Pacing Clin Electrophysiol 14:982-984, 1991. 23. Ferrick KJ, Johnston D, Kim SG, et al: Inadvertent AICD inactivation while playing bingo. Am Heart J 121:206-207, 1991. 24. Rasmussen MJ, Friedman PA, Hammill SC, et al: Unintentional deactivation of implantable cardioverter-defibrillators in health care settings. Mayo Clin Proc 77:855-859, 2002. 25. Kolb C, Deisenhofer I, Weyerbrock S, et al: Incidence of anti­ tachycardia therapy suspension due to magnet reversion in implantable cardioverter-defibrillators. Pacing Clin Electro­ physiol 27:221-223, 2004. 26. Levine PA, Moran MJ: Device eccentricity: postmagnet behavior of DDDR pacemakers with automatic threshold tracking. Pacing Clin Electrophysiol 23:1570-1572, 2000.

27. Laudon MK: Pulse output: design of cardiac pacemakers. New York, 1995, IEEE Press, pp 251-276. 28. Schoenfeld MH, Compton SJ, Mead RH, et al: Remote monitoring of implantable cardioverter defibrillators: a prospective analysis. Pacing Clin Electrophysiol 27:757-763, 2004. 29. Jung W, Rillig A, Birkemeyer R, et al: Advances in remote monitoring of implantable pacemakers, cardioverter-defibrillators and cardiac resynchronization therapy systems. J Interv Card Electrophysiol 23:73-85, 2008. 30. Toivonen L, Valjus J, Hongisto M, et al: The influence of elevated 50 Hz electric and magnetic fields on implanted cardiac pacemakers: the role of the lead configuration and programming of the sensitivity. Pacing Clin Electrophysiol 14:2114-2122, 1991. 31. Hayes DL, Carrillo RG, Findlay GK, et al: State of the science: pacemaker and defibrillator interference from wireless communication devices. Pacing Clin Electrophysiol 19:1419-1430, 1996. 32. Yesil M, Bayata S, Postaci N, et al: Pacemaker inhibition and asystole in a pacemaker dependent patient. Pacing Clin Electro­ physiol 18:1963, 1995. 33. Ruggera PS, Witters DM, Bassen HI: In vitro testing of pacemakers for digital cellular phone electromagnetic interference. Biomed Instrum Technol 31:358-371, 1997. 34. Bassen HI, Moore HJ, Ruggera PS: Cellular phone interference testing of implantable cardiac defibrillators in vitro. Pacing Clin Electrophysiol 21:1709-1715, 1998. 35. Tan KS, Hinberg I: Can wireless communication systems affect implantable cardiac pacemakers? An in vitro laboratory study. Biomed Instrum Technol 32:18-24, 1998. 36. Schlegel RE, Grant FH, Raman S, et al: Electromagnetic compatibility study of the in-vitro interaction of wireless phones with cardiac pacemakers. Biomed Instrum Technol 32:645-655, 1998. 37. University of Oklahoma Wireless EMC Center: In vitro study of the interaction of wireless phones and implantable cardioverterdefibrillators. Accessed December 2010. http://www.ou.edu/ engineering/emc/Side/Achievments/Research%20Projects/ ICDs.dwt. 38. Hayes DL, Wang PJ, Reynolds DW, et al: Interference with cardiac pacemakers by cellular telephones. N Engl J Med 336:1473-1479, 1997. 39. Naegeli B, Osswald S, Deola M, et al: Intermittent pacemaker dysfunction caused by digital mobile telephones. J Am Coll Cardiol 27:1471-1477, 1996. 40. Hekmat K, Salemink B, Lauterbach G, et al: Interference by cellular phones with permanent implanted pacemakers: an update. Europace 6:363-369, 2004. 41. Trigano A, Blandeau O, Dale C, et al: Reliability of electromagnetic filters of cardiac pacemakers tested by cellular telephone ringing. Heart Rhythm 2:837-841, 2005. 42. Sparks PB, Mond HG, Joyner KH, et al: The safety of digital mobile cellular telephones with minute ventilation rate adaptive pacemakers. Pacing Clin Electrophysiol 19:1451-1455, 1996. 43. Nowak B, Rosocha S, Zellerhoff C, et al: Is there a risk for interaction between mobile phones and single lead VDD pacemakers? Pacing Clin Electrophysiol 19:1447-1450, 1996. 44. Elshershari H, Celiker A, Ozer S, et al: Influence of D-net (EUROPEAN GSM-standard) cellular telephones on implanted pacemakers in children. Pacing Clin Electrophysiol 25:1328-1330, 2002. 45. Chiladakis JA, Davlouros P, Agelopoulos G, et al: In-vivo testing of digital cellular telephones in patients with implantable cardioverter-defibrillators. Eur Heart J 22:1337-1342, 2001. 46. Fetter JG, Ivans V, Benditt DG, et al: Digital cellular telephone interaction with implantable cardioverter-defibrillators. J Am Coll Cardiol 31:623-628, 1998. 47. Occhetta E, Plebani L, Bortnik M, et al: Implantable cardioverterdefibrillators and cellular telephones: is there any interference? Pacing Clin Electrophysiol 22:983-989, 1999. 48. Calcagnini G, Censi F, Floris M, et al: Evaluation of electromagnetic interference of GSM mobile phones with pacemakers featuring remote monitoring functions. Pacing Clin Electrophysiol 29:380-385, 2006. 49. Chiu CC, Huh J, De Souza L, et al: A prospective pediatric clinical trial of digital music players: do they interfere with pacemakers? J Cardiovasc Electrophysiol 20:44-49, 2009. 50. Bassen H: Low frequency magnetic emissions and resulting induced voltages in a pacemaker by iPod portable music players. Biomed Eng Online 7:7, 2008. 51. Thaker JP, Patel MB, Jongnarangsin K, et al: Electromagnetic interference with pacemakers caused by portable media players. Heart Rhythm 5:538-544, 2008. 52. Webster G, Jordao L, Martuscello M, et al: Digital music players cause interference with interrogation telemetry for pacemakers and implantable cardioverter-defibrillators without affecting device function. Heart Rhythm 5:545-550, 2008. 53. Lee S, Fu K, Kohno T, et al: Clinically significant magnetic interference of implanted cardiac devices by portable headphones. Heart Rhythm 6:1432-1436, 2009. 54. Sakakibara Y, Mitsui T: Concerns about sources of electromagnetic interference in patients with pacemakers. Jpn Heart J 40:737-743, 1999. 55. De Cock CC, Spruijt HJ, van Campen LM, et al: Electromagnetic interference of an implantable loop recorder by commonly encountered electronic devices. Pacing Clin Electrophysiol 23:1516-1518, 2000.

56. Thaker JP, Patel MB, Jongnarangsin K, et al: Electromagnetic interference in an implantable loop recorder caused by a portable digital media player. Pacing Clin Electrophysiol 31:13451347, 2008. 57. Tri JL, Trusty JM, Hayes DL: Potential for personal digital assistant interference with implantable cardiac devices. Mayo Clin Proc 79:1527-1530, 2004. 58. Santucci PA, Haw J, Trohman RG, et al: Interference with an implantable defibrillator by an electronic antitheft-surveillance device. N Engl J Med 339:1371-1374, 1998. 59. Tan KS, Hinberg I: Can electronic article surveillance systems affect implantable cardiac pacemakers and defibrillators? [abstract]. Pacing Clin Electrophysiol 21:960, 1998. 60. Mugica J, Henry L, Podeur H: Study of interactions between permanent pacemakers and electronic antitheft surveillance systems. Pacing Clin Electrophysiol 23:333-337, 2000. 61. Groh WJ, Boschee SA, Engelstein ED, et al: Interactions between electronic article surveillance systems and implantable cardioverter-defibrillators. Circulation 100:387-392, 1999. 62. US Food and Drug Administration, Center for Devices and Radiological Health: Guidance on labeling for electronic antitheft systems. Accessed December 2010. http://www.fda.gov/ downloads/MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/UCM070913.pdf. 63. Moss CE: Exposures to electromagnetic fields while operating walk-through and hand-held metal detectors. Appl Occup Environ Hyg 13:501-504, 1998. 64. Kolb C, Schmieder S, Lehmann G, et al: Do airport metal detectors interfere with implantable pacemakers or cardioverterdefibrillators? J Am Coll Cardiol 41:2054-2059, 2003. 65. Burlington DB: Important information on anti-theft and metal detector systems and pacemakers, ICDs, and spinal cord stimulators. Accessed January 2011. http://www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/PublicHealthNotifications/ucm062288. htm. 66. Dawson TW, Caputa K, Stuchly MA, et al: Pacemaker interference by magnetic fields at power line frequencies. IEEE Trans Biomed Eng 49:254-262, 2002. 67. Trigano A, Blandeau O, Souques M, et al: Clinical study of interference with cardiac pacemakers by a magnetic field at power line frequencies. J Am Coll Cardiol 45:896-900, 2005. 68. Chan NY, Wai-Ling Ho L: Inappropriate implantable cardioverter-defibrillator shock due to external alternating current leak: report of two cases. Europace 7:193-196, 2005. 69. Paraskevaidis S, Polymeropoulos KP, Louridas G: Inappropriate ICD therapy due to electrical interference: external alternating current leakage. J Invasive Cardiol 16:339, 2004. 70. Sabate X, Moure C, Nicolas J, et al: Washing machine associated 50 Hz detected as ventricular fibrillation by an implanted cardioverter defibrillator. Pacing Clin Electrophysiol 24:1281-1283, 2001. 71. Madrid A, Sanchez A, Bosch E, et al: Dysfunction of implantable defibrillators caused by slot machines. Pacing Clin Electrophysiol 20:212-214, 1997. 72. Pinski SL, Trohman RG: Interference in implanted cardiac devices. Part I. Pacing Clin Electrophysiol 25:1367-1381, 2002. 73. Manolis AG, Katsivas AG, Vassilopoulos CV, et al: Implantable cardioverter-defibrillator-an unusual case of inappropriate discharge during showering. J Interv Card Electrophysiol 4:265-268, 2000. 74. Lee SW, Moak JP, Lewis B: Inadvertent detection of 60-Hz alternating current by an implantable cardioverter defibrillator. Pacing Clin Electrophysiol 25:518-519, 2002. 75. Rickli H, Facchini M, Brunner H, et al: Induction ovens and electromagnetic interference: what is the risk for patients with implanted pacemakers? Pacing Clin Electrophysiol 26:1494-1497, 2003. 76. Binggeli C, Rickli H, Ammann P, et al: Induction ovens and electromagnetic interference: what is the risk for patients with implantable cardioverter defibrillators? J Cardiovasc Electro­ physiol 16:399-401, 2005. 77. Seifert T, Block M, Borggrefe M, et al: Erroneous discharge of an implantable cardioverter defibrillator caused by an electric razor. Pacing Clin Electrophysiol 18:1592-1594, 1995. 78. Garg A, Wadhwa M, Brown K, et al: Inappropriate implantable cardioverter defibrillator discharge from sensing of external alternating current leak. J Interv Card Electrophysiol 7:181-184, 2002. 79. Haegeli LM, Sterns LD, Adam DC, et al: Effect of a Taser shot to the chest of a patient with an implantable defibrillator. Heart Rhythm 3:339-341, 2006. 80. Lakkireddy D, Khasnis A, Antenacci J, et al: Do electrical stun guns (Taser-X26) affect the functional integrity of implantable pacemakers and defibrillators? Europace 9:551-556, 2007. 81. Van Lake P, Mattioni T: The effect of therapeutic magnets on implantable pacemaker and defibrillator devices [abstract]. Pacing Clin Electrophysiol 23:723, 2000. 82. Wayar L, Mont L, Silva RM, et al: Electrical interference from an abdominal muscle stimulator unit on an implantable cardioverter-defibrillator: report of two consecutive cases. Pacing Clin Electrophysiol 26:1292-1293, 2003. 83. Lau EW, Birnie DH, Lemery R, et al: Acupuncture triggering inappropriate ICD shocks. Europace 7:85-86, 2005.

1026

SECTION 4  Follow-up and Programming

84. Furrer M, Naegeli B, Bertel O: Hazards of an alternative medicine device in a patient with a pacemaker. N Engl J Med 350:1688-1690, 2004. 85. Cartwright CE, Breysse PN, Boother L: Magnetic field exposures in a petroleum refinery. Appl Occup Environ Hyg 8:587-592, 1993. 86. De Rotte AA, Van Der Kemp P: Electromagnetic interference in pacemakers in single-engine fixed-wing aircraft: a European perspective. Aviat Space Environ Med 73:179-183, 2002. 87. Fetter JG, Benditt DG, Stanton MS: Electromagnetic interference from welding and motors on implantable cardioverterdefibrillators as tested in the electrically hostile work site. J Am Coll Cardiol 28:423-427, 1996. 88. Marco D, Eisinger G, Hayes DL: Testing of work environments for electromagnetic interference. Pacing Clin Electrophysiol 15:2016-2022, 1992. 89. Gurevitz O, Fogel RI, Herner ME, et al: Patients with an ICD can safely resume work in industrial facilities following simple screening for electromagnetic interference. Pacing Clin Electro­ physiol 26:1675-1678, 2003. 90. A closer look. product information at a glance. Boston Scientific Corporation. Electrical arc welding and implantable device systems. Accessed: December 2010. http://www.bostonscientific. com/templatedata/imports/HTML/CRM/A_Closer_Look/pdfs/ ACL_Arc_Welding_080408.pdf. 91. Mehdirad A, Love C, Nelson S, et al: Alternating current electrocution detection and termination by an implantable cardioverter defibrillator. Pacing Clin Electrophysiol 20:1885-1886, 1997. 92. Sawyer-Glover AM, Shellock FG: Pre-MRI procedure screening: recommendations and safety considerations for biomedical implants and devices. J Magn Reson Imaging 12:510, 2000 93. Shellock FG, Crues JV: MR procedures: biologic effects, safety, and patient care. Radiology 232:635-652, 2004. 94. CDRH Magnetic Resonance Working Group: A primer on medical device interactions with magnetic resonance imaging systems. FDA Guidance Documents. http://www.fda.gov/Medi calDevices/DeviceRegulationandGuidance/GuidanceDocu ment/ucm107721.htm. 95. Irnich W, Irnich B, Bartsch C, et al: Do we need pacemakers resistant to magnetic resonance imaging? Europace 7:353-365, 2005. 96. Duru F, Luechinger R, Scheidegger MB, et al: Pacing in magnetic resonance imaging environment: clinical and technical considerations on compatibility. Eur Heart J 22:113124, 2001. 97. Vahlhaus C, Sommer T, Lewalter T, et al: Interference with cardiac pacemakers by magnetic resonance imaging: are there irreversible changes at 0.5 Tesla? Pacing Clin Electrophysiol 24:489-495, 2001. 98. Luechinger R, Duru F, Zeijlemaker VA, et al: Pacemaker reed switch behavior in 0.5, 1.5, and 3.0 Tesla magnetic resonance imaging units: are reed switches always closed in strong magnetic fields? Pacing Clin Electrophysiol 25:1419-1423, 2002. 99. Luechinger R, Duru F, Scheidegger MB, et al: Force and torque effects of a 1.5-Tesla MRI scanner on cardiac pacemakers and ICDs. Pacing Clin Electrophysiol 24:199-205, 2001. 100. Shellock FG, Tkach JA, Ruggieri PM, et al: Cardiac pacemakers, ICDs, and loop recorder: evaluation of translational attraction using conventional (long-bore) and short-bore 1.5- and 3.0Tesla MR systems. J Cardiovasc Magn Reson 5:387-397, 2003. 101. Roguin A, Zviman MM, Meininger GR, et al: Modern pacemaker and implantable cardioverter/defibrillator systems can be magnetic resonance imaging safe: in vitro and in vivo assessment of safety and function at 1.5 T. Circulation 110:475-482, 2004. 102. Shellock FG, Morisoli SM: Ex vivo evaluation of ferromagnetism and artifacts of cardiac occluders exposed to a 1.5-T MR system. J Magn Reson Imaging 4:213-215, 1994. 103. Anfinsen OG, Berntsen RF, Aass H, et al: Implantable cardioverter defibrillator dysfunction during and after magnetic resonance imaging. Pacing Clin Electrophysiol 25:1400-1402, 2002. 104. Rozner MA, Burton AW, Kumar A: Pacemaker complication during magnetic resonance imaging. J Am Coll Cardiol 45:161162; author reply 162, 2005. 105. Tandri H, Zviman MM, Wedan SR, et al: Determinants of gradient field-induced current in a pacemaker lead system in a magnetic resonance imaging environment. Heart Rhythm 5:462-468, 2008. 106. Fiek M, Remp T, Reithmann C, et al: Complete loss of ICD programmability after magnetic resonance imaging. Pacing Clin Electrophysiol 27:1002-1004, 2004. 107. Gimbel JR: Unexpected asystole during 3T magnetic resonance imaging of a pacemaker-dependent patient with a “modern” pacemaker. Europace 11:1241-1242, 2009. 108. Achenbach S, Moshage W, Diem B, et al: Effects of magnetic resonance imaging on cardiac pacemakers and electrodes. Am Heart J 134:467-473, 1997. 109. Luechinger R, Zeijlemaker VA, Pedersen EM, et al: In vivo heating of pacemaker leads during magnetic resonance imaging. Eur Heart J 26:376-383; discussion 325-377, 2005. 110. Martin ET, Coman JA, Shellock FG, et al: Magnetic resonance imaging and cardiac pacemaker safety at 1.5-tesla. J Am Coll Cardiol 43:1315-1324, 2004. 111. Del Ojo JL, Moya F, Villalba J, et al: Is magnetic resonance imaging safe in cardiac pacemaker recipients? Pacing Clin Elec­ trophysiol 28:274-278, 2005.

112. Gimbel JR, Bailey SM, Tchou PJ, et al: Strategies for the safe magnetic resonance imaging of pacemaker-dependent patients. Pacing Clin Electrophysiol 28:1041-1046, 2005. 113. Gimbel JR, Kanal E, Schwartz KM, et al: Outcome of magnetic resonance imaging (MRI) in selected patients with implantable cardioverter-defibrillators (ICDs). Pacing Clin Electrophysiol 28:270-273, 2005. 114. Gimbel JR, Zarghami J, Machado C, et al: Safe scanning, but frequent artifacts mimicking bradycardia and tachycardia during magnetic resonance imaging (MRI) in patients with an implantable loop recorder (ILR). Ann Noninvasive Electrocardiol 10:404-408, 2005. 115. Nazarian S, Roguin A, Zviman MM, et al: Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla. Circulation 114:1277-1284, 2006. 116. Faris OP, Shein MJ: Government viewpoint. US Food and Drug Administration: Pacemakers, ICDs and MRI. Pacing Clin Elec­ trophysiol 28:268-269, 2005. 117. Smith JM: Industry viewpoint. Guidant: Pacemakers, ICDs, and MRI. Pacing Clin Electrophysiol 28:264, 2005. 118. Stanton MS: Industry viewpoint. Medtronic: Pacemakers, ICDs, and MRI. Pacing Clin Electrophysiol 28:265, 2005. 119. Greatbatch W, Miller V, Shellock FG: Magnetic resonance safety testing of a newly-developed fiber-optic cardiac pacing lead. J Magn Reson Imaging 16:97-103, 2002. 120. Sutton R, Kanal E, Wilkoff BL, et al: Safety of magnetic resonance imaging of patients with a new Medtronic EnRhythm MRI SureScan pacing system: clinical study design. Trials 9:68, 2008. 121. Levine GN, Gomes AS, Arai AE, et al: Safety of magnetic resonance imaging in patients with cardiovascular devices: an American Heart Association scientific statement from the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and Council on Cardiovascular Radiology and Intervention: endorsed by American College of Cardiology Foundation, North American Society for Cardiac Imaging, and Society for Cardiovascular Magnetic Resonance. Circulation 116:2878-2891, 2007. 122. Obwegeser AA, Uitti RJ, Turk MF, et al: Simultaneous thalamic deep brain stimulation and implantable cardioverterdefibrillator. Mayo Clin Proc 76:87-89, 2001. 123. Rosenow JM, Tarkin H, Zias E, et al: Simultaneous use of bilateral subthalamic nucleus stimulators and an implantable cardiac defibrillator: case report. J Neurosurg 99:167-169, 2003. 124. Tavernier R, Fonteyne W, Vandewalle V, et al: Use of an implantable cardioverter-defibrillator in a patient with two implanted neurostimulators for severe Parkinson’s disease. Pacing Clin Elec­ trophysiol 23:1057-1059, 2000. 125. Senatus PB, McClelland S, 3rd, Ferris AD, et al: Implantation of bilateral deep brain stimulators in patients with Parkinson disease and preexisting cardiac pacemakers: report of two cases. J Neurosurg 101:1073-1077, 2004. 126. Monahan K, Casavant D, Rasmussen C, et al: Combined use of a true-bipolar sensing implantable cardioverter-defibrillator in a patient having a prior implantable spinal cord stimulator for intractable pain. Pacing Clin Electrophysiol 21:2669-2672, 1998. 127. Romano M, Zucco F, Baldini MR, et al: Technical and clinical problems in patients with simultaneous implantation of a cardiac pacemaker and spinal cord stimulator. Pacing Clin Elec­ trophysiol 16:1639-1644, 1993. 128. Ekre O, Borjesson M, Edvardsson N, et al: Feasibility of spinal cord stimulation in angina pectoris in patients with chronic pacemaker treatment for cardiac arrhythmias. Pacing Clin Elec­ trophysiol 26:2134-2141, 2003. 129. O’Flaherty D, Wardill M, Adams AP: Inadvertent suppression of a fixed rate ventricular pacemaker using a peripheral nerve stimulator. Anaesthesia 48:687-689, 1993. 130. Rozner MA: Peripheral nerve stimulators can inhibit monitor display of pacemaker pulses. J Clin Anesth 16:117-120, 2004. 131. LaBan MM, Petty D, Hauser AM, et al: Peripheral nerve conduction stimulation: its effect on cardiac pacemakers. Arch Phys Med Rehabil 69:358-362, 1988. 132. American Association of Neuromuscular and Electrodiagnostic Medicine: Risks in electrodiagnostic medicine. Accessed December 2010. http://www.aanem.org/AANEM/media/AANEM/ Documents/Practice/Position%20Statements/risksinEDX.pdf. 133. Chemali KR, Tsao B: Electrodiagnostic testing of nerves and muscles: when, why, and how to order. Cleve Clin J Med 72:3748, 2005. 134. Chen D, Philip M, Philip PA, et al: Cardiac pacemaker inhibition by transcutaneous electrical nerve stimulation. Arch Phys Med Rehabil 71:27-30, 1990. 135. Rasmussen MJ, Hayes DL, Vlietstra RE, et al: Can transcutaneous electrical nerve stimulation be safely used in patients with permanent cardiac pacemakers? Mayo Clin Proc 63:443-445, 1988. 136. Glotzer TV, Gordon M, Sparta M, et al: Electromagnetic interference from a muscle stimulation device causing discharge of an implantable cardioverter-defibrillator: epicardial bipolar and endocardial bipolar sensing circuits are compared. Pacing Clin Electrophysiol 21:1996-1998, 1998. 137. Occhetta E, Bortnik M, Magnani A, et al: Inappropriate implantable cardioverter-defibrillator discharges unrelated to supraventricular tachyarrhythmias. Europace 8:863-869, 2006.

138. Vlay SC: Electromagnetic interference and ICD discharge related to chiropractic treatment. Pacing Clin Electrophysiol 21:2009, 1998. 139. Pyatt JR, Trenbath D, Chester M, et al: The simultaneous use of a biventricular implantable cardioverter-defibrillator (ICD) and transcutaneous electrical nerve stimulation (TENS) unit: implications for device interaction. Europace 5:91-93, 2003. 140. Nuhr MJ, Pette D, Berger R, et al: Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure. Eur Heart J 25:136-143, 2004. 141. Crevenna R, Stix G, Pleiner J, et al: Electromagnetic interference by transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverterdefibrillators: a pilot safety study. Pacing Clin Electrophysiol 26:626-629, 2003. 142. Crevenna R, Wolzt M, Fialka-Moser V, et al: Long-term transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverter defibrillators: a pilot safety study. Artif Organs 28:99-102, 2004. 143. Crevenna R, Mayr W, Keilani M, et al: Safety of a combined strength and endurance training using neuromuscular electrical stimulation of thigh muscles in patients with heart failure and bipolar sensing cardiac pacemakers. Wien Klin Wochenschr 115:710-714, 2003. 144. Dolenc TJ, Barnes RD, Hayes DL, et al: Electroconvulsive therapy in patients with cardiac pacemakers and implantable cardioverter defibrillators. Pacing Clin Electrophysiol 27:1257-1263, 2004. 145. Feigal DW: FDA Public Health Notification: Diathermy interactions with implanted leads and implanted systems with leads. Accessed: December 2010. http://www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/PublicHealthNotifications/ucm062167. htm. 146. Rozner MA: Review of electrical interference in implanted cardiac devices. Pacing Clin Electrophysiol 26:923-925, 2003. 147. Gruber M, Seebald C, Byrd R, et al: Electrocautery and patients with implanted cardiac devices. Gastroenterol Nurs 18:49-53, 1995. 148. Guertin D, Faheem O, Ling T, et al: Electromagnetic interference (EMI) and arrhythmic events in ICD patients undergoing gastrointestinal procedures. Pacing Clin Electrophysiol 30:734-739, 2007. 149. Erdman S, Levinsky L, Strasberg B, et al: Use of the Shaw Scalpel in pacemaker operations. J Thorac Cardiovasc Surg 89:304-307, 1985. 150. Kott I, Watemberg S, Landau O, et al: The use of CO2 laser for inguinal hernia repair in elderly, pacemaker wearers. J Clin Laser Med Surg 13:335-336, 1995. 151. Lloyd Jones S, Mason RA: Laser surgery in a patient with Romano-Ward (long QT) syndrome and an automatic implantable cardioverter defibrillator. Anaesthesia 55:362-366, 2000. 152. Epstein MR, Mayer JE, Jr, Duncan BW: Use of an ultrasonic scalpel as an alternative to electrocautery in patients with pacemakers. Ann Thorac Surg 65:1802-1804, 1998. 153. Rasmussen MJ, Rea RF, Tri JL, et al: Use of a transurethral microwave thermotherapeutic device with permanent pacemakers and implantable defibrillators. Mayo Clin Proc 76:601-603, 2001. 154. Casavant D, Haffajee C, Stevens S, et al: Aborted implantable cardioverter-defibrillator shock during facial electrosurgery. Pacing Clin Electrophysiol 21:1325-1326, 1998. 155. Fiek M, Dorwarth U, Durchlaub I, et al: Application of radiofrequency energy in surgical and interventional procedures: are there interactions with ICDs? Pacing Clin Electrophysiol 27:293298, 2004. 156. Wong DT, Middleton W: Electrocautery-induced tachycardia in a rate-responsive pacemaker. Anesthesiology 94:710-711, 2001. 157. Cheng A, Nazarian S, Spragg DD, et al: Effects of surgical and endoscopic electrocautery on modern-day permanent pacemaker and implantable cardioverter-defibrillator systems. Pacing Clin Electrophysiol 31:344-350, 2008. 158. Lamas GA, Antman EM, Gold JP, et al: Pacemaker backup-mode reversion and injury during cardiac surgery. Ann Thorac Surg 41:155-157, 1986. 159. Roman-Gonzalez J, Hyberger LK, Hayes DL: Is electrocautery still a clinically significant problem with contemporary technology? [abstract]. Pacing Clin Electrophysiol 24:709, 2001. 160. Geddes LA, Tacker WA, Cabler P: A new electrical hazard associated with the electrocautery. Med Instrum 9:112-113, 1975. 161. Heller LI: Surgical electrocautery and the runaway pacemaker syndrome. Pacing Clin Electrophysiol 13:1084-1085, 1990. 162. Moran MD, Kirchhoffer JB, Cassavar DK, et al: Electromagnetic interference (EMI) caused by electrocautery during surgical procedures. Pacing Clin Electrophysiol 19:1009, 1996. 163. Peters RW, Gold MR: Reversible prolonged pacemaker failure due to electrocautery. J Interv Card Electrophysiol 2:343-344, 1998. 164. Nercessian OA, Wu H, Nazarian D, et al: Intraoperative pacemaker dysfunction caused by the use of electrocautery during a total hip arthroplasty. J Arthroplasty 13:599-602, 1998. 165. Kowalski M, Shepard RK, Kalahasty G, et al: An unusual source of electromagnetic interference: a device-device interaction. Pacing Clin Electrophysiol 33:994-998, 2010. 166. Goldschlager N, Epstein A, Friedman P, et al: Environmental and drug effects on patients with pacemakers and implantable cardioverter/defibrillators: a practical guide to patient treatment. Arch Intern Med 161:649-655, 2001.



167. Crossley GH, Poole JE, Rozner MA, et al: The Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) expert consensus statement on the perioperative management of patients with implantable defibrillators, pacemakers and arrhythmia monitors: facilities and patient management This document was developed as a joint project with the American Society of Anesthesiologists (ASA), and in collaboration with the American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Heart Rhythm 8:1114-1154, 2011. 168. Rozner M: Pacemaker misinformation in the perioperative period: programming around the problem. Anesth Analg 99:1582-1584, 2004. 169. Hayes JJ, Juknavorian R, Maloney JD: The role(s) of the industry employed allied professional. Pacing Clin Electrophysiol 24:398399, 2001. 170. El-Gamal HM, Dufresne RG, Saddler K: Electrosurgery, pacemakers and ICDs: a survey of precautions and complications experienced by cutaneous surgeons. Dermatol Surg 27:385-390, 2001. 171. Radiofrequency Identification (RFID). Accessed December 2010. http://www.fda.gov/Radiation-EmittingProducts/ RadiationSafety/ElectromagneticCompatibilityEMC/ucm11 6647.htm. 172. Seidman SJ, Brockman R, Lewis BM, et al: In vitro tests reveal sample radiofrequency identification readers inducing clinically significant electromagnetic interference to implantable pacemakers and implantable cardioverter-defibrillators. Heart Rhythm 7:99-107, 2010. 173. Mehta R, Doshi AA, Hasan AK, et al: Device interactions in patients with advanced cardiomyopathy. J Am Coll Cardiol 51:1613-1614, 2008. 174. Baran DA, Martin T, Blicharz D, et al: Simple method to eliminate interference between ventricular assist devices and cardiac rhythm devices. Pacing Clin Electrophysiol 32:1142-1145, 2009. 175. Hirose M, Tachikawa K, Ozaki M, et al: X-ray radiation causes electromagnetic interference in implantable cardiac pacemakers. Pacing Clin Electrophysiol 33:1174-1181, 2010. 176. Koneru JN, Huizar JF, Kaszala K, et al: Rate response or rad response? an unusual case of device-device interaction. Pacing Clin Electrophysiol 2011 (in press). 177. Doshi A, Love C, Daoud E, et al: Identification of a novel mechanism for inappropriate accelerometer activation during diagnostic fluoroscopy. Europace 11:826, 2009. 178. Leighton JA, Sharma VK, Srivathsan K, et al: Safety of capsule endoscopy in patients with pacemakers. Gastrointest Endosc 59:567-569, 2004. 179. Dubner S, Dubner Y, Gallino S, et al: Electromagnetic interference with implantable cardiac pacemakers by video capsule. Gastrointest Endosc 61:250-254, 2005. 180. Dubner S, Dubner Y, Rubio H, et al: Electromagnetic interference from wireless video-capsule endoscopy on implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 30:472-475, 2007. 181. Das G, Staffanson DB: Selective dysfunction of ventricular electrode-endocardial junction following DC cardioversion in a patient with a dual-chamber pacemaker. Pacing Clin Electro­ physiol 20:364-365, 1997. 182. Waller C, Callies F, Langenfeld H: Adverse effects of direct current cardioversion on cardiac pacemakers and electrodes: is

33  Electromagnetic Interference and CIEDs external cardioversion contraindicated in patients with permanent pacing systems? Europace 6:165-168, 2004. 183. Prakash A, Saksena S, Mathew P, et al: Internal atrial defibrillation: effect on sinus and atrioventricular nodal function and implanted cardiac pacemakers. Pacing Clin Electrophysiol 20:2434-2441, 1997. 184. Vanerio G, Maloney J, Rashidi R, et al: The effects of percutaneous catheter ablation on preexisting permanent pacemakers. Pacing Clin Electrophysiol 13:1637-1645, 1990. 185. Dick AJ, Jones DL, Klein GJ: Effects of RF energy delivery to pacing and defibrillation leads [abstract]. Pacing Clin Electro­ physiol 24:658, 2001. 186. Chin MC, Rosenqvist M, Lee MA, et al: The effect of radiofrequency catheter ablation on permanent pacemakers: an experimental study. Pacing Clin Electrophysiol 13:23-29, 1990. 187. Ellenbogen KA, Wood MA, Stambler BS: Acute effects of radiofrequency ablation of atrial arrhythmias on implanted permanent pacing systems. Pacing Clin Electrophysiol 19:1287-1295, 1996. 188. Chang AC, McAreavey D, Tripodi D, et al: Radiofrequency catheter atrioventricular node ablation in patients with permanent cardiac pacing systems. Pacing Clin Electrophysiol 17:65-69, 1994. 189. Sadoul N, Blankoff I, de Chillou C, et al: Effects of radiofrequency catheter ablation on patients with permanent pacemakers. J Interv Card Electrophysiol 1:227-233, 1997. 190. Proclemer A, Facchin D, Pagnutti C, et al: Safety of pacemaker implantation prior to radiofrequency ablation of atrioventricular junction in a single session procedure. Pacing Clin Electro­ physiol 23:998-1002, 2000. 191. Wolfe DA, McCutcheon MJ, Plumb VJ, et al: Radiofrequency current may induce exit block in chronically implanted ventricular leads [abstract]. Pacing Clin Electrophysiol 18:919, 1995. 192. Burke MC, Kopp DE, Alberts M, et al: Effect of radiofrequency current on previously implanted pacemaker and defibrillator ventricular lead systems. J Electrocardiol 34(suppl):143-148, 2001. 193. Van Gelder BM, Bracke FA, el Gamal MI: Upper rate pacing after radiofrequency catheter ablation in a minute ventilation rate adaptive DDD pacemaker. Pacing Clin Electrophysiol 17:14371440, 1994. 194. Sun DA, Martin L, Honey CR: Percutaneous radiofrequency trigeminal rhizotomy in a patient with an implanted cardiac pacemaker. Anesth Analg 99:1585-1586, table of contents, 2004. 195. Hayes DL, Charboneau JW, Lewis BD, et al: Radiofrequency treatment of hepatic neoplasms in patients with permanent pacemakers. Mayo Clin Proc 76:950-952, 2001. 196. Kufer R, Thamasett S, Volkmer B, et al: New-generation lithotripters for treatment of patients with implantable cardioverter defibrillator: experimental approach and review of literature. J Endourol 15:479-484, 2001. 197. Auge BK, Preminger GM: Update on shock wave lithotripsy technology. Curr Opin Urol 12:287-290, 2002. 198. Cooper D, Wilkoff B, Masterson M, et al: Effects of extracorporeal shock wave lithotripsy on cardiac pacemakers and its safety in patients with implanted cardiac pacemakers. Pacing Clin Elec­ trophysiol 11:1607-1616, 1988. 199. Fetter J, Patterson D, Aram G, et al: Effects of extracorporeal shock wave lithotripsy on single-chamber rate response and dual-chamber pacemakers. Pacing Clin Electrophysiol 12:14941501, 1989.

1027

200. Langberg J, Abber J, Thuroff JW, et al: The effects of extracorporeal shock wave lithotripsy on pacemaker function. Pacing Clin Electrophysiol 10:1142-1146, 1987. 201. Vassolas G, Roth RA, Venditti FJ, Jr: Effect of extracorporeal shock wave lithotripsy on implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 16:1245-1248, 1993. 202. Albers DD, Lybrand FE, 3rd, Axton JC, et al: Shockwave lithotripsy and pacemakers: experience with 20 cases. J Endourol 9:301-303, 1995. 203. Chung MK, Streem SB, Ching E, et al: Effects of extracorporeal shock wave lithotripsy on tiered therapy implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 22:738-742, 1999. 204. Drach GW, Weber C, Donovan JM: Treatment of pacemaker patients with extracorporeal shock wave lithotripsy: experience from 2 continents. J Urol 143:895-896, 1990. 205. Vaidyanathan S, Hirst R, Parsons KF, et al: Bilateral extracorporeal shock wave lithotripsy in a spinal cord injury patient with a cardiac pacemaker. Spinal Cord 39:286-289, 2001. 206. Bohay RN, Bencak J, Kavaliers M, et al: A survey of magnetic fields in the dental operatory. J Can Dent Assoc 60:835-840, 1994. 207. Trenter SC, Walmsley AD: Ultrasonic dental scaler: associated hazards. J Clin Periodontol 30:95-101, 2003. 208. Garofalo RR, Ede EN, Dorn SO, et al: Effect of electronic apex locators on cardiac pacemaker function. J Endod 28:831-833, 2002. 209. Beach CW, Bramwell JD, Hutter JW: Use of an electronic apex locator on a cardiac pacemaker patient. J Endod 22:182-184, 1996. 210. Hiller H, Weissberg N, Horowitz G, et al: The safety of dental mini-magnets in patients with permanent cardiac pacemakers. J Prosthet Dent 74:420-421, 1995. 211. Last A: Radiotherapy in patients with cardiac pacemakers. Br J Radiol 71:4-10, 1998. 212. Guidant Technical Services fact sheet. Impact of therapeutic radiation and Guidant ICD/CRT-D/(RT-P/pacing systems). 2004. 213. Mouton J, Haug R, Bridier A, et al: Influence of high-energy photon beam irradiation on pacemaker operation. Phys Med Biol 47:2879-2893, 2002. 214. Hurkmans CW, Scheepers E, Springorum BG, et al: Influence of radiotherapy on the latest generation of pacemakers. Radiother Oncol 76:93-98, 2005. 215. Hurkmans CW, Scheepers E, Springorum BG, et al: Influence of radiotherapy on the latest generation of implantable cardioverter-defibrillators. Int J Radiat Oncol Biol Phys 63:282289, 2005. 216. Kapa S, Fong L, Blackwell CR, et al: Effects of scatter radiation on ICD and CRT function. Pacing Clin Electrophysiol 31:727-732, 2008. 217. Marbach JR, Sontag MR, Van Dyk J, et al: Management of radiation oncology patients with implanted cardiac pacemakers: report of AAPM Task Group No 34. American Association of Physicists in Medicine. Med Phys 21:85-90, 1994. 218. Solan AN, Solan MJ, Bednarz G, et al: Treatment of patients with cardiac pacemakers and implantable cardioverter-defibrillators during radiotherapy. Int J Radiat Oncol Biol Phys 59:897-904, 2004.

1028

SECTION 4  Follow-up and Programming

34  34

Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories DANIEL B. KRAMER  |  WILLIAM H. MAISEL

P

acemakers and implantable cardiac-defibrillators (ICDs), two of the most remarkable technologic advances in medical history, have undergone significant product modifications since the first human implants.1 For example, although pacemakers became a clinically useful tool in the 1950s, initial models were large, electrically powered, and impractical for long-term patient use. Similarly, early ICDs, initially implanted in humans in 1980 and FDA approved in 1985, were cumbersome, required a thoracotomy for implantation, and had limited reprogramming and data storage capabilities.1,2 Since then, remarkable advances in pacemaker and ICD technology have resulted in substantial reductions in generator size, an exponential increase in computer memory, and advances in lead technology that have reduced diameter, improved chronic pacing thresholds, and with the advent of transvenous leads, greatly facilitated safe lead implantation.3,4 The resultant marked reduction in morbidity and mortality associated with device implantation has led to the widespread adoption of implantable arrhythmia device therapy to the benefit of many patients. Pacemaker and ICD systems must survive for years in the hostile environment of the human body, withstand hundreds of millions of repetitive cardiac cycles, and effectively provide pacing and/or defibrillation therapy at a moment’s notice. Because of the complex device design, sophisticated technology, and considerable demands placed on these systems, it is inevitable that devices will occasionally malfunction or fail to behave as anticipated. As a result, manufacturers or regulatory authorities occasionally issue product advisories to inform health care providers and patients about underperforming devices. Providers who care for pacemaker and ICD patients should have an understanding of device performance, rates and mechanisms of device malfunction, terminology and the threshold for activation of device advisories, communication methods of abnormal device performance, and clinical management of device advisories and malfunctions.

Pacemaker and ICD System Performance DEFINITIONS AND ASSESSMENT OF DEVICE PERFORMANCE Measuring pacemaker and ICD generator and lead performance is important for clinical decision making, to set realistic expectations for patients and physicians, for transparency, and to monitor and improve performance. Importantly, many factors affect device performance, including not only device design and manufacturing, but also physician and patient factors. In some cases, such as those involving lead dislodgments or perforations, differentiating device performance from a procedural or iatrogenic complication may be difficult. Pacemaker and ICD systems, consisting of a generator and lead, must be able to reliably monitor cardiac electrical activity and deliver life-sustaining therapy to the heart when needed. Device reliability measures the freedom of an ICD or pacemaker generator or lead from specific structural and electrical failures.5,6 Reliability is usually reported as the percentage of devices still implanted and functioning appropriately at a given point in time (prevalence) or a failure rate per unit of

1028

time, such as failure rate per month (incidence). Device performance is a more comprehensive assessment of device quality, clinical usability, freedom from failure (malfunction), and conformance to applicable regulatory labeling. Device performance depends on a number of factors, including device design; materials and manufacturing methods; implanting physician skill and technique; patient characteristics (e.g., age, anatomy, activity level); and the expertise of the caregivers providing postimplant care. Box 34-1 highlights common terms used to describe device performance.5,6 Pacemaker and ICD generators and leads may be removed from service because they are malfunctioning or for reasons unrelated to device performance (e.g., patient death, device infection, device upgrade). A malfunction occurs when an implanted device fails to meet its performance specifications or otherwise perform as intended. Although ideally the mechanism of a device malfunction should be confirmed by direct bench laboratory analysis, in many cases this is not possible. For example, malfunctioning ICD leads often are not explanted because of the hazards associated with lead extraction, or leads are damaged by the extraction process itself, making analysis difficult. In addition, devices may fail to perform as expected in ways not identifiable by bench analysis; for example, a design flaw resulting in an increased risk of perforation or dislodgment may be difficult to distinguish from a complication caused by a physician’s implant technique.6 Accurate and useful assessment of overall device performance and malfunctions demands monitoring, analysis, and reporting not only of device failures, but also of adverse clinical events when such events may be caused by device performance issues. Generator Performance and Mechanisms of Malfunction The importance of monitoring pacemaker and ICD performance has long been recognized. For example, the Bilitch Registry was started in 1974 and evaluated 22786 pacemakers from 6 sites over a 19.5-year period and 3520 ICDs from 13 sites over almost 12 years, ending in December 1993.7,8 Failures involving 50 different generator models were reported.7,8 Other long-term device failure registries reported 700 cases of pacemaker and ICD generator malfunction between 1988 and 1996, including 370 “dangerous” cases involving loss of output or decrease in pulse amplitude.7,9 More modern device performance is reflected by data compiled from manufacturer annual reports, submitted to the U.S Food And Drug Administration (FDA) from 1990 and 2002.10 Because pacemakers and ICDs represent “life-sustaining” therapies for many patients, the FDA requires manufacturers to submit annual reports detailing the number of device implants by model number and information concerning device malfunctions. From 1990 to 2002, 17,323 devices (8834 pacemakers and 8489 ICDs) were explanted because of confirmed malfunction.10 The annual number of malfunctions ranged from 366 to 1152 for pacemakers and 134 to 2228 for ICDs (Fig. 34-1). The device malfunction replacement rate (the number of devices removed in a given year because of malfunction indexed to the number of device implants in that same year) during the study period was 20.7 per 1000 implants for ICDs and 4.6 per 1000 implants for pacemakers.10 A meta-analysis of active device registries (including the Bilitch Registry, the Danish Pacemaker and ICD Register, and the United Kingdom [UK] Pacemaker and ICD Registry) provides additional



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories

Box 34-1 

DEFINITIONS OF DEVICE PERFORMANCE TERMS Malfunction Failure of a device to meet its performance specifications or otherwise perform as intended. Performance specifications include all claims made in the labeling for the generator or lead. The intended performance of a device refers to the intended use for which the generator or lead is labeled or marketed. Whenever possible, device malfunction should be confirmed by laboratory analysis. Malfunctions do not include physician-induced damage during the course of implanting, revising, or removing the generator or lead. Extrinsic malfunctions are those caused by external factors (e.g., therapeutic radiation, excessive physical damage, including subclavian crush and direct trauma to the device pocket) including, but not limited to, hazards that are listed in product labeling. Device performance A comprehensive assessment of device quality, usability, freedom from failure (malfunction), and conformance to applicable labeling. Device reliability A measure of a device to be free of specific structural and electrical failures, typically expressed at a given point in time or a failure rate per unit of time (e.g., failure rate per month). Device removed from service unrelated to malfunction A generator or lead that is removed from service (surgical abandonment, removal, extraction, or programmed of f) for reasons not related to device failure: infection, device upgrade (e.g., pacemaker to ICD), pacer/lead incompatibility, cardiac transplantation, mode change not caused by lead failure, patient death unrelated to device failure, etc.

insights into overall pacemaker and ICD generator performance as well as trends in device reliability.11 During 2.1 million pacemaker personyears of observation over 22 years, pacemaker malfunctions were observed in 2981 devices. Pacemaker reliability improved greatly during the study period, from an annual pacemaker malfunction rate of 12.4 malfunctions per 1000 person-years in 1983 to less than 1.0 malfunction per 1000 person-years in the latter study years (Fig. 34-2). Malfunctions in ICDs were observed during the 17-year study period in 384 devices during 14,821 person-years of observation. Annual ICD malfunction rates ranged from a high of 52.5 malfunctions per 1000 person-years in 1989 to a low of 5.6 malfunctions per 1000 personyears in 1998. A significant improvement in ICD reliability occurred during the decade beginning in 1988 until a transient increase in the malfunction rate was observed in the late 1990s and early 2000s (Fig. 34-3). Device reliability again improved greatly beginning in 2003. Overall, the annual ICD malfunction rate was about 20-fold higher

than the pacemaker malfunction rate (26.5 vs. 1.3 malfunctions per 1000 person-years).11 Analysis of FDA annual reports that include manufacturerconfirmed analysis of device malfunctions demonstrates that hardware abnormalities are by far the most common type of device malfunction requiring device replacement for both pacemakers and ICDs.10 Overall, hardware problems represent 79.8% of observed malfunctions. Of these, battery/capacitor abnormalities (23.6%) and electrical issues (27.1%) accounted for half the total device failures.10 Firmware (integral device software) abnormalities and miscellaneous problems (e.g., physical damage, foreign material contamination, manufacturing errors) were much less frequent causes of device malfunctions. In only 4.7% of cases could the manufacturer confirm device malfunction but not determine the cause. Battery/capacitor abnormalities account for a higher percentage of device malfunctions in ICDs than in pacemakers (31.7% vs. 15.8%).10 Miscellaneous electrical problems, such as broken wires, current leakage, and electrical short circuits, represented similar percentages of malfunctions in pacemakers and in ICDs. Meta-analysis of active device registries has yielded similar findings.11 Battery malfunctions, most often premature battery failure, were the most common cause of device failure in the Bilitch Registry, the Danish Pacemaker and ICD Register, and the UK Pacemaker and ICD Registry11 (Table 34-1). For pacemakers, an additional 14.3% of device malfunctions were caused by low-output or no-output states. A number of root causes, however, can masquerade as a battery abnormality, including rapid premature battery depletion, electrical short circuits, inappropriate high current drains, or hermetic seal abnormalities. Miscellaneous other types of device failures, such as programming malfunctions, device header abnormalities, magnetic switch malfunctions, and charge circuit abnormalities (for ICDs), accounted for the majority of the other reported device malfunctions.11 Lead Performance and Mechanisms of Malfunction Pacemaker and ICD lead performance is more difficult to assess than generator performance because malfunctioning leads are often not explanted, and even when they are, leads are often damaged during the explant process.6,12 In addition, reported lead performance varies widely depending on study design, performance definitions, physician and patient characteristics, implant methodology, duration and method of follow-up, and lead models studied. These factors explain some of the observed variability in lead performance.12 Manufacturer product reports describe the performance of atrial, right ventricular, left ventricular, and high-voltage leads and demonstrate lead survival probabilities for most leads of 92% to 99% at 5 years after initial implant.13-17 However, most of these lead survival estimates are significantly limited due to potential underreporting of device malfunctions, insufficient patient follow-up, lead surveillance

3000 2500

Malfunctions

Figure 34-1  Annual number of malfunctions for pacemakers and ICDs (1990-2002). The annual number of implantable cardioverterdefibrillator (ICD) malfunctions increased during this period, with more than 50% of the ICD malfunctions occurring in the last 3 years of the study interval (see text). (Adapted from Maisel WH et al: Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA 295:1901-1906, 2006.)

1029

ICD Pacemaker

2000 1500 1000 500 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 Year

1030

SECTION 4  Follow-up and Programming

Malfunctions per 1000 person-years

PACEMAKER MALFUNCTION RATES, 1983–2004 16

12

8

4

0 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 Year

Malfunctions per 1000 person-years

ICD MALFUNCTION RATE, 1988–2004 100 80 60 40 20 0 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 Year Figure 34-3  Annual ICD malfunction rates: 1988-2004. The annual rate of ICD malfunction decreased from 1988 to 1998 and increased significantly between 1998 and 2002 before experiencing a reduction in the later study years. Data from the Bilitch Registry (1988-1993) and the Danish Register (1994-2004) contributed to this analysis. Error bars represent 95% confidence intervals. (Adapted from Maisel WH: Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA 295:1929-1934, 2006.)

TABLE

34-1 

Figure 34-2  Pacemaker malfunction rates: 1983-2004. The annual pacemaker malfunction rates are displayed. Pacemaker malfunction rates decreased significantly during the study period. Error bars represent 95% confidence intervals. (Adapted from Maisel WH: Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA 295:19291934, 2006.)

based on voluntary reporting, and lack of uniform definitions of lead performance and malfunction.6,12 Some manufacturers have utilized prospective, multicenter lead studies in an effort to overcome these limitations. However, small sample sizes or slow enrollment can undermine the ability of these studies to accurately identify underperforming leads in a timely manner.18 Also, they may fail to identify important differences in lead performance between models. Other data sources also provide estimates of lead reliability. In Denmark, all lead implantations are entered into a longitudinal registry.19 Ten-year lead survival for unipolar and bipolar pacemaker leads implanted since 1993 was reported as 96.5% and 97.8%, respectively, and reliability has improved over time.19 Eckstein et al.20 conducted a retrospective analysis of 1317 consecutive patients who received ICD systems (including 38 different ICD lead models) at three centers in Germany between 1993 and 2004. Follow-up after implantation included noninvasive routine lead evaluation every 3 to 6 months. For the study, “lead failure” was defined as a lead-related problem requiring surgical revision performed at the discretion of the treating physician. Abnormalities were classified as either structural (insulation defects or lead fracture) or functional (far-field sensing; T-wave or physiologic oversensing, noise from contact with another lead, unstable impedance measurements, R-wave reduction, or loss of capture). During a median follow-up of 6.4 years, 38 ICD leads required surgical revision, resulting in a reported cumulative ICD lead survival rate of 97.5% at 5 years.20 A number of prior published studies report on the reliability and durability of ICD leads.21

Pacemaker and ICD Malfunctions Observed in Various Device Registries Pacemaker

Malfunction Battery No output or low output Programming malfunction Other† Unspecified TOTAL

UK Registry

Danish Register

Bilitch Registry

N (%)* 1395 (55.8) 306 (12.2) 78 (3.1) 278 (11.1) 444 (17.8) 2501 (100)

N (%)* 131 (41.1) 67 (21.0) 11 (3.4) 18 (5.6) 92 (28.8) 319 (100)

N (%)* 100 (62.1) 16 (9.9) 5 (3.1) 10 (6.2) 30 (18.6) 161 (100)

ICD Meta-analysis % (95% CI) 52.8 (42.3, 63.2) 14.3 (9.0, 20.6) 3.2 (2.6, 3.9) 7.9 (4.4, 12.3) 21.6 (14.8, 29.3) 100

Danish Register

Bilitch Registry

N (%)* 104 (77.6) 6 (4.5) 0 (0) 4 (3.0) 20 (14.9) 134 (100)

N (%)* 204 (81.6) 0 (0) 0 (0) 17 (6.8) 29 (11.6) 250 (100)

*Percentage of column totals; may not add to 100% due to rounding. †Includes device header abnormalities, magnetic switch malfunctions, charge circuit abnormalities, etc. See text for details.

Meta-analysis % (95% CI) 80.1 (76.0, 83.9) 1.5 (0.4, 9.3) 0 5.6 (3.5, 8.0) 12.9 (9.7, 16.4) 100



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories ICD LEAD PERFORMANCE

ICD lead survival (%)

100 90 80 70 60 50 0

2

4

6

8

10

Years postimplant Aass (2002), n = 80 Aass (2002), n = 72 Dorwarth (2003), n = 261 Eckstein (2008), n = 1317 Ellenbogen (2003), n = 76

Hauser (2002), n = 521 Kitamura (2006), n = 249 Kleeman (2007), n = 990 Kron (2001), n = 474 Luria (2001), n = 391

Figure 34-4  Results of selected studies of ICD lead performance. To be included, studies had to (1) be published in a peer-reviewed journal after 1999, (2) provide follow-up for at least 18 months after implantation, and (3) statistically account for patients who had died or were lost to follow-up. The data point represents the point estimate of the study for ICD lead survival. The size of the data point is proportional to the total number of patients in the study. The great variation observed in ICD lead survival is the result of variable study definitions of ICD lead malfunction, variable performance of different ICD lead models, and the impact of patient characteristics and physician implantation techniques on ICD lead performance. Primary author, year of publication, and number of patients in each study are displayed in the legend. (From Maisel WH, Kramer DB: ICD lead performance. Circulation 117:27212723, 2008.)

Reported ICD lead “survival” varies from 91% to 99% at 2 years, 85% to 98% at 5 years, and 60% to 72% at 8 years12,21-33 (Fig. 34-4). Importantly, the definition of ICD lead “survival” or lead “performance” varies among published studies, making it difficult to compare manufacturers or lead models.12 Typically, lead malfunction is defined as electrical abnormalities on lead testing, a chest radiograph consistent with a fracture, or evidence of oversensing unrelated to cardiac signals. Other studies, however, rely on physician clinical judgment and require replacement of the ICD lead in order to consider the lead to have malfunctioned.20 In most published studies, thresholds for action are poorly defined and ambiguous. TABLE

34-2 

1031

Although conceptually simple, pacemaker and ICD leads are complicated devices with lead designs that vary from model to model. These design differences may include variations in insulation, cable/ conductor, length, diameter, and fixation mechanism.34 Knowledge about lead abnormalities mainly comes from manufacturer analysis of returned products, which is a rich source of information that manufacturers utilize to support product improvements and enhancements.4 Mechanical or electrical abnormalities may develop in components such as insulation, conductors, the connector, the terminal pin, or the stimulation electrode. In addition to failure mechanisms that are intrinsic to the lead, extrinsic factors (lead damage from trauma, mishandling, lead dislodgment, etc.) may cause pacemaker and ICD leads to provide insufficient therapy.6 The clinical implications of a lead malfunction vary depending on the type of malfunction and the individual patient’s clinical condition. Notably, some structurally normal leads may provide insufficient therapy (e.g., lack of clinical improvement with cardiac resynchronization therapy), inappropriate therapy (e.g., shock delivery for rapid atrial fibrillation), or may need to be removed from service as a result of issues unrelated to the lead, such as the patient’s underlying illness, physiology, implant technique, or device upgrade (e.g., from pacemaker to ICD).6 Importantly, patient and physician characteristics—in addition to lead design—affect ICD lead performance.4 For example, patients with an ICD lead failure are eight times more likely to experience a second failure than a patient without a failure.20 Unfortunately, the tools available to detect impending ICD lead failure are limited. Fluoroscopy, radiography, electrical testing, or direct visualization may be used to detect lead abnormalities, but in many respects these methods are quite rudimentary, imprecise, and insensitive. Long-term, remote monitoring has provided insights into the sometimes intermittent nature of lead abnormalities and has allowed earlier detection of lead performance issues.12 The Heart Rhythm Society (HRS) Task Force on Lead Performance Policies and Guidelines proposed a classification scheme for pacemaker and ICD leads removed from service6 (Fig. 34-5).

SURVEILLANCE OF DEVICE PERFORMANCE The goal of post-market surveillance is to “enhance the public health by reducing the incidence of medical device adverse experiences.”35 The current surveillance system relies on regulators, medical device manufacturers, health care providers, hospitals and other medical care facilities, and patients to report device malfunctions. Regulatory authorities utilize several different methods to conduct post-market surveillance. For example, the FDA uses spontaneous reporting systems, analysis of large health care databases, scientific studies, registries, and field inspection of facilities5,6,35 (Table 34-2). Historically, the FDA has depended primarily on a passive, “adverse event” reporting system, relying on patients and the health care

Methods of Post-Market Surveillance

Method Returned Product Analysis

Definition Devices removed from patients and returned to the manufacturer for analysis

Complaints

Any communication received by a manufacturer that alleges deficiencies in product performance Observation study of device

Registries Post-Approval Clinical Studies Passive Reporting Systems

Advantages Best method for determining and understanding the actual in vivo failure mechanism Sometimes offers opportunity for direct clinician or patient communication

Disadvantages Device can be damaged during removal/ explant; low return rate; inability to determine failure rate Allegations often incomplete, unsubstantiated More difficult to determine, verify failure mechanisms

Prospective, multicenter studies

Opportunity to study real-world device performance; potential ability to compare products, study subgroups Provide actual device survival estimates

Relies on reports of observed clinical adverse events or device performance issues

Useful for identifying rare, unusual device-related adverse events

Often incomplete, unsubstantiated reports; underestimates true incidence of lead failure.

Expensive, time-consuming

Modified from Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009.

1032

SECTION 4  Follow-up and Programming

Classification of Leads Removed From Service CLINICAL DIAGNOSIS Compromised Pacing Failure to Capture High Pacing Threshold Extra-cardiac stimulation Other Compromised Sensing Undersensing Oversensing Lead Noise T Wave Oversensing Far-Field Oversensing Myopotential Oversensing Lead-Lead Interaction Other Compromised Defibrillation Failure to Defibrillate High Defibrillation Threshold Other

Post-Implant Timing:

30 days

> 30 days

Other Compromised Function ex. hemodynamic sensor, etc Electrical Abnormality WITHOUT Clinical Compromise Abnormal Pacing Impedance Abnormal High Voltage Impedance Low Amplitude Electrogram Other Other Clinical Adverse Event Lead Dislodgment, Displacement, Malposition Cardiac Perforation and/or Cardiac Tamponade Pericardial Effusion without Tamponade Infection Other Lead Not Needed (e.g., atrial lead in chronic AF) Recall/Advisory Patient Death (Not Lead Related) Unknown None

LEAD STRUCTURAL DIAGNOSIS Conductor Failure Insulation Failure Connector Failure Fixation Failure

Other Structural Failure Induced Structural Damage (e.g., iatrogenic, trauma) Unknown No Structural Abnormality Identified

METHOD USED TO CONFIRM LEAD ABNORMALITY Manufacturer Returned Product Analysis Device Interrogation (electrogram, marker channel, impedance, event recording from programmer or home monitor system) Imaging (Xray, fluroscopy, etc.) Physical Inspection or Testing at Time of Surgery Other No Lead Abnormality Unknown

CLINICAL ACTION(S) TAKEN TO CORRECT MALFUNCTIONING LEAD Lead Surgically Abandoned or Capped Lead Electronically Capped (mode reprogrammed) Lead Explanted Lead Repaired Device Reprogrammed (Polarity) Other Lead Related Surgery Performed (lead repositioned, partially abandoned) None Unknown Figure 34-5  Classification scheme for leads removed from service. A lead failure is a lead that does not perform its intended function as a result of a specific structural or electrical failure and that is removed from service because of clinical safety concerns associated with electrophysiologic or structural abnormalities. (From Maisel WH, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009.)

industry to identify and report adverse events, including rare but serious occurrences. Manufacturers are required to report to the FDA any medical device–related event or malfunction that may have caused or could cause a serious injury or death. Hospitals, nursing homes, and other medical facilities are required to report serious device-related injuries to the manufacturer and device-related deaths to both the manufacturer and the FDA.

The FDA annually receives more than 220,000 adverse event reports regarding medical devices of all types, including some that involve pacemakers, ICDs, or leads.36 The vast majority of reports are provided by manufacturers; fewer than 10,000 come directly from medical facilities. Postmortem device interrogation is rarely performed.37 Health care professionals and patients are encouraged, but not required, to report suspected device-related adverse events, but the FDA receives



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories

1033

WORLDWIDE REPORTED PERFORATION RATE FOR ST. JUDE RIATA ICD LEAD 1.00

Percent

0.75 0.50

St. Jude Riata Concerns Wall Street Journal November 12, 2007 Medtronic Fidelis Recall New York Times October 15, 2007

0.25 0.00 Dec 06– Feb 07– Apr 07– Jun 07– Aug 07– Oct 07– Dec 07– Feb 08– Apr 08– Jun 08– Jan 07 Mar 07 May 07 Jul 07 Sep 07 Nov 07 Jan 08 Mar 08 May 08 Jul 08 Date Figure 34-6  Worldwide St. Jude Riata ICD lead reported perforation rate. Both confirmed and suspected, for December 2006 to July 2008. Rates represent the worldwide number of reported perforations divided by the worldwide sales for each 2-month period. The reported perforation rate tripled in the wake of high-profile news media reports questioning the performance of ICD leads. (From Maisel WH: Implantable cardioverterdefibrillator lead complication: when is an outbreak out-of-bounds? Heart Rhythm 5:1673-1674, 2008.)

only several thousand reports from health care providers annually, and physicians, in particular, rarely report events.4-6,35,36 The Manufacturer and User Facility Device Experience (MAUDE) database was established to assist with adverse event reporting and information dissemination for medical devices of all types.38 It contains more than 1 million adverse event reports, including voluntary reports since June 1993 and manufacturer reports since August 1996.35,38 Selected information from this database is publicly searchable via the Internet, and the database has been successfully used to identify concerning safety signals.39,40 However, because submitted adverse event reports are sometimes cryptic or incomplete, it is often difficult to determine if a true device malfunction or patient injury has occurred. Furthermore, significant underreporting of device malfunctions and the absence of denominator data make it difficult to determine the true rate of an observed abnormality41 (Fig. 34-6). For example, all product experience reports from Italy related to one ICD lead were reviewed and demonstrated that only 126 of 454 physician product experience reports were accompanied by a returned lead—and 80% of the returns were related to implant procedures, not chronic use.42 Recognizing this shortcoming, the FDA established the Medical Product Safety Network (MedSun) and HeartNet.43 This active surveillance system utilizes health care facilities and individuals specially trained in device adverse event reporting to identify problems in both device function and user error in the clinical setting. HeartNet in particular focuses on identifying, understanding, and solving problems with medical devices used in electrophysiology laboratories.43 In addition, many manufacturers utilize post-market studies to track the performance of their products. The Centers for Medicare and Medicaid Services (CMS) mandated National Cardiovascular Data Registry (NCDR) collects data on ICD generators and leads and is being better adapted to track longitudinal device performance.44,45 Remote monitoring of device performance has revolutionized pacemaker and ICD patient care by providing automated checks of device functionality and wireless notification of device performance to manufacturers and health care providers46 (see Chapter 32). Device Recalls and Advisory Notices Manufacturers and regulators occasionally become aware of devices that are not performing as expected. The terminology used to describe regulatory actions related to abnormal device behavior can be confusing to health care providers and patients because they vary by jurisdiction and are often used by the media and public inappropriately and interchangeably. The FDA defines a recall as “an action taken to address

a problem with a medical device that violates FDA law.”5 Recalls occur when a medical device is defective and/or when it could constitute a risk to health. The FDA classifies recalls and safety alerts (collectively referred to as “advisories”) into four categories: class I, class II, class III, and safety alerts.7 Class I recalls are situations in which there is a reasonable probability that the use of or exposure to a product will cause serious adverse health consequences or death.7,47 Class II recalls are issued when use of product may cause temporary or medically reversible adverse health consequences or the probability of serious adverse health consequences is remote.7,47 Class III recalls mean that the use of the product is not likely to cause adverse health consequences.7,47 Product notifications or safety alerts are communications issued by a manufacturer to inform of an unreasonable risk of substantial harm from a medical device.7,47 In some cases, these situations are also considered recalls. Importantly, the term recall does not mean that an implanted device must be removed from a patient. Clinical management of advisory notices must be personalized and should reflect numerous factors related to the potential device malfunction, the patient risk profile, and physician and hospital expertise5,6 (see later discussion). Threshold for Activation.  The threshold for activation of an advisory notice may vary depending on the frequency of the device performance problem and the clinical implications of the malfunction.5,6,3,48 Even a single event, if it is systematic and associated with a significant risk for death or serious injury, may warrant early review by a manufacturer’s physician advisory committee. HRS has previously taken the position that it is inadvisable to determine a fixed percentage of device malfunctions or attempt to classify all of the particular types of malfunction that would automatically trigger a notification or advisory.5,6 Instead, HRS recommends regular review of data to determine when a pattern of inadequate device performance exists. In general, when a pattern of malfunction is recognized and associated with significant risk for patient harm, the manufacturer will retrieve affected, unimplanted devices from their sales force and hospital inventories. The timing and method of public notification as well as the clinical recommendations to health care providers and patients with advisory devices are made with involvement of industry, regulators, and arrhythmia experts. Number, Rate, and Reasons for Advisory.  More than 250,000 pulse generators, leads, and pacemaker/ICD programmers were subject to FDA recalls and safety alerts between 1974 and 1987. Furthermore, all five major manufacturers had an increase in the number of models of

1034

SECTION 4  Follow-up and Programming

PACEMAKER AND ICD ADVISORIES IN THE UNITED STATES, 1990–2000

9

Number of advisories

8 7

180000

PM advisories ICD advisories PM subject to advisories ICD subject to advisories

160000 140000 120000

6

100000

5

80000

4

60000

3 2

40000

1

20000

0

0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year

pulse generators, leads, and pacemaker/ICD programmers subject to FDA recalls and safety alerts between 1976 and 1995.7,49 From 1990 to 2000, there were 52 advisories affecting pacemaker and ICD generators. While recalls and safety alerts more often involved pacemakers than ICDs (67% vs. 35%; P = .002), the annual percentage of advisories involving ICDs increased between 1990 and 2000. Between January 1990 and December 2000, 408,500 pacemakers and 114,645 ICDs (523,145 total devices) were subject to recalls or safety alerts7 (Fig. 34-7). The annual number of affected devices varied from a low of 0 in 1990 to a high of 182,647 in 1999. Of the devices recalled from 1990 to 2000, 65% were recalled in 1999 and 2000, including 71% of the recalled pacemakers and 42% of the recalled ICDs. In total, since 1990, more than 60 advisories have affected over 1 million arrhythmia devices.3 Of the advisories issued from 1990 to 2000, three-quarters were classified by the FDA as class I or II recalls.7 The majority (35 of 52 advisories, 67%) were issued because of hardware malfunctions such as electrical/circuitry malfunction, battery/capacitor malfunction, inadequate hermetic seal, defective crystals, or device header abnormalities. Firmware (integral device computer programming) errors accounted for an additional 10 (19%) advisories.7 Overall, hardware (54%) and firmware (41%) malfunctions accounted for 95% of all advisory devices. The remaining recalls and alerts resulted from either environment-device interactions (e.g., ICD interactions with magnetic fields) or to non-device-related problems (mislabeling of product, inappropriate product distribution). The annual advisory rate for devices ranged from 0 to 27 per 100 person-years for pacemakers, 0 to 71 per 100 person-years for ICDs, and 0 to 25 per 100 person-years for total devices.7 The overall pacemaker and ICD generator advisory rate for 1990-2000 was 7.7 advisories per 100 person-years.7 The ICD advisory rate was significantly greater than the pacemaker advisory rate (16.4 vs. 6.7 advisories per 100 person-years). Notably, between 1995 and 2000 the advisory rate increased for pacemaker and ICD generators. Recent studies suggest as many as 25% of ICD patients are affected by an advisory.50 In addition, a changing pattern of causes of device advisories has been observed, with a threefold increase in the number of devices affected per advisory and a threefold increase in the number of devices affected by hardware advisories, (primarily from a 700-fold increase in electrical/circuitry abnormalities and a 20-fold increase in potential battery/capacitor malfunctions).51 Other hardware abnormalities (defects in the device header, hermetic seal, etc.) became less common. The number of devices recalled because of firmware abnormalities also more than doubled. Many of these observations are consistent with the changing

Number of devices subject to advisory

10

Figure 34-7  Annual number of pacemaker (PM) and ICD advisories: 1990-2000. The annual number of actual devices affected by these advisories is also shown. One 1997 recall involved both PMs and ICDs. (Adapted from Maisel WH, et al: Recalls and safety alerts involving pacemakers and implantable cardioverter-defibrillator generators. JAMA 286:793-799, 2001.)

design and manufacturing of pacemaker and ICD generators and the exponential growth in their computer memory and reliance on transistors and microprocessors.1,3,52 Communication After Device Malfunction Identified Although transparency and timely disclosure are paramount to ensure patient safety, premature notification of generator or lead performance concerns can trigger unnecessary physician and patient anxiety and promote clinical overreaction.5,6 Premature or poorly communicated notifications about abnormal pacemaker or ICD system performance may result in unnecessary operations, lead extractions, and device replacements. The ultimate goal of communication is to promote patient safety and well-being. To achieve that goal, communication must be timely, succinct, and unambiguous so that patients and physicians are not needlessly alarmed or driven to hasty, unsafe, and unwise reactions. Communication from industry and health care providers to patients should not only identify the problem but also offer guidance, when possible, as to the clinical management and mitigation of patient risk. The 2006 HRS Device Performance Policies and Guidelines provide a standardized Physician Device Advisory Notification form (Fig. 34-8) and Patient Device Advisory Notification letter to ensure that all critical information regarding device performance is communicated in an easily understood manner.5 In some cases, national heart rhythm societies have effectively established communication networks to disseminate important information rapidly to health care providers.53 Manufacturers typically attempt to contact patients affected by advisory using the patient registration information obtained at the initial device implantation. Health care providers should contact their patients as soon as possible after advisory notification to minimize patient anxiety and promote evidence-based clinical management.54 In addition to providing patients with information regarding device advisories, health care providers should communicate with patients regarding other device-related information. For example, to make informed decisions, patients should be told not only of the benefits and risks associated with device-related therapy and procedures, but also of the expected performance of the device that they are to receive, including battery life, lead performance, and the expected rate of component and device malfunction. Knowledge of these factors will facilitate informed decisions and appropriate expectations for therapy by physicians and patients. Patients should be provided updated generator and lead performance information, particularly whenever such information may impact the clinical management strategy.



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories

1035

Standardized Physician Advisory Notification Form PHYSICIAN DEVICE ADVISORY NOTICE Advisory Date: Manufacturer(s) Product(s) Manufactured on or before (Date) Performance Failure Root Cause (if known) Date Manufacturer Corrected Product Available (if known) Has all affected product been retrieved?

Trade Name

Model Number

Yes

No

When?

FDA CLASSIFICATION STATUS Class: (USA)

Advisory classification CLINICAL ACUITY a) Total number of units currently implanted b) Estimated number of potentially affected devices of this mode worldwide c) Estimated instances of this performance failure over the projected life of the device d) Total number with observed Performance Failure % of Performance Failures d/b × 100 = e) Mean age of product in implanted population f) Patient deaths reported Number of deaths = g) Patient deaths with probable relationship to device failure Number of deaths =

Decision Pending (Worldwide)

Yes

No

*The data analysis provided in this report was generated by the manufacturer and may be subject to change DEVICE COMPONENTS AT RISK OF PERFORMANCE FAILURE Battery Failure Diagnostic Data Failure Brady Therapies (lower rate pacing) Brady Therapies (runaway pacing) Tachy Therapies (ATP) Tachy Therapies (shock) PATIENT MANAGEMENT RECOMMENDATIONS Verify normal device function (at normal follow-up interval) Verify normal device function (as soon as possible) Specific measures to assess: Programming changes If programming changes are required, specify changes: Accelerated device follow-up Timeline – months:

CRT (left ventricular pacing) Lead Failure Hermiticity or internal component EMI Susceptibility Telemetry Failure Other (specify)

Yes Yes

No No

Required

Recommended

Yes

No

CONTACT Industry Name Address1 Address2 City, State, Zip Phone Fax Email Website Figure 34-8  Standardized physician advisory notification form. (From Carlson MD, et al: Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines. Heart Rhythm 3:1250-1273, 2006.)

Clinical Management of Device Advisory Notices OVERVIEW AND CLINICIAN RESPONSIBILITIES The clinical management of device advisories can be challenging. Important clinical decisions affecting the well-being of patients sometimes must be made with incomplete or insufficient information.

Clinical management of device advisories is made easier when clinicians thoroughly discuss device performance issues before initial device implantation and when they take a methodical evidence-based approach to clinical management when advisories do arise. The setting of realistic expectations for patients during the informed-consent process is among the most important clinician tasks.5,6 Informed consent for a permanently implanted, potentially life-sustaining device should include a discussion of the clinical

1036

SECTION 4  Follow-up and Programming

benefits and risks of device implantation as well as anticipated device and lead longevity, reliability expectations, and the potential for generator and lead performance abnormalities. In addition, routine clinical monitoring of device performance is recommended, with the frequency and method of follow-up determined by such factors as the patient’s medical status and the type and age of the implanted device.55 Remote device interrogation increasingly offers the ability to monitor device performance more closely and to detect device abnormalities earlier, potentially averting adverse clinical consequences of device failure.6,12 In many cases, close, routine, conservative monitoring of an advisory device is the safest clinical management option.5,6 Patients and clinicians confronted by a pacemaker or ICD generator or lead advisory face a wide and sometimes confusing array of clinical management options, ranging from watchful waiting to noninvasive device modifications to surgical revision or device explantation. Balancing the safety concerns identified by an individual product advisory with the risks and potential benefits of the available management strategies requires a systematic approach to each notification. BALANCING CLINICAL RISKS AND BENEFITS The appropriate clinical management of a pacemaker or ICD generator or lead advisory depends on a critical assessment of the risk/benefit balance in individual patients. Overall, clinician management of pacemaker and ICD advisories has been widely disparate, with some physicians recommending the replacement of most or all advisory devices, whereas others replace none or very few.56 Importantly, although generator or lead malfunctions can have important clinical consequences, so can the complications of prophylactic device replacement. For example, the Telectronics Accufix atrial J lead was susceptible to fracture; however, more patients died from lead removal than from the lead fracture itself.57 Even generator replacement for devices under advisory has been associated with a major complication rate of up to 5.8% and may be riskier than initial implantation.58,59 These cautionary tales emphasize the need for great discretion in management of advisories. Physicians must carefully consider patient- and device-specific factors that influence the balance of risks and benefits, while also considering the clinical experiences of their own institution with device replacement in different patient populations.60-62 Striking the proper clinical balance can be difficult. A low threshold to remove a device may unnecessarily expose patients to increased risks. However, too restrictive an approach to device replacement may leave patients vulnerable to potentially life-threatening device malfunction. Patient and device factors should be carefully considered, although no single factor should dictate the treatment decision6 (Box 34-2). Importantly, the expertise of the physician and the hospital where the patient receives care are also important factors in the decision-making process; patient outcomes generally improve with operator and medical center experience.63,64 Several analyses have attempted to develop treatment algorithms and define the patient populations who are best served by conservative or aggressive advisory management strategies.61,62,65 However, improvements in remote monitoring, lead extraction technologies, and procedural quality control can alter this calculus. CLINICAL MANAGEMENT OPTIONS The development of an individualized patient advisory clinical management strategy depends on numerous factors. In general, noninvasive management may be considered when the risk of advisory device malfunction is low, particularly for patients who are not pacemaker dependent, and for primary prevention ICD patients with a low probability of future therapy. In contrast, device revision or replacement should be considered if the risk of malfunction is substantial, if the malfunction is likely to lead to patient death or serious harm, and if the risk of device revision or replacement is less than the risk of patient harm from device malfunction. Because the risk of invasive

Box 34-2 

RISK/BENEFIT ANALYSIS OF MANAGEMENT STRATEGIES FOR ADVISORY DEVICES Patient Factors* Pacemaker dependence† Prior history of ventricular arrhythmia Patient prognosis Risk of future arrhythmia Surgical risk of revision/replacement procedure Patient anxiety about device failure Impending battery depletion Device Factors* Rate of abnormal performance (observed or projected) in advisory device Device failure rates Malfunction characteristics (e.g., gradual vs. sudden, predictable vs. unpredictable) Identified device subset with higher failure rate (e.g., serial numbers, vascular access) Malfunction mechanism known/understood Adverse clinical consequences of device failure Availability of reprogramming to mitigate clinical risk Availability of algorithms for early detection of device abnormality Data from Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009. *No single factor should determine the clinical management plan. †Pacemaker dependence refers to patients who have no hemodynamically stable underlying heart rhythm in the absence of pacing.

management can be significant, and because remote monitoring offers the potential for close clinical follow-up, noninvasive management sometimes offers the lowest risk management strategy.6,12 Health care providers should communicate to the patient the risks and potential benefits of available clinical management strategies, including device revision or replacement, reprogramming the device to mitigate the risk of an adverse event from device malfunction, and routine or intensified follow-up. Patient anxiety caused by device performance concerns should also be carefully considered when developing a management strategy. In addition, patients should be provided updated device performance information whenever such information may impact the clinical management strategy. When considering the available clinical management options, the clinician must understand the potential risks of invasive management strategies (including the risks of generator replacement and lead extraction) as well as more conservative, noninvasive management strategies. Risks of Generator Replacement and Lead Placement The risks of pacemaker and ICD implantation have been well described66-69 (Table 34-3). Infection rates (0.2%-1.8%) and lead dislodgment rates (1.5%-2.4%) are low but significant and may be higher for device replacement compared to initial implantation.58 The complication rate related to advisory generator replacement has been evaluated in a large, multicenter cohort of 2635 patients with advisory devices, 451 of which were replaced.70 The acute complication rate was 5.8%.58 Over almost 1 year of follow-up, 9.1% of patients undergoing replacement experienced complications, including 27 requiring reoperation and two procedure-related deaths.70 Notably, generator replacement was riskier in patients with multiple previous pocket interventions.70 Similarly, a single-center experience of 237 advisory devices resulted in a 5.5% major complication rate, including a 2.1% rate of complications requiring reoperation but no deaths.71 A major complication rate of 4.1% with no deaths was also observed among 222 patients undergoing advisory generator replacements.72 Importantly, not all medical centers demonstrate similar complication rates.73 Adjunctive medical therapy with anticoagulants and antiplatelet agents has been shown to increase the likelihood of bleeding



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories

TABLE

34-3 

1037

Complications Associated with Pacemaker and ICD Implantation

Study AVID66 Gold67 Rosenqvist68 Kiviniemi69

Device ICD ICD ICD PM

N 539 1000 778 446

Follow-up (mo) 12 >6 4 60

Death (%) 1* — 0.8 0

Lead Fracture (%) 4/1.5† 0.5/0.3§ — —

Lead Dislodgment (%) 1.5 2.3/0.5§ 2.4 1.6

Infection (%) 5/1‡ 0.2 0.7 1.8

Other Pocket Complication (%) — 2 3.5 —

Pneumothorax (%) 1.1 — — 1.1

Perforation (%) 0.4 — — 0.7

Modified from Carlson MD, Wilcoff BL, Maisel WH, et al: Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines. Heart Rhythm 3:1250-1273, 2006. *Death within 30 days; not all device implant related. †Subclavian/cephalic. ‡Abdominal/pectoral. §Subcutaneous/submuscular. PM, Pacemaker.

complications from generator changes.74-77 Depending on the specific indications (e.g., recently implanted drug-eluting coronary stents), the timing of a device replacement may need to be carefully considered.77 Risks of Lead Extraction Although lead extraction has historically been associated with a small but significant mortality risk, improvements in lead extraction technology and increased operator experience challenge the reliability of earlier estimates of morbidity and mortality associated with the procedure. For example, among a retrospective cohort of 348 patients undergoing 349 ICD lead extractions (mean implant duration of 27.5 months) at five high-volume extraction centers between May 2005 and August 2009, complete removal of the index lead was accomplished in every case with no major complications, and minor complications were observed in only 0.57% of patients. Simple traction was used in 49.7% of cases, with additional specialized extraction tools required in the remainder.78 In contrast, registry data from both American and European experiences with 7823 extraction procedures involving 12,833 pacemaker and ICD leads demonstrated a major complication rate of 1.6%.79 These studies identified implant duration of the oldest lead, ICD leads (compared to pacemaker leads), female gender, low-volume extraction hospitals, and the need for laser assistance as risk factors for adverse outcomes.79 Similarly, among 2561 pacemaker and ICD leads in 1684 patients undergoing laser lead extraction in the PLEXES Trial, 1.9% experienced a major complication, with 0.8% in-hospital mortality.80 A study of 2405 laser-assisted lead extractions in 1449 patients resulted in a 97.7% clinical success rate, 1.4% major adverse event rate, 0.28% procedure-related mortality, and 1.86% in-hospital mortality.81 Contemporary registries involving high-volume centers similarly report high procedural success rates and very low rates of serious complications (0.4%-0.9%).82,83 Several studies have demonstrated a significant learning curve associated with lead extraction, particularly for operators with fewer than 20 to 30 cases. Even experienced lead extractors continued to improve with time and volume.84-87 HRS guidelines particularly emphasize the importance of operator experience for procedural success and clinical safety.79 Notably, the favorable complication rates associated with lead extraction, which typically involves both lead removal and device system reimplantation, actually appear better than generator replacement alone. This apparent paradox relates to the terminology used to define major and minor complications; even those complications defined for study purposes as “minor” may be clinically important. The HRS Transvenous Lead Extraction Consensus Document defines minor complications to include: hematoma at implant site requiring reoperation, venous thrombosis of implant veins requiring medical intervention, vascular repair at extraction site, blood loss requiring transfusion, pulmonary embolism not requiring surgical intervention, and hemodynamically significant air embolism.79 Clearly, some of the “minor” events are also clinically relevant.

Review of device-assisted lead extraction adverse events reported to FDA revealed 57 deaths and 48 serious cardiovascular injuries between 1995 and 2008, with almost 40% occurring in the final 2 study years.88 Most alarming was the observation that some extraction injuries cannot be mitigated—even by emergency cardiac surgery. These uncommon but catastrophic events should serve as a reminder to consider carefully other advisory device clinical management options before embarking on an invasive and potentially harmful strategy. Indeed, not all advisory or malfunction leads need be removed. Lead abandonment rather than extraction may be an option for some patients with suitable anatomy. Abandoned leads do not appear to have a clinically important interaction with defibrillation threshold or sensing, and did not lead to increased thromboembolic complications, in a small study of 78 patients.89 This approach has also be proven effective in pediatric patients.90 Conservative Management and Device Reprogramming Health care providers and patients may choose to monitor a device under advisory with a strategy of routine or enhanced surveillance, although this may not be applicable to all advisories and may not prevent serious outcomes in cases where manifestations of malfunction may be sudden and drastic.91 The availability of patient-managed, remote, and home monitoring devices may be particularly important in the early detection of problems in a patient known to be at risk for malfunction. In some cases, automated remote alerts have identified performance concerns before an important clinical adverse event.12 Patients, however, may not be aware of audible device alerts or may not interpret them correctly;92 as such, this approach must be individualized for appropriate patients. In some cases, device programming changes or software upgrades may help mitigate the clinical impact of an advisory or device performance issue. For example, algorithms can reduce the incidence of inappropriate shocks in patients with lead fracture.93,94 Device and Patient Factors Impacting Clinical Decision Making In addition to the general procedural risks previously discussed, other device- and patient-related characteristics that may impact the risk/ benefit balance of a specific management strategy include the observed or projected rates of device failure and the clinical manifestation of malfunction. Generator and lead failure may present suddenly (e.g., sudden, catastrophic short circuit) or gradually (e.g., premature battery depletion), predictably or without warning. In some cases, specific subcategories of devices under an advisory may be identified according to features such as serial numbers or technical factors related to the initial implant. Similarly, each patient’s clinical characteristics and individual risk profile influences the best clinical management strategy for their problematic device (see Box 34-2). For example, pacemaker dependence or past burden of tachyarrhythmia may influence the potential consequences of device malfunction for that patient. Duration since implant may also influence decision making; more recently implanted leads are

1038

SECTION 4  Follow-up and Programming

Box 34-3 

RECOMMENDATIONS FOR CLINICIANS MANAGING PACEMAKER AND ICD ADVISORIES 1. Conservative noninvasive management with periodic device monitoring (remote or in person, as appropriate) should be strongly considered particularly for: • Patients who are not pacemaker dependent.* • Patients with an ICD for primary prevention of sudden cardiac death who have not required device therapy for a ventricular arrhythmia. • Patients whose operative risk is high or patients who have other significant competing morbidities, even when the risk of device malfunction or patient harm is substantial. 2. Device system revision or replacement should be considered if in the clinician’s judgment: • The risk of malfunction is likely to lead to patient death or serious harm, and • The risk of revision or replacement is believed to be less than the risk of patient harm from the device malfunction. 3. Reprogramming of the pacemaker or ICD should be performed when this can mitigate the risk of an adverse event from a lead malfunction. Data from Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009. *Pacemaker dependence refers to patients who have no hemodynamically stable underlying heart rhythm in the absence of pacing.

generally easier to extract than older leads.79 Patient comorbidities influence clinical decision making as well. A patient’s overall prognosis from either their underlying cardiac pathology, as with advanced heart failure, or other conditions, such as malignancies, chronic obstructive pulmonary disease, or end-stage renal disease, may render device replacement excessively risky or imprudent because of the poor prognosis. In general, noninvasive management of generator or lead advisories is preferable when the risk of malfunction is deemed to be low, particularly for patients who are not pacemaker dependent or who have not manifested clinical arrhythmia. However, device replacement or system revision merits consideration if the risk of malfunction is likely to lead to patient death or serious harm, and if the risk of revision or replacement is believed to be less than the risk of patient harm from generator or lead malfunction (Box 34-3).6

PSYCHOLOGICAL IMPACT OF RECALLS AND ADVISORIES Anxiety, depression, and posttraumatic stress disorder are common diagnoses in cardiac implantable electronic device (CIED) patients in the absence of device advisories.95,96 Clinicians should therefore remain alert to the potential emotional and psychological impact on patients of learning that their permanent device has become subject to an advisory. Investigations of device advisory impact on patients’ psychological well-being have yielded mixed results. One study examining associations between ICD recalls and anxiety, depression, and quality of life (QOL) found that recalls reduced patient trust in the health care system and that more severe recalls (FDA class I vs. class II) decreased QOL.97 However, not all studies have demonstrated an untoward psychological impact. For example, in 86 patients with advisory Medtronic Marquis ICDs, there was no evidence of long-term psychological morbidity.98 Other investigations also demonstrate that QOL and psychological features are similar in patients with advisory ICDs and those with nonadvisory ICDs.99,100 However, some studies suggest that younger patients and those who previously received shocks may be more likely to experience advisory-related anxiety.101 Timely, quality physician communication is critical to maintaining patient trust and reducing patient anxiety.54 Patients who exhibit persistent, significant anxiety benefit from formal counseling.102 Although most patients with advisory devices do not experience significant, long-term anxiety, some patients may experience ongoing psychological impact. In some the clinical management strategy may need to be adjusted to account for and potentially alleviate significant symptoms.5,6

Conclusion Pacemaker and ICD systems are complex, sophisticated technologies that will occasionally malfunction or fail to behave as anticipated. As a result, manufacturers or regulatory authorities occasionally issue product advisories to inform health care providers and patients about underperforming devices. To manage device advisories optimally, health care providers should know the rates and mechanisms of device malfunction, terminology and threshold for activation of device advisories, communication methods of abnormal device performance, and clinical management of device advisories and malfunctions.

REFERENCES 1. Maisel WH: Cardiovascular device development: lessons learned from pacemaker and implantable cardioverter-defibrillator therapy. Am J Ther 12:183-185, 2005. 2. Mirowski M, Reid PR, Mower MM, et al: Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 303:322-324, 1980. 3. Maisel WH: Safety issues involving medical devices: implications of recent implantable cardioverter-defibrillator malfunctions. JAMA 294:955-958, 2005. 4. Maisel WH, Hauser R: Proceedings of the ICD Lead Performance Conference. Heart Rhythm 5:1331-1338, 2008. 5. Carlson MD, Wilcoff BL, Maisel WH, et al: Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines. Heart Rhythm 3:1250-1273, 2006. 6. Maisel WH, Hauser RG, Hammill SC, et al: Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines. Heart Rhythm 6:869-885, 2009. 7. Maisel WH, Sweeney MO, Stevenson WG, et al: Recalls and safety alerts involving pacemakers and implantable cardioverterdefibrillator generators. JAMA 286:793-799, 2001. 8. Song SL: Bilitch Report: performance of implantable cardiac rhythm management devices. Pacing Clin Electrophysiol 17:692708, 1994. 9. Kawanishi DT, Song S, Furman S, et al: Failure rates of leads, pulse generators, and programmers have not diminished over the last 20 years: formal monitoring of performance is still needed. Bilitch Registry and STIMAREC. Pacing Clin Electrophysiol 19:1819-1823, 1996. 10. Maisel WH, Moynahan M, Zuckerman BD, et al: Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA 295:1901-1906, 2006.

11. Maisel WH: Pacemaker and ICD generator reliability: metaanalysis of device registries. JAMA 295:1929-1934, 2006. 12. Maisel WH, Kramer DB: ICD lead performance. Circulation 117:2721-2723, 2008. 13. Biotronik Cardiac Rhythm Management Product Performance Report, January 2010. http://www.biotronik.com/sixcms/ media.php/162/BIOTRONIK%20Product%20Performance%20 Report%20January%202010.pdf. 14. Boston Scientific CRM Product Performance Report 2010, Q2 Summary Edition. http://www.bostonscientific.com/ templatedata/imports/HTML/CRM/Product_Performance_ Resource_Center/report_archives/q2_10_ppr.pdf. 15. Medtronic Cardiac Rhythm Disease Management Product Performance Report 2010, ed 1, issue 62. http://www.medtronic. com/crm/performance/downloads/mdt-prod-performance2010-1-en.pdf. 16. Sorin Group Cardiac Rhythm Management Product Performance Report. November 2009. http://www.sorin-crm.com/ uploads/Media/SorinCRM_PPR-worldwide.pdf. 17. St. Jude Medical Cardiac Rhythm Management Product Per­ formance Report. May 2010. http://www.sjmprofessional.com/ Resources/reference-guides/~/media/Cardiac%20Pro/ Reference%20and%20Resources/Reference%20Guides/ Product_Performance_Report_CRM_May2010.ashx. 18. Maisel WH: Semper Fidelis: consumer protection for patients with implanted medical devices. N Engl J Med 358:985-987, 2008. 19. Danish Pacemaker and ICD Register 2007 Annual Report. Odense, Denmark. http://www.pacemaker.dk. 20. Eckstein J, Koller MT, Zabel M, et al: Necessity for surgical revision of defibrillator leads implanted long-term: causes and management. Circulation 117:2727-2733, 2008.

21. Aass H, Ilvento J: Short and medium time experience with a tined, multilumen steroid eluting defibrillation lead. J Interv Card Electrophysiol 6:81-86, 2002. 22. Kron J, Herre J, Renfroe EG, et al: Lead- and device-related complications in the Antiarrhythmics versus Implantable Defibrillators Trial. Am Heart J 141:92-98, 2001. 23. Dorwarth U, Frey B, Gugas M, et al: Transvenous defibrillation leads: high incidence of failure during long-term follow-up. J Cardiovasc Electrophysiol 14:38-43, 2003. 24. Ellenbogen KA, Wood MA, Shepard RK, et al: Detection and management of an implantable cardioverter defibrillator lead failure: incidence and clinical implications. J Am Coll Cardiol 41:73-80, 2003. 25. Luria D, Glikson M, Brady PA, et al: Predictors and mode of detection of transvenous lead malfunction in implantable defibrillators. Am J Cardiol 87:901-904, 2001. 26. Kleemann T, Becker T, Doenges K, et al: Annual rate of transvenous defibrillation lead defects in implantable cardioverterdefibrillators over a period of >10 years. Circulation 115:24742480, 2007. 27. Kitamura S, Satomi K, Kurita T, et al: Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead. Circ J 70:273-277, 2006. 28. Hauser RG, Cannom D, Hayes DL, et al: Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads. Pacing Clin Electrophysiol 25:879-882, 2002. 29. Borleffs CJW, Van Erven L, Van Bommel RJ, et al: Risk of failure of transvenous implantable cardioverterdefibrillator leads. Circ Arrhythm Electrophysiol 2:411-416, 2009.



34  Guidelines for Managing Pacemaker and Implantable Defibrillator Advisories 30. Corbisiero R, Armbruster R: Does size really matter? A comparison of the Riata lead family based on size and its relation to performance. Pacing Clin Electrophysiol 31:722-726, 2008. 31. Koplan BA, Weiner S, Gilligan D, et al: Clinical and electrical performance of expanded polytetrafluoroethylene-covered defibrillator leads in comparison to traditional leads. Pacing Clin Electrophysiol 31:47-55, 2008. 32. Kupper B, Yee R, O’Hara G, et al: Do small (6.6 Fr.) active and passive fixation defibrillation leads perform as well as larger sized leads? A multi-centre analysis. Europace 9:657-661, 2007. 33. Luria D, Bar-Lev D, Gurevitz O, et al: Long-term performance of screw-in atrial pacing leads: a randomized comparison of J-shaped and straight leads. Pacing Clin Electrophysiol 28:898902, 2005. 34. Maisel WH: Transvenous implantable cardioverter leads—the weakest link. Circulation 115:2461-2463, 2007. 35. Maisel WH: Medical device regulation: an introduction for the practicing physician. Ann Intern Med 296-302, 2004. 36. US Food and Drug Administration Center for Devices and Radiological Health Annual Reports. http://www.fda.gov/ AboutFDA/CentersOffices/CDRH/CDRHReports/ucm 109733.htm. 37. Kirkpatrick JN, Ghani SN, Burke MC, Knight BP: Postmortem interrogation and retrieval of implantable pacemakers and defibrillators: a survey of morticians and patients. J Cardiovasc Electrophysiol 18:478-482, 2007. 38. US Food and Drug Administration: MAUDE: Manufacturer and User Facility Device Experience. http://www.accessdata.fda. gov/scripts/cdrh/cfdocs/cfmaude/search.cfm. 39. Shah JS, Maisel WH: Recalls and safety alerts affecting automated external defibrillators. JAMA 296:655-660, 2006. 40. Hauser RG, Kallinen LM, Almquist AK, et al: Early failure of a small-diameter high-voltage implantable cardioverterdefibrillator lead. Heart Rhythm 4:892-896, 2007. 41. Maisel WH: Implantable cardioverter-defibrillator lead complication: when is an outbreak out-of-bounds? Heart Rhythm 5:1673-1674, 2008. 42. Padeletti L, Pappone C, Curnis A, et al: Product-experience reporting on endocardial defibrillation leads: a 4-year national perspective. Expert Rev Med Devices 6:383-388, 2009. 43. US Food and Drug Administration: MedSun: Medical Product Safety. www.fda.gov/MedicalDevices/Safety/MedSunMedical ProductSafetyNetwork/default.htm. 44. National Cardiovascular Data Registry: ICD Registry. https:// www.ncdr.com/webncdr/ICD/Default_ssl.aspx. 45. Hammill SC, Kremers MS, Kadish AH, et al: Review of the ICD Registry’s third year, expansion to include lead data and pediatric ICD procedures, and role for measuring performance. Heart Rhythm 6:1397-1401, 2009. 46. Duru F, Luechinger R, Scharf C, Brunckhorst C: Automatic impedance monitoring and patient alert feature in implantable cardioverter defibrillators: being alert for the unexpected! J Cardiovasc Electrophysiol 16:444-448, 2005. 47. US Food and Drug Administration: Background and definitions. http://www.fda.gov/Safety/Recalls/ucm165546.htm. 48. Basile EM, Lorell BH: The Food and Drug Administration’s regulation of risk disclosure for implantable cardioverterdefibrillators: has technology outpaced the agency’s regulatory framework? Food Drug Law J 61:251-272, 2006. 49. Tyers GF: FDA recalls: how do pacemaker manufacturers compare? Ann Thorac Surg 48:390-396, 1989. 50. Mahajan T, Dubin AM, Atkins DL, et al: Impact of manufacturer advisories and FDA recalls of implantable cardioverterdefibrillator generators in pediatric and congenital heart disease patients. J Cardiovasc Electrophysiol 19:1270-1274, 2008. 51. Maisel WH, Stevenson WG, Epstein LM: Changing trends in pacemaker and implantable-cardioverter-defibrillator generator advisories. Pacing Clin Electrophysiol 25:1670-1678, 2002. 52. Levine PA, Stanton MS, Sims JJ: High quality performance of pacemakers and implantable defibrillators. Pacing Clin Electrophsyiol 25:1667-1669, 2002. 53. Krahn AD, Simpson CS, Parkash R, et al: Formation of a national network for rapid response to device and lead advisories: the Canadian Heart Rhythm Society Device Advisory Committee. Can J Cardiol 25:403-405, 2009. 54. Stutts LA, Conti JB, Aranda JM, Jr, et al: Patient evaluation of ICD recall communication strategies: a vignette study. Pacing Clin Electrophysiol 30:1105-1111, 2007. 55. Wilkoff BL, Auricchio A, Brugada J, et al: HRS/EHRA Expert Consensus on the monitoring of cardiovascular implantable electronic devices (CIED): description of the techniques, indications, personnel, frequency and ethical considerations. Heart Rhythm 5:907-925, 2008. 56. Maisel WH: Physician management of pacemaker and implantable cardioverter-defibrillator advisories. Pacing Clin Electrophysiol 27:437-442, 2004.

57. Kay GN, Brinker JA, Kawanishi DT, et al: Risks of spontaneous injury and extraction of an active fixation pacemaker lead: report of the Accufix Multicenter Clinical Study and Worldwide Registry. Circulation 100:2344-2352, 1999. 58. Gould PA, Krahn AD: Complications associated with implantable cardioverter-defibrillator replacement in response to device advisories. JAMA 295:1907-1911, 2006. 59. Klug D, Balde M, Pavin D, et al: Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study. Circulation 116:1349-1355, 2007. 60. Priori SG, Auricchio A, Nisam S, Yong P: To replace or not to replace: a systematic approach to respond to device advisories. J Cardiovasc Electrophysiol 20:164-170, 2009. 61. Amin MS, Ellenbogen KA: Should recent defibrillator and lead advisories affect decisions to refer patients for implantable cardioverter-defibrillator therapy? Curr Opin Cardiol 25:23-28, 2010. 62. Amin MS, Wood MA, Shepard RK, et al: Clinical judgment versus decision analysis for managing device advisories. Pacing Clin Electrophysiol 31:1236-1240, 2008. 63. Al-Khatib SM, Lucas FL, Jollis JG, et al: The relation between patients’ outcomes and the volume of cardioverter-defibrillator implantation procedures performed by physicians treating Medicare beneficiaries. J Am Coll Cardiol 46:1536-1540, 2005. 64. Curtis JP, Luebbert JJ, Wang Y, et al: Association of physician certification and outcomes among patients receiving an implantable cardioverter-defibrillator. JAMA 301:1661-1670, 2009. 65. Amin MS, Matchar DB, Wood MA, Ellenbogen KA: Management of recalled pacemakers and implantable cardioverterdefibrillators: a decision analysis model. JAMA 296:412-420, 2006. 66. Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators: A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 337:1576-1583, 1997. 67. Gold MR, Peters RW, Johnson JW, Shorofsky SR: Complications associated with pectoral cardioverter-defibrillator implantation: comparison of subcutaneous and submuscular approaches. Worldwide Jewel Investigators. J Am Coll Cardiol 28:1278-1282, 1996. 68. Rosenqvist M, Beyer T, Block M, et al: Adverse events with transvenous implantable cardioverter-defibrillators: a prospective multicenter study. European 7219 Jewel ICD Investigators. Circulation 98:663-670, 1998. 69. Kiviniemi MS, Pirnes MA, Eranen HJ, et al: Complications related to permanent pacemaker therapy. Pacing Clin Electrophysiol 22:711-720, 1999. 70. Gould PA, Gula LJ, Champagne J, et al: Outcome of advisory implantable cardioverter-defibrillator replacement: one-year follow-up. Heart Rhythm 5:1675-1681, 2008. 71. Moore JW III, Barrington W, Bazaz R, et al: Complications of replacing implantable devices in response to advisories: a single center experience. Int J Cardiol 134:42-46, 2009. 72. Costea A, Rardon DP, Padanilam BJ, et al: Complications associated with generator replacement in response to device advisories. J Cardiovasc Electrophysiol 19:266-269, 2008. 73. Anderson KP: Estimates of implantable cardioverter-defibrillator complications: caveat emptor. Circulation 119:1069-1071, 2009. 74. Tompkins C, Cheng A, Dalal D, et al: Dual antiplatelet therapy and heparin “bridging” significantly increase the risk of bleeding complications after pacemaker or implantable cardioverterdefibrillator device implantation. J Am Coll Cardiol 55:23762382, 2010. 75. Thal S, Moukabary T, Boyella R, et al: The relationship between warfarin, aspirin, and clopidogrel continuation in the periprocedural period and the incidence of hematoma formation after device implantation. Pacing Clin Electrophysiol 33:385-388, 2010. 76. Jamula E, Douketis JD, Schulman S: Perioperative anticoagulation in patients having implantation of a cardiac pacemaker or defibrillator: a systematic review and practical management guide. J Thromb Haemost 6:1615-1621, 2008. 77. Kaluza GL, Joseph J, Lee JR, et al: Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 35:1288-1294, 2000. 78. Maytin M, Love CJ, Fischer A, et al: Multicenter experience with extraction of the Sprint Fidelis ICD lead. J Am Coll Cardiol 56, 2010. 79. Wilkoff BL, Love CJ, Byrd CL, et al: Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications, and patient management. Heart Rhythm 6:10851104, 2009.

1039

80. Byrd CL, Wilkoff BL, Love CJ, et al: Clinical study of the laser sheath for lead extraction: the total experience in the United States. Pacing Clin Electrophysiol 25:804-808, 2002. 81. Wazni O, Epstein LM, Carrillo RG, et al: Lead extraction in the contemporary setting: the LExICon study: an observational retrospective study of consecutive laser lead extractions. J Am Coll Cardiol 55:579-586, 2010. 82. Jones SO, IV, Eckart RE, Albert CM, Epstein LM: Large, singlecenter, single-operator experience with transvenous lead extraction: outcomes and changing indications. Heart Rhythm 5:520-525, 2008. 83. Kennergren C, Bjurman C, Wiklund R, Gabel J: A single-centre experience of over one thousand lead extractions. Europace 11:612-617, 2009. 84. Wilkoff BL, Byrd CL, Love CJ, et al: Trends in intravascular lead extraction: analysis of data from 5339 procedures in 10 years. XIth World Symposium on Cardiac Pacing and Electrophysiology, Berlin. Pacing Clin Electrophysiol 22(6 pt II):A207, 1999. 85. Bracke FA, Meijer A, Van Gelder B: Learning curve characteristics of pacing lead extraction with a laser sheath. Pacing Clin Electrophysiol 21:2309-2313, 1998. 86. Smith HJ, Fearnot NE, Byrd CL, et al: Five-years experience with intravascular lead extraction. U.S. Lead Extraction Database. Pacing Clin Electrophysiol 17:2016-2020, 1994. 87. Ghosh N, Yee R, Klein GJ, et al: Laser lead extraction: is there a learning curve? Pacing Clin Electrophysiol 28:180-184, 2005. 88. Hauser RG, Katsiyiannis WT, Gornick CC, et al: Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction. Europace 12:395-401, 2010. 89. Glikson M, Suleiman M, Luria DM, et al: Do abandoned leads pose risk to implantable cardioverter-defibrillator patients? Heart Rhythm 6:65-68, 2009. 90. Silvetti MS, Drago F: Outcome of young patients with abandoned, nonfunctional endocardial leads. Pacing Clin Electrophysiol 31:473-479, 2008. 91. Kallinen LM, Hauser RG, Lee KW, et al: Failure of impedance monitoring to prevent adverse clinical events caused by fracture of a recalled high-voltage implantable cardioverter-defibrillator lead. Heart Rhythm 5:775-779, 2008. 92. Simons EC, Feigenblum DY, Nemirovsky D, Simons GR: Alert tones are frequently inaudible among patients with implantable cardioverter-defibrillators. Pacing Clin Electrophysiol 32:12721275, 2009. 93. Kallinen LM, Hauser RG, Tang C, et al: Lead integrity alert algorithm decreases inappropriate shocks in patients who have Sprint Fidelis pace-sense conductor fractures. Heart Rhythm 7:1048-1055,2010. 94. Swerdlow CD, Gunderson BD, Ousdigian KT, et al: Downloadable algorithm to reduce inappropriate shocks caused by fractures of implantable cardioverter-defibrillator leads. Circulation 118:2122-2129, 2008. 95. Sears SF, Todaro JF, Lewis TS, et al: Examining the psychosocial impact of implantable cardioverter-defibrillators: a literature review. Clin Cardiol 22:481-489, 1999. 96. Sears SF, Matchett M, Conti JB: Effective management of ICD patient psychosocial issues and patient critical events: clinical reviews. J Cardiovasc Electrophysiol 20:1297-1304, 2009. 97. Undavia M, Goldstein NE, Cohen P, et al: Impact of implantable cardioverter-defibrillator recalls on patients’ anxiety, depression, and quality of life. Pacing Clin Electrophysiol 31:1411-1418, 2008. 98. Birnie DH, Sears SF, Green MS, et al: No long-term psychological morbidity living with an implantable cardioverter-defibrillator under advisory: the Medtronic Marquis experience. Europace 11:26-30, 2009. 99. Gibson DP, Kuntz KK, Levenson JL, Ellenbogen KA: Decisionmaking, emotional distress, and quality of life in patients affected by the recall of their implantable cardioverterdefibrillator. Europace 10:540-544, 2008. 100. Cuculi F, Herzig W, Kobza R, Erne P: Psychological distress in patients with ICD recall. Pacing Clin Electrophysiol 29:12611265, 2006. 101. Sears SF, Jr, Conti JB: Psychological aspects of cardiac devices and recalls in patients with implantable cardioverter defibrillators. Am J Cardiol 98:565-567, 2006. 102. Fisher JD, Koulogiannis KP, Lewallen L, et al: The psychological impact of implantable cardioverter-defibrillator recalls and the durable positive effects of counseling. Pacing Clin Electrophysiol 32(8):1012-1016, 2009.

1040

SECTION 4  Follow-up and Programming

35  35

Ethical Issues RACHEL LAMPERT  |  DAVID HAYES

CASE 1 The family member of a recently deceased ICD patient recounted the following in an interview1: “His defibrillator kept going off. … It went off 12 times in one night. … He went in, and they looked at it; they said they adjusted it, and they sent him back home. The next day we had to take him back because it was happening again. It kept going off and going off, and it wouldn’t stop going off.” CASE 2 A 65-year-old man (FG) received an ICD 10 years ago after a cardiac arrest (ejection fraction, 30%). He had shock-treated ventricular tachycardia at 250 bpm four times in the last 10 years. He was last seen in person 8 months ago while being followed transtelephonically. In the meantime, his wife called his electrophysiologist and said FG was currently on the oncology floor, having been diagnosed 4 months ago with metastatic cancer. Despite multiple rounds of chemotherapy, FG still had lesions in his brain and bone. He was to be discharged to hospice the following day on a morphine drip. The patient and family requested that ICD therapies be turned off. The EP team deactivated therapies, and FG died in hospice 2 days later, “peacefully,” according to his wife.

The most common ethical issue facing physicians and other health care providers who care for patients with cardiac implantable electronic devices (CIEDs) is that of device deactivation in patients nearing the end of their life or who otherwise request that device therapies be deactivated. Most clinicians (physicians, nurses, and other health care providers) who care for patients with CIEDs have participated in device deactivations.2 However, their understanding of the legal and ethical issues surrounding device deactivation varies, as do clinicians’ attitudes toward deactivation.2,3 Further, as one study reported, 20% of implantable cardioverter-defibrillator (ICD) patients receive shocks in the last weeks of their lives, as illustrated by Case 1. Few patients or families discuss the option with device deactivation with their physicians before the days preceding death, even patients with “do not resuscitate” orders.1 Likewise, few clinicians initiate discussions with patients or family members regarding device deactivations, even when the patient’s situation is terminal. As the population of patients benefiting from and receiving CIEDs continues to grow, clinicians will increasingly care for CIED patients dying of nonarrhythmic, often slow processes, such as cancer and heart failure. Situations such as described in Case 1, in which CIEDs cause pain and reduce quality of life in patients at the end of their life, may likely become more common. Case 2 illustrates how management of CIED therapies in dying patients can be addressed in ways more beneficial to patients and families. To address the uncertainties surrounding CIED deactivation and provide direction for clinicians in these difficult circumstances, the Heart Rhythm Society (HRS) published recommendations regarding deactivation, with input from electrophysiologists, patients, and representatives from the fields of geriatrics, palliative care, psychiatry, nursing, law, ethics, and divinity, as well as industry and patient groups.4

1040

Ethical and Legal Principles Underlying CIED Deactivation Basic ethical principles applicable to patient care include respect for patient autonomy (the duty to respect patients and their rights of selfdetermination), beneficence (the duty to promote patient interests), nonmaleficence (the duty to prevent or not harm patients), and justice, referring in part to the duty to treat patients and distribute health care resources fairly.5 Informed consent, the most important legal doctrine in the clinician-patient relationship, derives from the ethical principle of respect for persons; autonomy is maximized when patients understand the nature of their diagnoses and treatment options and participate in decisions about their care. The rationale for informed consent is simple: it is the patient’s body and life—the patient must live with the consequences of the treatment—and thus the patient has the most at stake in the decision.6 Clinicians are ethically and legally obligated to ensure that patients are informed about their diagnoses and treatment options.7,8 The U.S. courts have ruled that the right to make decisions about medical treatments is both a common law (derived from court decisions) right based on bodily integrity and self-determination and a constitutional right based on privacy and liberty.6 A corollary to informed consent is informed refusal. A patient has the right to refuse any treatment, even if the treatment prolongs life, or death would follow a decision not to use it. A patient also has the right to refuse a previously consented treatment if the treatment no longer meets the patient’s health care goals, if those goals have changed (e.g., from prolonging life to minimizing discomforts), or if the perceived burdens of the patient’s illness (e.g., quality of life) and ongoing treatment outweigh the perceived benefits of ongoing treatment.6,9-11 Honoring these decisions is an integral part of patient-centered care. If a clinician initiates or continues a treatment that a patient has refused, then ethically and legally the clinician is committing “battery,” regardless of the clinician’s intent.7 Finally, granting requests to withdraw life-sustaining treatments from patients who do not want them, is respecting a right to be left alone and to die naturally of the underlying disease, a legally protected right based on the right to privacy. This has been phrased as “a right to decide how to live the rest of one’s life.” A patient’s right to withdraw unwanted treatment has been consistently upheld by U.S. courts (Table 35-1). In the In re Quinlan case, the New Jersey Supreme Court ruled that the patient had both common law and constitutional rights to refuse continued ventilator support, even though her clinicians believed she would die without it.12 In the Cruzan v. Director, Missouri Department of Health case, which involved a feeding tube, the U.S. Supreme Court ruled the same way; that is, patients have the right to refuse life-sustaining treatments. The Court also ruled that a feeding tube was a medical treatment and that it did not have unique status.13 Whether a feeding tube had unique status was raised again during the Terri Schiavo case. The courts again ruled adult patients have a constitutional right to refuse any treatment, including life-sustaining treatments, and that there is no legal difference between withdrawing an ongoing treatment and not starting it in the first place.14



35  Ethical Issues

TABLE

35-1 

1041

Landmark Legal Cases Confirming the Right to Withhold or Withdraw Life-Sustaining Therapies

Case In re Quinlan Saikewicz In the matter of Shirley Dinnerstein Spring Barber Bouvia Cruzan v. Director, Missouri Department of Health Schiavo*

Year 1976 1977 1978 1980 1983 1985 1990

Court Supreme Court of New Jersey Massachusetts Superior Judicial Court Massachusetts Court of Appeals Massachusetts Superior Judicial Court California Court of Appeals California Court of Appeals U.S. Supreme Court

Withhold/Withdraw Withdrawal Withholding Withholding Withdrawal Withdrawal Both Withdrawal

Therapy Ventilator Chemotherapy Cardiopulmonary Resuscitation Hemodialysis Intravenous fluids Feeding tube Feeding tube

2005

Florida Court of Appeals*

Withdrawal

Feeding tube

*The Florida Supreme Court declined to consider case, the U.S. Supreme Court declined to hear related case.

In none of these cases did the courts distinguish between types of life-sustaining treatments. The law applies to the person, and informed consent is a right of the patient—it is not specific to any one medical intervention.6,14-16 Thus, even though the Supreme Court has not specifically commented on the question of pacemaker or ICD deactivation, because CIEDs deliver life-sustaining therapies, discontinuation of these therapies is clearly addressed by the previous Supreme Court precedents upholding the right to discontinue life-sustaining treatment. In addition, these rights extend to patients who lack decisionmaking capacity, through previously expressed statements (e.g., advance directive) and surrogate decision makers.11,14,17 When patients lack decision-making capacity because of medical illness (e.g., dementia), clinicians must rely on surrogates to make decisions. If the patient has an advance directive (AD) that identifies a surrogate, the patient’s choice of surrogate should be respected7 (see later). In the absence of an AD, clinicians must identify the legally recognized appropriate surrogate. The ideal surrogate is one who best understands the patient’s health care–related goals and preferences. Many U.S. states, however, specify by law a hierarchy of surrogate decision makers (e.g., spouse, followed by adult child, and so on). When making decisions, a surrogate should adhere with the instructions in the patient’s AD (if one exists) and base decisions on the patient’s—not the surrogate’s— values and preferences if known (i.e., the “substituted judgment” standard).18 Although both the law and ethics are clear—a patient has the right to refuse and request the withdrawal of CIED therapies regardless of whether he or she is terminally or irreversibly ill, and regardless of whether the therapies prolong life and death would follow a decision not to use them7—some clinicians who care for patients with CIEDs see a moral distinction between deactivating an ICD and deactivating a pacemaker, particularly in a dependent patient.2 However, while some have questioned whether pacemaker deactivation is similar to assisted suicide or euthanasia,2 there are several key differences between withdrawal of CIED therapies and assisted suicide. First is the issue of clinician intent. When a physician complies with a patient’s request to deactivate a device, the physician’s intent is to remove a treatment that is perceived by the patient as burdensome or is simply unwanted. Although this may have the effect of allowing the patient to die of an underlying disease,12,16,19 hastening death should not be the clinician’s primary intent.7,10,20 In contrast, in assisted suicide, the patient intentionally terminates his own life using a lethal method provided or prescribed by a clinician. In euthanasia, the physician directly and intentionally terminates the patient’s life (e.g., lethal injection). The second point differentiating withdrawal of an unwanted therapy from assisted suicide and euthanasia lies in the cause of death. In assisted suicide or euthanasia, death is caused by the intervention provided, prescribed, or administered by the clinician. In contrast, when a patient dies after a treatment is refused or withdrawn, the cause of death is the underlying disease. There are clearly nuances to this issue. For example, a pacemaker-dependent patient with depression

may request deactivation of the pacemaker because life itself is burdensome. In such situations it is important to determine the decisionmaking capacity of the patient. The U.S. Supreme Court decisions have made a clear distinction between withdrawing life-sustaining treatments and assisted suicide and euthanasia. In the case of Vacco v. Quill,21 Chief Justice Rehnquist wrote: The distinction comports with fundamental legal principles of causation and intent. First, when a patient refuses life-sustaining medical treatment, he dies from an underlying fatal disease or pathology; but if a patient ingests lethal medication prescribed by a physician, he is killed by that medication. … [In Cruzan] our assumption of a right to refuse treatment was grounded not. … on the proposition that patients have a … right to hasten death, but on well established, traditional rights to bodily integrity and freedom from unwanted touching. The Court ruled that all patients have a constitutional right to refuse treatment, but no one has a constitutional right to assisted suicide or euthanasia. In another case,22 the Court ruled that clinicians can legally (and should, from an ethical perspective) provide patients with whatever treatments needed to alleviate suffering, such as morphine, even if the treatments might hasten death. Criminality is determined by the clinician’s intent. Legal precedent does not distinguish between types of unwanted therapies, but there are aspects of pacing therapies in a dependent patient that some clinicians have found problematic. For example, ICD therapies are intermittent whereas pacemaker therapy in a pacemakerdependent patient is continuous; death might not occur immediately after ICD deactivation, whereas death might occur quickly after pacemaker deactivation. However, widespread agreement exists that withdrawing other continuous life-sustaining treatments, such as mechanical ventilation, is ethically and legally permissible. Similarly, clinicians may consider duration of therapy as morally important when considering requests to withdraw life-sustaining treatments. However, withdrawal of other long-term life-sustaining treatments, such as hemodialysis and artificial hydration and nutrition, is well accepted.23 Another concern expressed about withdrawing CIED therapies is that the devices, unlike other life-sustaining treatment, are completely internal. However, the ethical and legal principles involved in the right to refuse treatment are not based on the location of the therapy. Thus, the fact that pacemakers provide therapy that is continuous, internal, and of long duration does not detract from the permissibility of carrying out requests to withdraw this therapy from patients who no longer want it. Some disagreement exists regarding whether a pacemaker is a substitutive therapy, one that substitutes for a pathologically lost function, or a replacement therapy, one that replaces a pathologically lost function. There is agreement that substitutive life-sustaining treatments, such as hemodialysis for kidney failure or a ventilator for respiratory failure, can be withdrawn. A replacement therapy, such as kidney

1042

SECTION 4  Follow-up and Programming

transplantation for kidney failure, literally becomes “part of the patient” and provides the lost function in the same fashion as did the patient’s own body. Replacement therapies also respond to physiologic changes in the host and are independent of external energy sources and control of an expert. Removing or withdrawing a replacement life-sustaining treatment has been characterized as “euthanasia.”23 CIED therapies, including pacemaker support in a pacemakerdependent patient, lack the features of replacement therapies and therefore are most often characterized as “substitutive,”24 although this distinction has been questioned.19 A transplanted kidney, however, has all the features of a replacement therapy. Most would regard carrying out a request to deactivate a pacemaker in a terminally-ill patient as far less morally problematic than carrying out a request to remove a transplanted kidney in the same patient. Deactivating a pacemaker is noninvasive and does not introduce a new pathology (although it may precipitate heart failure symptoms). Removing a kidney, however, is invasive and introduces a new pathology (i.e., a wound). ETHICAL PRINCIPLES UNDERLYING, THE DECISION-MAKING PROCESS Who decides about device deactivation? Ethically and legally, competent patients (or their surrogates) have authority to make decisions. Patients’ decisions have priority over clinicians’ decisions. Because a clinician regards a patient’s decision as “wrong” does not mean the decision is irrational. What criteria should go into making the decision? The patient and physician together must determine a treatment’s effectiveness and the benefits and burdens in the context of the patient’s illness and quality of life. A treatment’s effectiveness is its ability to alter the natural history of a disease. CIEDs are effective, for example, in bypassing life-threatening cardiac conduction abnormalities or treating fatal arrhythmias. However, treatment effectiveness is not the same as treatment benefits and burdens. Benefit is determined by the patient: the patient’s assessment of the treatment’s value. Burden is also determined by the patient: the patient’s assessment of the existing and potential discomforts, costs, and inconveniences associated with the illness and its treatment as the patient perceives it.9 Each patient is unique and weighs such benefits and burdens in relation to their own values, preferences, and health care–related goals. What one patient perceives as beneficial and nonburdensome may be viewed by another patient as nonbeneficial and burdensome. Because benefit and burden are determined by the patient, a patient may decide the burden of CIED therapy outweighs the benefit even if he is not terminally ill. Although patients are the ultimate decision makers, conflicts between caregivers and patients can arise, often when there is misunderstanding among patients and clinicians on goals of care. For example, a clinician may view ongoing CIED therapy in a terminally ill patient as effective, beneficial, and nonburdensome. The patient (or surrogate), however, may strongly disagree. Multidisciplinary care conferences, ethics consultation, and palliative care consultation can be very helpful in resolving these conflicts, especially in clarifying goals of care, establishing the permissibility of withdrawing CIED therapies (and contingency plans if a decision is made not to withdraw CIED therapies), and formulating care plans. Ethics consultation is not required before device deactivation. However, this may be helpful in ambiguous situations such as conflict between members of a family or disagreement between members of the health care team caring for a patient, or caregivers may find that additional support is needed when pursuing a particular treatment course.25 If the decision-making capacity of the patient is in question, or if there are suspicions of coercion, ethics consultation can also be helpful. The Joint Commission requires that health care institutions have processes for addressing ethical concerns that arise in the care of patients.26 Case 3, describing disagreement among both family and caregivers, and case 4, an ambiguous case illustrating possible coercion, illustrate examples in which ethics consultation may be helpful:

CASE 3 An 81-year-old woman with complete atrioventricular (AV) block and no structural heart disease received a permanent DDD pacemaker 18 years ago; the generator was replaced 8 years ago. She is now in a nursing home with progressive dementia. Her son calls and asks if her cardiologist can come and turn off her pacemaker. The cardiologist feels uncomfortable honoring this wish, although the pacemaker nurse who would actually perform the deactivation does not. Before any decisions are made, a daughter calls saying her mother would never want her pacemaker deactivated. CASE 4 An 85-year-old woman had received a pacemaker for congestive heart block 2 years ago. Although her religious group does not believe in implanted devices, she agreed to the device in the hospital. Now, however, she wants to enter an assisted-living/ nursing facility run by her group, but they will not accept her with an active pacemaker. She requests deactivation.

Advance care planning can often prevent ethical dilemmas at the end of life. In this process, which promotes patient autonomy, a patient identifies his or her values, preferences, and goals regarding future health care (e.g., at the end of life) and a surrogate decision maker in the event the patient loses decision-making capacity.7 Ideally, the patient should discuss values and preferences with care providers and potential surrogate decision makers, who should document them in the patient’s medical record, and the patient should complete an advance directive. There are two forms of ADs: the durable power of attorney for health care and the living will. The durable power of attorney for health care allows the patient to specify a surrogate in the event the patient loses decision-making capacity. The living will allows the patient to list specific health care–related values, goals, and preferences. From an ethics standpoint, clinicians should view the AD as an extension of the autonomous person and therefore should respect the values, goals, and preferences listed in the AD. From a legal standpoint, all 50 U.S. states recognize ADs as an extension of the autonomous person. In fact, the Patient Self-Determination Act, passed by Congress in 1990 in response to the Cruzan decision, requires that health care institutions that participate in Medicare and Medicaid programs ask patients whether they have an AD, inform patients of their rights to accept or refuse medical treatments and to create and execute an AD, and to incorporate ADs into patients’ medical records.27 Rights and Responsibilities of Clinicians for Whom Deactivation Is Counter to Their Personal Beliefs Regardless of the ethical and legal permissibility of carrying out requests to withdraw CIED therapies from patients who have (or their surrogate has) made this decision, clinicians—like patients—are moral agents whose personal values and beliefs may lead them to prefer not to participate in device deactivation. A recent survey found that about 10% of clinicians who care for patients with CIEDs view pacemaker deactivation in a pacemaker-dependent patient as a form of assisted suicide or euthanasia.2 Others object to pacemaker deactivation because they believe pacemaker therapy does not prolong the dying process or cause physical discomfort (unlike ICD shocks) and that pacemaker deactivation may cause discomfort (e.g., worsened heart failure symptoms).28 These burdens are ultimately determined by the patient, but clinicians and others, including industry employed allied professionals, should not be compelled to carry out device deactivations if they view the procedure as inconsistent with their personal values.8,28 Under these circumstances, the clinician should inform the patient of the clinician’s preference not to perform CIED deactivation. However, as described in the American Medical Association (AMA) Code of Medical Ethics,29 the clinician should not impose his or her values on or abandon the patient and should ensure that they do not cause the patient emotional distress.30 Instead, the clinician and patient should work to achieve a mutually agreed-upon care plan. If such a



35  Ethical Issues

TABLE

35-2 

1043

Physician-Initiated Discussions with Implant Patients

Timing of Conversation Before implantation

After an episode of increased or repeated firings from an ICD Progression of cardiac disease, including repeated hospitalizations for heart failure and/or arrhythmias When patient/surrogate chooses a “do not resuscitate” (DNR) order* Patients at end of life

Points to Discuss Clear discussion of benefits and burdens of device. Brief discussion of potential future limitations or burdensome aspects of device therapy. Encourage patients to have some form of advance directive. Inform of option to deactivate device in the future. Discussion of possible alternatives, including adjusting medications, adjusting device settings, and cardiac procedures to reduce future shocks. Reevaluation of benefits and burdens of device. Assessment of functional status, quality of life, and symptoms. Referral to palliative and supportive care services. Reevaluation of benefits and burdens of device. Exploration of patient’s understanding of device and how patient conceptualizes it with regard to external defibrillation. Referral to palliative care or supportive services. Reevaluation of benefits and burdens of device. Discussion of option of deactivation addressed with all patients, although deactivation not required.

Helpful Phrases to Consider “It seems clear at this point that this device is in your best interest, but you should know at some point if you become very ill from your heart disease or another process you develop in the future, the burden of this device may outweigh its benefit. While that point is hopefully a long way off, you should know that turning off your defibrillator is an option. ” “I know that your device caused you some recent discomfort and that you were quite distressed. I want to work with you to see if we can adjust the settings to assure that the device continues to work in the appropriate manner. If we can’t get you to that point, then we may want to consider turning it off altogether, but let’s try some adjustments first.” “It appears as though your heart disease is worsening. We should really talk about your thoughts and questions about your illness at this point and see if your goals have changed at all.” “Now that we’ve established that you would not want resuscitation in the event your heart were to go into an abnormal pattern of beating, we should reconsider the role of your device. In many ways it is also a form of resuscitation. Tell me your understanding of the device, and let’s talk about how it fits into the larger goals for your medical care at this point.” “I think at this point we need to reconsider your [device]. Given how advanced your disease is, we need to discuss whether it makes sense to keep it active. I know this may be upsetting to talk about, but can you tell me your thoughts at this point?”

Modified from Lampert R, Hayes DL, Annas GJ, et al: Heart Rhythm Society Expert Consensus Statement on the management of cardiovascular implantable electronic devices (CIEDs) in patients nearing end of life or requesting withdrawal of therapy. Heart Rhythm 7:1008-1026, 2010. *Patients may choose to forego intubation, CPR, and external defibrillation while at the same time deciding to keep the defibrillation function of their ICD active. A patient’s choice to be “DNR” may or may not be concomitant with a decision to withdraw CIED therapy, as resuscitation interventions and the ICD each carries its own benefits and burdens.

plan cannot be achieved, the primary clinician should involve a second clinician who is willing to comanage the patient and provide legally permissible care and procedures, including CIED deactivation.28,29 It is important for the health care team to recognize and address any conflicts within the team. It is also the responsibility of the institution to ensure that services that are legal and that may be requested by the patient are available. Preventing Both Ethical Dilemmas and Painful Shocks at End of Life: Importance of Early, Proactive Communication “It hadn’t occurred to me to turn it off until [the cardiology fellow said] you could turn these things off and I’m like, ‘oh, okay.’ I mean it wasn’t something that I had ever encountered, and it crossed my mind on a technical level, but not really, ‘Oh, I should have this conversation.’ ” ICD patient31 CASE 5 A 74-year-old woman had an ICD inserted 5 years ago after her first episode of ventricular tachycardia. As her heart disease progressed, the episodes of ventricular tachycardia increased. While at home one afternoon, her defibrillator shocked her several times, and she was admitted to the hospital. She went in and out of consciousness and was hemodynamically unstable for the next 72 hours. After a long family meeting, her family and cardiologist decided that no further aggressive treatments would be continued and that her care would focus on comfort. During the night, her ICD shocked her 10 times, while her nurse tried desperately to contact someone to turn off her ICD. Finally, at 3 am, the cardiologist came in and deactivated the ICD. She died 2 hours later.17

Timely and effective communication among patients, families, and health care providers is essential to informed consent and to prevent situations such as described in Case 5. Effective communication includes determining the patient’s goals of care, helping the patients weigh the benefits and burdens of device therapy as his clinical situation changes, clarifying the consequences of deactivation, and

discussing potential alternative treatments, as well as encouraging the patient to complete an AD. Clinicians must take a proactive role in discussions about the option of deactivation in the context of the patient’s goals for care. These conversations should continue over the course of the patient’s illness. As illness progresses, patient preferences for outcomes and the level of burden acceptable to a patient may change.32,33 Advanced care planning conversations improve outcomes for both patients and their families,34 as patients with ICDs who engage in advance care planning are less likely to experience shocks while dying because ICD deactivation has occurred.35 Studies show that patients and families desire conversations about end-of-life care.36-38 Few patients with CIEDs discuss device deactivation with their clinicians or know that device deactivation is an available option.1,3,31 Even though many patients with CIEDs have ADs, very few of them mention the device specifically in their ADs.39 Clinicians must take a proactive role in initiating discussions about the option of deactivation, from the time of implantation throughout a patient’s life as the clinical situation changes (Table 35-2). The complexity of these conversations, however, is evident in data from physicians demonstrating that although they believe they should engage in these types of conversations with patients, they rarely do.1,3,31 DISCUSSION OF DEVICE DEACTIVATION WITH OVERALL GOALS OF CARE Communication techniques used to discuss the role of the device need to move from treatment-directed conversations to goal-directed conversations. In other words, asking patients and their families, “Do you want the device to remain on?” is often as misleading and misunderstood by them as the question, “Do you want everything done?” Without a better understanding of their current state of health and the role of the cardiac device, patients cannot make fully informed decisions. Table 35-3 outlines the steps needed for goal-directed communication and some useful phrases to begin conversations at each point. These conversations should include a discussion of quality of life, functional status, perceptions of dignity, and both current and potential future symptoms, because each of these elements can influence

1044

TABLE

35-3 

SECTION 4  Follow-up and Programming

Steps for Communicating with Patients and Families about Goals of Care with CIEDs

Step 1.  Determine what patients/families know about their illness. 2.  Determine what the patient and family know about the role that the device plays in their health both now and in the future. 3.  Determine what additional information the patient and family want to know about the patient’s illness. 4.  Correct or clarify any misunderstandings about the current illness and possible outcomes, including the role of the device. 5.  Determine the patient and family’s overall goals of care and desired outcomes.

6.  Using the stated goals as a guide, work to tailor treatments, and in this case the management of the cardiac device, to those goals.

Sample Phrase to Begin Conversation “What do you understand about your health and what is occurring in terms of your illness?” “What do you understand the role of the [CIED] to be in your health now?

“What else would be helpful for you to know about your illness or the role the [CIED] plays within it?

“I think you have a pretty good understanding of what is happening in terms of your health, but there are a few things I would like to clarify with you.” “Given what we’ve discussed about your health and the potential likely outcomes of your illness, tell me what you want from your health care at this point.” Note: Sometimes patients and families may need more guidance at this point, so some potential guiding language might be: “At this point some patients tell me they want to live as long as possible, regardless of the outcome, whereas other patients tell me that the goal is to be as comfortable as long as possible while also being able to interact with their family. Do you have a sense of what you want at this point?” Phrases to be used here depend on the goals as set by the patient and family. For a patient who states that her desired goal is to live as comfortably as possible for whatever remaining time she has left: “Given what you’ve said about assuring that you are as comfortable as possible it might make sense to deactivate the shocking function of your ICD. What do you think about that?” or For a patient who states he wants all life-sustaining treatments to be continued, an appropriate response might be, “In that case, perhaps leaving the antiarrhythmia function of the device active would best be in line with your goals. However, you should understand that this may cause you and your family discomfort at the end of life. We can make a decision at a future point in time about turning the device off. Tell me your thoughts about this.”

Table adapted from references 1, 35, 38, 48, and 49. CIEDs, Cardiac implantable electronic devices.

how patients set goals for their health care. Step 2 is particularly important, because data shows that some patients with ICDs do not understand the role the device plays in their health, particularly in terms of care at the end of life.40 The goal is not to overburden patients with decisions, but to determine an overall set of guiding principles by which clinicians can help patients make decisions. These conversations should follow the model of “shared decision making” in which clinicians work together with patients and families to ensure that patients understand, in the context of their illness, the benefits and burdens of a particular treatment and the potential outcomes that may result from its continued use or discontinuation.41 Clinicians must also recognize that while the ultimate power for decision making rests with patients, they may be influenced by factors such as family, culture, or religion. Likewise, although cost should not play a role in the ways that clinicians counsel patients and families, cost does influence the way that some patients make decisions. Studies of patients with serious illness note that many families often lose their savings as well as a major source of income from either the illness itself or from other family members having to care for the patient.41,42 In addition, many of these factors may influence a patient to cede the power of decision making to other individuals. Benefits/Burdens of Ongoing Device Therapy; Consequences/Uncertainties of Deactivation An important role for the clinician is to provide factual information concerning the beneficial and negative effects of continuing device therapy. The patient can then assess how the benefits and burdens of continued therapy fit with ongoing health care goals. It is also vital for both the health care provider and the patient to have an accurate understanding of the expected consequences of device deactivation. Although in some cases (e.g., patients who are 100% pacemaker dependent) this may be relatively straightforward, in many situations it will be difficult to predict a patient’s clinical course after deactivation. The timing and lethality of tachyarrhythmias are unpredictable, and bradyarrhythmias may variously manifest with syncope, heart failure, angina, fatigue, or sudden death. Consultation with a clinical electrophysiologist may help clarify the clinical picture, although significant

uncertainty will remain in many cases. Case 6 illustrates the importance of communication with the family regarding the unpredictability of consequences of deactivation of ICD therapies: CASE 6 An 80-year-old man with dilated cardiomyopathy in rural Florida received a biventricular ICD for left bundle branch block (LBBB) and congestive heart failure (CHF). He later developed progressive CHF and became bedbound and hypotensive. He had no history of ventricular arrhythmias treated with shocks or antitachycardia pacing (ATP). His daughter asks if the ICD can be turned off immediately. An industry-employed allied professional (IEAP) went to the home and deactivated ATP therapies. The daughter then became angry toward both the IEAP and electrophysiology (EP) team when her father did not die immediately, stating she had a plane to catch to return home.

Once a patient’s goals of care are determined, knowledge about a specific device, whether pacemaker, ICD, or cardiac resynchronization therapy (CRT) device, is essential to determining how to change its settings consistent with the patients’ goals regarding survival and quality of life. Pacemaker and CRT therapy are indicated for the amelioration of symptoms caused by bradycardia and heart failure, respectively.43 For patients who have no underlying intrinsic rhythm (“pacemaker dependent”), pacing also provides life-sustaining therapy. Pacemaker dependence, however, can vary over time.44 In a pacemakerdependent patient, death may follow immediately after cessation of pacing therapy. If the patient is not pacemaker dependent, the dying process is unpredictable, and patients need to be assessed closely for symptoms of distress. Deactivation of pacing therapy may result in symptoms that worsen the quality of life (QOL) of a patient who is not pacemaker dependent, but appropriate symptom control in this group can be used effectively to ensure comfort.44 If CRT improves heart failure or reduces arrhythmia burden, discontinuation may impact survival as well as symptoms and QOL. However, ICDs do not improve symptoms, and shocks from an ICD have added to patient and family suffering when the device has fired at the end of life.1,17,28



35  Ethical Issues

Deactivation of ICD shock therapy may thus improve QOL in such patients by eliminating the pain and emotional distress associated with the delivery of noxious ICD discharges. Elimination of defibrillation therapy is less likely to result in immediate death unless the patient is experiencing incessant or increasingly frequent ventricular arrhythmias. In addition to deactivation, other options for treatment withdrawal are available. Patients and their surrogates may choose not to replace devices as their generators become depleted.45,46 Further, partial or selective deactivation of therapies is an option. Patients or surrogates can determine whether they wish to terminate the ATP or CRT components, or only the shocking function. The complex interaction between determining a patient’s goals of care and the options for CIED management shows that there is no “one size fits all” approach to decision making in patients with advanced illness. Instead, only by clearly examining a patient’s understanding and desired (and undesirable) outcomes can clinicians work with patients and families to ensure appropriate device management at the end of a patient’s life to enhance quality of care while maintaining function and reducing symptom burden. Discussion of Potential Alternative Treatments CASE 7 A 21-year-old man presented with recurrent syncope caused by polymorphic ventricular tachycardia and received a defibrillator as therapy. Multiple shocks caused by recurrent episodes of torsades de pointes (electrical storm) resulted in his request to have the defibrillator removed. Prolongation of the number of intervals to detect, as well as eventual success of empirical antiarrhythmic therapy, resulted in resolution of the episodes of torsades de pointes and resultant shocks. The patient withdrew his request for defibrillator removal.

As part of the decision-making process for deactivation of some or all CIED therapies in a particular patient, the physician should consider and advise the patient of alternative therapies that might impact the decision. For example, patients with recurrent ventricular arrhythmias resulting in painful ICD shocks may be candidates for reprogramming of ATP therapies, catheter ablation, or pharmacologic treatments and may benefit from referral to a center with expertise in these techniques. Patients with worsening congestive heart failure may be candidates for advanced therapies such as left ventricular assist devices (LVADs) or cardiac transplantation. SUPPORTING PARTICIPANTS IN THE DECISIONMAKING PROCESS The Family Although the ultimate decision regarding treatments rests with the patient (or legal surrogate), conversations about device deactivation optimally occur with the support of the family. Although the primary individuals providing a patient support are generally the partner or blood relative,47 it is important for the health care team to understand the patient’s extended support network, both to help maintain the patient’s overall health and for guidance when the patient can no longer make decisions. In addition to the formal written AD, conversations among members of the health care team, patient, and family in early phases of the patient’s course of disease will help put the entire family “on the same page” in terms of the goals of medical care.48 Health care providers play an important role in supporting the patient’s surrogate and facilitating communication and support of additional family members. Health Care Providers Key members of the patient’s health care team should be included in deactivation discussions. The patient’s electrophysiologist and cardiologist should be included in deactivation conversations whenever possible, both because they are a member of the care team for these patients, and also to assure that all therapeutic options available to

1045

meet the patient’s goals can be evaluated. An interdisciplinary approach is essential to support the patient and family. Nurses, social workers, and clergy often play a key role in helping patients understand the device in terms of the overall context of their health and help them better comprehend aspects of their care related to device management. Psychiatric Consultation CASE 8 A 69-year-old man with coronary artery disease (CAD), left ventricular ejection fraction (LVEF) of 30%, and New York Heart Association (NYHA) Class I received a prophylactic ICD 2 years earlier. He has never used the ICD. After his wife dies, he comes to clinic and asks that his ICD be turned off. CASE 9 A 20-year-old woman with tetralogy of Fallot underwent surgical repair at age 6 complicated by congestive heart block requiring a permanent pacemaker (PPM). She was married at age 19, but less than 1 year later divorced and returned to live with her mother. She comes to clinic and asks that the pacemaker be turned off.

Routine psychiatric consultation is not needed for patients who are considering device deactivation. It should be reserved for cases where health care providers or families have concerns that a particular psychiatric disorder may be interfering with the patient’s ability to make informed decisions. Examples include major depression, where a “death wish” exists in the patient with untreated depression or thought disorders (e.g., paranoid delusions). For example, in cases 8 and 9, the potential for depression should be evaluated by a psychiatrist. Neuropsychiatric disorders, including delirium and dementia, can also impact decision-making ability. When in doubt, a psychiatric consultation can help the team assess for adequate decision-making ability at a specific point of time. Palliative Care Specialists CASE 10 A 74-year-old man (JE) was admitted to the cardiac care unit in cardiogenic shock. He was intubated, an intra-aortic balloon pump was emergently inserted, and multiple vasoactive agents were started. JE was weaned from the intra-aortic balloon pump 3 days later and extubated 1 week later. However, JE’s condition progressively worsened, with the onset of sepsis and early signs of renal and liver failure. His level of consciousness vacillated between periods of confusion and periods of lucidity. Several family meetings occurred, and working with the palliative care team, a decision was made to stop aggressive treatments. A fentanyl drip was started at 2 mg/hr, and all JE’s vasoactive agents were stopped and ICD therapies deactivated. Within minutes, JE had chest pain, which diminished after he received further fentanyl. His opiate drip was gradually titrated until his chest pain was relieved. JE died 4 hours later.17

Palliative care relieves suffering and improves quality of life for patients with advanced illness and their families. Unlike hospice care, palliative care can be provided simultaneously with appropriate life-prolonging therapies.49 Most U.S. hospitals have some form of a palliative care program.50 Because changing or deactivating device settings can result in gradual worsening of chronic symptoms or onset of new symptoms, it may be helpful to involve palliative care in the care of patients before devices settings are altered, because these concerns can often be eliminated with early symptoms assessment and treatment. In addition to symptom management, palliative care clinicians are experts at complex conversations surrounding progressive illness. Their involvement in discussions about CIEDs helps to ensure that the patient and family have the opportunity to understand fully the nuances of these decisions and the implications for device management for the patient. Studies show that patients who receive palliative

1046

SECTION 4  Follow-up and Programming

care are more likely to have their treatment wishes followed and have better QOL at the end of life.34 Palliative care also plays a key role in supporting families of patients with advanced disease, who themselves undergo declines in physical and mental health and have an increased risk of death compared with nonfamily controls.51-53 Discussions about deactivation may be misconstrued by patients and families as the beginning of abandonment. They must understand that even if they choose to deactivate the device, the clinicians involved in their care will continue to work with them to ensure that their needs (physical and otherwise) are met. Palliative care can assist with safe and seamless transitions from one system of care to another. Hospice care is provided to patients with a prognosis of 6 months or less to live who have decided to forgo all treatments aimed at curing their underlying terminal illness.54 Hospice clinicians should be included in conversations for patients as they near the end of life to ensure continuity in implementing the goals of care regarding a CIED. Currently, most hospices do not have practices in place to ensure that these conversations occur at enrollment. Both specialists and generalists must partner with hospices to facilitate these conversations and ensure the availability of clinicians who can deactivate CIEDs for patients near the end of life. Further, both hospice and palliative care clinicians can help clarify concerns and misperceptions about the device after the patient has died. For example, some families have erroneous concerns that they may be shocked by touching their deceased relative, or that the device must be explanted after death (which is only true in the case of cremation). Likewise, the clinician can dispel the myth that continued pacemaker function after a patient has died is unnecessarily prolonging life, or even that the impulses from the device are capturing or affecting the heart in some way. IMPROVING COMMUNICATION ABOUT END-OF-LIFE CARE: IMPORTANCE OF EDUCATION To improve communication about device management for patients with advanced disease, educational endeavors need to be instituted for both health care professionals and trainees. Ongoing education for clinicians in practice, including physicians, nurses, social workers, clergy, and device manufacturer representatives, should incorporate teaching about the importance of conversations on device management to improve communication skills and create practice change. Training programs for health care professionals have been shown to improve their knowledge and increase the likelihood they will put new skills into practice.55-57 In addition, fellows and other clinicians in training must also learn the importance of these conversations, as well as undergo training specifically aimed at improving skills in communication. Senior health care providers modeling these conversations for learners are key to improving trainee education about these complex discussions.

Logistics of CIED Deactivation On notification by the patient or a health care provider, the patient’s attending physician then assumes responsibility for addressing the request, counseling the patient, and making a written order in the patient’s medical record. In many cases the attending physician will require consultation with the patient’s cardiologist or cardiac electrophysiologist to determine the specific CIED therapies that are to be deactivated. These specifics should be a part of the written order. Although the nuances of medical practice require a tailored approach to each patient, HRS recommends that the following series of procedures be consistently applied4: 1. Confirming mental capacity requirements to make the decision to withdraw CIED support. The responsible clinician should assess whether the patient or surrogate adequately understands the facts of the patient’s medical condition and the likely consequences of withdrawal of therapy, and that the patient is free of coercion by others. Accurately gauging

patient understanding in this context requires that the responsible clinician be qualified to discuss in detail the benefits and any potential negative effects of ongoing device therapy. Depending on the clinical context, this may require consultation with a clinical electrophysiologist, if one is not already directly involved in the patient’s care. Patients who have psychological or cognitive problems that may benefit from counseling or pharmacologic therapies should have these addressed before deactivation proceeds. 2. Identifying the legal surrogate if the patient lacks capacity. 3. Ensuring documentation requirements for withdrawing or withholding a CIED. Deactivation of CIED therapies requires a written order from the attending physician. This should preferably precede deactivation. In emergent situations, a verbal order should be followed by written documentation within 24 hours. The person responsible for ordering device deactivation may be the patient’s primary care physician, cardiologist, cardiac electrophysiologist, a hospitalist, or a palliative care specialist. Any of these specialists may be the most appropriate physician for such an order, although collaboration among the patient’s physicians is ideal. The written documentation in the medical record needs to address the following: a. Confirmation that the patient (or legal surrogate) has requested device deactivation. b. Capacity of the patient to make the decision, or identification of the appropriate surrogate. c. Confirmation that alternative therapies have been discussed, if relevant. d. Confirmation that consequences of deactivation have been discussed. e. Specific device therapies to be deactivated. f. Notification of family if consistent with patient’s wishes. 4. Establishing palliative care interventions and providing patient and family support. For patients at the end of life, device deactivation should be viewed as one of many potential interventions aimed at preventing discomfort or prolonged suffering. Patients must also be offered the full range of palliative measures to treat symptoms associated with the progression of their underlying illness, especially any new symptoms that may emerge from cessation of device therapy. To allow the patient to experience these symptoms without sedation or analgesia is contrary to humane end-of-life care. Clinical care of patients with arrhythmias does not end with device deactivation, and patients may benefit significantly from pharmacologic measures that minimize symptoms. In addition, the families of patients may often require considerable emotional support, especially if they have acted as the patient’s decision-making surrogate. Setting expectations for family members regarding the consequences and uncertainties of deactivation is imperative. It may be especially important to have a member of the clergy present for patients with a well-defined faith tradition. Formal consultation with palliative care experts is available in most hospital settings and frequently in long-term care facilities or other nonhospital care settings. This may be particularly appropriate when there is any uncertainty about symptom management before and after device deactivation. It is generally appropriate to discontinue rhythm monitoring when pacing therapy is withdrawn. 5. Knowing how to deactivate the device. Deactivation should be performed whenever possible by individuals with EP expertise, such as physicians or device clinic nurses or technicians. In situations where this expertise is not available (see later), deactivation should be performed by medical personnel, such as a hospice physician or nurse, with guidance from IEAPs.58 Pacing therapy, given the caveats indicated for a pacemakerdependent patient, may be withdrawn by programming to specific modes (OOO, ODO, or OSO). If such modes are not available for the device in question, the rate can be lowered and the output adjusted to subthreshold levels so as to render the pacemaker nonfunctional. Deactivation of shocking and ATP functions in an ICD



35  Ethical Issues may be accomplished by reprogramming of the device or continuous application of a magnet over certain pulse generators. Notably, there may be differences in the response to magnet application among different manufacturers’ devices and individual device programmed features. This further emphasizes the importance of consulting individuals with EP expertise to ensure that the process is as smooth as possible. Since the most urgent need for deactivation of CIEDs is the situation of repetitive ICD shocks, the recent HRS statement on deactivation suggests that, for patients who are diagnosed with a terminal illness, consideration should be given to providing them with a doughnut magnet and that they be given detailed instructions on its use.4 Application of a magnet over ICDs usually will temporarily suspend antitachycardia therapies while not disabling bradycardia pacing functions. However, it should be emphasized that although ICD shocks may be very painful and frightening, they may be lifesaving; therefore, deactivation of the device may not be warranted even in the presence of repetitive shocks, unless the patient has made the decision to forego further device therapies.

ROLE OF INDUSTRY-EMPLOYED ALLIED PROFESSIONAL In many situations, IEAPs may be asked to assist available medical personnel in deactivation when EP expertise is not available. The role of the IEAP is to provide technical assistance to medical personnel,58 who will then perform actual deactivation. Available data from a survey of HRS members and IEAPs suggests that IEAPs perform deactivation 50% of the time,2 the recent HRS statement on deactivation recommends that the IEAP should always act under direct supervision of medical personnel.4 IEAPs experience significant role conflicts when asked to perform clinical functions, in particular device deactivation,59 as illustrated by the following quotes from IEAP interviews59: I never physically ever hit the program button. I will set it all up, and then I will have someone hit it … if that makes me sleep at night, maybe that is what it is. The first time I ever had to do it, I was fine until I walked to my car and thought, ‘Oh my God.’ I just lost it when it was over with. Everyone has got their war story … where they almost couldn’t be professional about it or they almost couldn’t do their job. Most IEAPs are comfortable deactivating all ICDs, but many are not in the case of pacemakers. Clinicians must provide medical supervision to IEAPs in performance of device deactivation. Each manufacturer has policies for their personnel that apply to deactivation of CIED therapies, and it is the responsibility of IEAPs to ensure adherence to these policies. If the representative is asked by the patient and the attending physician to deactivate therapies that conflict with the policies of the company, the IEAP has the right to object to programming of the device. In this situation the attending physician assumes responsibility to find another mechanism for device programming, usually by contacting the physician who implanted or who follows the patient’s CIED. Communication with IEAPs by medical personnel at the scene, as well as physicians with EP expertise, needs to include specific instructions regarding features to deactivate, as well as information about the patient’s overall goals. Indeed, once the IEAP has a better understanding of the purpose of changing a device’s settings, the representative may be able to provide suggestions or clarify misperceptions. IEAPs stress this in interviews: “[Clinicians] should not say, ‘Turn off device,’ but they should say, ‘Disable or turn off—discontinue all tachyarrhythmia therapies. …”59 CONSIDERATIONS IN SPECIFIC CLINICAL SETTINGS How the request for deactivation is handled and who will perform deactivation often depends on the setting: (1) acute care hospital with EP expertise, (2) acute care hospital without EP expertise or

1047

nonhospital health-care facility, (3) at home. For each of these settings, the initial steps previously described are the same. Acute Care Hospital with Electrophysiologic Expertise For patients who are hospitalized in a center with EP expertise at the time that deactivation of the CIED is requested, their attending physician should arrange for a cardiac electrophysiologist or other clinician with expertise in CIED programming to perform deactivation. An order is documented in the chart by the attending physician that precisely specifies which CIED therapies are to be deactivated (bradycardia pacing, cardiac resynchronization pacing, ATP, or ICD shocks). The cardiologist, cardiac electrophysiologist, or their trained designee would then program the CIED in accordance with the order and should document the programming in the patient’s medical record. Inpatient Facilities Without Electrophysiologic Expertise For patients at a hospital, hospice, or long-term care facility without EP expertise, the attending physician should contact the physician responsible for following the patient’s CIED for consultation as to which therapies should be deactivated. For patients who are able to be discharged and are well enough to travel to a clinic with programming capability, an outpatient visit may be acceptable for device deactivation. However, because deactivation of therapies may be followed by the patient’s rapid demise, such as deactivation of pacing therapy in a dependent patient, clinic setting may not always be appropriate. For patients who are unable to travel, the attending physician should arrange for a programmer to be brought to the patient. This may require the assistance of a physician who follows CIED patients. In many cases, IEAPs who represent the specific manufacturer of the patient’s CIED will be asked to bring a programmer to the patient’s bedside. Medical personnel (ideally the attending physician) would deactivate the CIED using the programmer, with technical assistance provided by the IEAP. Patients at Home Patients who are at home on notifying their physician of their request for CIED deactivation may present logistical challenges. For patients who are too ill to travel to a clinic or in whom deactivation would result in rapid demise, arrangements must be made for a programmer to be brought to their home by medical personnel or IEAP. The attending physician should write an order in the patient’s medical record, including specific therapies to be deactivated. This information must be communicated to the on-site personnel, preferable in written/faxed format, unless the urgency of the situation requires verbal communication. An IEAP then should be provided to assist the physician’s clinical designee (e.g., visiting nurse, home hospice personnel) with the programmer and provide the technical assistance necessary to deactivate the specific therapies requested. If no medical personnel can be arranged, in rare cases the IEAP may be asked to perform deactivation after appropriate communication with and documentation by the attending physician. In situations where the requested deactivation is not in keeping with the manufacturer’s policies, the attending physician assumes responsibility for resolving this conflict. This may involve further consultation with a physician who has expertise in CIED therapy.

Device Deactivation in the Pediatric Patient A full discussion of end-of-life issues in minors is beyond the scope of this chapter. However, patients age 24 or under account for 1% to 2% of device implants,60 and it should be recognized that there will be unique situations where quality survival may be unattainable even for a child, and a “good death”61 may be the more appropriate goal. Two major questions may arise when one is considering forgoing lifesustaining treatment for a seriously ill juvenile patient: should the young person be informed about the gravity of his illness? And if so,

1048

SECTION 4  Follow-up and Programming

to what extent should that young person participate in the end-of-life decision? Management of CIEDs in children nearing end of life or requesting withdrawal of treatment requires an assessment of the child’s decision-making capacity. Whether or not the child has capacity, communication of decisions should be provided to the child, recognizing developmental level and individual preferences. An ongoing dialogue is required with the juvenile patient, in which his or her concerns are probed and assurance is given that any questions about the illness and its treatment will be answered truthfully. If a child does not have decision-making capacity, a parent or guardian should make decisions in the child’s best interest. (See also Chapter 18.)

Withholding Device Therapy A second, less frequently-discussed ethical aspect of device therapy lies in the decision to withhold this therapy from a patient who may not benefit or in whom benefit is less clear. The ACC/AHA guidelines for device-based therapy clearly state that “recommendations for consideration of ICD therapy, particularly those for primary prevention, apply only to patients who … have a reasonable expectation of survival with a good functional status for more than one year.”43 However, as recently described by Beauregard,62 palliative care experts may be

consulted regarding device deactivation in patients with more recent implants. How often this occurs and why are unknown. The question has been raised whether implanting electrophysiologists may ignore severe comorbidities that might limit the benefit of ICDs.62 However, in one reported series of patients requesting deactivation, the three patients diagnosed with malignancy before device implant had all been given life expectancy of longer than 1 year by their oncologist.63 Ethics requires that physicians not impose on patients therapies that may be medically futile, as outlined by the AMA Code of Ethics.8 However, “medical futility” may be difficult to determine. A “reasonable expectation of survival for more than one year,” a relatively “hard” endpoint, can already be difficult to predict in many cases; “reasonable expectation of survival with good functional status” is even more difficult to define. To prevent the situation of device implantation in individuals who may shortly be requesting deactivation, it is important first for the physician to weigh carefully the ICD benefit in the context of the patient’s overall medical condition. Also, similar to deactivation discussions, discussions about initial implant should also follow patientcentered, “shared decision-making” models.64 Especially in older individuals, discussion of ICD implantation should focus on overall goals of care for a patient’s remaining years.

REFERENCES 1. Goldstein NE, Lampert R, Bradley E, et al: Management of implantable cardioverter-defibrillators in end-of-life care. Ann Intern Med 141:835-838, 2004. 2. Mueller PS, Jenkins SM, Bramstedt KA, Hayes DL: Deactivating implanted cardiac devices in terminally ill patients: practices and attitudes. Pacing Clin Electrophysiol 31:560-568, 2008. 3. Goldstein N, Bradley E, Zeidman J, et al: Barriers to conversations about deactivation of implantable defibrillators in seriously ill patients: results of a nationwide survey comparing cardiology specialists to primary care physicians. J Am Coll Cardiol. 54:371373, 2009. 4. Lampert R, Hayes DL, Annas GJ, et al: Heart Rhythm Society Expert Consensus Statement on the management of cardiovascular implantable electronic devices (CIEDs) in patients nearing end of life or requesting withdrawal of therapy. Heart Rhythm 7:1008-1026, 2010. 5. Beauchamp TL: Principles of biomedical ethics, ed 6, New York, 2009, Oxford University Press. 6. Annas GJ: The rights of patients: the authoritative ACLU guide to the rights of patients, ed 3, New York, 2004, New York University Press. 7. Snyder L, Leffler C: Ethics manual, fifth edition. Ann Intern Med 142:560-582, 2005. 8. American Medical Association Council on Ethical and Judicial Affairs. AMA 2008–2009. Code of Medical Ethics: current opinions and annotations. Chicago, 2010, AMA Press. 9. Pellegrino ED: Decisions to withdraw life-sustaining treatment: a moral algorithm. JAMA 283:1065-1067, 2000. 10. Rhymes JA, McCullough LB, Luchi RJ, et al: Withdrawing very low-burden interventions in chronically ill patients. JAMA 283:1061-1063, 2000. 11. Quill TE, Barold SS, Sussman BL: Discontinuing an implantable cardioverter-defibrillator as a life-sustaining treatment. Am J Cardiol 74:205-207, 1994. 12. In re Quinlan. 70 N.J. 10, 355 A.2d 647 New Jersey Supreme Court. 1976. 13. Cruzan v. Director Missouri Department of Health. 497 U.S. 261 88-1503, 1990. 14. Annas GJ: “Culture of life” politics at the bedside—the case of Terri Schiavo. N Engl J Med 352:1710-1715, 2005. 15. Burt RA: Death is that man taking names, Berkeley, 2002, University of California Press. 16. Schneider C: The practice of autonomy: patients, doctors, and medical decisions, New York, 1998, Oxford University Press. 17. Wiegand DL, Kalowes PG: Withdrawal of cardiac medications and devices. AACN Adv Crit Care 18:415-425, 2007. 18. Belcherton State School v. Saikewicz. 370 N.E. 2d. 417, 1977. 19. Kay GN, Bittner GT: Should implantable cardioverterdefibrillators and permanent pacemakers in patients with terminal illness be deactivated? Deactivating implantable cardioverter-defibrillators and permanent pacemakers in patients with terminal illness: an ethical distinction. Circ Arrhythmia Electrophysiol 2:336-339, 2009. 20. Meisel A, Snyder L, Quill T, American College of Physicians– American Society of Internal Medicine End-of-Life Care Consensus: Seven legal barriers to end-of-life care: myths, realities, and grains of truth. JAMA 284:2495-2501, 2000. 21. Vacco v. Quill. 521 U.S. 793, 95-1858. Supreme Court of the United States, 1997. 22. Washington v. Glucksberg. 521 U.S. 702, 96-110. Supreme Court of the United States, 1997.

23. Sulmasy DP: Within you/without you: biotechnology, ontology, and ethics. J Gen Intern Med 1:69-72, 2008. 24. Zellner RA, Aulisio MP, Lewis WR: Deactivating permanent pacemakers in patients with terminal illness; patient autonomy is paramount. Circ Arrhythmia Electrophysiol 2:340-344, 2009. 25. Swetz KM, Crowley ME, Hook C, Mueller PS: Report of 255 clinical ethics consultations and review of the literature. Mayo Clin Proc 82:686-691, 2007. 26. The Joint Commission. Joint Commission Requirements, 2010. 27. PSDA-90. Ominbus Budget Reconciliation Act of 1990. [Patient Self-Determination Act of 1990]. Pub. L. 101–508, 4206, and 4751. (Medicare and Medicaid, respectively), 42 U.S.C. 1395cc(a) (I) (Q), 1395 mm (c) (8), 1395cc(f), 1396(a)(57), 1396a(a) (58), and 1396a(w) (Suppl 1991). U S, 2010. 28. Braun TC, Hagen NA, Hatfield RE, Wyse DG: Cardiac pacemakers and implantable defibrillators in terminal care. J Pain Symptom Manage 18:126-131, 1999. 29. AMA Council on Ethical and Judicial Affairs: Physician objection to treatment and individual patient discrimination: CEJA Report 6-A-07, Chicago, 2007, AMA Press. 30. May T: Bioethics in a liberal society, Baltimore, 2002, Johns Hopkins University Press. 31. Goldstein NE, Mehta D, Teitelbaum E, et al: “It’s like crossing a bridge”: complexities preventing physicians from discussing deactivation of implantable defibrillators at the end of life. J Gen Intern Med 1:2-6, 2008. 32. Fried TR, Bradley EH, Towle VR, Allore H: Understanding the treatment preferences of seriously ill patients. N Engl J Med 346:1061-1066, 2002. 33. Fried TR, Byers AL, Gallo WT, et al: Prospective study of health status preferences and changes in preferences over time in older adults. Arch Intern Med 166:890-895, 2006. 34. Wright AA, Zhang B, Ray A, et al: Associations between end-oflife discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA 300:1665-1673, 2008. 35. Lewis WR, Luebke DL, Johnson NJ, et al: Withdrawing implantable defibrillator shock therapy in terminally ill patients. Am J Med 119:892-896, 2006. 36. Singer PA, Martin DK, Kelner M: Quality end-of-life care: patients’ perspectives. JAMA 281:163-181, 1999. 37. Nicolasora N, Pannala R, Mountantonakis S, et al: If asked, hospitalized patients will choose whether to receive life-sustaining therapies. J Hosp Med 1:161-167, 2006. 38. Fried TR, O’Leary JR: Using the experiences of bereaved caregivers to inform patient- and caregiver-centered advance care planning. J Gen Intern Med 23:1602-1607, 2008. 39. Berger JT, Gorski M, Cohen T: Advance health planning and treatment preferences among recipients of implantable cardioverter-defibrillators: an exploratory study. J Clin Ethics 17:72-78, 2006. 40. Goldstein NE, Mehta D, Siddiqui S, et al: “That’s like an act of suicide”: patients’ attitudes toward deactivation of implantable defibrillators. J Gen Intern Med 1:7-12, 2008. 41. Goldstein NE, Back AL, Morrison RS: Titrating guidance: a model to guide physicians in assisting patients and family members who are facing complex decisions. Arch Intern Med 168:1733-1739, 2008. 42. Covinsky KE, Goldman L, Cook EF, et al: The impact of serious illness on patients’ families. SUPPORT Investigators. Study to

Understand Prognoses and Preferences for Outcomes and Risks of Treatment. JAMA 272:1839-1844, 1994. 43. Epstein AE, DiMarco JP, Ellenbogen KA, et al: ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation 117:e350-e408, 2008. 44. Schoenfeld MH: Follow-up assessments of the pacemaker patient. In Ellenbogen KA, Wood MA, editors: Cardiac pacing and ICDs, ed 5, Hoboken, NJ, 2008, Wiley-Blackwell, pp 498-545. 45. Schoenfeld MH: Deciding against defibrillator replacement: second-guessing the past? Pacing Clin Electrophysiol 23:20192021, 2000. 46. Wilkoff BL, Auricchio A, Brugada J, et al: Heart Rhythm Society, European Heart Rhythm Association, American College of Cardiology, American Heart Association, European Society of Cardiology Heart Failure Association, Heart Failure Society of America. HRS/EHRA expert consensus on the monitoring of cardiovascular implantable electronic devices (CIEDs): description of techniques, indications, personnel, frequency and ethical considerations. Heart Rhythm 5:907-925, 2008. 47. Emanuel EJ, Fairclough DL, Slutsman J, et al: Assistance from family members, friends, paid care givers, and volunteers in the care of terminally ill patients. N Engl J Med 341:956-963, 1999. 48. Lynn J, Goldstein NE: Advance care planning for fatal chronic illness: avoiding commonplace errors and unwarranted suffering. Ann Intern Med 138:812-818, 2003. 49. Morrison RS, Meier DE: Clinical practice: palliative care. N Engl J Med 350:2582-2590, 2004. 50. Goldsmith B, Dietrich J, Du Q, Morrison RS: Variability in access to hospital palliative care in the United States. J Palliat Med 11:1094-1102, 2008. 51. Schulz R, Beach SR: Caregiving as a risk factor for mortality: the Caregiver Health Effects Study. JAMA 282:2215-2219, 1999. 52. Schulz R, Newsom J, Mittelmark M, et al: Health effects of caregiving: the Caregiver Health Effects Study: an ancillary study of the Cardiovascular Health Study. Ann Behav Med 19:110-116, 1997. 53. Lee S, Colditz GA, Berkman LF, Kawachi I: Caregiving and risk of coronary heart disease in U.S. women: a prospective study. Am J Prev Med 24:113-119, 2003. 54. National Consensus Project for Quality Palliative Care: Clinical practice guidelines for quality palliative care, 2009. 55. Ersek M, Grant MM, Kraybill BM: Enhancing end-of-life care in nursing homes: Palliative Care Educational Resource Team (PERT) program. J Palliat Med 8:556-566, 2005. 56. Robinson K, Sutton S, von Gunten CF, et al: Assessment of the Education for Physicians on End-of-Life Care (EPEC) Project. J Palliat Med 7:637-645, 2004. 57. Unutzer J, Katon W, Callahan CM, et al: Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. Treatment IIIM-PAtC. JAMA 288:2836-2845, 2002. 58. Lindsay BD, Estes NA, 3rd, Maloney JD, et al: Heart Rhythm Society policy statement update: recommendations on the role of industry-employed allied professionals (IEAPs). Heart Rhythm 5, 2008.



59. Mueller PS, Ottenberg AL, Hayes DL: Role conflicts among industry employed allied professionals: characteristics and recommendations for addressing them. Heart Rhythm 7:S11, 2010. 60. Zhan C, Baine WB, Sedrakyan A, Steiner C: Cardiac device implantation in the United States from 1997 through 2004: a population-based analysis. J Gen Intern Med 1:13-19, 2008.

35  Ethical Issues 61. Baines P: Medical ethics for children: applying the four principles to paediatrics. J Med Ethics 34:141-145, 2008. 62. Beauregard L: Ethics in electrophysiology: a complaint from palliative care. Pacing Clin Electrophysiol 33:226-267, 2010.

1049

63. Kobza R, Erne P: End-of-life decisions in patients with malignant tumors. Pacing Clin Electrophysiol 30:845-849, 2007. 64. Mead N, Bower P: Patient-centredness: a conceptual framework and review of the empirical literature. Soc Sci Med 51:1087-1110, 2000.

Acute myocardial infarction (Continued)

Acute myocardial infarction (Continued)

INDEX

Acute myocardial infarction (Continued)

Page numbers followed by f indicate figures; t, tables; b, text in boxes.

A AAI atrial hysteresis, timing interval for, 816f AAI mode atrial refractory period, timing interval for, 816f AAI mode blanking period, timing interval for, 816f AAI pacing, 223-224. See also Atrial pacing contraindications for, 320t hypertrophic obstructive cardiomyopathy during, 229f pacemaker syndrome during, 227-228 refractory period for, 400f timing interval for, 815-816, 815f-816f ventricular tachycardia during, 319f AAIR pacing contraindications for, 320t managed ventricular pacing and AVB during exercise, 351f criteria for switching, 351f pacemaker syndrome during, 227-228 refractory period for, 400 sinus node disease and, 318-320 AAI(R) pacing mode, MVP algorithm and, 833-834 AAI(R)-to-DDDR mode switching, 833-834, 834f AAIR vs. AAI/VVI, 156 AAIsafeR mode, 316-317, 834-835 AAT pacing mode, 836 Abdominal pacemaker, radiography of, 773f-774f Abdominal pocket, for ICD, 496, 496f Absolute risk reduction, for sudden cardiac death, 260 Accelerometer, 146 monitoring walking distance, 159f Accelerometer-based pacemaker, 147-149 Acoustic energy, 435-439 Acoustic radiation, 1005 Acoustic window, 437, 437f Acquired AV block causes of, 333-336, 333t permanent pacing for, 337t Action potential, 7 fibrillation and, 41 from heart cells, 9f secondary source model for, 46 Action potential duration (APD) diastolic interval and, 41 restitution relationship of, 41f Activation polarization, 177 Active discrimination, 101 Active-fixation electrode acute endocardial placement of, 411f chronic long-term thresholds for, 408f Active-fixation helix, 127, 133f in epicardial active-fixation steroid-eluting lead, 135f Active-fixation lead in atrium, advantages of, 475 in coronary venous system, 135-136, 136f current of injury and, 476 dexamethasone-eluting reservoir in, 133f

Active-fixation screw, positioning of, 783f, 791 Active screw-in, sensing and, 58 Activity of daily living programming, 147 Activity sensing, 145-146 Activity-sensing device limitations of, 149 types of, 147-148 Activity-sensing pacemaker, 147f types of, 147-149 Activity sensor, 145-146 clinical results of, 148-149 types of, 147f Acuity Spiral LV lead, 598-600 in target vein, 599f Acuity Steerable LV lead, 598 in target vein, 599f Acute atrial epicardial electrode threshold, 406f Acute care hospital with electrophysiologic expertise, device deactivation and, 1047 Acute decompensated heart failure (ADHF), 156-157 hospitalization for, 167f, 999 symptoms, signs, and investigations, limitations of, 157-158 triggers of, 156-157 Acute myocardial infarction anterior or anteroseptal, effects of, 338, 339t atrioventricular block and, 338 with BBB, 339-341, 340t without BBB, 338, 339t AV node conduction disturbances during, 323 bundle branch block in, 340t electrocardiogram of, 341f mortality and sudden death rate, 341 high-grade AV block and, 340f BBB after recovery, 343 inferior or posterior, effects of, 338, 339t occurrence of, 338 onset of, 338 pacing in permanent, 345-346, 345t temporary, 344-345 thrombolytic therapy for, 341-343 Adapter categories of, 734 older models of, 733f pocket bulk from, 736f Adaptive-rate pacing, 825-827 Advanced Elements of Pacing Randomized Controlled Trial (ADEPT), 236-237 Advisory notice. See Product advisory Air embolism prevention of, 467b risk of, 466 Alignment error, 90, 92f Alternans Before Cardioverter-Defibrillator (ABCD) observational study, 272 Alternative medicine device, electromagnetic interference and, 1013 Alternative-ventricular site pacing, 801-803 ALTITUDE study, 296

Aluminum electrolytic capacitor components of, 187 cutaway view of, 188f photomicrograph of, 187f Ambulatory electrocardiographic monitoring, 414-415 Ambulatory failure, 448 Ambulatory pacemaker implantation, 448-449 analysis of, 448t protocol for, 448b Ambulatory surgery, definition of, 448 American College of Cardiology/American Heart Association AV block risks, pacemaker recommendations on, 328 cardiac channelopathy risk stratification/ treatment guidelines, 385 ICD and CRT implantation guidelines and, 491-492 ICD therapy recommendations by, 273t pacing mode selection guidelines, 253 Aminophylline, 338 Amiodarone, defibrillation threshold and, 907f Amiodarone versus Implantable CardioverterDefibrillator Trial (AMIOVIRT) for ICD therapy, 266 criteria, comparison groups and results, 264t population details/mortality results, 265t Ampere-hour, 176 Amplatz Goose Neck, 761, 763f Amplitude, 56-59 of electrogram, 58 exercise effect on, 58 during retrograde atrial activation, 58-59 undersensing and, 58 Amplitude Safety Margin, LVCM and, 927 Anchor balloon technique, 558 coronary sinus cannulation with, 693 for coronary sinus cannulation, 697f coronary sinus recovery using, 694-695 equipment for, 697b Andersen-Tawil syndrome, 332 Anesthesia general endotracheal, 754 for lead extraction, 754 for pacemaker implantation, 452 types of, 452t Anesthetist, for pacemaker implantation, 444 Angel Med Guardian, 170, 170f Angioplasty, of collateral vein, 677f, 682f Angioplasty balloon, 623-625 rupture of, 687f Angioplasty wire, 631f, 699, 700f coronary balloon and delivery guide, loading, 696f Anisotropy ratio, 47 Anodal capture, 924 ventricular activation sequence, effect of, 925f Anodal shock, 376-377 Anodal stimulation, 11-13 action potential initiation by, 12f

1051

1052

Index

Anodal stimulation (Continued) cathodal stimulation versus, 23 tachyarrhythmias, generation of, 23 threshold at coupling intervals, 23, 23f Anode, 4 batteries and, 175, 176f corrosion of, 23 definition of, 175 resistance of, 16 Anode break computer simulation of, 12f occurrence of, 12f Anode make computer simulation of, 12f effects of, 11-12 Anterior septum, contraction patterns in, 209f Anterior subpectoralis muscle approach, for ICD implantation, 502f Anterolateral chest, anatomy of, 454f Antiarrhythmic drug, stimulation threshold and, 32 Antiarrhythmic versus Implantable Defibrillator (AVID) trial CIDS, CASH and, pooled analysis of, 263 for ICD therapy, 261-262 criteria, comparison groups and results, 262t population details/mortality results, 262t shock incidence in, 902 Antibiotic-impregnated pouch, 738f Antibiotic prophylaxis, for infection prevention, 452-453 Antibradycardia pacing revised NASPE/BPEG generic code for, 196, 197t examples of, 198t Antibradycardia therapy, in Long QT Syndrome, 386-387 Antimicrobial irrigation protocol, 453t Antishoplifting gate, electromagnetic interference and, 1012 Antitachycardia device, oversensing in, 722f Antitachycardia pacing advantage of, 380 burst versus ramp, 379-380 in children, 421 electrode placement/selection, 421 indications for, 83, 379-380 problems with, 907-908, 908t stimulation threshold and, 15 VT shock therapy and, 904 Antitheft device, electromagnetic interference and, 1012 AOO pacing mode, 836 Aortic pressure tracings, in heart failure patient, 217f Aortic velocity time interval by ECG method versus EGM-based method QuickOpt, 967f pacemaker AVI change effect on, 926 semi-automatic adjustment of, 968 Arrhythmia atrial electrogram during, 58-59 detection of, 56 event notification for, 999 failure to convert, cause of, 904-905 Arrhythmogenic right ventricular dysplasia (ARVD) computed tomography and, 808 magnetic resonance imaging and, 808

Artificial electrical stimulation, of cardiac tissue, 8-13 Ascorbic acid, 622 Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients, 314 Asynchronous activation, 209-210 Asynchronous heart failure, cause of, 913-915 Asynchronous LV contraction, hemodynamic consequences of, 913 Asynchronous pacing mode, AOO, VOO, DOO, 836 Asynchronous ventricular activation, 914f Asynchrony, 913 Atonic stage, of ventricular fibrillation, 41f development of, 40 Atrial activation/contraction, 205 Atrial activation time (AAT), 949-950 analysis of, 951f Atrial antiarrhythmic pacemaker, diagnostic data stored in, 115f Atrial antitachycardia pacemaker, SVT-VT detection and, 112-116 Atrial antitachycardia pacing therapy, 311f atrial fibrillation frequency and, 312f median AT/AF burden before and after, 312f at baseline and years after, 312f Atrial arrhythmia cause of, 880 detection of, 902 Atrial-based timing, 823-825 Atrial-based timing cycle, 829f Atrial-based timing pacemaker, prolongation of AEI in, 829f Atrial blanking period, 815f Atrial capture latency, 949 Atrial capture management, 79, 84f Atrial Capture Management feature, 34 Atrial coupling, atrial fibrillation disrupting, 911 Atrial desynchronization, 911-915 Atrial/dual-chamber pacing, ventricular single-chamber pacing versus, 238-239 Atrial Dynamic Overdrive Pacing Trial (ADOPT), 310 AF suppression and, 832 Atrial electrode, placement of, 475f atrial positioning for, 475, 475f techniques for, 474-476, 475f using straight/non-preformed lead, 475 through persistent left superior vena cava, 489f Atrial electrogram (AEGM), 86f-87f amplitude of, 56 during arrhythmias, 58-59 during atrial fibrillation, 58-59 atrioventricular pacing and, 216f exercise effect on, 58 in heart failure patient, 217f high-rate episodes on, 857f respiratory variation in, 58 Atrial endocardial electrogram, 61f Atrial epicardial electrode implantation, 405 Atrial escape interval (AEI), 823-824, 824f prolongation in atrial-based timing pacemaker, 829f Atrial fibrillation. See also Atrial antitachycardia pacing therapy atrial coupling, disruption of, 911

Atrial fibrillation (Continued) atrial/dual-chamber pacing versus ventricular single-chamber pacing, 239 atrial electrogram during, 58-59 atrial flutter, organizing into, 311f atrial pacing causing, 833 cardiac desynchronization caused by, 972f CIEDs and, 858 complete heart block and, 326 detection of, 306-307 algorithm for, 120f for atrial therapy, 114-115 factors influencing, 307t principles of, 114 frequency in, 312f Holter recording of, 117f home monitoring for, 994f hospitalization for, 307f inappropriate detection of, 100f inappropriate shocks for, 389f monitoring for, 114 multiple shocks and, 902, 903f pacing algorithms in prevention of, 308-311 in termination of, 311-312 pacing mode and, 246f, 306-313 impact on, 307t in prevention of, 307-308 RCT for, 244f, 246 pacing mode and mortality, studies on, 239t postshock early recurrence of, 119f prevention of, 832-833 right ventricular apical pacing and, 503 site-specific pacing for prevention, 312-313 suppression algorithm for, 833f symptomatic, time spent in, 310f termination of, 118f thromboembolism risk and, 313-314 undersensing in QRS complex in, 875f ventricular pacing and, 314-315, 315f, 317-318 VVI pacing mode for, 813 Atrial fibrillation lead system, 793 radiographic view of, 796f Atrial Fibrillation Reduction Atrial Pacing Trial, 314 Atrial flutter appropriate rejection of, 101f detection algorithm for, failure of, 831f electrograms of children in, 415f mode switching during, 830-831 algorithms for, 831, 831f organizing into from AF, 311f Atrial high rate episode (AHRE), 159-160 Atrial ICD atrial sensing in, 67 SVT-VT detection and, 112-116 Atrial lead with fracture/protrusion, 794f lead dislodgment with, 483 positioning of, 312-313, 313f radiography of, 780-781 in RA appendage, 784f Atrial muscle, action potential of, 9f Atrial natriuretic factor (ANF), 205-206 Atrial oversensing, 970-971 Atrial pacing (AAI). See also AAI pacing for AF prevention, 312-313 atrial fibrillation and, 833



Atrial pacing (Continued) cardiac output versus mean atrial pressure during, 209f competitive versus noncompetitive, 833 DDD pacing versus, 243 clinical events in, 244t electrogram method and, 950f hemodynamic effects of, 210f optimal pacemaker AVI during, 953f pacemaker AVI interaction with, 949-952 for stressing His-Purkinje system, 328 ventricular pacing versus, meta-analysis of, 243 for ventricular synchrony, 218 Atrial pacing preference (APP), 832 Atrial pressure, atrial pacing and, 209f Atrial proarrhythmia, 105f Atrial rate dual-chamber rhythm classification and, 96f ventricular rate versus, 95 Atrial refractory period AAI mode, 816f hysteresis and, 815-816 Atrial sensing, 223-224 in dual-chamber and atrial ICDs, 67 electrogram method and, 950f far-field R wave rejection by, 71f loss of, 64f optimal pacemaker AVI during, 953f postventricular atrial blanking effect on, 69f Atrial sensitivity, mode switching and, 831f Atrial septal pacing, 509-510 selective site pacing and, 509 Atrial Septal Pacing Clinical Efficacy Trial (ASPECT), 310 Atrial shock, detection considerations for, 115-116 Atrial single-chamber pacing dual-chamber pacing versus, clinical trials for, 243-247 in sinus node disease, 237-238, 237t Atrial switch operation, 393 endocardial electrode implantation after, 412f Atrial synchronized ventricular pacing, ventricular single-chamber pacing versus, 235 Atrial tachyarrhythmia detection of, 116f pacemaker implantation and, 395 with rapid ventricular conduction, 971-973 Atrial tachycardia detection of for atrial therapy, 114-115 principles of, 114 therapy and, 118f false-positive detection of, 308f monitoring for, 114 termination of, 118f Atrial Therapy Efficacy and Safety Trial (ATTEST), 311-312 Atrial tracking, sensor-driven appearance of, 826f Atrial tracking preference (ATP), 970, 971f Atrial tracking recovery (ATR), 970f-971f CRT, minimizing loss of, 970 Atrial transport block, cause of, 943f Atrial uncoupling, 911 Atrial undersensing, 64f forms of, 968 ventricular safety pacing resulting from, 819f

Index

Atrial-ventricular activation time, by surface ECG and local EGM timing, 951, 951f Atrial vulnerable period, 830-831 Atrioventricular block acquired causes of, 333-336, 333t permanent pacing for, 337t acute myocardial infarction and, 338 with BBB, 339-341, 340t without BBB, 338, 339t in AV node, 325f cardiac pacing and, 234 cause of, 323 chronic, permanent pacing in, 337 classification of, 329 as congenital, 331-332 crosstalk and, 877f diagnosis of sites for, 325 diastolic dysfunction causing, 943-944 exercised-induced transient, 336 first-degree, 329 as high-grade definition of, 330 rhythm strip of, 330f in His-Purkinje system atropine, 326f LV cavity volume, effects on, 212f Lyme disease and, 335 mortality rates of, 342f pacing mode for selection of, 346-353 survival rate with, 239t Paroxysmal, 330-331 radial artery pressure with, 226f rhythm strips of, 325f right ventricular apical pacing in, 350 risk factors for, 328-329 second-degree, 330 single-lead VDD versus dual-chamber DDD pacing, 235 site-specific ventricular pacing for, 350-353 symptoms of, 329 syncope with incomplete RBBB, tracings from, 336f types and characteristics of, 323 type II second-degree, 325f type I second-degree, 325f vagally mediated, 336 ventricular versus “physiologic” pacing modes, 238 Atrioventricular conduction system anatomy of, 323 representative diagram of, 324f atropine improving, 325-326 diagnosis of disturbances in electrocardiography, 323-327 electrophysiologic study, 327-328 Atrioventricular conduction system disease connective tissue disorder and, 336 diagnosis, pathophysiology and prognosis for, 323-360 inherited, 332-333 Atrioventricular conduction time, 927 Atrioventricular coupling, 911 schematic representation of, 912f Atrioventricular decoupling excessively long pacemaker AVI causing, 944f schematic representation of, 912f

1053

Atrioventricular delay interval, 216f automatic rate-responsive atrioventricular delay (RAAVD), 350f exercise and activity, 215f factors influencing, 214t in long-term CRT, optimization studies, 293-294 LV outflow recording at, 214f optimization of, 225-226, 225f pacemaker syndrome and, 318 programming of hemodynamic effects of, 214f PQ interval, effect of, 215f purpose of, 214 Atrioventricular desynchronization arrhythmia, 884 Atrioventricular dyssynchrony, pacemaker syndrome and, 228-229 Atrioventricular electromechanical time, RA pacing effect on, 951-952, 952f Atrioventricular interval, 817-819 biventricular capture and, 837 determination of, 213 determining optimal, 349f hemodynamic effects of, 912f programming of, 348-350 rate-adaptive shortening/delay, 349 Atrioventricular interval hysteresis, 818-819 positive, 820f Atrioventricular interval prolongation, diagrammatic representation of, 825f Atrioventricular mechanical latency (AML), 946-947 Atrioventricular mechanics, optimal AV resynchronization and, 915 Atrioventricular nodal ablation, 335 Atrioventricular nodal cell action potential of, 9f characteristics of, 7 Atrioventricular node, 323 acute myocardial infarction and, 323 anatomy of, 323 Atrioventricular pacing, 216f hemodynamic effects of, 210f rate smoothing leading to, 842f sequential, 213 surface ECG, AEG, VEG, PCW recordings during, 216f Atrioventricular resynchronization, 947-948 approaches to comparison of, 948-949 conventional echocardiography, 944-947 optimization of, 943-944 LV inflow analysis and, 944-947 methods to guarantee, 936-938 optimal pacemaker AVI for, 948 Ritter method for, 944-945, 945f summary of, 946f using acute changes in aortic pressure, 949f using electrogram analysis, 950f using invasive hemodynamic monitoring, 947, 947f Atrioventricular search hysteresis (AVSH), 272 Atrioventricular synchronous pacing, 234 Atrioventricular synchrony, 144 importance of, 213 physiologic effects of, 211-219

1054

Index

Atrioventricular timing (AV timing) automatic adjustment of QuickOpt, 966-968 SmartDelay optimization, 963-968 Atrioventricular uncoupling, 911 Atrium active-fixation leads in, advantages of, 475 function of, 213 Atropine, AV conduction and, 325-326 Autocapture, 132f Autocapture fusion avoidance, in St. Jude Medical pacemaker, 355f Autocapture pacemaker, sense amplifier for, 353-354 Autocapture pacing advantages/benefits of, 353 adverse effects of, 353 Autocapture threshold search, 354f Automated capture feature, 34, 353 Automatic capture verification, pacing output management and, 353-355 Automatic drug delivery systems, 371 Automatic Gain Control, 65 Automaticity, cardiac action potential and, 8 Automatic mode switching (AMS), 78 in pacemaker, 830 sensitivity and specificity of, 82f Automatic pulse amplitude (APA), 34 Automatic rate-responsive atrioventricular delay (RAAVD), fixed AV delay versus, 350f Automatic remote monitoring, 989 with daily screening, 996 data transmission for, 990f speed/time for, 991f event notification, 989t follow-ups for, 998 Autosensing, for sensing safety margin, 66f Auxotonic relaxation, ventricular pacing versus sinus rhythm, 209 A-V Rate Branch, 102f Axillary approach, for ICD implantation, 501-502 Axillary-subclavian junction, high-grade stenosis of, 649f Axillary/subclavian venography, showing venous anatomy, 780f Axillary vein, 453-454 pectoralis minor muscle and, anatomic relation of, 459f ultrasonic image of, 463f Axillary vein approach, for endocardial electrode implantation, 410 Axillary venipuncture Nichalls’ landmarks for, 460f using guidewire as landmark, 484f Axillary venous access contrast venography and, 462 cutdown technique for, 462 Doppler flow detection/ultrasound techniques for, 462-463, 463f lateral access to, 463 retention wire, before/after insertion, 533f techniques for, 453b for transvenous pacemaker placement, 459-468 using first rib, 460, 462f using guidewire as landmark, 485f using J-tipped polytetrafluoroethylene guidewire, 462, 463f

Azygos vein anatomy of, 500f sheath insertion from right axillary vein, 716f Azygos vein cannulation, 712b catheter for, 712f advanced over glide wire, 713f from right side, 715f Azygos vein coil placement, 714f interventional approach to, 711-713 Azygos vein defibrillation coil, 498-499 Azygos vein defibrillation lead, 793 radiographic view of, 797f Azygos vein occlusion venography, 781f Azygos venography, 803

B Bachmann’s bundle, 509 Balanced Endless-loop tachycardia (ELT), 881 Balloon. See also Anchor balloon technique aramid fiber (Kevlar), 652f compliance of, 623-624 compliant versus noncompliant, 624f-625f types of, 623-624 coronary sinus cannulation with, 693 coronary sinus venogram, 693 diameter of, 625, 625f inflation pressure of, 625 length of, 625 long versus peripheral balloon, 651f in myocardium, inflating, 681, 690f for occlusive coronary sinus venography, 589 compliant versus noncompliant, 588-589, 589f trauma from, 588-589 over-the-wire versus monorail, 624f predilation of small vein for larger balloon, 678f profile of, 625, 625f short, total occlusion dilation with, 652f for subclavian vein venoplasty, 647-652 technique considerations for, 624 Balloon catheter, 623 Balloon venoplasty, of main coronary sinus, 664f-665f Baseline left bundle branch block, pressure-volume graphs of, 280f Baseline left bundle branch block activation, lead positions and, 936f Battery as case negative/positive, 176 charge available for, 3 charge drain from, minimizing, 16 chemistries in defibrillators, 182-183 cutaway view of, 183f chemistries in pacemakers lithium-carbon, 181-182 lithium-hybrid cathode, 182 lithium-iodine, 181, 181f classification of, 176 primary, 176 secondary, 176 components of anode and cathode, 175 electrolytes, 175-176 separator, 176 defibrillation performance, effect on, 189-190 end-of-service indication, 180-181 elective replacement indicator, 180 false triggering, 180-181 methods for monitoring, 180

Battery (Continued) functional characteristics of capacity, 176 energy and energy density, 176-177 stoichiometry and cell balance, 177 function and electrochemistry of chemical reactions, 175 energy storage, 175 generator survival code and, 396f in ICD, 183-184 lithium-layered silver vanadium oxide-carbon monofluoride, 184 lithium-manganese dioxide, 184 lithium-silver vanadium oxide (LiSVO), 183-184 impedance optimization for minimal consumption of, 22 in implantable cardiac rhythm management devices average versus instantaneous current drain, 178 design requirements for, 178 power requirements for, 178 pulse amplitude on pacing current, effect of, 179 pulse width on pacing current, effect of, 179, 179f shape, size, and mass constraints, 178 size, energy density, and current drain, 178 load voltage versus capacity plot, 177f load voltage versus current drain plot, 177f longevity of, 16 programming voltage versus pulse width for, 35, 35f measured data in, 844-846 non-ideal behavior of polarization, 177 self-discharge, 177-178 power sources for capacitors, 186-189 rechargeable lithium-ion battery, 185-186 pulse generator, longevity of, 178-179 safety concerns with, 184-185 schematic representation of, 176f sealing of, 176 Battery anode, 4 Battery cathode, 4 Battery depletion behavior during, 875 ICD follow visit and, 722 indicators of, 720, 720b mode, rate, parameter change, cause of, 866, 866b Battery discharge, monitoring, 180 Battery impedance, 180 for pacemaker, 846f Battery replacement indications for, 181 reoperation for, 729-730 Battery status indicator, 721f dataset measuring, 866-867 Battery voltage, 180 for pacemaker, 846f Beat-by-beat behavior. See Timing cycle BEST sensor, 151 tracings for, 151f Beta-2 adrenergic receptor gene transfer, biologic pacemaker and, 191



Beta-adrenergic blocker in Brugada syndrome, 390 for cardiac channelopathies CPVT, 385 Long QT Syndrome, 383-384 for vasovagal syncope, 366 BEta-blocker STrategy plus Implantable Cardioverter-Defibrillator Study (BEST-ICD) for ICD therapy, 270 criteria, comparison groups and results, 268t population details/mortality results, 269t Betacel, 434 Bezold-Jarisch reflex, 338 Bidirectional telemetry, 844 Bidomain model, 47-48 circuit diagram of, 47f Bidomain theory, 18 Bifascicular block, 326-327 chronic, permanent pacing in, 338t progression of, 331 Bilateral occlusion, lead extraction for, 751f Biologic pacemaker, 439-440 advances in development of, 320 cell therapy strategies for, 193-194 development of, 191-194 gene therapy approach to beta-2 adrenergic receptor gene transfer, 191 IF manipulations, 191-193 IK1 knockout, 191 Biomedical endocardial Sorin transducer, 151f Biotronik dual-sensor pacemaker, 153t Biotronik LV lead, 598 Biotronik SMART algorithm, 102f Biphasic stimulation energy requirements for, 26 in rabbit/frog ventricles, 26, 26f Biphasic stimulus effect, on voltage decay, 19, 19f Biphasic waveform, 42-45 charge burping theory and, 375-376, 376f definition of, 374 Bipolar electrocoagulation, 1019 Bipolar electrode system, 56 Bipolar electrogram, unipolar electrogram versus, 61f Bipolar IS-1 connector, 872f Bipolar pacing lead, 23, 127 example of, 614f stimulation threshold of, 127-128 Bipolar pacing system electrocardiogram of, 12-lead, 868f electrodes and leads in, 23 electrode sensing for, 405f implantation thresholds for, 405f unipolar pacing versus, 404-405 Bipolar split-cathodal configuration, 33 Bipolar stimulation, 23-24 Bipolar ventricular electrogram, telemetered, 853f Biventricular capture, atrioventricular interval and, 837 Biventricular cardiac resynchronization system, upgrading to, 725 Biventricular cart, 529, 530f Biventricular device, troubleshooting of, 911-986 Biventricular impedance clinical studies for, 169 intrathoracic impedance versus, 169t measurement of, 168-169

Index

Biventricular pacemaker, 219-220 upgrading to, 732-733 precautions for, 733 venous access for, 732 venous stenosis, 732-733 Biventricular pacing, 33-34, 839f atypical QRS hieroglyphic signatures during, 939f configurations for, 921f CT for patient not responding to, 808f effect on ventricular repolarization, 983f electrical activation times for RV/LV during, 223f functional conduction block line manipulation during, 955f incomplete ventricular activation fusion during, 937f increase during AT/AF caused by VRR, 977f leads and electrodes for, 922f left ventricular dysfunction and, 352-353 loss of, 840-841, 841f LV activation fusion, heterogenous effects on, 957f with LV paced event before RV sensed event, 837f percentage of, 160-161 polymorphic ventricular tachycardia during, 983f pulse generator for, 923f refractory periods and, 840 right ventricular pacing versus, trial evaluating, 252-253 with RV-based timing after atrial event, 837f competitive pacing and, 841f LV refractory extension and, 841f with RV sensed event before LV paced event, 837f sensing and, 838-841, 839f-840f sequential versus simultaneous, 963 neural effect of, 965f spontaneous/pacing-induced conduction blocks implications during, 958-959 timing cycle in, 837 goals of, 836-837 premature beats and, 840 ventricular activation wavefront fusion during, 939f at shortened AVD, 938f Biventricular pacing cable, 532f Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace) study, 252, 295-296 Biventricular RV-LV interval, 838f RV sensing with, 839f Biventricular sensing pacing and, 838-841, 839f-840f response to, 838f unipolar pacing and, 840f with univentricular pacing, 839 Biventricular versus RV Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) study, 295-296, 352-353 Blanking period, 56 AAI mode, 816f in cardiac resynchronization ICDs event markers illustrating, 71f DDD atrial, 819f

1055

Blanking period (Continued) for DDD(R) pacing mode, 65f definition of, 874-875 for pacemakers and ICDs, 61 sensing and, 60 short same-chamber, 66 ventricular, 813 BLOCK-HF trial, 252 Blunt microdissection, Frontrunner XP CTO Catheter for, 633f Booster pump, 213 Borrelia burgdorferi, 335 Boston Scientific activity-sensing device, 148 Boston Scientific Acuity Bear-Away Inner Catheter, 591f-592f Boston Scientific dual-sensor pacemaker, 152-154, 153t Boston Scientific ICD Automatic Gain Control for, 65 Guidant Model 1831 as, 901f Boston Scientific LV lead, 598-600 Boston Scientific over-the-wire LV pacing lead, 598f Boston Scientific pacemaker, 34 autocapture threshold test from, 353f Boston Scientific Rhythm ID algorithm, 101f Boston Scientific ventilation-sensing device, 149 Bradycardia cardiac pacing and, 234 vasovagal syncope and, 364-365 implantable recorder, 365 loop recordings, 370 pacemaker memory, 365 tilt-table test, 365 Bradycardia pacing, 211-213 goal of, 836 problems with, 907-908, 908t stimulation threshold and, 15 Bradycardia pulse generator, 179 Bradycardia timing cycle, dual-chamber, 816-825 Brain natriuretic peptide (BNP), 157 heart failure status and, 167f Branching atrioventricular bundle, 324f British Pacing and Electrophysiology Group (BPEG), 813 pacemaker codes by, 195 Brugada syndrome, 332, 384-385 beta-adrenergic blocker in, 390 inappropriate shocks for AF in, 389f risk stratification for, 384-385 sinus tachycardia during exercise, 388f therapeutic recommendations for, 385 ICD therapy, 386t ventricular fibrillations in, 386f Buddy wire technique, 655-656 for straightening vein segment, 656f for LV lead placement, 657f Bulldog lead extender, 761 Bundle branch, action potential of, 9f Bundle branch aberrancy, 93, 93f Bundle branch block (BBB), 323 acute myocardial infarction and, 340t electrocardiogram of, 341f mortality and sudden death rate, 341 after AMI and high-grade AV block, 343 diagnosis/prognosis for, 331 electrophysiologic study for, 328 Burst antitachycardia pacing, 379-380

1056

Index

Byrd Femoral Workstation, 762f, 766f Byrd’s technique, for access to subclavian vein, 459-460, 460f

C Cameron Heald S-ICD detection algorithm, 430 Canadian Implantable Defibrillator Study (CIDS) AVID, CASH and, pooled analysis of, 263 for ICD therapy, 262-263 criteria, comparison groups and results, 262t population details/mortality results, 262t Canadian Trial of Physiologic Pacing (CTOPP), 242 clinical events in, 242t critical appraisal of, 242, 249 intolerance to VVI(R) in, 250f sinus node disease and pacing, 305 Cannon A wave, 864 Cannulation catheter, 538-541 Can-to-patch shocking vector, 430-431 Capacitance, 4 at electrode-tissue interface, relationship to polarization voltage, 21-22 membrane depolarization and, 22-23 polarization versus, 18-19 sine-wave voltage and, 17 Capacitive current flow, 21 Capacitive reactance, inductive reactance versus, 17 Capacitor, 4 as battery power source, 186-189 as charged, 20 components of, 186 defibrillation performance, effect on, 189-190 energy delivery for, 187 energy density, 187 energy storage for, 186 failure modes of, 189 dielectric oxide degradation, 189 short circuit, 189 future of, 189 in ICD, 187 construction of, 187-188 non-ideal behavior of, 188-189 deformation, 188 internal resistance, 188-189 leakage current, 188 schematic representation of, 186f Capacitor charging initiation of, 88f rapid VT/VF detection and, 89f Capacity plot, load voltage versus, 177f Capture automated, 34 cause of loss of, 873b changes in, pacing system malfunction and, 867 Capture hysteresis (Wedensky effect), 15 Capture latency, 949 effect on EGM timing to electrical activity, 951, 951f Capture management, 79 algorithm/graph for, 867f Capture threshold, factors increasing, 873, 873b Carbon dioxide, iodinated contrast versus, 621 Cardiac action potential, 7-8 events producing, 7 origination of, 203 phases of, 7

Cardiac action potential (Continued) automaticity and conduction system, 8 final repolarization, 8 initial repolarization, 8 rapid depolarization, 7-8 Cardiac Arrest Study Hamburg (CASH) AVID, CIDS and, pooled analysis of, 263 for ICD therapy, 263 criteria, comparison groups and results, 262t population details/mortality results, 262t Cardiac automaticity gene therapy approach to, 191-193 molecular therapy experiments to induce, 192t Cardiac catheterization laboratory for pacemaker implantation, 444 view of, 444f Cardiac channelopathy Brugada syndrome as, 384 catecholaminergic polymorphic ventricular tachycardia as, 385 considerations for, 385-386 ICD therapy for, 383-392, 386t complications from, 387-390 Long QT Syndrome as, 383-384 Short QT Syndrome as, 384 Cardiac compass report, 861f Cardiac contractility modulation (CCM), 296 Cardiac cycle, events of, 205f Cardiac depolarization. See Depolarization Cardiac desynchronization, atrial fibrillation causing, 972f Cardiac electrical stimulation, 3-39 concepts of, 3-5 effects of, 3 Cardiac excitation ion channel and, 6f occurrence/mechanism for, 11 types of, 12f virtual electrode causing, 11 Cardiac implantable electronic device (CIED) atrial fibrillation and, 858 benefits/burdens of, 1044-1045 cardioversion or defibrillation, 1021-1022, 1022b communicating about goals of care, 1044t complications from hemothorax from, 742-743 implantation-related, 741 intrathoracic introducer approaches as, 742f lead dislodgment as, 741-742 lead stress/fracture, 742f perforation, 743 pneumothorax from, 742 pocket hematoma, 743 vein thrombosis, 743 deactivation of, 1040 logistics of, 1046-1047 direct-current cardioversion and defibrillation and, 1021-1022 electromagnetic interference and, 1004-1027 CIEDs, effect on, 1014b follow-up for scheduled, 988t unscheduled, 988b indications for, 741 infection and bacteriology of, 744-746 erosion and, 745f erythema and fluctuance, 744f

Cardiac implantable electronic device (Continued) fat necrosis, 745f incidence of, 744-746 management of, 746 presentation of, 744 prevention of, 744 purulent discharge, 745f risk factors for, 744 lead and device performance for, 999-1001 magnetic resonance imaging and, 1016f monitoring of. See also Automatic remote monitoring; Home monitoring economic/regulatory considerations, 1001-1002 HM event notification, 991f in-person, 987 manufacturer resources for, 989t patient-activated remote, 988-989 purpose of, 987 remote, 987-999 pain and, 743-744 patient’s right to refuse, 1040-1046 rights/responsibilities of clinicians, 1042-1043 physician choice for, 741 physician-initiated discussion and, 1043t programmer and, communication between, 1010 psychological impact of, 1038 radiofrequency current effect on, 1023 timing cycles and, 813 types of, 987 withholding therapy, 1048 Cardiac index, changes to, 397f Cardiac mechanical cycle, 938, 940f Cardiac memory, 210 repolarization abnormalities and, 210-211 Cardiac output atrial pacing and, 209f Doppler echocardiography examination/ calculation of, 216 Cardiac pacemaker. See Pacemaker Cardiac pacing. See also Pacing charge conduction/transmembrane potential changes in, 17-18 electric current flow, opposition to, 4 gradient for, 11 physiology and hemodynamics of, 203-233 principle of, 9 sinus node dysfunction and, 393 for symptomatic bradycardia, 211 for syncope treatment, 234 Cardiac perforation. See Perforation Cardiac pump function asynchronous ventricular muscle contraction and, 210 electromechanical events and, 911-920 LBB block and, 209 reduced, cause of, 210 Cardiac resynchronization ICD blanking period in, 71f sensing in, 68 SVT-VT discrimination in, 95-96 Cardiac Resynchronization in Heart Failure (CARE-HF), 285-288 endpoints in, 282t Kaplan-Meier estimates in, 288f extension phase, 289f types, criteria, endpoints and results for, 281t



Cardiac resynchronization therapy (CRT), 33 in acute settings, 279-280 advent of, 443 benefits of, 134, 516 cardiac function improvement with, 280t, 927-943 clinical trials of, 279-299, 295t complications from non-pacing operation-related, 980-981 complications of arterial versus venous system, 585-587 pacing operation-related, 976-980 coronary sinus access for, 535-541 contrast use in, 535-537 coronary sinus and, 489-490 coronary sinus lead positions in, 789f coronary venoplasty techniques for buddy wire technique, 655-656 Doppler echo optimization on hemodynamics in, impact of, 293f echocardiography for assessing response to, 294-295 future populations for, 295-296 goal of, 221 hardware system for leads and electrodes, 920 pulse generator, 920-922 heart failure and devices for, 296-297 hemodynamic/long-term remodeling effects of, 221f implant table for, 623f indications for, 836-837 lead design for, 136 loss of, causes for LV capture loss, 974-976 native ventricular activation competition, 971-973 pacing operation-related, 968-971 prevention of pacing on T wave, 971 LV ejection fraction and, 434 LV lead implantation and, 134, 519, 520f responders versus non responders, 521f LV remodeling and, 434 maintaining continuous, strategies for, 968 mechanical dyssynchrony, measurement of, 422f mechanisms of, 915-920 pacemaker AVI during, 936-938 pacemaker syndrome and, 226-227 pacing in, 434 physiology of, 220-221 programming considerations for LV pacing output voltage, automatic adjustment of, 925-927 pacing modes, 922-923 pacing outputs, 925 programming goal of, 928 response to, 294t comparison of, 974f echocardiography for assessing, 294-295 predictors of, 294-295 reverse volumetric LV remodeling, maximizing probability of, 927-943 sequential ventricular timing in, 959-961 for structural cardiac disease, 421-423 synchrony, strategies to restore, 219-226 ventricular activation wavefront fusion after, 933f

Index

Cardiac resynchronization therapy (Continued) ventricular activation wavefront fusion during, 927-929, 931, 933f Cardiac resynchronization therapy (CRT) defibrillator, left ventricular lead in, 790f Cardiac resynchronization therapy (CRT) trial, 281-290 for evaluating device features/programming, 292-294 long-term in special populations, 291-292 procedural safety and LV performance in, 290-291, 290t types, criteria, endpoints and results for, 281t Cardiac Resynchronization Therapy in Patients with Heart Failure and Narrow QRS trial (RethinQ), 291 Cardiac sarcoidosis, 271 complete heart block and, 335-336 Cardiac stimulation. See also Stimulation threshold metabolic effects on, 32 pharmacologic effects on, 32 Cardiac tamponade echocardiography diagnosing, 807-808 lead extraction and, 752 transvenous approach and, 765 as postimplantation complication, 806-807 Cardiac tissue, artificial electrical stimulation of, 8-13 Cardiomyocyte electric field, response to, 9f membrane composition of, 5 phospholipid bimembrane of, 5f Cardiomyopathy Trial (CAT) for ICD therapy, 266 criteria, comparison groups and results, 264t population details/mortality results, 265t Cardiopulmonary exercise testing, DDDR vs DDD pacing modes, 236 Cardiovascular mortality, pacing and, 246f Cardioversion, 1021-1022, 1022b CARE trial, 621 Carotid sinus, 362-363 Carotid sinus hypersensitivity, carotid sinus syncope and, 363 Carotid sinus massage cardioinhibitory and vasodepressor response to, 363f carotid sinus hypersensitivity and, 363 complications from, 363-364 indications for, 362-363 physiological responses to, 363 Carotid sinus reflex, 361 Carotid sinus syncope. See also Carotid sinus massage carotid sinus hypersensitivity and, 363 clinical perspective for, 361 diagnosis of, 362-364 history of, 361 occurrence of, 361 pacing for, 362t benefits of, 362 contraindications, 364 patient selection for, 362 physiology, 361 studies for, 362t support for, 364

1057

Carotid sinus syncope (Continued) symptoms of, 361 treatment of, 361-362 CAST study, 238 Catecholaminergic polymorphic ventricular tachycardia (CPVT), 385 nonsustained polymorphic ventricular tachycardia in, 390f risk stratification for, 385 therapeutic recommendations for, 385 ICD therapy, 386t Catheter, intimal flap, effects of, 586f Cathodal shock, 376-377 Cathodal stimulation, 11-13 action potential initiation by, 12f anodal stimulation versus, 23 isochronal activation maps after, 47f threshold at coupling intervals, 23, 23f Cathode, 4 batteries and, 175, 176f definition of, 175 resistance of, 16 Cathode break computer simulation of, 12f occurrence of, 12 Cathode limitation battery, 183 Cathode make computer simulation of, 12f occurrence of, 11, 12f Cell, as balanced, 177 Cell membrane, 5 Cell therapy strategy, for biologic pacemaker, 193-194 Cellular action potential, 41-42 defibrillating shock field effect on, 48 Cellular phone, electromagnetic interference and, 1011-1012 Cephalic vein, 454, 457 lead introduction into, 457f Cephalic venous access, for transvenous pacemaker placement, 456-457 Certification phase, of sensing, 117 CHADS-2 score-enhanced thromboembolic risk assessment, 999 Charge burping theory, 375-376, 376f Charge conduction, 17-18 Charge movement, in wires and tissue, 18 Chemical energy, batteries and, 175 Chemotherapy, heart block and, 335 Chest radiography. See also Preprocedural chest radiography CRT, lack of response to, 772 of dual-chamber pacing system, 786f of hemothorax, 806f of pneumothorax, 806f Children antitachycardia pacing in with congenital heart disease, 417-421 electrode placement/selection, 421 in atrial flutter, electrogram of, 415f congenital CHB and pacemaker free, 395, 395f CRT therapy for structural cardiac disease in, 421-423 device systems in, 798f dextrocardia in, 801f dual-chamber pacing contraindications for, 399 features for, 401

1058

Index

Children (Continued) dual-coil intrathoracic defibrillator system in, 420f dual-coil single-lead transvenous defibrillator system in, 419, 421f epicardial patch in, 419, 420f exit block and, 35 heart rate and exercise, 400f-401f ICD use in, 417 follow-up procedures for, 420-421 implantation approaches, 418-419 patient selection for, 417-418 programming considerations for, 419-420 support groups for, 425 initial pacemaker implantation in, 394f LQTS and pacemaker implantation, 395 pacemaker implantation and ambulatory electrocardiographic monitoring, 414-415 clinic visit, 412-413 exercise testing, 413-414 follow-up methods for, 412-417 follow-up periods for, 416 indications for, 395-396 intracardiac electrogram, 413, 414f prophylactic medication, 423 psychosocial adjustment, 423-425 remote/transtelephonic monitoring, 415-416 selection of, 396-409 support groups for, 425 survival rate with, 396f pacemaker implantation in anesthesia for, 486 expertise for, 486 leads for, 486 pacemaker pocket in, 486 permanent cardiac pacemaker in, 393 QRS complex in, 419 Rate-responsive pacing features for, 400-401 right ventricular pacing effects on, 217 single-coil transvenous defibrillator system in, 419, 421f transvenous permanent pacemaker implantation approach in, 485-486 unipolar versus bipolar pacing in, 404-405 Chronaxie, 13-14, 13f Chronic AV block, permanent pacing in, 337 Chronic bifascicular block, permanent pacing in, 338t Chronic circadian threshold variation, 35 Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF), 162, 163f, 296 diagnostic parameters for, 171t Chronotropic incompetence, 144, 154-156 definition of, 236, 825-827 in dual-chamber pacing, 235-236 incidence of, 144 lower rate limits and, 223-224 prevalence of, 155f for rate-adaptive pacing, 827 sensors in patients with, 154f sinus node disease and rate-adaptive pacing, 320 Circulating nurse, for pacemaker implantation, 444 Classic Mobitz type II, 324-325 Clavicle displacement, 455-456 anterior, 455f posterior, 455f

Clavicle-first rib lead discontinuity, 895f CLEAR trial, 225-226 Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT), 992 Closed-loop sensor system, 144, 145f Closed-loop simulation sensor, 146 advantages and limitations of, 151 syncope recurrence with, 371f types of, 151 unipolar ventricular impedance and, 150-151 Clot formation, venoplasty failure and, 660, 660f Coagulation, 1019 Coaxial lead, 128, 128f Cognis/Teligen model, Automatic Gain Control for, 65 Colapinto needle, 635 Combined heart failure diagnostics, 171f PARTNERS and, 170-171 Combipolar sensing, 880 Common bundle, action potential of, 9f Common law, 1040 Communicating, 195 Compact node, 323 Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), 284-285 clinical characteristics of, 285t for ICD therapy, 266 criteria, comparison groups, and results, 264t population details/mortality results, 265t Kaplan-Meier estimates in, 286f patient characteristics and hazard ratios in, 287f study design for, 284f types, criteria, endpoints, and results for, 281t COMPASS-HF, 162, 163f Compensatory hyperventilation, 169-170 Competitive atrial pacing, 833 after premature ventricular complex, 835 prevention of, 833 Competitive ventricular pacing, 841 biventricular pacing with RV-based timing and, 841f Complete AV block, 334 Complete heart block (CHB). See also Heart block as acute or chronic, 330 ambulatory electrocardiogram showing, 395f cardiac sarcoidosis and, 335-336 congenital, 394-395 diagnosis of, 326 escape rhythm in, 326 incidence of, 342f infectious diseases and, 335 Stokes-Adams attack and, 330 symptoms/prognosis for, 330 Composite-wire conductor design, 129-130, 129f Computed tomography biventricular pacing, as nonresponder to, 808f device implantation and, 808 for LV lead repositioning, 808f Concentration polarization, 177 Concomitant symptomatic heart block, sick sinus syndrome and, 334 Conducted atrial fibrillation response effect on BiV pacing delivery, 975f pacing rate changes and, 972, 974f Ventricular Sense Response, combined effects of, 979f

Conducted electromagnetic interference, 1004 Conduction abnormal, activation sequence during, 206 cardiac action potential and, 8 of heart impulse, 204f Conduction block anterior line interaction, schematic view of, 956f-957f fixed versus functional, 952-953 implications of, 954 LV activation fusion, heterogenous effects on, 957f negative effects of, 959f posterior line interaction, schematic view of, 956f spontaneous/pacing-induced, implications during BiV pacing, 958-959 Conduction loss, 16-17 Conductor for pacing leads, 129-130 design of, 129 fracture of, 129 Conductor fracture, 791, 791f-792f, 807 non-physiologic, rapid make-break potential in, 902f Conductor resistance, 16-17 Conduit, creation of, 751-752 Confirmation/reconfirmation, 83-85, 88f Congenital AV block, 331-332 Congenital complete heart block, 394-395 children pacemaker free and, 395, 395f Congenital heart disease in children ICD use, 417 dextrocardia and, 797 Fontan procedure for, 797 Senning/Mustard procedure for, 797 special considerations for, 794-797 persistent left superior vena cava, 794 tetralogy of Fallot and, 797 transatrial endocardial atrial pacing in, 487f Congestive heart failure (CHF). See also Heart failure heart block and, 212 pacing and, 314 signs of, 157 sinus node remodeling in, 301-304 Connective tissue disorder, AV conduction disease and, 336 Connector terminal pin, 134, 134f high-voltage and low-voltage elements of, 140f CONNECT trial, 891 Conscious sedation, protocols for, 452t Constant-current stimulation, 25-26 constant-voltage stimulation versus, 24-26, 25f logarithmic plots of, 25f Constant-voltage stimulation, 25-26 constant-current stimulation versus, 24-26, 25f logarithmic plots of, 25f Constitutional right, 1040 Consumed charge, of battery, 180 Contact mapping, 207f CONTAK CD Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) and, 283-284 study design for, 283f Continuous atrial pacing algorithm, 832



Contraction pattern abnormal during LBBB and ventricular pacing, 206-211 at LV lateral wall pacing, 209f Contrast-induced nephropathy comparison of ionic versus nonionic, 621 low-osmolar nonionic versus iso-osmolar nonionic, 621 contrast volume and, 621 definition of, 620 periprocedural hydration for fluids for, 620 parts of, 620-621 protocol for, 620-621 prevention of, 620-622 risk factors for, 620b Contrast injection, 532f approach to, 530 coronary sinus cannulation with, 541-585 coronary sinus os and anatomy surrounding, 541-547, 544f-545f, 547f locating with, 538-541 defining obstruction, 637, 637f high-grade stenosis, demonstration of, 534f indications and recommendations for, 529 by operator and assistant, 532f simplified system for, 530f into subclavian vein occlusion revealing opening, 627f revealing total occlusion, 627f after venoplasty with previous cardiac surgery, 685f-686f without previous cardiac surgery, 689f venous access for, 530-533 Contrast media half-strength versus full-strength, 548, 548f importance of, 620 iodinated, 529 kidneys and, 620 occlusive coronary sinus venogram with with full-strength contrast, 549f with half-strength contrast, 548f osmolality of, 621 types of, 621 use of, 620 volume of, 621 Contrast staining cause of, 588-589, 589f balloon-induced trauma, 588-589 delivery guide, 590f extravasation, 588 from trauma, 588, 588f vein perforation, 590f subclavian venoplasty and, 655f Contrast venography, 464, 464f axillary venous access and, 462 Conus arteriosus, 507 Conventional echocardiography, LV inflow analysis and, 944-947 Conventional versus Multisite Pacing for Bradyarrythmia Therapy (COMBAT) study, 295-296 Convulsive incoordination stage, of ventricular fibrillation, 40, 41f

Index

Cook locking stylet first-generation, 760-761, 760f second-generation, 761 third-generation, 761, 762f Cook Pacemaker, 760-761 Cook’s Needle’s Eye Snare, 761, 763f Coping methods, for children with pacemakers, 423 Coradial bipolar lead, 128 Coronary Artery Bypass Graft (CABG) Patch trial, 257 for ICD therapy, 269 criteria, comparison groups and results, 268t population details/mortality results, 269t Coronary balloon anchored to regain venous CS, and target vein, 696f anchoring pacing wire, 694f angioplasty wire, loading on, 696f characteristics of, 693 indications for, 650 LV lead placement using, 693-694 subclavian vein occlusion, predilation of, 651f for subclavian venoplasty, 647-650 types of, 650 Coronary sinus advancing sheath or guide into, 558-585 balloon venoplasty of, 664f-665f composite illustration with guide in, 546f-547f coronary venoplasty and, 656-660 dissection of, on LAO clarified on AP view, 552f in LAO projection, 509f lateral wall vein and, RAO view of, 550f lead extraction from, 769, 769f left atrium, draining into, 560f for pacing, 489-490 in RAO projection, 509f venoplasty of, 662-664 after lead dislodgment, 667f-670f Coronary sinus access catheter definition of, 516, 618 intimal flap, effects of, 586f peel-away sheath for kink in, 537f use of, 537f removal of, 572-579, 581f anatomical, 537f nonanatomical, 536f, 572-578 shape of, 533 braided guide (core), 542f CS cannulation difficulties and, 555 with proximal curve, 558f-559f sheath for, 536f torque control and, 542f types of, 541f telescoping cannulation assist for, 526f Touhy-Borst valve, wire inserted through, 547f-548f types of Medtronic Attain Command 6250 series, 593f St. Jude, 596f vein perforation by, 524f vein selector and guide deploying through, 568 loading into, 571f Coronary sinus aneurysm, 587f Coronary sinus balloon venography, 788f

1059

Coronary sinus cannulation anchored balloon effect on, 697f braided guide (core) for, 565f catheter above proximal curve, 541f counterclockwise torque, effects of, 561f above CS, 540f below CS, 540f device combination for, 543f difficulties in, 556f anatomic variants, 555 balloon catheter, 563f downward sigmoid CS, 564f finding CS os, 555 small target veins, 567f stenotic CS, 564f tortuous initial segment, 561f valve preventing, 563f eustachian ridge/thebesian valve and assisting, 539f inhibiting, 539f process with contrast injection, 541-585 techniques for, 572 vein selector and guide of proximal target vein, 575f in tortuous vein, 570f vein selector failure and, 569f Coronary sinus defibrillation lead, 793 Coronary sinus fibrosis, 770f Coronary sinus lead positions in CRT, 789f radiography of positioning of, 782 Coronary sinus lead delivery system, 591f Coronary sinus os anatomy surrounding, 538, 538f contrast injection defining, 541-547, 544f-545f, 547f locating with contrast injection, 538-541 location of, 555, 559f high versus low CS, 559f variability of on anteroposterior projection, 543f high-to-low, 543f Coronary sinus vein balanced/anterior lateral patterns of, 558f cannulation of, 557f identification of, 556f midlateral/posterolateral patterns of, 557f Coronary sinus venogram balloon, 693 traction on, for cannulation, 693f-694f Coronary vein rupture of, 688f stent to straighten, 683f-684f Coronary venoplasty before and after, 522f, 684f coronary sinus and, 656-660 elements of, 662b equipment for, 693b left ventricular lead implantation and, 662-681 techniques for, 655-656 Coronary venous system active-fixation lead in, 135-136, 136f anatomy of, 547-554 basic patterns of, 554 LV lead fixation in, 135 Cost-effectiveness, of ICD therapy, 258-259 Coulomb, 176 Coulomb’s law, 3 Counterpressure, 757

1060

Index

Countertraction, 756-757, 757f CPS Universal Slitter, 597f Creatinine level, 622 Crista supraventricularis, 507 Crista terminalis, 505-506 Critical point formation of, 40 types of, 48 Cross-chamber blanking period, 60, 66 Cross-stimulation definition and cause of, 883-884 ECG rhythm strip showing, 883f Crosstalk, 127-128, 817-818 AV block and, 877f ECG rhythm strip showing, 877f factors promoting, 877, 877b inhibition of, 876-879 prevention of, 877-878 safety output pulse for, 878 safety pacing and, 878f Crosstalk sensing, 817 Crosstalk sequelae, prevention of, 878-879 Cross-ventricular endless-loop tachycardia, 976 CRT. See Cardiac resynchronization therapy (CRT) Cruzan v. Director, Missouri Department of Health case, 1040 Cumulative radiation, effects of, 1024 Current, 17-18 Current amplitude, 13 Current collector, in batteries, 176, 176f Current density, depolarization and, 10 Current of injury, 58 active lead fixation and, 476 at implantation, 61f Curved electrode/generator, 428, 429f Cutdown technique for axillary venous access, 462 for electrode placement, 456-457, 456f Cutter and telescoping hub guide, 582f-583f Cutting-balloon venoplasty focused-force venoplasty versus, 661-662 for stenotic target vein, 663f Cylindrical aluminum electrolytic, construction of, 187

D Daily life, electromagnetic interference and, 1011-1013 Damped sinusoidal monophasic waveform, 42 Danish multicenter randomized trials, 245 Danish study, 237 DDD atrial blanking period, 819f DDD-LV pacing, acute hemodynamics of, 435f DDD mode upper rate response, with Wenckebach AV block, 824f DDD pacemaker diagrammatic representation of function of, 817f intracardiac marker channel and, 65f DDD pacing atrial pacing versus, 243 clinical events in, 244t dual-chamber devices in, 816 indications for, 234 monoplane ventriculography during, 229f timing interval for, 816f two-lead electrocardiogram showing, 825f with ventricular-based lower rate timing, 828f

DDD refractory period, 818f DDD safety pacing window, 818f DDI pacing mode timing cycle in, 835-836, 836f VDI mode versus, 836 DDIR pacing mode, mode switching to, 830f DDD(R) pacing mode, 34 blanking and refractory period for, 65f managed ventricular pacing and AVB during exercise, 351f criteria for switching, 351f mode switching to, 833-834 mode switching to DDIR, 830f MVP versus, 317f DDD(R)-to-AAIR mode switching, 834f DDDR vs DDD, 156 Debridement of ICD pocket, 731f after lead extraction, 754 Decision-making process ethical principles underlying, 1042-1043 rights/responsibilities of clinicians, 1042-1043 participant support in family, 1045 health care provider, 1045 palliative care specialist, 1045-1046 psychiatric consultant, 1045 Defibrillation batteries and capacitor effect on, 189-190 causing refibrillation, 49-53 charge conduction/transmembrane potential changes in, 17-18 CIED patient undergoing, 1021-1022, 1022b direct depolarization/hyperpolarization, 10 dual-chamber versus ventricular pacing with, 247-249 effects of, 18 efficacy of, 43-44 electric (power-on) reset, 1009-1010 electric current flow, opposition to, 4 electric potential gradients/currents for, 10-11 gradient for, 11 membrane depolarization in, 22-23 minimum potential gradient requirement for, 44 monophasic versus biphasic stimulation, 26 postshock activation after failure of, 52f postshock cycles after failed and successful shocks, 51f after failure of, 50f principles of, 40-55 sawtooth model and, 45-46 sensing function, loss of, 875-876 strength-duration curve for, 375f strength-duration relationship for, 374 success of, 40, 42-53, 375f Defibrillation lead header, evolvement of, 733 Defibrillation system echocardiography and, 807 identification of, 771 radiography of, 771 Defibrillation testing at ICD implantation electroporation, 377-378 energy testing, 377-378 indications for, 377 as programming guide, 378 risks of, 378-379

Defibrillation threshold, 42, 498f, 710f amiodarone increasing, 907f azygos vein defibrillation coil for, 498-499 drugs and clinical conditions affecting, 375t high, interventional approach to, 711, 711f increase in, factors contributing to, 904-905, 905t patient with high, 379 management of, 380f phase maps for shock, 44f potential gradient value and, 44 RV electrode polarity influence on, 376t subcutaneous coil placement for, 717f subcutaneous defibrillation electrode for, 497-498, 498f for subcutaneous ICDs, 430f Defibrillator. See also Implantable cardioverterdefibrillator (ICD) battery chemistries in, 182-183 cutaway view of, 183f electric circuits of, 4 increased standards for, 734 pediatric pacing and, 393-427 power systems for, 175-190 voltage-time curve during shock by, 183f Defibrillator adapter, 735t Defibrillator code, 196-197 Defibrillator lead design of, 128-129 in large posterior lateral vein, 552f radiography of, 771-794 Defibrillators in Acute Myocardial Infarction Trial (DINAMIT) for ICD therapy, 269-270 criteria, comparison groups and results, 268t population details/mortality results, 269t Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, 257 ICD shocks and, 258 for ICD therapy, 268 criteria, comparison groups, and results, 264t population details/mortality results, 265t Defibrillators to Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) trial, 273-275, 275t Defibrillator therapy. See also Implantable cardioverter-defibrillator (ICD) therapy clinical trials of, 257-278 randomized controlled trials for, 261f Delayed afterdepolarization (DAD), 49 indications for CPVT, 385 Delayed AV coupling, 911 Delivered capacity lithium-iodine battery and, 181 resistance and voltage, relationship between, 180f Delivery catheter system, 437 Delivery guide angioplasty wire, loading on, 696f contrast staining from, 590f coronary sinus, advancing into, 517f CS access catheter and deploying through, 568 loading into, 571f definition of, 516, 523, 618 for lead placement, 525f advancing to target vein, 574f advantages and limitations of, 576f



Delivery guide (Continued) lumen size of, 568 Medtronic Attain over-the-wire 4194 pacing lead requirement for, 606f removal of, 572, 579f lead length and, 581f renal-shaped, with vein selector, 528f shape of, 523f new approach to, 526 previous approach to, 524-526 selection of, 568 supporting Quarter lead, 612f tip section, comparison of, 524-526, 526f-527f in tortuous vein, 570f types of comparison of, 597f Pressure Products, 595f St. Jude, 597f use of, 524-526, 524f Deltopectoral area, anatomy of, 502f Deltopectoral groove, 460 anatomy of, 456f needle and syringe trajectory, 462f subpectoral approach and, 502f superficial landmarks of, 461f view of incision perpendicular to, 461f Dental equipment, electromagnetic interference and, 1023-1024 Depolarization, 7-8. See also Direct depolarization; Rapid depolarization approaches to, 10 cardiac action potential and, 7 electrical stimulus and, 10 initiation of, 8 Ohm’s law and, 10 prevention of, 11 sensing of, 56 ventricular, recording of, 57-58 Detection, 56-126 of atrial tachycardia, 118f programming/troubleshooting for, 104-109 using subcutaneous electrocardiogram, 116-117 zones/zone boundaries for, 104-106 Detection algorithm, 56 Detection duration of ventricular fibrillation, 106-108 of ventricular tachycardia before ATP, 106 Device advisory notice. See Product advisory Device circuitry, EMI in, 1015 Device deactivation, 1040 clinical settings for, 1047 acute care hospital with electrophysiologic expertise, 1047 at home, 1047 inpatient facilities without electrophysiologic expertise, device deactivation and, 1047 consequences/uncertainties of, 1044-1045 end-of-life, preventing shock and ethical dilemmas in, 1043 ethical and legal principles of, 1040-1046 industry-employed allied professional, role of, 1047 logistics of, 1046-1047 overall goals of care and, 1043-1045 in pediatric patient, 1047-1048 rights/responsibilities of clinicians, 1042-1043

Index

Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE HF), 223, 292-293 Device implantation computed tomography and, 808 in D-transposition of great arteries after Mustard procedure, 802f fluoroscopy and venography of, 801-806 in infants and children, 798f interventional techniques for, 618-718 electrophysiologic versus, 618-619 special skill set, 619 morbidity and mortality rate, 619 preimplant preparation, 622b catheter manipulation/contrast injection, 622 room setup and table position, 622 preparation for, 622-625 Device malfunction communication after identification of, 1034 replacement rate for, 1028 Device performance definition of, 1029 factors affecting, 1028 surveillance of, 1031-1034 Device recall, 1033-1034 psychological impact of, 1038 Device registry for CIED performance, 1028-1029 National Cardiovascular Device Registry (NCDR), 1002 pacemaker and ICD malfunctions in, 1030f Device reliability definition of, 1029 role of, 1028 Device removed from service unrelated to malfunction, 1029 Device replacement elective or repair, 730-732 guidelines and techniques for, 730 surgical considerations for, 729-733 tools for, 737f venography and, 729 Device therapy, withholding, 1048 Dexamethasone-eluting reservoir, 133f Dextrocardia, 797 radiographic view of, 800f-801f DF-1 header standards, 197-198 DF-4 dual-coiled ICD header, 199f DF-4 dual-coiled ICD lead, 199f DF-4 header/lead technology, 197-198 DF-4 lead configuration, 735f Diagnostic radiation, electromagnetic interference and, 1021 Diaphragmatic myopotential, 77 oversensing of, 81f Diaphragmatic sensing, high-grade AV block and, 899f Diaphragmatic stimulation, 864 Diastolic dysfunction atrioventricular block and, 943-944 echocardiographic filling patterns of, 941f Diastolic function, 938 asynchronous activation effect on, 209-210 atrial pacing effect on, 953f electrocardiographic patterns of before/after preload reduction, 940-941 preload changes modifying, 940-941, 941f

1061

Diastolic function (Continued) increased contraction/relaxation times on, 941f loading conditions, effects of change in, 940f pacing rate change effect on, 942f pressure gradient and, 940f Diastolic interval (DI) action potential duration and, 41 fibrillation and, 41 Diathermy, 1018-1019 Dielectric, 4 Differential atrial sensing, 883 Differential atrioventricular interval (AVI), 818f, 820f Digoxin toxicity, 326 Dilated cardiomyopathy (DCM), 912 LBBB as cause of, 914 Dilator complications from, 648f directing glide wire, 628f exchanging, 626-627, 629f subclavian venoplasty versus, 646-655 “Dip” phenomenon, 23 Direct-current cardioversion and defibrillation, electromagnetic interference and, 1021-1022, 1022b Direct depolarization, defibrillation and, 10 Directed needle catheter, for total occlusion, 636f Direct electrical stimulation, 3 Direct His bundle pacing, 511 Direct needle puncture, 635 Direct traction, 755-756, 756f Discoordination, mechanical asynchrony versus, 222 Discrimination building blocks for, 85-88 of tachycardia atrial rate equal to ventricular rate, 96t atrial rate greater than ventricular rate, 97t Discriminator confirmation/redetection/episode termination by, 83-85 overriding, features for, 101-103 role of, 83-85 single-chamber versus dual chamber, 96 of tachycardia, 98f Disease-related biomedical factors, children with pacemakers and, 423 Distal conduction system, pharmacologic stress testing of, 328 Dog boning, 623 DOO pacing mode, 836 Doppler echocardiography, cardiac output examination/calculation with, 216 Doppler flow detection, for axillary venous access, 462-463, 463f Dotter snare, 761 Drain plot, load voltage versus, 177f Draping, for pacemaker implantation, 450-451, 451f Drawn brazed strand (DBS) method, of conductor design, 129f Drawn filled tube method, of conductor design, 129f Drift velocity, 18 Drug-induced bradycardia, 336 D-transposition of the great arteries, 797 device systems in, 802f pacemaker system in, 803f

1062

Index

Dual Chamber and Atrial Tachyarrhythmias and Adverse Events Study (DATAS) clinical events in, 248f purpose of, 248 Dual Chamber and VVI Implantable Defibrillator (DAVID) trial, 223-224 clinical endpoints in, 248t RVA pacing and, 350 RV pacing and, 725 with VVI backup pacing, 248 Dual-chamber building block atrial versus ventricular rate, 85 purpose/weaknesses of, 89t Dual-chamber DDD pacing, single-lead VDD pacing versus, 235 Dual-chamber discriminator, 96 Dual-chamber generator, longevity of, 397f Dual-chamber hysteresis, 835 Dual-chamber ICD atrial sensing in, 67 EMI and EAS in, 1006f sinus tachycardia during exercise with, 388f SVT-VT discrimination in, 95-96 Dual-chamber pacemaker crosstalk inhibition in, 876-879 DDD pacing and, 234 fusion avoidance algorithm for, 355 mode, rate, parameter change, cause of, 866, 866b noise reversion/electrical reset responses of, 1008t rate drop-responsive pacing with, 370 sensing system of, 56 Dual-chamber pacing mode advantages of, 234 atrial-single chamber pacing versus, clinical trials for, 243-247 chest radiograph of, 786f in children, features for, 401 in chronotropic incompetence, 235-236 contraindications for children, 399 cost-effectiveness of, 253 double-blind crossover studies for, 239-243 event markers for, 851 Medicare trial and, 239 pacemaker syndrome and atrioventricular dyssynchrony during, 228-229 postventricular atrial refractory period (PVARP) and, 401 randomized controlled trials for, 234 rate-adaptive ventricular pacing (VVIR) versus, 235t rate-modulated, laddergramming from, 853f rate response, with versus without, 236-237 runaway pacemaker in, 879 sick sinus syndrome, RCT for, 245 superiority of, 234 timing cycle in, 836 AOO, VOO, DOO modes, 836 DDI mode, 835-836, 836f VDD mode, 835, 836f VDI mode, 836 triggered versus inhibited mode, 235 upgrading to, 725 venous access for, 468b ventricular pacing versus, 238-243 in defibrillator patients, 247-249 ventricular pacing with rate response versus, 234-235

Dual-chamber pulse generator PVARP extension on PVE, 882f tracings for, 854f Dual-chamber rhythm classification, 96f Dual-chamber timing cycle, 816-825 Dual-chamber venous access, methods of, 468-469 Dual-coil intrathoracic defibrillator system, 419, 420f Dual-coil single-lead transvenous defibrillator system, 419, 421f Dual-sensor pacemaker justification for, 153f patient selection for, 154t principles guiding, 152 types of, 152-154, 153t DVI-committed mode (DVI-C), 878-879 Dynamic atrial overdrive (DAO) pacing algorithm, 310 Dynamic atrioventricular delay, 818 Dyspnea, acute decompensated heart failure and, 156-157 Dyssynchrony, occurrence of, 911

E Early afterdepolarization (EAD), 49 Early recurrence of atrial fibrillation (ERAF), 119f EasyTrak LV lead, 598-600 instability of, 602f phrenic pacing and, 601f target vein, before/after placement of, 601f types of, 600 Echocardiography CRT therapy, assessment of, 294-295 for native/lead vegetation diagnosis, 808, 808f for pacemaker and defibrillation systems, 807 for pericardial effusion and tamponade diagnosis, 807-808 Echocardiography Guided Cardiac Resynchronization Therapy (Echo-CRT), 291 Edema, venoplasty failure and, 660, 660f Education, for vasovagal syncope, 365 Effective pressure, of balloon, 625 Effective refractory period, 8 Efficacy of ICD in Patients with Non-Ischemic Systolic Heart Failure (DANISH) trial, 274-275, 275t ELA-Sorin dual-sensor pacemaker, 153t, 154 ELA-Sorin over-the-wire LV pacing lead, 600, 603f stylet-driven, 603f ELA-Sorin ventilation-sensing device, 149, 151 algorithm for, 155f tracings for, 151f Elective replacement indicator battery changes and, 846 in implantable pulse generators, 180 Elective replacement time (ERT), 846 Electric (power-on) reset, electromagnetic interference and, 1009-1010 contemporary ICDs, 1010t dual-chamber pacemakers set to DDDR, 1008t Electrical activation abnormal sequence of, 206 as asynchronous cardiac structure/function, 210 clinical consequences of, 217-218 reduced pump function, 210 in LBB block, 206 physiology of, 203-211

Electrical activation (Continued) of RV/LV during baseline LBBB and BIV pacing, 223f during sinus rhythm, 203-204 three-dimensional isochronic representation of, 204f Electrical charge movement, in wires and tissue, 18 Electrical defibrillation, ventricular fibrillation versus, 40 Electrical dyssynchrony (asynchrony), 134 Electrical energy, batteries and, 175 Electrical impedance, 177 Electrical insulator, 8 Electrical noise artifact, 901f Electrical remodeling, 158 Electrical resynchronization, 960f Electrical signal oversensing, 127-128 Electrical stimulus capture by, 10 depolarization and, 10 single-cell excitation by, 9-10 threshold for, 10 Electrical storm, 258 Electrical testing clinician, for pacemaker implantation, 444 Electric charge, 3 Electric circuit, of defibrillator, 4 Electric current, 3 opposition to flow of, 4 Electric field, 3, 1004 cardiomyocyte response to, 9f decrease in, 1011 stimulus threshold and, 10 strength/directionality of, 3 Electric field gradient depolarization and, 10 electric charge and, directed motion of, 17-18 Electric potential gradient/current membrane depolarization and, 22-23 for stimulation/defibrillation, 10-11 Electric power, electromagnetic interference and, 1013 Electrocardiogram (ECG) of acute myocardial infarction, 341f after aortic valve surgery and AF, 327f atrioventricular pacing and, 216f AV conduction, P-R interval prolongation, RBBB, 327f of bipolar pacing system, 868f DDD pacing and, 825f electrode placement for, 56 for Long QT Syndrome, 383 LV/RV capture and, 923-925 from sick sinus syndrome, 394f simultaneous, rhythm strip and event markers, 848f surface versus intracardiac, 56 Electrocardiogram (ECG) tracing endless-loop tachycardia on, 882f with event marker legend, 852f functional noncapture and, 871f latency showing on, 874f of pacemaker programmed to VVI demand rate of 50 bpm, 869f demand rate of 60 bpm, 869f pseudofusion beats in, 875f pseudo-ventricular tachycardia on, 879f



Electrocardiogram (ECG) tracing (Continued) from pulse generator beyond elective replacement interval, 872f rhythms on different systems, 865f safety pacing on, 878f ventricular pacing on, 864-865, 864f Electrocautery for battery change, 730 contraindications for, 480 electromagnetic interference and, 1019 for pacemaker implantation, 446 Electrocoagulation, 1019 Electroconvulsive therapy (ECT), 1018 Electrode atrial, placement of, 474-476, 489f in bipolar pacing, 23 collagenous capsule around, 26f corrosion of, 23 as curved, 428, 429f design of fixation mechanism, 31 location, 32 materials for, 31 spatial/size relationship between pairs of, 31 electrical characteristics of, 410-411 epicardial, placement of, 478 features affecting performance, 26-28 geometric surface area of, 26-27 for ICD implantation, 494f in ICD lead, 138-139 ideal versus non-ideal, 22 for implantable leadless pacing system, 437 implantation of, 456-457, 456f increasing size, effects of, 56-57 longevity of, 397f microporous surfaces of, 27f, 30 in pacing leads design of, 131, 131f-132f implantation reaction from, 132-133 placement of, 403f for atrial endocardial electrogram, 61f for electrocardiogram, 56 with pores, 27 collagen formation, 30 repositioning of, 487 shock parameters and, 43 for single-chamber ventricular pacing, 398-399 size versus sensing performance of, 27-28 steroid-eluting, 30-31 strength-duration curve for, 411f surface area of maximizing, 27 porous versus microporous, 30 ventricular, placement of, 470-474, 489f virtual description of, 11 importance of, 11 occurrence of, 11 Electrode-electrolyte interface, 16 circuit representation of, 19f processes of, 21-22 reactance and charge movement at, 17 Electrode-myocardium interface EMI causing damage to, 1010 mechanical instability at, 31 Electrode polarity, 4 Electrode polarization, 18f Electrodessication, 1019

Index

Electrode system for subcutaneous ICDs, 121f types of, 56 Electrode-tissue interface capacitance at, relationship to polarization voltage, 21-22 Helmholtz capacitance and, 16 impedance at, 16-17 micrograph of, 30f Electrofulguration, 1019 Electrogram (EGM), 56-60 amplitude and slew rate of, 58 AV resynchronization, analysis for, 950f clinical descriptors of, 60f elements of, 852 pacemakers storing, 854 peak-to-peak amplitude measurements of, 853-854 recording of, 57f sensing occurrence in, 62f sinus rhythm with PVC, 890f tracings with event markers, 852f ventricular fibrillation, variability during, 63f Electrogram telemetry, 852-854 limitations of, 854 qualitative versus quantitative, 854 Electrogram truncation, 90, 92f Electrolyte, 4 batteries and, 175-176, 176f Electrolytic capacitor, 189 Electromagnetic compatibility, 1004 Electromagnetic field, 1004 types in MRI, 1014-1015 Electromagnetic interface (EMI), 56 minimizing, 827 Electromagnetic interference (EMI) CIEDs and, 1004-1027 definition and risk factors for, 1004 diagnosis of, 1006 dual-chamber ICD shock caused by, 1009f electronic article surveillance and, 1006f electrosurgery and, 1020 electric (power-on) reset, 1009-1010 generation, 1018-1021 management of, 1020, 1020b factors influencing, 1011b frequency of, 1004 knowledge of, 1005-1006 testing protocols, 1006 in vitro testing, 1006 in vivo testing, 1006 pacemaker and ICD response to, 1006-1011 communication inhibition, 1010 determinants of, 1010-1011 electric (power-on) reset, 1009-1010 electrode-myocardium interface damage, 1010 mode switching, 1007-1008, 1007f noise reversion/asynchronous pacing/electrical reset responses of, 1010t noise reversion/electrical reset responses of, 1008t noise reversion mode, 1008-1009 pacing interference, 1006-1011 rapid/premature pacing, 1007-1008 reed switch closure, 1010 spurious tachyarrhythmia detection, 1008 sources of, 1004-1005, 1005b acoustic radiation, 1005

1063

Electromagnetic interference (Continued) conducted, 1004 in daily life, 1011-1013 ionizing radiation as, 1004-1005 medical equipment and, 1021-1024 radiated, 1004 in working environment, 1014 Electromagnetic interference, causes of, 871t Electromagnetic spectrum, 1005f Electromechanical order, 911 Electromechanics, LBBB effect on, 916f Electromotive, 3 Electron charge of, 3 flow of, 3 Electron drift current, 18 Electron flow, ion flow versus, 18 Electronic article surveillance, 1006f Electronic article surveillance device, 1012-1013 Electrophysiologic study (EPS), 331t of atrioventricular conduction system disturbances, 327-328 limitations of, 328-329 usefulness of, 328 Electrophysiology (EP) catheter extravasation of contrast from from trauma, 588, 588f Electrophysiology laboratory testing, investigational sensor during, 122f Electroporation, 44-45 risk of, 377-378 Electrosection, 1019 Electrosurgery, electromagnetic interference and electric (power-on) reset and, 1009-1010 generation of, 1018-1021 management of, 1020, 1020b Electrosurgical dissection sheath (EDS), 759-760, 759f EMPIRIC study, 380 Empty heart syndrome, 361 Encapsulation, in leads, 748f Endless-loop tachycardia (ELT), 829-830 cross-ventricular, 976 detection and termination of, 883, 883f ECG rhythm strip showing, 882f initiation of, 881f occurrence of, 880-883 overview of, 881b prevention of, 881-883 rate of, 881 Endocardial activation, total, 208f Endocardial approach, for ICD implantation, 495 pectoral pocket for, 500-501 Endocardial bipolar lead, 872f Endocardial CRT, 435f Endocardial electrode system bipolar electrodes for, 404f in congenital heart disease, 487f at corrective cardiac surgery, 487 implantation technique for, 409-410 after atrial switch operation, 412f axillary vein approach, 410 transcutaneous pacing, 409-410 venous angiography, 410 longevity of, 397f long-term pulse-width thresholds for, 404f pediatric pacing and, 402-404, 402f types of, 406-408

1064

Index

Endocardial electrode system (Continued) acute thresholds for, 408f distribution of use, 407f Endocardial electrogram, 58f Endocardial lead placement alternatives to, 487-490 during thoracotomy, 487f-488f Endocardial LV stimulation, leadless pacing and, 434 Endocardial pacemaker, implantation of, in child, 402f Endocardial pacing contraindications to, 404b in right ventricular apex, 498f Endocardial stimulation, current amplitude/voltage for, 13 Endocardial unipolar lead, 872f Endocytosis, 29f End-of-life improving communication about, 1046 preventing shock and ethical dilemmas in, 1043 End of service (EOS), 846 ENDOTAK transvenous endocardial pace and shock electrode, 495, 495f Energy, 13-14, 13f joule as, 176 storage of, 21 Energy density, 176-177 for capacitors, 187 Energy output, generator and, 399 Enoxaparin, bolus dosing of, 725 Environment stress cracking cause of, 130f polyurethane degradation and, 130 Epicardial active-fixation steroid-eluting lead, 135f Epicardial approach, to ICD implantation, 493-495, 493f Epicardial CRT, acute hemodynamics of, 435f Epicardial defibrillation patch, 419, 420f Epicardial electrode system implantation technique for, 409 left thoracotomy approach, 409 median sternotomy approach, 409 subxiphoid approach, 409 longevity of, 397f long-term pulse-width thresholds for, 404f pediatric pacing and, 402-404 changes in, 402f placement of, 478 approaches to, 478 indications for, 478 types of, 405-406, 405f as unipolar or bipolar, 56 Epicardial lead, 782 Epicardial LV lead placement. See Surgical epicardial LV lead placement Epicardial LV pacing lead, as unipolar or bipolar, 920 Epicardial permanent pacemaker implantation approach, 453 Epicardial RA/RV pacing lead, radiography of, 790f Epimyocardial electrode, 405-406 Epinephrine, 33 Episode termination, 83-85 Eroding device, 736-737 Erosion, 736, 745f cause of, 745f of leads through implant pocket, 745f

Erythema, 744f ESTEEM-CRT trial, 291 Ethical issues, in device deactivation, 1040-1046 European Society of Cardiology (ESC), pacing mode selection guidelines, 253-254 Event counter telemetry histogram for, 856f information provided by, 858 limitations of, 858 objective of, 854-858 types of subsystem performance counter, 856-858 time-based system performance counter, 858 total system performance counter, 855-856 Event detection phase, of sensing, 117 Event marker, 848f annotations for, formerly used, 850-851, 851f displays for, 850-851 for dual-chamber pacing, 851 limitations of, 851-852 single-chamber pacing with, 851 surface ECG and, 850f telemetry for, 849-852 Event marker legend, ECG and EGM tracings with, 852f Event notification. See Home monitoring Event record display, 859f Evoked response, 34 automatic sensing of, 79 postpacing polarization artifact and, 83f Evolution sheath, 760, 760f Excimer laser sheath, 758-761, 758f Excitable gap, 41-42 Excitation. See also Cardiac excitation types of, 12f Excitation-contraction (E-C) coupling, 204, 204f-205f Exercise Atrioventricular delay interval and, 215f DDDR vs DDD pacing modes, 236 dyssynchronous activation effect on, 209 heart contractility and, 150 identification of, 151 heart failure and, 144 heart rate and, 144 in children, 400f-401f hemodynamics of, 825-827 sinus tachycardia during, 388f Exercise-induced transient AV block, 336 Exercise testing acute intermittent loss of capture during, 418f ECG recording, 416f multiblock development and syncope, 417f pacemaker follow-up in children, 413-414 strength-duration curve for, 419f change with time, 419f using treadmill, 153f Exercise test report, 860f Exertion response programming, 147 Exit block, children experiencing, 35 Exocytosis, 29f Extended bipolar ventricular electrogram, 86f-87f Extension of refractoriness hypothesis, 48 External defibrillator, 42 External electromagnetic interference, 74-75 cause of electric drill, 76f electroconvulsive therapy, 76f

External jugular vein, 454 Extracardiac signal, 74-77 Extracardiac stimulation, 864 causes of, 864b Extracellular space, 45-46 Extracorporeal shock wave lithotripsy (ESWL) effects of, 1023 indications for, 1023 Extra support wire, 516 definition of, 618 Extrinsic deflection, 852

F Failure to capture, 868-869, 872-874 Fallback response, heart rate and, 832 Family, supporting in decision-making process, 1045 Faraday, Michael, 21 Faradic current flow, 21 Far-field QRS wave, 862f Far-field R wave (FFRW), 57-58 oversensing, 74 minimizing, 62 prevention of, 67-68 postventricular atrial blanking/rejection of, 67-68 rejection of by atrial sensing features, 71f by Medtronic ICD, 68 by pattern analysis, 70f Femoral vein, lead extraction through, 766-767 Fibrillation action potential and, 41 diastolic interval (DI) and, 41 heart, mechanical activity of, 40 stages of, 40, 41f Fibrosis coronary sinus, 770f from encapsulated lead, 749f lead extraction and, 748f-749f Finger photoplethysmography (FPPG), 947-948 optimizing AV resynchronization and, 949f Firmware, 1029 First-degree AV block, 329 First-generation locking stylet, 760-761, 760f First-generation multisite pacing pulse generator, 922 First Multicenter Automatic Defibrillator Implantation Trial (MADIT-I) for ICD therapy, 263 criteria, comparison groups and results, 262t population details/mortality results, 262t Fishhook electrode, 405 acute implantation voltage and current threshold for, 406f threshold for, 406, 406f-407f Five-position ICHD pacemaker code, 195, 196t, 813 pacing modes described by, 197t Fixation mechanism, 133 Fixed conduction block anterior zone interaction of, 958f cause of, 952-953, 954f characteristics of, 953 implications of, 954 Fixed-rate ventricular pacing, 234 Fixed-rate ventricular single-chamber pacing (VVI), rate-adaptive ventricular pacing versus, 234, 235t



Flow of electrons, 3 Fluctuance, 744f Fludrocortisone acetate, for vasovagal syncope, 366 Flunarizine, 49 Fluoroscopy device implantation and, 801-806 for pacing system malfunction, 867-868 Flux density, 1004 Focused-force venoplasty, 618 of collaterals between veins, 663f cutting-balloon venoplasty versus, 661-662 for elastic obstruction, 654f Kevlar balloon and, 652-653 to resolve focal obstruction, 653f Fontan procedure, 393, 398 for congenital heart disease, 797 Footprint number, 159, 160f Formule fondamentale, 13 Frank-Starling relation, 205 failing ventricle and, 940f FREEDOM trial, 225-226 Frontrunner XP CTO Catheter, 632, 633f Functional atrial undersensing, 968 Functional conduction block, 952-953 implications of, 954 line of correlation with regional mechanical delay, 956f during LBBB activation, 955f manipulation during BiV pacing, 955f LV pacing and, 954 physiologic basis of, 954 Functional mitral regurgitation, 921f reduction in, 918-920, 920f Functional noncapture, 870-871 cause of, 873, 884f ECG rhythm strip showing, 871f Functional oversensing, 870-871 Functional undersensing, 874-875 “Funny” current, 7

G Gadolinium contrast agent, 621 Galvanometer, 13 Gap junction, 8-9, 45-46 General endotracheal anesthesia, 754 Generator characteristics of, 399-400 as curved, 428, 429f features for, 399-401 selection of, 396 single-chamber versus dual chamber, 399f survival curve for, 396f Generator mode selection, 396-399 Gene therapy approach, to biologic pacemaker, 191-193 Global Utilization of Streptokinase and TissueType Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial, 342-343 Glucocorticoid pacing thresholds, effect on evolution of, 31 stimulation threshold, effect on, 33 Gooseneck snare to control distal end of wire antegrade approach, 699f retrograde approach, 698f into sheath/out of hub, 700f view of, 698f

Index

Gouy-Chapman model, 20 Gouy-Chapman-Stern model, 20 Gravitational field, 3 Great arterial switch procedure, 804f Guardian device, 170 recordings from, 170f Guidant Endotak ICD lead, pseudofracture of, 797f Guidant Model 1831 ICD, 901f Guide support-based delivery system, 516-617. See also Left ventricular lead implantation components of, 523-524 indications for, 522-523 limitations of, 516 use of, 516 Glide wire, dilator directing, 628f

H Harvey, William, 8 HCN4 protein, 303f Health care provider children with pacemakers and implications for, 423 provider-family interactions, 424 decision-making process, participant support in, 1045 Heart anatomy of, 506f spatial relationships and, 456, 456f axial section of, 510f left anterior oblique (LAO) of, 507, 508f right anterior oblique (RAO) of, 507, 508f sections of, 507 Heart block. See also Complete heart block; Surgically induced heart block cause of, 334 congestive heart failure and, 212 development of, 394 effects of, 211-212 radiation therapy/chemotherapy and, 335 ventricular rates at rest in, 212f ventricular septal defect (VSD) and, 394 Heart contractility, exercise and, 150-151 Heart failure. See also Acute decompensated heart failure (ADHF); Congestive heart failure; Impedance AEG, VEG, and aortic pressure tracing in, 217f brain natriuretic peptide and, 167f cardiac resynchronization therapy (CRT) and, 296-297 cause of, 279 contact/noncontact mapping in, 207f detection of, 159-160 event notification for, 999, 1000f-1001f exercise and, 144 heart rate versus, 223-224 history and frequency of, 172f ICD therapy clinical trials for, 264-270 criteria, comparison groups and results, 264t pooled analysis of, 268 population details/mortality results, 265t map of RV and LV activation, 220f MID-Heft Study data and, 166f minute ventilation predicting, 169-170 monitoring of accelerometer, 159f pathologic changes, 158 physiologic changes, 158 mortality from, 161f

1065

Heart failure (Continued) OptiVol and, 166-167 level changes in, 165f prevention of, clinical trials for Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADITCRT), 289-290 Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), 289 QRS delay and, 279 right ventricular pressure and, 161-162 sensors for, 158-170 activity monitoring, 159 heart rate variability, 159-160 monitoring, 156-171 types of, 158t transseptal time, total endocardial activation time, total QRS duration in, 208f ventricular asynchrony and, factors contributing to, 914 ventricular pacing and, 315-316, 315f “physiologic” pacing modes versus, 239 Heart failure hospitalization incidence of, 279, 999 randomized controlled trials for, 245f survival versus death with AT/AF vs no AT/AF, 973f HeartNet, 1033 HeartPOD LA pressure monitoring device, 163 Heart rate age and, 156 change, cause of, 866b drug therapy and mortality rate with changes in, 224f exercise and, 144 in children, 400f-401f fallback response for, 832 heart failure versus, 223-224 hemodynamics of, 825-827 histogram for, 856f myocardial perfusion and, 207-208 physiologic effects of, 211-219 rate-drop response to, 832, 833f sensor-indicated histogram for, 857f smoothing algorithms for, 832, 832f Heart rate variability footprint number and, 160f heart failure and, 159-160 Heart Rhythm Society (HRS) ICD and CRT implantation guidelines by, 491-492 pacemaker codes by, 195 Task Force on Lead Performance Policies and Guidelines, 1031 Helmholtz capacitance, 4 concept of, 22 decay of, 19, 19f electrode-tissue interface and, 16 pacing configuration of, 19f Helmholtz capacitor, 4 Helmholtz double layer capacitance effect of, 20 structure of, 21f Hemodialysis, 622 Hemodynamic Guided Home Self-Therapy in Severe Heart Failure Patients trial, 163, 296

1066

Index

Hemodynamic monitoring invasive finger photoplethysmography, 947-948 for optimal AV resynchronization, 947, 947f noninvasive, 947-948 Hemodynamic sensor for ICD, 121 investigational ICD, stored EMG and pressure tracing from, 123f Hemofiltration, 622 Hemothorax chest radiograph of, 806f in CIED implantation, 742-743 as postimplantation complication, 806 Heparin, bolus dosing of, 725 High defibrillation threshold management of, 380f transvenous ICD system and, 793, 795f-796f High-energy defibrillation lead header, evolvement of, 733 High-grade AV block acute myocardial infarction and, 340f BBB after recovery, 343 definition of, 330 diaphragmatic sensing in, 899f rhythm strip of, 330f, 337f High-intensity headlamps, for pacemaker implantation, 446f High osmolar contrast agent, 621 High-power battery, safety concerns with, 184-185 High right ventricular septal, 218 High-voltage coil, for ICD lead, 138-139, 138f High-voltage lead pin configuration, 725f His bundle capture, criteria for, 511 His bundle electrogram (HBE), 343, 343f His bundle pacing indications for, 218 radiography of, 787f His-Purkinje system AV block in, 325 atropine, 326f intracardiac tracing for, 326f Holter recording, of atrial fibrillation, 117f Holt-Oram syndrome, 332-333 Homburg Biventricular Pacing Evaluation (HOBIPACE) study, right ventricular versus biventricular pacing, 252 Home monitoring, 989 data transmission for speed/time for, 991f early detection with, 993f event notification for, 991f arrhythmia, 999 for atrial fibrillation, 994f generator malfunction, 996f heart failure, 999 heart failure diagnostics, 1000f-1001f lead fracture, 995f lead function, 998f follow-ups for, 998 Hook vein selector, 573f, 576f Hospitalization. See also Heart failure hospitalization acute decompensated heart failure and, 167f for atrial fibrillation, 307f Hydration fluid protocol for, 620-621 types of

Hydration fluid (Continued) hypotonic saline, 620 isotonic saline, 620 sodium bicarbonate, 620 Hydrophilic wire/catheter and balloons, 517, 618 Hyperglycemia, 33 Hyperkalemia, stimulation threshold, effect on, 33 Hyperpolarization, 9f defibrillation and, 10 Hyperpolarization-activated cyclic nucleotide (HCN), 439 Hypertension, ventricular remodeling and, 211 Hypertrophic cardiomyopathy (HCM), 271 oversensing in, 898f-899f pacemaker implantation and, 396 R wave versus T wave, 897 Hypertrophic obstructive cardiomyopathy during AAI pacing, 229f pacing in, 229 Hypothyroidism, 33 Hypotonic saline, 620 Hysteresis rate, 815, 815f atrial periods and, 815-816 dual-chamber and search, 835

I ICD capsule, scar tissue debridement in, 731f ICD header DF-4 dual-coiled, 199f standard IS-1/DF-1 dual coiled, 199f ICD-induced proarrhythmia, 892b ICD lead adapters for, 734-735 body uniformity, 141f connector terminals for, 139-140 defibrillation threshold for, 728 development of, 136-142 DF-4 dual-coiled, 199f electrodes and high-voltage coils for, 138-139, 138f engineering and construction of, 127-143 evolution of, 136-137 evolvement of, 733 extraction of, 140-141, 140f failure of, 141-142 shock coil ingrowth, 141f signs and symptoms of, 142b failure rate of, 897 insulation for, 139 interchangeability of, 724, 724f upgrade to adapter, 724f pacing/sensing capabilities for, 727-728 perforation of, 743f performance of, 429f placement of, 793-794 on anteroseptal wall of RV outflow tract, 794f positioning in tetralogy of Fallot with persistent left superior vena cava, 804f pseudodiscontinuity of, 793-794 pseudofracture of, 793f recent developments in, 140-141 sensing design for, 137-138 special issues for, 722-723 standard IS-1/DF-1 dual coiled, 198f structure of, 137, 137f study results of, 1031f survival rate of, 428 ICD lead adapter, 736f

ICD lead connector, 743f ICD pocket, debridement of, 731f-732f ICD. See Implantable cardioverter-defibrillator (ICD) ICD shock, 258 ICHD (Inner-Society Commission for Heart Disease Resources) five-position pacemaker code by, 195 pacing modes described by, 197t three-position pacemaker code by, 195, 196t modification to, 195 pacing modes described by, 196t Iliac venous access, 482-483, 483f Iloprost, 622 Immediate Risk-Stratification Improves Survival Study (IRIS) for ICD therapy, 270 criteria, comparison groups, and results, 268t population details/mortality results, 269t Impedance battery consumption, optimizing for minimum, 22 definition of, 17, 846-847 in extracellular electrolyte, 22-23 insulation defect and, 16 intracardiac, 168-169 intrathoracic, 164-168 pacing, effects of, 25f after lead implantation, 29 Medtronic Model 5880A, 24f principle of, 146 unipolar ventricular impedance and, 168 value measure by all vectors, 168f Implantable cardiac rhythm management device batteries in average versus instantaneous current drain, 178 design requirements for, 178 power requirements for, 178 pulse amplitude on pacing current, effect of, 179 pulse width on pacing current, effect of, 179, 179f shape, size, and mass constraints, 178 size, energy density, and current drain, 178 Implantable cardioverter-defibrillator (ICD), 117, 428-433, 499-500. See also Defibrillator; Subcutaneous ICD advisories for, 1033-1034, 1034f antiarrhythmia drugs effect on, 906b atrial/ventricular signals in EGM, 892f-893f automatic optimization of, detection algorithm for, 77-79 automatic sensitivity adjustment of, 67f batteries used in, 183-184 lithium-layered silver vanadium oxide-carbon monofluoride, 184 lithium-manganese dioxide, 184 lithium-silver vanadium oxide (LiSVO), 183-184 blanking and refractory period for, 61 capacitors used in, 187 construction of, 187-188 in children, 417 follow-up procedures for, 420-421 implantation approaches, 418-419 patient selection for, 417-418 programming considerations for, 419-420



Implantable cardioverter-defibrillator (Continued) psychosocial adjustment, 424-425 support groups for, 425 complications from device defects, 387 implantation, 387 inappropriate shocks, 387, 389f infection, 387 major versus minor, 749b never used device, 387-389 reoperation, 725 strategies to avoid, 389-390, 390t design of, implications of, 190 detection algorithm for, 84f electromagnetic interference and communication inhibition, 1010 determinants of, 1010-1011 electric (power-on) reset, 1009-1010 electrode-myocardium interface damage, 1010 mode switching, 1007-1008, 1007f noise reversion mode, 1008-1009 pacing interference, 1006-1011 rapid/premature pacing, 1007-1008 reed switch closure, 1010 shock by, 1009f spurious tachyarrhythmia detection, 1008 electromotive force for, 3 endocardial electrogram configuration for, 58f equipment for, 730f evolvement of, 889 extraction complications for, 429t follow-up for interventions for, interval/unscheduled, 738 noncompliance of, 729f header configurations for, 734f hemodynamic sensors for, 121 history of, 443 identification of, 863 implantation of approaches to, 493-495, 493f complications from, 1037t considerations for, 493 cosmetic approach, 503, 504f equipment for, 492-493, 493b indications for, 999 leads and electrodes for, 494f location for, 492-493 parts of, 492 personnel for, 491-493, 491b submuscular pouch for, 501-503, 502f techniques for, 490-491 with unipolar pacemaker, 905f implanted loop memory event recorder capability in, 855-856 inactivation of, 111 intervention for acute problems, 737-738 interventions for, interval/unscheduled, 738 longevity of, 179-180 malfunction of, 1028 annual number, 1028, 1029f-1030f mechanisms of, 1028-1029 registries of, 1030t MRI and, 809 neurostimulators and, 1018 noise reversion/asynchronous pacing/electrical reset responses of, 1010t oversensing in, 722, 722f

Index

Implantable cardioverter-defibrillator (Continued) correction of, 897 pacing algorithms in, 841-842 pacing problems with, 907-908, 908t P and R wave, sensing of, 60f performance of, 1028-1034 permanent cardiac pacemaker and, 443-515 pocket creation for, 496-503 abdominal, 496, 496f subcutaneous versus submuscular, 496t postimplant testing arrhythmia detection, 377 defibrillation testing, 377-379 pacing thresholds, 377 of tachyarrhythmia therapy, 379-380 power systems for, 175-190 product advisories for, 1028 programming recommendations for, 380, 381t radiation oncology center protocols for, 1024 radiography of, 773f-775f rate detection zones for, 88f removal from service, classification of, 1031-1032, 1032f replacement of, 729-733 resynchronization devices as, 279 selective site pacing for, 503-512, 505f sense amplifier, diagram for, 64f sensitivity, automatic adjustment of, 64 subcutaneous defibrillation electrode in, 497-498, 498f for sudden death prevention, 328 truncated exponential biphasic waveforms and, 42 tunneling and, 496-497 VT/VF detection failure by, 906-907 withholding therapy, 1048 Implantable cardioverter-defibrillator (ICD) malfunction clinical history of, 889 electrocardiography recordings and, 889 lead problems causing, 891 physical examination for, 889 radiographic evidence of, 891-892 remote telemetry for determining, 891 telemetry for, 889-891 troubleshooting of, 889-910 principles of, 889-892 ventricular fibrillation, failure to detect, 900f Implantable cardioverter-defibrillator (ICD) pulse generator older models of, 733f performance of, 1028 radiography of, 771, 778f-779f replacement of, 719 indications for, 720-721, 720b, 723-725 invasive evaluation for, 727-729, 729f noninvasive evaluation for, 719-729 reoperation, factors to reduce need for, 720b risks of, 1036 special considerations for, 719 tools for, 735-736, 735b, 737f Implantable cardioverter-defibrillator (ICD) therapy. See also specific trial names for ACC/AHA recommendations for, 273t for cardiac channelopathies, 383-392, 386t complications from, 387-390 for cardiac sarcoidosis, 271

1067

Implantable cardioverter-defibrillator therapy (Continued) clinical trials of, 257-278 assessing mortality, 275t contraindications for, 274t cost-effectiveness of, 275 efficacy: randomized trials, review of, 261-273 evolution of, 257, 260-261 growth of use of, 258f guidelines for, 273 for heart failure or LV dysfunction clinical trials of, 264-270 criteria, comparison groups and results, 264t pooled analysis of clinical trials, 268 population details/mortality results, 265t for hypertrophic cardiomyopathy, 271 indications for, 274t limitations of cost-effectiveness of, 258-259 reliability, 258 shocks, 258 utilization, 259 nonrandomized studies of, 270-271 primary versus secondary prevention in, 259 problems with, 905 prophylactic catheter ablation reducing, 904 quality of life and, clinical trials for, 257 risk assessment for, 275 for spontaneous/inducible ventricular arrhythmias, 261-264 criteria, comparison groups and results, 262t pooled analysis of clinical trials, 263 population details/mortality results, 262t Implantable device imaging of, 771-810 timing cycles of, 813-843 Implantable hemodynamic monitor (IHM) system, 162f, 296 Implantable leadless pacing system development of, 437-439 infection risk in, 438 intracardiac electrode for, 438f pulse generator for, 438f sensed signal, transmission of, 439 ultrasound transmission/focusing in, 439f Implantable loop recorder (ILR), 116 atrial fibrillation detection algorithm by, 120f radiography of, 771 stored EGM recording by, 119f nonsustained tachycardia, 120f types of, 780f Implantable pulse generator (IPG), 127 elective replacement indicator in, 180 Implantable sensor characteristics of, 144-146 chronotropic incompetence, in patients with, 154f classification of, 144-146, 146t technical, 145-146 for heart failure monitoring, 156-171 performance of, 146t for rate adaptation/hemodynamic monitoring, 144-174 role of, 144 Implantable subcutaneous monitoring, 116 Implanted loop memory event recorder, 855-856 Implant table, for CRT, 623f

1068

Index

Implied total atrial refractory period, interventricular refractory period and, 970f Impress Azygous Left (JL-3.5) catheter, 712f Indirect traction, 756 Inducible ventricular arrhythmia ICD therapy clinical trials for, 261-264 criteria, comparison groups and results, 262t population details/mortality results, 262t Inductance, 4-5 sine-wave voltage and, 17 Induction technology, 439 Inductive reactance, 5 capacitive reactance versus, 17 Industry-employed allied professional, role of, 1047 Infants device systems in, 798f transvenous permanent pacemaker implantation approach in, 485-486 Infarction ventricular remodeling and, 211 Infection CIED implantation and bacteriology of, 744-746 erosion and, 745f erythema and fluctuance, 744f fat necrosis, 745f incidence of, 744-746 management of, 746 presentation of, 744 prevention of, 744 purulent discharge, 745f risk factors for, 744 lead extraction for, 747-749 pacemaker implantation and, 444 antibiotic prophylaxis/wound irrigation, 452-453 antimicrobial irrigation protocols, 453t Infectious disease, complete heart block (CHB) and, 335 Inferior vena cava, pacemaker and generator lead insertion through, 489, 489f Inflammation exit block and, 35 lead implantation and, 29 Informed consent, for lead extraction, 754 Informed refusal, 1040 Infraclavicular pocket, 483f Infraclavicular space, musculoskeletal anatomy of, 458f Inherited AV conduction system disease, 332-333 Inhibition of Unnecessary RV Pacing with AVSH in ICDs (INTRINSIC-RV), 272 Injury. See Current of injury Inner-Society Commission for Heart Disease Resources (ICHD) five-position pacemaker code by, 195 pacing modes described by, 197t three-position pacemaker code by, 195, 196t modification to, 195 pacing modes described by, 196t Inotropy Controlled Pacing in Vasovagal Syncope (INVASY), 371 Inpatient facilities without electrophysiologic expertise, device deactivation and, 1047 Inpatient pacemaker implantation, 448-449 In-person monitoring, for CIEDs, 987

Instrument table custom-built, 529-530, 531f positioning for LV lead implantation, 529-530, 531f Insulation in pacing leads, 130-131 defect in, 16 recent developments in, 130 Integrated bipolar electrode system, 56 Integrated sliceable hemostatic hub technology for CS access catheter removal, 581f example of, 582f Intensified follow-up indicator, 846 Interatrial conduction time (IACT), 348 QuickOpt for estimating, 966f SmartDelay and, 966 Interface, between ion drift current and electron drift current, 18 Inter/intraventricular resynchronization, cardiac function improvement with, 280t Internal jugular vein, 454-455 International Study on Syncope of Uncertain Etiology, 369 Interpenetrating domains, 18 InterVA, 918f Interventricular asynchrony, 221 Interventricular conduction delay, 917 Interventricular decoupling, 912 Interventricular dyssynchrony, 912 Interventricular interval timing cycle, 965f Interventricular refractory period, 968 role of, 970f Interventricular timing (VV timing) automatic adjustment of QuickOpt, 966-968 SmartDelay optimization, 963-968 considerations for, 952-968 semi-automatic adjustment of, 968 Interventricular timing delay, 837-838 Intra-atrial electrogram, 876f Intracardiac electrocardiogram (ICEGM), of intrinsic beats and PVC, 876f Intracardiac electrogram (IEGM), 56 as pacemaker follow-up in children, 413 in DDD mode, 414f with left atrial pacing, 414f from unipolar atrial lead, 869f Intracardiac electrogram determination, 413 Intracardiac impedance, 168-169 intrathoracic impedance versus, 169t Intracardiac marker channel, 65f Intracardiac pacemaker, implantation procedure for, 435f Intracardiac shunting, 403 Intracardiac signal, ventricular oversensing and, 69-74 Intracardiac ventricular electrogram, 146 Intracellular calcium “sinkhole”, 49, 52f Intracellular space, 45-46 Intradevice interaction, 111-112 VT detection failure by, 113f Intra-Hisian block, 323 Intramyocardial electrode, 405 Intraprocedural complication, 747 Intrathoracic impedance advantages and limitations of, 168 algorithm performance for validation data set, 166f

Intrathoracic impedance (Continued) intracardiac impedance versus, 169t measurement of, 164f for pulmonary fluid status clinical outcome studies for, 165-167 device description, 164 feasibility studies for, 165 monitoring of, 165f variation in, 169f Intrathoracic subclavian vein puncture, anatomic orientation of safety zone for, 459f IntraVA, 918f Intraventricular asynchrony, 221 Intraventricular conduction system, 203 Intraventricular delay interval, 226 Intrinsic atrioventricular interval (iAVI), 911 definition of, 964 Intrinsic beat, ICEGM and surface ECG of, 876f Intrinsic deflection recording of, 56-57 slew rate and, 56 Introducer set, 457, 457f Invasive hemodynamic monitoring finger photoplethysmography and, 947-948 for optimal AV resynchronization, 947 Investigational ICD, 123f Iodinated contrast media. See also Contrast injection; Contrast media carbon dioxide versus, 621 indications and recommendations for, 529 simplified system for, 530f types of, 621 Ion, movement of, 3 Ion channel cardiac excitability and, 6f electrical activity and, 41-42 types of, 6 Ion drift, 8 Ion drift current, 18 Ion flow, 8 electron flow versus, 18 processes of, 21 Ionic contrast agent, 621 Ionizing radiation, 1004-1005 IS-1 connector, 872f IS-1 technology, 197-198 IS-4 lead configuration, 735f Isoelectric window, 49 Iso-osmolar contrast agent, 621 Isoproterenol, 33 Isotonic saline, 620

J Jackson-Pratt drainage system, 447f Johns Hopkins Protocol, for MRI studies with CIEDs, 1015-1016, 1016f Joule (j), 176 J-tipped polytetrafluoroethylene guidewire, axillary venous access using, 462, 463f Jugular venous access, 482

K Kaplan-Meier estimates in Cardiac Resynchronization in Heart Failure (CARE-HF), 288f extension phase, 289f



Kaplan-Meier estimates (Continued) in Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION), 286f in Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), 290f Kearns-Sayre syndrome, 333 Kevlar balloon, focused-force venoplasty and, 652-653 Key dual-chamber building block, 89t Kidney, contrast material and, 620 Kinetic energy, 435 Kirchoff ’s voltage law, 3 Koch’s triangle landmarks, 507f

L Laddergramming, 851 from rate-modulated dual-chamber pacing system, 853f LA-LV transmitral pressure gradient, 938 Laser crossing client/patient characteristics for, 637t complications, prevention of, 638-639 procedural characteristics for, 637t of superior vena cava occlusion, 641f of total occlusions, 635-639 limitations of, 638 orthogonal view, 639-646, 639f Latency definition of, 874 ECG tracing showing, 874f Lateral cardiac vein pacing, ventricular activation during, 932f Lateral wall vein LAO projection of, 551f LV lead implantation on, 566f occlusion of, 588f RAO view of, 550f-551f with selective injection of contrast, 553f Lead. See also Insulation; Pacing lead abandoned, radiography of, 791f in bipolar pacing, 23 broken/insulation defect in, 16, 722f, 807 oversensing from, 75-77, 79f performance effect from, 128 in cardiac resynchronization therapy, 134 complications from, 749b, 803-806 detection of, 803-806 conductor fraction and insulation break in, 807 design of, 128f, 136 encapsulation of, 748f engineering and construction of, 127-143 epicardial active-fixation steroid-eluting, 135f extracted/dislodged, replacement of, 664 failure of documentation of, 721-722 ICDs and, 428 signs and symptoms of, 142b fixation mechanism for, 133f, 135-136 for ICD implantation, 494f improper positioning of, 864 interchangeability of, 724 Lead Integrity Alert and, 80f long-term, testing sensing/pacing capabilities of, 727-728

Index

Lead (Continued) malfunction of, 721-722 identification of, 793-794 monitoring of function of, 998f performance, 999-1001 MRI-compatible, 809f older models of, 733f passively fixed, 30-31 perforation of, 589 preexisting, crossing obstructed/occluded vein in, 625-646 protrusion of, 794f radiographic/fluoroscopic identification of, 726-727 radiography of, 771 removal of, 747 classification of, 1031-1032, 1032f replacement of, 664 securing of, 478-481 in situ, replacement of, 664 stimulation impedance, importance of, 866-867 stress and fracture of, 742f structural integrity of, 728-729 structure and polarity of, 127-129 upgrade to adapter, 724f venous access, sacrificing for, 629-632, 632f Lead anchoring sleeve, 134, 134f Lead anode, 4 Lead cathode, 4 Lead clinical success rate, 747 Lead code, 197 Lead connector, 733-734, 743f configurations for, 734t Lead connector pin, device for, 780f Lead discontinuity, clavicle-first rib, 895f Lead dislodgment, 133 in CIED implantation, 741-742 EGM of, 894f example of, 892f-893f left ventricular, incidence of, 979-980 macro-dislodgment of, 741-742 micro-dislodgment of, 741-742 occurrence of, 737-738 perforation and, 807f postimplantation chest radiography of, 807 radiographic evidence of, 891-892 reducing risk of, 525f Lead extraction anesthesia for, 754 approaches to, 761-763 surgical, 767-769 transvenous, 764-767 clinical considerations for informed consent, 754 patient information/preparation, 753-754 pocket management, 754-755 procedure room, 754 clinical outcome of, 748t complications/risks of, 1037 conduit creation and, 751-752 from coronary sinus, 769, 769f definition of, 747 fibrosis, canine model of, 748f fluoroscopy during, 803 goals and outcomes for, 747 inactive leads, 752 indications for, 747-752

1069

Lead extraction (Continued) bilateral occlusion, 751f infection, 747-749 noninfected systems, 749 risk to patient, 751 thrombosis or venous stenosis, 751-752, 752f instruments for, 757-758 electrosurgical dissection sheath (EDS), 759-760, 759f evolution sheath, 760, 760f excimer laser sheath, 758-761, 758f locking stylets, 760-761, 760f mechanical sheath, 757-758, 758f snares, 761 left-sided implantation and, 769f MRI-related indications, 752 replacement of, 664 risks and outcomes of, 752-753 SVC tears, 752, 752f tamponade, 752 techniques and devices for, 747-770 techniques for, 755-761 counterpressure, 757 countertraction, 756-757, 757f direct traction, 755-756, 756f indirect traction, 756 traction, 755 training and skills for, 755 view of, 751f Lead failure cause of, 130 insulation failure and, 77f multiple shocks and, 897 Twiddler’s syndrome and, 891-892 Lead fracture home monitoring event notification for, 995f inappropriate shocks and, 723f oversensing and, 79f radiographic evidence of, 891-892 radiograph of, 895f view of, 727f Lead-generator interface, structural integrity of, 728-729 Lead impedance, 846-847 increase in, cause of, 848 measurements for, 848 measurements for pacemaker, reporting, 848, 849f pacing current and, 179-180 bradycardia pulse generator, 179 ICD longevity, 179-180 role of, 76-77 telemetry for, 848 Lead Integrity Alert, 80f Leadless pacemaker, 439f Leadless pacing challenges in development for, 438b concepts for, 434-440 experimental setup for, 436f induction technology for, 439 Lead perforation, 891-892 chest radiograph of, 897f Lead pin configuration, 725f Lead placement for baseline LBBB activation, 936f body response to, 29 pacing impedance, effect on, 29 platform for

1070

Index

Lead placement (Continued) catheter shape, 533 lumen size, 533 removal, cutting versus peeling, 533-535 sites for, 135-136 stimulus threshold and, 26 threshold changes as function of time after, 28, 28f ventricular undersensing/oversensing, 377 Lead slack, 805f Lead status, 846-848 Lead tip stabilization, sensing and, 58 Learned helplessness, 424 Left anterior oblique (LAO), 507, 508f coronary sinus in, 509f view of, 512f Left anterolateral thoracotomy approach, for ICD implantation, 494, 494f Left atrial contraction, after mitral valve closure, 224f Left atrial pacing, intracardiac electrogram with, 414f Left atrial pressure, 163 changes in, 164f monitoring of, 163, 296 Left atrial pressure sensing device, 163f Left atrium, coronary sinus draining into, 560f Left bundle branch, 323 Left bundle branch block (LBBB), 134 abnormal activation sequence during, 206 abnormal contraction during, 206-211 cardiac pump function, impaired, 209 effects of, 217-218 cardiac structure/function and, 211 characterization/registration of, 929 contact/noncontact mapping in, 207f dilated cardiomyopathy, cause of, 914 effects of, 912 electrical activation in, 206 electrical activation times for RV/LV during, 223f electromechanics, effects on, 916f impulse conduction in, 206 local energetic efficiency, effect on, 207-209 map of RV and LV activation, 220f pressure-volume loops during, 917f prognosis for, 217 trifascicular block and, 326-327 ventricular activation characterization during, 928-929 Left bundle branch block (LBBB) activation, 928-929, 955f Left bundle branch block (LBBB)-induced asynchrony, 915f Left bundle branch block (LBBB) ventricular activation lead position for, 936f LV longitudinal strain map and, 934f Left subcostal approach, for ICD implantation, 494-495, 495f Left superior vena cava, patient with, 554f-555f Left thoracotomy approach for epicardial electrode implantation, 409 for ICD implantation, 494, 494f Left ventricle filling pressure, 163 Left ventricular activation, in heart failure and LBBB, 220f

Left ventricular activation fusion, conduction block and BiV pacing effect on, 957f Left ventricular activation time (LVAT), 929 calculation using surface ECG, 930f Left ventricular assist device (LVAD), electromagnetic interference and, 1021 Left ventricular breakthrough time, 206 Left ventricular capture electrocardiography for determining, 923-925 loss of, 927, 974f single-cycle, 927 Left ventricular capture management (LVCM) diagnostic reporting and, 926 limitations and complications of, 927 operating constraints for, 927 operating details for, 926-927, 926f performance of, 927 programming options for, 926 purpose/role of, 925-926 short-long-short sequences/pseudo-crosstalk during, 928f threshold determination for, 927 uncertain atrial capture and, 927 Left ventricular conduction block anterior line interaction, schematic view of, 956f-957f posterior line interaction, schematic view of, 956f Left ventricular conduction delay, by stimulation proximal to line of block, 958f Left ventricular dysfunction biventricular pacing and, 352-353 ICD therapy clinical trials for, 264-270 criteria, comparison groups and results, 264t, 268t pooled analysis of, 268 population details/mortality results, 265t, 269t in specific circumstances, 268 Left ventricular ejection fraction, 210-211 cardiac resynchronization therapy and, 434 Left ventricular endocardial activation, 913 Left ventricular epicardial activation, 913 Left ventricular epicardial lead, 135-136 benefits of, 134 fixation mechanism for, 135 Left ventricular free wall, contraction patterns in, 209f Left ventricular free wall pacing, external work values during, 209f Left ventricular lateral wall pacing, contraction patterns at, 209f Left ventricular lead. See also Over-the-wire LV pacing lead in CRT-D, 790f CT for repositioning of, 808f dislodgment by stylet, 585f with electrode and tool, 614f failure of, 600f misplacement of, 490 procedural safety and performance of, 290-291, 290t replacing unstable, 610f in target vein, 598f types of Biotronik, 598, 598f Boston Scientific, 598-600, 598f EasyTrak, 598-600 Medtronic, 600-608 as unipolar or bipolar, 920

Left ventricular lead delivery system evolution of, 591-610 types of, 591 Boston Scientific, 591f-592f Pressure Products, 595f Situs LDS-2, 593f Left ventricular lead dislodgment, 979-980 Left ventricular lead implantation. See also Guide support-based delivery system abnormal, radiographic view of, 784f-785f anchor balloons for, 681-695 approaches to, 517-519 complications of EP versus open-lumen catheter with contrast, 587 lead perforation, 589 radiation exposure, 589 contrast material use for, 620 with coronary balloon as anchor, 693-694 coronary venoplasty and, 662-681 CRT and, 519, 520f responders versus non responders, 521, 521f equipment for, 711b extraction and, 769f failed antegrade/difficult retrograde push-pull technique, 679f-681f fluoroscopy/chest radiography at fluoroscopic error, 519-521, 519f second implantation, 520f with interventional techniques catheter/lead movement, preventing restricted, 530-532 contrast, 529, 530f details and rationale for, 529-530 equipment and room setup for, 529, 531f platform for, 533-535 steps summary for, 526-541 on lateral wall, 566f location for, 519 mid-thoracotomy/thorascopic approaches to, 613f repositioning of, 522f slack for lead, 585 insufficient, 586f snare for, 695-699, 700b types of, 698f target vein absence/phrenic pacing present, 691f-692f transseptal approach to, 517-518, 700-701, 701f-702f Selectsite snare approach to, 703f-706f types of, 519f venoplasty and, 664, 666f after dislodgment, 667f-670f venous access sheaths for, 535f Left ventricular outflow analysis, 947 Left ventricular pacing effect on ventricular repolarization, 983f functional conduction block emergence during, 954 fusion beats during, 917-918 pressure-volume diagrams during, 210f pressure-volume loops during, 917f sites for, 222 site-specific effects on VT initiation/termination, 982f ventricular proarrhythmias during, 980-981 Left ventricular pacing fusion, 917-918



Left ventricular protection period (LVPP), 68, 971-973 Left ventricular pump function, 912f Left ventricular refractory period (LVRP), 68 Left ventricular refractory period (LVRP) extension, 841f Left ventricular remodeling cardiac resynchronization therapy and, 434 reverse volumetric, 917-918 Left ventricular scar volume, quantification of, 925, 930f Left ventricular wall, three-dimensional reconstruction of, 218f Lenègre’s disease, 333-334 Lev’s disease, 333-334 Life-sustaining therapy patient’s right to refuse, 1040 legal cases confirming, 1041t Light-emitting diode (LED), 122f Line of block, 206 Lithium-carbon monofluoride battery, 181-182 discharge curve of, 182f Lithium-cobalt oxide, 185-186 Lithium-hybrid cathode battery, 182 discharge curve of, 182f Lithium-iodine battery, 181 cell structure of, 181 charge available for, 3 cutaway view of, 181f delivered capacity, effects of current drain on, 181 discharge curve of, 181 Lithium-ion battery. See also Rechargeable lithium–ion battery diagram of, 185f discharge curve for, 186f Lithium-layered silver vanadium oxide-carbon monofluoride battery, 184 discharge curve for, 185f Lithium-manganese dioxide battery, 184 voltage and internal resistance with extent of discharge, 184f Lithium-silver vanadium oxide (LiSVO) battery, 183-184 area-normalized resistance of, 184f charge time-optimized, 183-184, 184f discharge characteristics, plot of, 183f discharge of, 182f Lithotripsy, electromagnetic interference and, 1023 Load voltage capacity plot versus, 177f drain plot versus, 177f Locking stylet, 760-761, 760f Longevity, 178-179 Long QT Syndrome, 383-384 antibradycardia therapy in, 386-387 pacemaker implantation and, 395 risk stratification for aborted cardiac arrest, 383-384 age and gender, 383 electrocardiogram, 383 EPS study and family history, 383 genotype, 383 symptoms of, 383 therapeutic recommendations for, 384 ICD therapy, 386t ventricular tachycardia and, 903f

Index

Long-term high-energy lead, testing DFT for, 728 Long-term lead, testing sensing/pacing capabilities of, 727-728 Los Angeles County-University of Southern California Medical Center (LAC-USCMC) Coronary Care Unit (CCU) acute myocardial infarction with AV block, 338 AV block progression, 339 with BBB, 339 without BBB, 339 Low atrial septum lead, 511f Lower rate behavior, 823-825 Lower rate limits (LRL), 223-224, 823-824 Low osmolar contrast agent, 621 Low-pass filter, 42 Low-voltage lead pin configuration, 725f L-transposition of the great arteries, 797 in pacemaker system after Senning and great arterial switch procedures, 804f Lung wetness monitoring system, 875 Lyme disease, 335

M Magnet-activated paced rate, change in, 719 Magnetic field, 1004 decrease in, 1011 Magnetic reed switch closure, electromagnetic interference and, 1010 Magnetic resonance imaging (MRI) contraindications for, 808-809 implantable cardioverter-defibrillator (ICD), 809 device implantation and, 808 electromagnetic interference and, 1014-1018 CIEDs, effect on, 1014b types of, 1014-1015 high pacing rates caused by, 880 lead/generator artifact in, 1017f pacemaker and lead compatible, 809f radiofrequency field and, 1015 Magnet rate, for pacemaker, 846f Magnet response, of pulse generator, 721b, 863 Magney approach, to subclavian venipuncture, 461f Main coronary sinus balloon venoplasty of, 664f-665f venoplasty of, 662-664 Malfunction. See also Implantable cardioverterdefibrillator (ICD) malfunction; Lead, malfunction of definition of, 1029 Managed ventricular pacing (MVP), 219, 316 during AAI pacing, 319f AAI/R+ versus DDD/R mode AVB during exercise, 351f criteria for switching, 351f algorithm for, 833-834 causing ventricular tachycardia, 352f DDD(R) mode versus, 317f example of, 398f rhythm strips of, 317f in sinus node dysfunction, 398 Manufacturer and User Facility Device Experience (MAUDE) database, 1033 Manufacturer’s representative, for pacemaker implantation, 444 Maximum tracking rate (MTR), 822-823 P-wave tracking and, 826f

1071

McLeod Crossover Study, 368 Mean atrial interval (MAI), 830 Measured data, 844-848 battery status, 844-846 Measured data telemetry, 847f Mechanical activation physiology of, 203-211 during sinus rhythm, 204-206 Mechanical asynchrony determination of, 221-222 discoordination versus, 222 Mechanical dyssynchrony measurement, before CRT therapy, 422f Mechanical sheath, 757-758, 758f Median sternotomy approach for epicardial electrode implantation, 409 for ICD implantation, 494, 494f Medical Product Safety Network (MedSun), 1033 Medicare Recovery Audit program, 448-449 Medicare trial, 239 Medtronic activity-sensing device, 147, 147f Medtronic Atrial Capture Management feature, 34 Medtronic Attain Ability 4196 lead, 608 venous anatomy suitable for, 608f-609f Medtronic Attain Command 6250 series CS access catheter, 593f Medtronic Attain hybrid guidewire, 594f instability of, 602f phrenic pacing and, 601f Medtronic Attain left-sided heart lead, 604f Medtronic Attain over-the-wire 4194 pacing lead, 604, 604f coil anode of, 605f delivery guide, requirement of, 606f pacing threshold for, 606f proximal lead alignment phrenic pacing and, 607f with venous anatomy and withdrawal, 607f Medtronic CareLink Programmer 2090, features of, 447t Medtronic Chronic IHM, 161 Medtronic delivery guide and slicing tools, 594f Medtronic dual-sensor pacemaker, 152, 153t Medtronic ICD, far-field R wave rejection by, 68 Medtronic lead, 600-608 Medtronic Lead Integrity Alert (LIA), 76-77, 80f Medtronic Model 10295A, 407f Medtronic Model 1356, 24f Medtronic Model 3830, 408 implantation technique for, 410 Medtronic Model 4951 acute implantation voltage and current threshold for, 406f threshold for, 406f Medtronic Model 4951M(P), 406f Medtronic Model 4951P, 407f Medtronic Model 4965 acute implantation voltage and current threshold for, 406f Kaplan-Meier survival curve for, 407f threshold for, 406f Medtronic Model 4968, 407f Medtronic Model 5069, 406f Medtronic Model 5880A external pulse generator, 24f Medtronic Model 6917, 406f Medtronic Model 6937A, 498 Medtronic Model 7000A, 24f

1072

Index

Medtronic pacemaker, event log and histogram for, 861f Medtronic PR logic algorithm, 103f Medtronic Protecta ICD, 103 Medtronic ventilation-sensing device, 149 Medtronic Ventricular Capture Management feature, 34 Membrane space constant, 45 Metabolic storage disorder, 333 Metal detector, electromagnetic interference and, 1013 Metal ion oxidation, polyurethane degradation and, 130 Microdissection failure of, 635f success of, 632 of total occlusions, 634f Frontrunner XP CTO Catheter for, 632, 633f Microporosity, 27 Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients (MASTER), 272 Middle cardiac vein pacing, ventricular activation during, 932f MID-Heft Study data, 166f Midlateral free wall, LV lead placement and, 519 Midwest Pediatric Pacemaker Registry (MPPR), 393 data collected for, 394t Millivolt amplitude, 853-854 Minimum potential gradient, 43-44 for defibrillation, 44 sawtooth model and, 46 Minute ventilation, 169-170 Minute ventilation sensing, 149-150 limitations of, 150 Minute ventilation-sensing device clinical experience of, 149-150 types of, 149 Mitochondrial disorder, 333 Mitral valve closure, left atrial contraction after, 224f Mitral valve surgery sigmoid coronary sinus after, 562f tortuous proximal coronary veins after, 566f M-mode endocardiography, 207 Moderator band, 507 Mode Selection in Sinus Node Dysfunction (MOST), 240-241 clinical events in, 241t critical appraisal of, 241, 249 intolerance to VVI(R) in, 250f pacemaker syndrome in, 241, 241f pacing mode, clinical events according to, 309f RVA pacing and, 350 sinus node disease and pacing, 305 Mode switching AAI(R) to DDD(R), 833-834 activation from DDDR to DDIR, 830f during atrial flutter, 830-831 algorithms for, 831, 831f atrial sensitivity and, 831f cause of, 866b far-field R wave, 970-971 effect on frequency, duration, and symptoms, 831f electromagnetic interference and, 1007-1008, 1007f

Mode switching (Continued) histogram for, 856f, 861f in pacemaker, 830 purpose of, 970-971 Modified Elencwajg-Cardinal femoral approach, to transseptal left ventricular lead placement, 707f-710f Monitoring. See specific devices Monitor-only zone, for ventricular tachycardia, 83 Monochamber LV activation, 939f Monochamber LV pacing QRS hieroglyphic signatures during, 937f as atypical, 939f ventricular activation during, 931, 931f Monochamber LV pacing threshold, 925f Monochamber RV activation, 939f Monochamber RV apical pacing, 924 Monochamber RV pacing QRS hieroglyphic signatures during, 937f as atypical, 939f Monochamber RV pacing threshold, ventricular activation sequences during, 925f Monophasic stimulation energy requirements for, 26 in rabbit/frog ventricles, 26, 26f Monophasic waveform, 42-45 definition of, 374 Mortality in acute myocardial infarction and BBB, 341 atrial/dual-chamber pacing versus ventricular single-chamber pacing, 238-239 in atrioventricular block, 342f from heart failure, 161f ICD therapy clinical trials assessing, 275t pacing mode and, studies on, 239t sinus node disease and, 305-306 in relation to pacing mode, 238t “Mother rotor” hypothesis, of ventricular fibrillation, 40-41 Movement of ions, 3 mRNA, in sinus node, 302f Multicenter Automatic Defibrillator Implantation Trial. See also First Multicenter Automatic Defibrillator Implantation Trial (MADIT-I); Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), 272-273, 295t for heart failure prevention, 289-290 Kaplan-Meier estimates in, 290f Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD), 281t CONTAK CD and, 283-284 study design for, 283f types, criteria, endpoints, and results for, 281t Multicenter InSync Randomized Clinical Evaluation (MIRACLE), 281t, 283 study design for, 283f Multicenter Investigation of the Limitation of Infarct Size (MILIS), 340-341 Multicenter Unsustained Tachycardia Trial (MUSTT) for ICD therapy, 263-264 criteria, comparison groups and results, 262t population details/mortality results, 262t Multichannel ECG recording system, for pacemaker implantation, 445

Multilumen ICD lead, 128-129, 128f Multiple shocks cause of, 892-904, 892t atrial fibrillation and, 902, 903f drugs or ICD, 902-904 lead failure as, 897 P wave, T wave, and atrial flutter, over sensing of, 897 supraventricular arrhythmias, 902 management of, 892 Multipolar impedance, 168-169 Multisite Stimulation in Cardiomyopathy (MUSTIC), 282-288 crossover study for, 282f Multisite Stimulation in Cardiomyopathy-Atrial Fibrillation (MUSTIC-AC), 281t Multisite Stimulation in Cardiomyopathy-Sinus Rhythm (MUSTIC-SR), 281-282 types, criteria, endpoints, and results for, 281t Muscular stimulation, 1018 Mustard procedure for congenital heart disease, 797 device systems in DTGA after, 802f Myocardial infarction, 257 Myocardial perfusion, heart rate and, 207-208 Myocardial scar, 925 Myocardial stimulation cellular aspects of cell membrane characteristics, 5 phospholipid bimembrane, 5 resting transmembrane potential, 5-6 by pacemakers, clinical aspects of, 28-33 Myocardium balloon inflation in, 681, 690f excitation-contraction (E-C) coupling in, 204, 204f fibrillation of, 40 Myocardium-electrode interface, 31 Myopotential inhibition inappropriate inhibition caused by, 870f oversensing and, 869-870 Myopotential oversensing, 77, 897, 900f Myopotential sensing, 897, 900f Myopotential tracking cause of, 880 ECG rhythm strip showing, 880f

N N-acetylcysteine, 621-622 NASPE/BPEG defibrillator (NDB) code, 196, 198t short form for, 197, 198t NASPE/BPEG generic (NBG) pacemaker code, 195-196, 197t revision to, 196, 197t, 814t examples of, 198t short form for, 197 NASPE/BPEG pacemaker-lead (NBL) code, 197, 198t examples of, 198t National Cardiovascular Device Registry (NCDR), 1002, 1033 Native ventricular activation, 971-973 Neck, anatomic structures of, 453, 454f-455f Needle’s Eye Snare, 761, 763f Negative AV/PV hysteresis, 821f Negative charge, 3 NEPHRIC Study, 621 Nephrotoxic drug, 620



Net reactance, 5 Neurally mediated syncope syndrome definition/types of, 361 pacing in neurally mediated, 361-373 Neuromuscular disease, 335 Neuronal axon conduction, voltage-gated channel and, 6 Neurostimulator, electromagnetic interference and, 1018 New York Heart Association (NYHA) diagnostic class, 223 right ventricular versus biventricular pacing, 252 Nichall’s landmarks, for axillary venipuncture, 460f Nighttime heart rate, 159-160, 161f Node, 4 Noise response algorithm, 827 Noise response pacing, 876f Noise-reversion mode, electromagnetic interference and, 1008-1009 Nominal pressure, of balloon, 625 for subclavian/innominate venoplasty, 647 Noncapture, 873b Noncompetitive atrial pacing, 833 ventricular timing and, 834f Noncontact mapping, 207f Nonfaradic current flow, 21 Noninvasive hemodynamic monitoring, 947-948 Nonsustained polymorphic ventricular tachycardia (NSVT), 390f No-output condition, 868-869, 868b Normal rhythm, sensitivity, automatic adjustment of, 64 North American Society of Pacing and Electrophysiology (NASPE), Mode Code Committee of, 195, 813 AV block risks, pacemaker recommendations on, 328 North American Vasovagal Pacemaker Study (VPS-I), 367, 367f Nurse anesthetist, for pacemaker implantation, 444

O Occlusion. See Total occlusion Occlusive coronary sinus venography, 548-550 balloons for, 589 compliant versus noncompliant, 589f trauma from, 588-589 contrast staining in, 588-589, 589f balloon-induced trauma, 588-589 delivery guide, 590f extravasation of contrast, 588, 588f unmasking of trauma, 588 vein perforation, 590f with full-strength contrast, 549f with half-strength contrast, 548f lateral wall vein and, RAO view of, 550f potential risks from, 589 target vein identified on, 576f Ohmic, 4 Ohmic polarization, 17 Ohm’s law, 4 depolarization and, 10 One-dimensional cable model, 45-46 bidomain model and, 47-48 Open-circuit voltage, of battery, 177

Index

Open-heart surgery for lead extraction, 768-769 surgical epicardial LV pacing for, 611 venoplasty after, 671f Open-loop sensor system, 144, 145f Operating room, for pacemaker implantation, 445 benefits of, 445-446 pitfalls for, 445 Optical sensor, 146 OptiVol, 166-167 increased fluid index, cause of, 168t level changes in, 165f threshold for, 167 Osmolality, of nonionic contrast agents, 621 Outpatient pacemaker implantation, 448-449 analysis of, 448t protocol for, 448b Overdrive Atrial Septum Stimulation (OASIS), 832 Overinflated balloon, 625 Oversensing. See also T-wave oversensing in antitachycardia device, 722f confirmation of, 870-871 definition of, 68-69, 847 of diaphragmatic myopotentials, 81f electromagnetic interference and, 1007 of external electromagnetic interference, 74-75 in far-field R wave (FFRW), 74 minimizing, 62 prevention of, 67-68 in hypertrophic cardiomyopathy (HCM), 898f-899f in ICD correction of, 897 ventricular fibrillation, 900f in implantable cardiac rhythm management devices, 722, 722f lead/connector problems causing, 75-77 lead fracture causing, 79f lead insulation failure causing, 77f myopotential and, 77, 869-870 output pulse, lack of, 869 pacing system inhibition and, 870 of pectoral myopotentials, 90-93 P-wave, 74, 75f of P waves, T waves, and atrial flutter, 897 types of, 72f ventricular, 814 VVI ventricular, 814f Over-the-wire balloon, 623, 624f Over-the-wire LV pacing lead Biotronik, 598f Boston Scientific, 598f ELA-Sorin, 600, 603f stylet-driven, 603f Medtronic, 604f Oxidation definition of, 175 occurrence of, 4

P Paced atrial event, 818 Pacemaker. See also Pacemaker implantation advisories for, 1033-1034, 1034f automated capture features of, 34 automatic capture verification, 353-355 automatic drug delivery systems, 371 automatic mode switching in, 78, 830

1073

Pacemaker (Continued) automatic optimization of, detection algorithm for, 77-79 battery chemistries in lithium-carbon, 181-182 lithium-hybrid cathode, 182 lithium-iodine, 181, 181f blanking and refractory period for, 61 Boston Scientific, 34 in children ambulatory electrocardiographic monitoring, 414-415 clinic visit, 412-413 exercise testing, 413-414 follow-up methods for, 412-417 follow-up periods for, 416 indications for, 395-396 intracardiac electrogram, 414f prophylactic medication and, 423 psychosocial adjustment, 423-425 remote/transtelephonic monitoring, 415-416 selection of, 396-409 support groups for, 425 survival rate with, 396f complications requiring reoperation, 725 current flow in, factors opposing, 16-22 current sensor-driven, 147-152 of defibrillator, 4 diagnostics for, 112, 113f dual-chamber, 56 electromagnetic interference and communication inhibition, 1010 determinants of, 1010-1011 electric (power-on) reset, 1009-1010 electrode-myocardium interface damage, 1010 mode switching, 1007-1008, 1007f noise reversion mode, 1008-1009 pacing interference, 1007 rapid/premature pacing, 1007-1008 reed switch closure, 1010 spurious tachyarrhythmia detection, 1008 electromotive force for, 3 endocardial electrogram configuration for, 58f equipment for, 730f equivalent circuit for, 20f event log and histogram for, 861f evolvement of, 443, 844 extraction complications for, 429t goal of, 223 for hypertrophic cardiomyopathy, 396 identification of, 863 implanted loop memory event recorder capability in, 855-856 increased standards for, 734 interventions for, interval/unscheduled, 738 leadless pacemaker and, co-implant of, 439f magnet rate, battery voltage and impedance of, 846f malfunction of annual number, 1028, 1029f-1030f registries of, 1030t measured data in, 844-848 battery status, 844-846 MRI-compatible, 809f myocardial stimulation, clinical aspects of, 28-33 neurostimulators and, 1018 operational modes of, 813 P and R wave, sensing of, 60f

1074

Index

Pacemaker (Continued) parameters and measured data in, 845f performance of, 1028-1034 power systems for, 175-190 product advisories for, 1028 rate modulation in, 346 replacement of, 729-733 safety, adequate margin of, 34-35 sense amplifier, diagram for, 64f sensing threshold in, 62 Sorin Group, 34 St. Jude Medical, 34 SVT-VT detection and, 112-116 telemetry in, 844 troubleshooting and follow-up for, 844-888 ventricular capture verification schemes for, 79 ventricular pacing, minimizing, 156 voltage threshold, determining, 399-400 Pacemaker adapter, 735t Pacemaker atrioventricular interval atrial pacing interaction with, 949-952 changes in, effect on aortic VTI, 926 effects of, 938-943 excessively long, atrioventricular coupling from, 944f optimal, during atrial sensing/pacing, 953f Ritter method for, 944-945, 945f summary of, 946f short, atrial transport block from, 943f use during CRT, 936-938 Pacemaker battery depletion, 721b, 721f Pacemaker capture, automatic assessment of, 79 Pacemaker clinic visit, 412-413 Pacemaker code five-position ICHD code as, 195 NASPE/BPEG generic (NBG) code as, 195-196 three-position ICHD code as, 195 Pacemaker-ICD interaction, 111 Pacemaker implantation anatomic approaches for, 453-456 antibiotic prophylaxis/wound irrigation, 452-453 in children anesthesia for, 486 expertise for, 486 leads for, 486 pacemaker pocket in, 486 complications from, 749b, 1037t day of anesthesia, sedation, and pain relief, 452, 452t draping process, 450-451, 451f patient preparation, 450 site preparation, 450-451 equipment for, 445 electrocautery device, 446 high-intensity headlamps, 446f monitoring equipment, 445, 445b multichannel ECG recording system, 445 pacing system analyzer, 445 spare parts/service kits, 446, 447b surgical instruments, 445, 445b, 445f facility for, 444 infection risk and, 444 inpatient versus outpatient procedure, 448-449 intervention for acute problems, 737-738 leads, pockets, and closure in, 478-481 neck, upper extremities, thorax, anatomic structures of, 453 payment for, 448-449

Pacemaker implantation (Continued) personnel for, 444 anesthetist or nurse anesthetist, 444 circulating nurse, 444 electrical testing clinician, 444 manufacturer’s representative, 444 OR versus CCL personnel, 444 physician or surgeon, 443-444 scrub nurse/technician, 444 uniform for, 451 postoperative care for activity, 481 discharge, 481 documentation, 481 follow-up, 482 monitoring, 481 preoperative orders for, 449-450 preoperative patient assessment for, 449 preoperative planning for, 447-450 radiography alternatives in, 486-487 site for, 456 special considerations for iliac venous access, 482-483, 483f jugular venous access, 482 transaxillary retropectoral, 485f wound drainage and, 480 Pacemaker lead engineering and construction of, 127-143 fracture of, 727f lead dislodgment in, 133 malfunction of, identification of, 782-793 radiography of positioning of, 780-793 removal from service, classification of, 1031-1032, 1032f Pacemaker lead conductor fracture, radiography of, 791f Pacemaker lead impedance, measurements for, reporting, 848, 849f Pacemaker-mediated tachycardia (PMT), 820-822, 821f algorithms for, 829-830 cause of, 879-883, 976 endless-loop tachycardia and, 880-883 intervention using PVARP extension, 830f ventricular extrasystole, terminated/initiated by, 822f Pacemaker memory, 365 Pacemaker pocket alternative cosmetic locations for, 483-485 anterior axillary line, 485f inframammary placement of, 484f in children, 486 creation of, 479 Pacemaker pocket stimulation, 864 Pacemaker pulse generator battery depletion, documentation of, 719-720 general magnet responses of, 721b magnet placement response, 726 malfunction of, 1028 mechanisms of, 1028-1029 performance of, 1028 radiography of, 771 reattachment of, 728f replacement of, 719 indications for, 720b, 723-724 invasive evaluation for, 727-729 noninvasive evaluation for, 719-729 reoperation, factors to reduce need for, 720b

Pacemaker pulse generator (Continued) risks of, 1036 tools for, 735-736, 735b, 737f Pacemaker Selection in Elderly Study (PASE), 240 clinical events in, 240t critical appraisal of, 240, 249 intolerance to VVI(R) in, 250f Pacemaker syndrome, 226-229 during AAI or AAIR pacing, 227-228 AAIR pacemaker recording, 228f atrioventricular dyssynchrony and, 228-229 continuous rhythm strip for, 227f long AV delays causing, 318 in MOST study, 241, 241f pacemaker system upgrade for, 476-478 pacing and, 314 pathophysiology of, 227 reflex pathways in, 228f sinus node disease and, 234 symptoms of, 227t, 314t treatment of, 227 Pacemaker system in D-transposition of great arteries after Senning procedure, 803f echocardiography and, 807 in L-transposition of great arteries after Senning and great arterial switch procedures, 804f radiography of, 773f-774f in subpectoral position, 772f Pacemaker system upgrade, 476-478 lead compatibility and, 476-478 tunneling and, 477 Penrose drain and lead for, 477f techniques for, 477-478 venous access for, 476 using contralateral subclavian venin, 477f Pace/sense connector pin, 134f Pace/sense connector pin terminal, 134f Pacing. See also Cardiac pacing antitachycardia and bradycardia, 15 APD restitution relationship during, 41f atrial fibrillation and, RCT for, 244f, 246 for atrioventricular block selection of, 346-353 survival rate with, 239t in cardiac resynchronization therapy, 434, 922-923 cardiovascular mortality and, 246f in chronic AV block, 337 congestive heart failure (CHF) and, 314 coronary sinus for, 489-490 Danish study on, 237 DDD(R) mode, 34 future perspectives on, 254 guidelines for selection of, 253-254 in hypertrophic obstructive cardiomyopathy, 229 leadless concepts for, 434 experimental setup for, 436f long-term leads for, 727-728 membrane depolarization in, 22-23 monophasic versus biphasic stimulation, 26 mortality and, randomized trials of, 239t, 243f pacemaker syndrome and, 314 patient preference of, 236f



Pacing (Continued) physiologic/pharmacologic effects on, 32-33 in post-AMI period permanent, 345-346, 345t temporary, 344-345 problems with, 907-908, 908t quality of life and, 314 radiofrequency current effect on, 1023 radiofrequency field causing inhibition of, 1016-1017 randomized controlled trials on, 237 critical appraisal of, 249-250 issues to consider, 249-250 limitations of, 253 sensor-driven, 154-156 for sinus node disease, 300-322 indications for, 318t survival rate with, 238t sites for, 222-223, 801 alternate, 801-803 strength-duration curve in, 374 Pacing artifact, ECG displaying, 868-869 Pacing current lead impedance and, 179-180 bradycardia pulse generator, 179 ICD longevity, 179-180 pulse amplitude, effect of, 179 pulse width, effect of, 179, 179f Pacing electrode features affecting performance, 26-28 geometric surface area of, 26-27 placement of, 403f Pacing impedance effects of, 25f after lead implantation, 29 Medtronic Model 5880A, 24f Pacing-induced conduction block, implication on BiV pacing, 958-959 Pacing lead anchoring sleeves for, 134 conductor design for, 129-130 connector terminal pins for, 134 development of, 127 electrodes and, 131-133 fixation mechanism for, 133 insulation for, 130-131 as isodiametric and lumenless, 129, 129f radiography of, 771-794 replacing unstable, 608f screw-in versus screw-on, 614f sensed signal, transmission of, 439 structure and polarity of, 127-129 subclavian venous access without, 642f-643f total occlusion without, 644f-646f unipolar and bipolar, 614f Pacing lead adapter/sleeves, 735f Pacing rate changes in, cause of, 866b diastolic function and changes, 942f rheobase voltage and, 15f stimulation threshold, effect on, 15 Pacing system failure of, 868b follow-up for, 885 high impedance, effects of, 22 identification of, 771 monitoring of frequency of, 885

Index

Pacing system (Continued) remote, 885 transtelephonic, 885 radiography of, 771 Pacing system analyzer (PSA), 10 EGM amplitude, measuring of, 852-853 for pacemaker implantation, 446, 446f Pacing system code, 195, 814t revised, 813 Pacing system malfunction behavior mistaken as, 863 capture/sensing threshold changes and, 867 differential diagnosis of, 868-876 failure of output, 868-872 fluoroscopic evaluation for, 867-868 oversensing and, 870 patient evaluation for, 860-862, 860b history/physical examination, 862 invasive analysis, 862b noninvasive testing, 862, 862b physical examination and telemetry, 864-868 radiography for, 867 undersensing and, 875 Pacing Therapies in Congestive Heart Failure (PATH-CHF), 283 types, criteria, endpoints and results for, 281t Pacing Therapies in Congestive Heart Failure II (PATH-CHF II), 281t Pacing threshold, 15f drugs increasing, 874b glucocorticoids effect on, 31 at ICD implantation, 377 long-term/diurnal variations in, 35 for Medtronic Attain, 4193 versus 4194, 606f metabolic abnormalities and drugs effect on, 58 Pacing to Avoid Cardiac Enlargement (PACE) trial, 292, 295t, 315-316 Pain, in CIED implantation, 743-744 PainFREE Rx study, 380 Pain relief, for pacemaker implantation, 452 Paired Transvenous Defibrillation trial, 430 Palliative care specialist, supporting in decisionmaking process, 1045-1046 Palliative surgery, for congenital heart disease, 797 Parallel circuit, 4 Paranodal area, HCN4 protein in, 303f Paroxysmal atrial fibrillation: DDD(R) with mode switching, 235-236 Paroxysmal AV block, 330-331 Paroxysmal high-grade AV block, 337f Parsonnet pouch, 501, 738f PARTNERS. See Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in patients with Heart Failure (PARTNERS-HF) Passive-fixation electrode, acute thresholds for, 408f Passive-fixation lead, dexamethasone-eluting reservoir in, 133f Passive-fixation tine, 133f development of, 127 dislodgment of, 133 Passive tines, sensing and, 58 Patient-activated remote monitoring, 988-989, 990f Patient advisory model (PAM), 163 Patient preparation, for pacemaker implantation, 450

1075

Peak endocardial acceleration (PEA), 146, 170 advantages and limitations of, 152 atrioventricular delay interval and, 225-226 clinical results of, 152 sensor and algorithm for, 151-152 types of devices for, 152 Pectoralis minor muscle, 459f Pectoral myopotentials, 90-93 Pectoral pocket, 500-501 for ICD implantation, 504f Pectoral sheath extraction, 629 Pediatric pacemaker implantation anesthesia for, 486 expertise for, 486 leads for, 486 Pediatric pacing defibrillator use and, 393-427 electrode placement for endocardial versus epicardial system, 402-404, 402f electrode selection for, 402-409 generator features for, 399-401, 402b characteristics of, 399-400 dual-chamber pacing, 401 rate-responsive pacing, 400-401 Pediatric patient, device deactivation in, 1047-1048 Pediatric transvenous ICD system, after Senning procedure, 803f Peel-away sheath kink in, 537f removal of, 584f use of, 537f Peeling, 533-535 Penetrating bundle, 323, 324f Penrose drain and lead, 477f Percentage biventricular pacing, 160-161 Percutaneous approach, for venous access, 457, 463f Percutaneous coronary venoplasty (PCV), 656 Percutaneous subclavian venipuncture, 460, 461f air embolization risk with, 466 prevention of, 467b complications of, 469-470, 469b introducer sheath buckling, 466f method for, 465, 465f figure-eight stitch, 466f Percutaneous transhepatic cannulation, 489-490 Perforation in CIED implantation, 743 echocardiography diagnosing, 808 of ICD lead, 743f of lead, 589, 891-892 chest radiograph of, 897f lead dislodgment and, 807f as postimplantation complication, 806-807 Pericardial effusion echocardiography diagnosing, 807-808 as postimplantation complication, 806-807 Pericardium cardiac tamponade and, 765 wall integrity, loss of, 765 Peripheral nerve stimulator, 1018 Peripheral subclavian vein occlusion, dilation of, 534f Peripheral venogram, for subclavian vein occlusion, 625-646, 626f, 781f

1076

Index

Permanent cardiac pacemaker in children, 393 implantable cardioverter-defibrillator (ICD) and, 443-515 implantation of, 489 indications for sinus node dysfunction, 393 surgically induced heart block, 394 Persistent left superior vena cava (SVC), 488, 488f, 794 absence of, 489 with absence of right superior vena cava, 488f atrial/ventricular electrode placement through, 489f ICD lead positioning in tetralogy of Fallot with, 804f radiographic view of, 799f types of, schematic representation of, 799f Personal media player, electromagnetic interference and, 1011-1012 Phantom reprogramming, 866 Pharmacologic stress testing, 328 Phase, 47-48 Phase angle, 17 Phase singularity, 47-48 shock-induced, creation of, 48f Phospholipid bimembrane, 5 of cardiomyocyte, 5f Phrenic nerve stimulation, 976 Phrenic pacing EasyTrak LV lead and, 601f LV lead placement absent of target vein and, 691f-692f Medtronic Attain hybrid guidewire and, 601f Medtronic Attain over-the-wire 4194 pacing lead and, 607f venoplasty and, 671, 674f push-pull technique, 675f Physical counterpressure maneuver, for vasovagal syncope, 365-366 Physician for ICD and CRT implantation, requirements for, 491-492 for pacemaker implantation, 443-444 Physiologic pacing mode atrioventricular block and, 238 heart failure and, 239 sinus node disease and, 319f Piezoelectric crystal, 146 use of, 158-159 Pinacidil, 49 Plasmablade, 480 Plateau phase, of cardiac action potential, 7-8 Pneumothorax chest radiograph of, 806f in CIED implantation, 742 as postimplantation complication, 806 from subclavian venipuncture, 470 Pocket erosion, 745f Pocket hematoma, 737 in CIED implantation, 743 Pocket infection, 744 Pocket management, after lead extraction, 754-755 Pocket twitch, 725, 737 Polarity, 3 Polarization, 4 of battery, 177 capacitance versus, 18-19

Polarization (Continued) definition of, 20 distorting effects of, 28 electrode, effect of, 18f Polarization overvoltage, 17, 18f Polyester (Dacron) Parsonnet pouch, 447f Polymorphic ventricular tachycardia. See also Catecholaminergic polymorphic ventricular tachycardia during BiV pacing, 983f Polytetrafluoroethylene (PTFE), 130 Polyurethane characteristics/types of, 130 degradation of, 130 Pore structure, on electrodes, 27 Positive atrioventricular interval hysteresis, 820f Positive charge, 3 Post-AV nodal ablation evaluation (PAVE), 252, 291-292 Postimplantation radiography, 806-807 complications from, 806-807 Post-market surveillance goal of, 1031 methods of, 1031-1032, 1031t Postpacing polarization artifact, 83f Postshock activation, 44, 49 during failed shock, 52f Postshock cycles, 50f-51f recordings/activation time for, 53f Postshock sensing, 67 Postventricular atrial blanking (PVAB), 60 atrial sensing, effects on, 69f of far-field R wave, 67-68 Postventricular atrial refractory period (PVARP), 60, 820-822, 821f dual-chamber pacing and, 401 endless-loop tachycardia and, 881-882 PVE and, 882f P-wave tracking caused by, lack of, 822f VDD system, pacemaker programming on, 348 Potassium channel gene, 332 Potential difference, 3 Potential gradient, 43-44 Power density, 1004 Power frequency, 1004 P-R dissociation building block, 85-88 Prediction of ICD Therapies Study (PREDICTS), 274 Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT), 295t Premature ventricular complex (PVC) after competitive atrial pacing, 835 EGM displaying, 890f extension of PVARP in response to, 822 ICEGM and surface ECG of, 876f ventricular electrogram during, 58 PREPARE study, 380 Preprocedural chest radiography, 771 dextrocardia and, 797 overlay of diagram on, 772f pacing/defibrillation system, identification of, 771 patient anatomy, identification of, 771 Pressure Products CS access catheter, 595f Pressure Products delivery guide, 595f Pressure sensor left atrial sensor as, 163 right ventricular, 161-162

Pressure-volume loops, during LBBB and LV pacing, 917f PREVENT-HF trial, 252 Procedural success rate, 747 Product advisory annual number of, 1034f clinical management of, 1038, 1038b balancing risks versus benefits, 1036 options for, 1036-1038 overview and clinician responsibilities, 1035-1036 device recalls and, 1033-1034 number, rate, and reasons for, 1033-1034 for pacemaker and ICDs, 1028 psychological impact of, 1038 threshold for activation of, 1033 Product notification, 1033 Programmed sensitivity, 62 Programmer CIED and, communication between, 1010 for implantable leadless pacing system, 437 pacemaker/ICD identification by, 863 Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in patients with Heart Failure (PARTNERS-HF), 170-171 diagnostic parameters for, 171t Progressively large dilator drawbacks of, 647 hemodynamic collapse in using, 648f subclavian venoplasty versus, 646-655 Propagation depolarization and, 10 electrical pacing stimulus and, 10 Prophylactic medication, for children with pacemakers, 423 Proton, 3 Proximal/distal subtotal venous occlusion, dilation of, 535f P-R patterns/relationship building block, 85-88 Pseudo-atrial undersensing Atrial Tracking Recovery and, 970 loss of CRT from, 968, 969f Pseudo-crosstalk, during LVCM, 928f Pseudodiscontinuity, of ICD lead, 793-794 Pseudofracture of Guidant Endotak ICD lead, 797f of ICD lead, 793f types of, 791 Pseudofusion beat, ECG tracing showing, 875f Pseudonormalization, 940-941 Pseudo-pacemaker syndrome, 911 Pseudo-ventricular tachycardia, 879 ECG rhythm strip showing, 879f Psychiatric consultant, supporting in decisionmaking process, 1045 Psychosocial adjustment, for children with pacemakers, 423-425 Pullback, 138f Pulmonary arterial pressure sensor, 163-164 Pulmonary artery pressure, 161 Pulmonary capillary wedge pressure, atrioventricular pacing and, 216f Pulmonary fluid status. See Intrathoracic impedance Pulmonic valve, 507



Pulse amplitude, 14f in generator, 399 pacing current and, 179 pacing threshold and, 15f programming of, 14f Pulse artifact present, 872-874 Pulse duration, 13, 14f programming of, 14f Pulse duration threshold, 13 Pulse generator, 16 for biventricular pacing, 923f for cardiac resynchronization therapy, 920-922 component failure of, 871-872 elective replacement indicator in, 180 failure of, 872b first-generation multisite pacing, 922 identification of, 726b make and model of, 726-727 radiographic/fluoroscopic, 726, 726f for implantable leadless pacing system, 437 inframammary placement of, 484f lead adaptability for, 733-737 location of, 771 longevity of, battery and, 178-179 magnet response of, 721b, 863 malfunction of, 1028 mechanisms of, 1028-1029 manufacturer and type of, 771 migration of, 771 radiography of, 771, 776f-777f with radiopaque identification tags, 863f replacement of approaches to, 719-740 indications for, 720b, 723-725 invasive evaluation for, 727-729, 729f noninvasive evaluation for, 719-727 procedure for, 730, 731f reoperation, factors to reduce need for, 720b risks of, 1036-1037 tools for, 735-736, 735b, 737f second-generation multisite pacing, 922 skin erosion from, 736 with vascular overload and abandoned lead, 727f ventricular IEGM telemetered by, 870f Pulse generator connector block, 733 Pulse generator-lead interface malfunction, 723 Pulse width, 13 battery longevity, programming for, 35, 35f in generator, 399 pacing current and, 179, 179f shock waveform and, 375f importance of, 375 Pure capacitance, 17 Pure inductance, 17 Purkinje fiber action potential of, 9f resistance of, 8-9 Purkinje-myocardial junction, 203 Purkinje network, 203 Purkinje system, 203 Push-pull technique definition of, 618 failed antegrade/difficult retrograde LV lead placement, 679f-681f to gain guide support, 661, 661f venoplasty to avoid phrenic pacing and, 675f PVC PVARP extension, 822

Index

P-wave amplitude, 58 P-wave oversensing, 74, 75f P-wave tracking, 822f long PVARP causing in, 828f maximum tracking rate and, 826f P-wave undersensing, 827f

Q QRS activation, total, in heart failure, 208f QRS complex, 217f in children, 419 undersensing of, 875f, 878f QRS delay, heart failure and, 279 QRS duration, 218, 912 QRS notching, 929 QT interval, 146 Quality of life ICD shocks and, 258 ICD therapy and, clinical trials for, 257 pacing and, 314 product advisories and, 1038 Quarter pacing lead, 610 delivery guide support for, 612f QuickFlex 1156T OTW LV pacing lead, 610 QuickFlex Micro 1258 OTW LV pacing lead, 610, 611f-612f QuickFlex XL 1158T OTW LV pacing lead, 610, 610f QuickOpt clinical performance of, 967 for IACT estimating, 966f limitations of, 967-968 operating specifics for, 966 purpose of, 966

R Radial artery pressure, with atrioventricular block, 226f Radiated electromagnetic interference, 1004 Radiation therapy, heart block and, 335 Radiofrequency catheter ablation, 334 indications for, 1022-1023 Radiofrequency current, CIEDs and, 1023 Radiofrequency field effects of MRI on CIEDs, 1014b electromagnetic interference and in device circuitry, 1015 MRI and, 1015 pacing inhibition and, 1016-1017 Radiofrequency guidewire, for subclavian vein occlusion, 632-635 Radiofrequency identification technology (RIT), 1021 Radiography of abandoned leads, 791f of abdominal pacemaker/ICD systems, 773f-774f of abnormal LV lead placement, 784f-785f of atrial fibrillation lead system, 796f of azygos vein defibrillation lead, 797f of dextrocardia, 800f in child, 801f of epicardial RA/RV pacing lead, 790f of His bundle pacing, 787f of ICD pulse generator, 778f-779f of ICD with defibrillation leads, 775f of pacemaker/ICD pulse generators/ILR, 771 pacemaker implantation and, 486-487 of pacemaker lead conductor fracture, 791f

1077

Radiography (Continued) of pacing/defibrillator leads, 771-794 atrial lead positions, 780-781 coronary sinus lead positions, 782 epicardial lead positions, 782 pacemaker leads, 780-793 transvenous leads, 782f venous anatomy for localization of, 772 ventricular lead positions, 781 for pacing system malfunction, 867 of persistent left superior vena cava, 799f postimplantation, 806-807 complications from, 806-807 preprocedural chest, 771 pacing/defibrillation system, identification of, 771 patient anatomy, identification of, 771 of pulse generator, 776f-777f of single-lead VDD pacing system, 787f of ventricular pacing/atrial leads, 784f of ventricular pacing lead in RV outflow tract, 786f Radiotherapy, electromagnetic interference and, 1024, 1024b Ramp antitachycardia pacing, 379-380 Randomized controlled trial for atrial fibrillation and pacing mode, 244f, 246 Danish study as, 237 for dual-chamber pacing, 234 hospitalization for heart failure, 245f on pacing mode, 237 for sick sinus syndrome, 245 for sinus node disease, 245 Rapid depolarization. See also Depolarization Rapid exchange balloon, 623, 624f Rapidly conducted atrial fibrillation, 100f Rapidly conducted atrial flutter, 101f Rate-adaptive algorithm, 827 Rate-adaptive atrioventricular delay, 818 Rate-adaptive pacing mode, 156 for chronotropic incompetence, 827 sensors for, 144-156 for SND and chronotropic incompetence, 320 Rate-adaptive PVARP, 827 Rate-adaptive system, 158-170 curves used in, 145f design of, 145f Rate-adaptive ventricular pacing (VVIR), 234 dual-chamber pacing versus, 235t fixed-rate ventricular single-chamber pacing versus, 234, 235t VVI versus, 156 Rate burst pressure, of balloon, 625 Rate-drop response, heart rate and, 832, 833f Rate drop-responsiveness study blinded randomized studies McLeod Crossover Study, 368 Second Vasovagal Pacemaker Study (VPS-II), 368-369 Vasovagal Syncope and Pacing Trial (SYNPACE), 369 open-label randomized studies early termination of, 369 North American Vasovagal Pacemaker Study (VPS-I), 367 Vasovagal Syncope International Study (VASIS), 367-368 Rate drop-responsive pacemaker, 367

1078

Index

Rate drop-responsive pacing, 366t, 367 with dual-chamber programming, 370 Rate hysteresis, 367 Rate-modulated dual-chamber pacing system, laddergramming from, 853f Rate modulation, in pacemaker, 346 Rate profile optimization, 147, 148f Rate-related aberrancy, 93 morphology algorithm, error in, 94f Rate-response curve, 148f Rate-responsive pacing, 400-401 Rate smoothing, 367 algorithms for, 832, 832f AV pacing, leading to, 842f RD-CHF study, 252 Reactance, 5 capacitive versus inductive, 17 at electrode-electrolyte interface, 17 Real-time telemetry, 854 Rechargeable lithium-ion battery, 185-186 characteristics of, 185 end of service life, 186 method of recharge, 186 principles of operation, 185-186 Recommended replacement time (RRT), 846 RECOVER Study, 621 Rectus sheath, anatomy of, 497f Redetection, 83-85, 107f duration for, 108 SVT-VT discrimination in, 103-104, 108f Reduced battery voltage, 721 Reduction, 175 Reel syndrome, 791 Refibrillation, 49-53 Refractory period for AAI pacing, 400f for AAIR pacing, 400 biventricular pacing and, 840 for DDD(R) pacing mode, 65f events during, purpose of, 874-875 extension due to noise, 81f for pacemakers and ICDs, 61 relative versus effective, 8 sensing and, 60 total atrial, 823 ventricular, 813 Relative refractory period, 8 electromagnetic interference and, 1008 Relative risk reduction, for sudden cardiac death, 260 Reliability, of ICD therapy, 258 Remote monitoring. See also Automatic remote monitoring; Home monitoring for CIEDs databases for, 1001 implementation of, 992-999 manufacturer resources for, 989t medicolegal issues, 1002 patient-activated, 988-989 regulations for, 1002 service integration, 1001-1002 systems for, 988 technologic advances, 987-992 wand-based versus automatic, 990f device clinic implications and, 992-997 patient aspects of, 998-999 of pediatric pacemaker, 415-416 surveillance for, 997f

Renal failure drugs preventing ascorbic acid, 622 iloprost, 622 N-acetylcysteine, 621-622 sodium bicarbonate, 621 hemofiltration and hemodialysis for, 622 RENEWAL-AVT, 292 concomitant conversion in, 292f RENEWAL Study, 292-293 Repetitive non-reentrant ventriculoatrial synchronous rhythm definition and cause of, 884 management of, 884 Replacement therapy, 1041-1042 Repolarization cardiac action potential and, 7 final, 8 initial, 8 cardiac memory and, 210-211 cause of, 8 re Quinlan, 1040 Resistance, 4, 846-847 voltage and delivered capacity, relationship between, 180f Resistor-capacitor (RC), 42, 43f Resting membrane potential, 7 Resting transmembrane potential, 5-6 Restitution curve, 41f Restitution hypothesis, of ventricular fibrillation, 41 Resynchronization/Defibrillation for Advanced Heart Failure Trial (RAFT), 273 Resynchronization for the Hemodynamic Treatment for Heart Failure Management (RHYTHM II ICD) study, 961-963 Resynchronization lead, 134-136 pacing polarity configurations for, 136f placement and fixation mechanism for, 135-136 types of, 135f Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), 295t hazard ratios in, 289f for heart failure prevention, 289 Resynchronizer, 223 Retention wire, axillary vein venogram of, 533f Retrograde atrial activation, 58-59 Retrograde microdissection, of total occlusion, 634f Reverse remodeling, 917-918 Reverse volumetric LV remodeling, 917-918 baseline/post-CRT predictors of, 929f cardiac resynchronization therapy and, 927-943, 928f global measure of ventricular fusion predicting, 929f Revised pacing system code, 813 Rheobase, 13-14, 13f, 42 Rheobase voltage, pacing rate and, 15f Right anterior oblique (RAO), 507, 508f coronary sinus in, 509f image of, 512f Right atrial appendage lead, 511f Right atrial pacing effect on AV electromechanical timing, 951-952, 952f effect on multi-chamber timing, 951, 952f selective sites for, 509

Right atrium characteristics of, 505f composite illustration with guide in, 545f HCN4 protein in, 303f Koch’s triangle landmarks on, 507f selective site pacing and, 506 view of, 506f Right bundle branch (RBB) anatomy of, 323 trifascicular block and, 326-327 Right bundle branch block (RBBB), syncope with and AV block, tracings from, 336f Right-sided heart bypass, 393 Right ventricle anteroposterior view of, 512f characteristics of, 507 composite illustration with guide in, 544f dissection opening of, 507f Right ventricular activation, in heart failure and LBBB, 220f Right ventricular activation time (RVAT), 929 calculation using surface ECG, 930f Right ventricular apex pacing, 209f Right ventricular apical pacing, 316 atrial fibrillation and, 503 in atrioventricular block, 350 effects of, 316t harmful effects of, 350 ventricular activation sequence and, 936 Right ventricular based timing biventricular pacing with competitive pacing and, 841f LV refractory extension and, 841f Right ventricular capture, 923-925 Right ventricular outflow tract (RVOT), 218, 352 RV selective site pacing and, 510 Right ventricular outflow tract pacing, 218 Right Ventricular Outflow versus Apical Pacing (ROVA) trial, 352 Right ventricular pacing, 156, 838f abnormal activation sequence during, 206 biventricular pacing versus, trials evaluating, 252-253 in children, effects of, 217 hemodynamics and, 833-834 local energetic efficiency, effect on, 207-209 unnecessary, role of prevention in, 250-251 Right ventricular pressure, 161-162 sensor measuring, 157f Right ventricular pressure waveform, in real time, 162f Right ventricular selective site pacing, 510 Right ventricular sensing heart failure, measuring pressure in, 157f with positive RV-LV interval, 839f with premature LV extrasystoles, 838f Right ventriculotomy, for lead extraction, 768 Ring-coil impedance, 891f Risk Estimation Following Infarction Noninvasive Evaluation–ICD Efficacy (REFINE-ICD), 274, 275t Ritter method, 944-945, 945f summary of, 946f Rolling threshold, 147 Runaway pacemaker definition of, 879 example of, 879f



R-wave double-counting, 66, 74, 86f-87f cause of, 75f

S Safety adequate margin of, 34-35 autosensing for, 66f with high-power batteries, 184-185 Safety alert, 1033 Safety output pulse crosstalk and, 878 delivery effects of, 878-879 Safety pacing, crosstalk and, 878f Salt/fluid, for vasovagal syncope, 365 same-chamber blanking period, short, 66 Sarcolemma, 8 Sawtooth effect, 18 Sawtooth model, 45-46 minimum potential gradient and, 46 of transmembrane potential during shock, 46f Scatter radiation, 1024 Schiavo, Terri, 1040 ScoutPro ACS Introducer System, 591f Scrub nurse/technician, for pacemaker implantation, 444 SDAAM, 159-160, 161f SDANN, heart rate variability and, 159 Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) trial, 317-318 Search AV hysteresis, 316 Search hysteresis, 835 Secondary source model, 46-47 computer mode of, 46f Second-degree AV block, 330 Second Dual Chamber and VVI Implantable Defibrillator (DAVID-II) trial, 272 Second-generation locking stylet, 761 Second-generation multisite pacing pulse generator, 922 Second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II), 248, 257 ICD shocks and, 258 for ICD therapy, 264-266 criteria, comparison groups and results, 264t population details/mortality results, 265t RVA pacing and, 350 Second Thrombolysis in Myocardial Infarction (TIMI II), 338 Second Vasovagal Pacemaker Study (VPS-II), 368-369 outcome of, 369 Sedation, for pacemaker implantation, 452 conscious, protocols for, 452t Seldinger technique, 457 Selective serotonin reuptake inhibitor, for vasovagal syncope, 366 Selective site pacing considerations for, 505 future of, 512 for ICD implantation, 503-512 radiographic anatomy and, 507-509 for right atrium, 509 right atrium and, 505-507 right ventricle and, 507 Selectsite steerable catheter, 505f Selectsite steerable stylet, 505f

Index

Selectsite snare approach, to transseptal left ventricular lead placement, 703f-706f Self-contained intracardiac pacemaker, 434-439 Self-discharge, of battery, 177-178 Selvester QRS score, 929 Senning procedure for congenital heart disease, 797 pacemaker system in DTGA after, 803f pacemaker system in LTGA after great arterial switch procedure and, 804f pediatric transvenous ICD system implanted after, 803f Sensed atrial event, 818 Sensed event, 56 Sensing, 56-126 in cardiac resynchronization ICDs, 68 concepts of, 60 event detection and certification phases of, 117 failure of, 874-876 in ICD lead, 137-138 long-term leads for, 727-728 minute ventilation, 149-150 occurrence of, 62f in pacemakers and ICDs, 60-68 parameters for, 146 postshock, 67 refractory/blanking period and, 874-875 subcutaneous ICD and, 117 with subcutaneous lead, 431 in surface electrocardiogram, 62f tachyarrhythmias detection and, 117 of ventricular electrograms, 66-67 of ventricular fibrillation, 64 evaluation at implantation, 67 Sensing integrity counter (SIC), 75 Sensing latency, 949 effect on EGM timing to electrical activity, 951, 951f Sensing threshold EGM peak-to-peak measurement as, 853-854 in pacemakers, 62 pacing system malfunction and, 867 Sensing-threshold voltage, 60 Sensitivity automatic adjustment of, 64-65, 66f in ICDs, 67f methods of, 64 in normal rhythm, 64 postpacing, 64f of automatic mode switching algorithms, 82f Sensor. See also Implantable sensor for heart failure, 158-170 activity monitoring, 159 heart rate variability, 159-160 types of, 158t for rate adaptation, 158 Sensor blending, 152 Sensor cross-checking, 152 Sensor-driven appearance, of atrial tracking, 826f Sensor-driven atrial stimulus, P wave inhibiting, 826f Sensor-driven pacemaker, 147-149 Sensor-driven pacemaker tachycardia causes of, 879b occurrence of, 879-880 Sensor-driven pacing, 144, 825-827 benefits of, factors affecting, 154-156, 155t rate-adaptive pacing modes for, 156

1079

Sensor-driven pacing (Continued) timing cycles of, 827 upper-rate limit and, 156 ventricular pacing site and, 156 Sensor-driven rate smoothing, 823 Sensor-indicated heart rate histogram, 857f Sensor rate profile, 147, 148f Separator, of battery, 176 Sequential R-L ventricular activation despite simultaneous BiV pacing, 961f LV capture latency causing, 961f LV capture latency/differential paced activation wavefront conduction times, 962f during simultaneous BiV pacing, 964f Sequential ventricular stimulation, 961-963 Sequential ventricular timing in CRT, implementation of, 959-961 Series circuit, 4 Service kit, for pacemakers, 446, 447b Sheath removal of, 579f-580f lead length and, 581f Shock. See also Multiple shocks causing refibrillation, 49-53 defibrillation success and, 40 electrode placement and, 43 ICD therapy limitations and, 258 inappropriate for AF in Brugada syndrome patient, 389f morbidity of, 904 lead fracture causing, 723f parameters for, 42-43 phase maps of, 44f postshock activation after failure of, 52f postshock cycles after failed and successful shocks, 51f after failure of, 50f sawtooth model of transmembrane potential during, 46f supraventricular tachycardia after, 93-95 ventricular fibrillation from, 377f waveform, altering strength of, 45 Shock coil ingrowth, 141f Shock-induced phase singularity, 48f Shocking electrode, in right ventricular apex, 498f Shock waveform components of, 374 pulse width and, 375f Short balloon for SVC-innominate vein junction occlusion, 652 total occlusion dilation with, 652f Short QT Syndrome, 384 risk stratification for, 384 therapeutic recommendations for, 384 ICD therapy, 386t Sick sinus syndrome cardiac pacing and, 393 concomitant symptomatic heart block and, 334 electrocardiogram from, 394f single-chamber pacing for, 398 single-lead atrial versus dual-chamber pacing in, RCT for, 245 Sigmoid coronary sinus preventing guide advancement, 564f with previous mitral valve repair, 562f

1080

Index

Silicone rubber, 130 insulation failure, mechanisms of, 131f Simultaneous BiV pacing despite sequential R-L ventricular activation, 961f LV capture latency causing, 961f LV capture latency/differential paced activation wavefront conduction times, 962f during sequential R-L ventricular activation, 964f Simultaneous electrocardiogram, rhythm strip and event markers for, 848f Simultaneous LV sensing, double-counting and, 978 Simultaneous RV sensing, double-counting and, 978 Single-chamber atrial building blocks, 88 purpose/weaknesses of, 89t Single-chamber discriminator, 96 Single-chamber ICD SVT-VT discrimination in R-R interval regularity, 88 sudden onset, 88-90 ventricular electrogram morphology, 90 Single-chamber pacing with event markers, method for, 851 mode, rate, parameter change, cause of, 866, 866b runaway pacemaker in, 879 timing cycles and, 813-816 SSI mode, 813 ventricular blanking and refractory periods, 813 VVI mode, 813-815 venous access for, 468b Single-chamber ventricular building blocks, 85 purpose/weaknesses of, 89t Single-chamber ventricular demand (VVI), double-blind crossover studies for, 239-243 Single-chamber ventricular pacing, electrode system for, 398-399 Single-coil transvenous defibrillator system, 419, 421f Single-lead atrial pacing, sick sinus syndrome and, RCT for, 245 Single-lead VDD pacing dual-chamber DDD pacing in atrioventricular block, 235 radiography of, 787f Sinoatrial nodal cell, 7 Sinus bradycardia, lower rate limits and, 223-224 Sinus node action potential of, 9f anatomy of, 323 HCN4 protein in, 303f mRNA in, 302f Sinus node disease. See also Atrial fibrillation; Thromboembolism AAIR versus DDDR, RCT for, 245 atrial versus ventricular single chamber pacing in, 237-238, 237t bipolar voltage mapping in, 304f cardiac pacing and, 234 chronotropic incompetence and rate-adaptive pacing, 320 clinical outcomes in, 305-306 course of, 305

Sinus node disease (Continued) diagnosis of, 305, 305t electrocardiographic manifestations of, 300 mortality relating to pacing mode, 238t pacemaker diagnostics for, 306-313, 306f pacemaker syndrome and, 234 pacemaking mechanisms in, 301f pacing for, 300-322 indications for, 318t pathophysiology and diagnosis of cellular electrophysiology, 300 clinical electrophysiology, 300 physiologic pacing mode and, 319f symptoms of, 304-305, 305t treatment of AAIR pacing, 318-320 pacing modalities, 318-320 Sinus node dysfunction. See also Sick sinus syndrome managed ventricular pacing in, 398 permanent cardiac pacemaker for, 393 Sinus rhythm auxotonic relaxation and, 209 electrical activation during, 203-204 failure to detect, 108f mechanical activation during, 204-206 pressure-volume diagrams during, 210f Sinus tachycardia, 388f Site preparation, for pacemaker implantation, 450-451 Situs LDS-2 lead delivery system, 593f Slew rate, 56-59 definition of, 852 of electrogram, 58 exercise effect on, 58 during retrograde atrial activation, 58-59 undersensing and, 58 SmartDelay optimization, 963-966 clinical performance of, 966 limitations of, 966 operating constraints of, 965-966 operating specifics for, 963-964 Snare Byrd Femoral Workstation, 762f clinical circumstances for use of, 698 for left ventricular lead implantation, 695-699 types of, 698f ten-mm single loop system, use of, 698f use and types of, 761 Social-environmental factors, children with pacemakers and, 423 Sodium bicarbonate, 620 for renal failure prevention, 621 Sodium channel, 7 Sodium channel gene, 332 Sorin Group pacemaker, 34 Sorin Parad+ algorithm, 104f Special procedures room, for pacemaker implantation, 444 Specific absorption rate (SAR), 1004 Specificity, of automatic mode switching algorithms, 82f Speckle tracking, 221-222 Spinal cord stimulation, 1018 Split-cathodal configuration, 33 Spontaneous conduction block, implication on BiV pacing, 958-959

Spontaneous ventricular arrhythmia ICD therapy clinical trials for, 261-264 criteria, comparison groups, and results, 262t population details/mortality results, 262t Spontaneous ventricular depolarization, 822 Square waveform, 42, 45 effects of, 45f SSI pacing, 813 Stab-in electrode, 405 Stacked-plate aluminum electrolytic construction of, 187-188 cutaway view of, 188f Standard IS-1/DF-1 dual-coiled ICD header, 199f Standard IS-1/DF-1 dual-coiled ICD lead, 198f Staphylococcus aureus, 452 Staphylococcus epidermis, 452 Staphylococcus species, CIED implantation infections and, 744-746 StarFix lead, 608 in target vein, 609f START study, 117 Static current drain, 179 Static electrical charge, 3 Static magnetic field, 1004 effects of on generator, 1014 MRI on CIEDs, 1014b Stenosis, view of, 752f Stenotic coronary sinus lateral wall vein and, RAO view of, 550f-551f preventing guide advancement, 564f Stent, coronary vein, straightening of, 683f-684f Steroid-eluting electrode, 30-31 acute implantation voltage and current threshold for, 406f acute thresholds for, 408f in children, 405-406 threshold for, 406, 406f-407f Stimulation anodal and cathodal, 11-13 electric potential gradients/currents for, 10-11 Stimulation impedance, 846-847 importance of, 866-867 Stimulation threshold, 13 antitachycardia/bradycardia pacing and, 15 electrode design effect on, 31-32 glucocorticoids effect on, 33 mechanism of fixation effect on, 31 metabolic effects on, 32 pacing rate effect on, 15 pharmacologic effects on, 32 strength-duration relationship and, 14 St. Jude A-V Rate Branch, 102f St. Jude CS access catheter, 596f St. Jude Medical activity-sensing device, 147-148 rate-response curve and “auto” slope in, 148f St. Jude Medical delivery guide, 597f St. Jude Medical ICDs, Automatic Gain Control for, 65 St. Jude Medical Model V193 ICD, 889-890, 890f St. Jude Medical Model V242 ICD, 889-890, 891f St. Jude Medical over-the-wire LV pacing lead types of, 610, 610f QuickFlex 1156T, 610 QuickFlex Micro 1258, 610, 611f-612f QuickFlex XL 1158T, 610, 610f



St. Jude Medical pacemaker autocapture fusion avoidance in, 355f automated capture features of, 34 Stokes-Adams attack, 329 Complete heart block (CHB) and, 330 Strength-duration curve, 13, 13f-14f for defibrillation, 375f logarithmic plots of, 25f in pacing, 374 stability of, 28 Strength-duration relationship, 13-15, 13f battery longevity and, 35, 35f stimulation threshold and, 14 Strength-interval curve, 16f Strength-interval relationship, 15-16 Stroke impedance, 168-169 Stroke index, changes to, 398f Stroke. See Thromboembolism Structural cardiac disease, CRT therapy for, 421-423 ST-segment shift, 170 Study of Atrial Fibrillation Reduction (SAFARI) trial, 310 Stylet characteristics of, 579-585 LV pacing lead dislodged by, 585f removal of, 579-585 Subclavian clavicle-first rib crush syndrome, 791, 792f Subclavian crush phenomenon, 458 Subclavian/innominate occlusion, crossing, 625-646, 628f Subclavian/innominate venoplasty, 647-653 complications of, 653 deceptive wire location, 655f dilation of occlusion, 650f training required to perform, 653-655 Subclavian vein, 454 Byrd’s technique for access to, 459-460, 460f location/deformities of, 455-456 Subclavian vein approach, for endocardial electrode implantation, 410 Subclavian vein occlusion (stenosis) contrast injection into revealing opening, 627f revealing total occlusion, 627f crossing, 626-627 system for, 628f defining obstruction, 626 dilation of, 649f dilator for, 650 injection system for defining, 626f peripheral venography of, 781f predilation with coronary balloon, 651f preexisting leads and, 625-646, 626f progressively large dilators, hemodynamic collapse using, 648f radiofrequency guidewire for, 632-635 subclavian venoplasty versus progressively large dilator, 646-655 venoplasty equipment for, 647b venous access without pacing leads, 642f-643f Subclavian venipuncture Magney approach to, 461f pneumothorax from, 470 using contrast venography, 464, 464f

Index

Subclavian venoplasty balloons for, 647-652 coronary balloon for, 647-650 elements of, 656b progressively large dilators versus, 646-655 staining and, 655f Subclavian venous access, for transvenous pacemaker placement, 457-459 Subclavian window, 457, 457f Subcutaneous defibrillation electrode, 497-498, 498f Subcutaneous electrocardiogram, 116-117 Subcutaneous electrocardiography, 59-60 Subcutaneous electrode/lead, sensing with, 431 Subcutaneous emphysema, 872 Subcutaneous ICD. See also Implantable cardioverter-defibrillator (ICD) crossing angled hydrophilic catheters for, 628f curved generator/electrode for, 428, 429f defibrillation threshold for, 430f early investigation experience with, 428 electrode system for, 121f future of, 432-433 history/background of, 428 lead and pulse generator location for, 500f locations for components in situ, 431, 431f optimal defibrillation configuration for, 428-430, 430f parasternal electrode for, 430f programming screen for, 432f sensing and, 117 sensing vector for, automatic selection of, 121f Subcutaneous patch/coil/array, 803 Subcutaneous tunneling, 484f Subeustachian space, composite illustration with guide in, 546f Submuscular pectoral pouch, 501-503, 502f anterior axillary line, 502f Subpectoralis muscle approach, for ICD implantation anterior, 502f anterior axillary fold, 503f deltopectoral groove and, 502f Substitutive therapy, 1041-1042 Subsystem performance counter, 856-858 Subxiphoid approach for epicardial electrode implantation, 409 for ICD implantation, 494, 494f Sudden cardiac death definition/implications for clinical trials for, 257 individual risk versus population impact of, 259-260, 259f specificity versus sensitivity, 260f relative versus absolute risk reduction for, 260 risk groups for, 259-260 Sudden Cardiac Death Heart Failure Trial (SCD-HeFT), 257 ICD shocks and, 258 for ICD therapy, 266-267 criteria, comparison groups and results, 264t population details/mortality results, 265t tachyarrhythmia therapy and, 379 Superior mediastinum, anatomic structures of, 454f Superior vena cava, lead extraction and, 752

1081

Superior vena cava-innominate vein junction occlusion dilation of long versus peripheral balloon, 651f short balloon for, 652 Superior vena cava occlusion, 640f laser opening of, 641f Support group, for children with pacemakers/ICD, 425 Supraventricular arrhythmia, multiple shocks and, 902 Supraventricular tachycardia atrial proarrythmia caused by, 105f detection as diagnostic tool, 112-116 inappropriate classification of, 95 rejection of, 97f after shock, 93-95 ventricular antitachycardia effect on, 106f ventricular therapy for, 104 Surface electrocardiogram, 56, 876f of intrinsic beats and PVC, 876f RV/LV activation time calculation using, 930f sensing occurrence in, 62f simultaneous event markers and, 850f Surgeon for ICD and CRT implantation, requirements for, 491-492 for pacemaker implantation, 443-444 Surgical epicardial LV lead placement, 518 for biventricular pacing, 518f equipment for, 613 safety with, 518 transvenous versus, 611-613 Surgical epicardial LV pacing indications for, 611-613 open-heart surgery, 611 unsuccessful percutaneous insertion, 611 Surgical lead extraction approach, 767-769 open-heart procedure, 768-769 right ventriculotomy as, 768 transatrial approach to, 767-768, 768f Surgically induced heart block, 393, 394f incidence of, 394f permanent cardiac pacemaker for, 394 structural cardiac defects associated with, 394t Surgical smoke cause and prevention of, 480 risks associated with, 480b Surveillance of device performance, 1031-1034 post-market goal of, 1031 methods of, 1031-1032, 1031t for remote monitoring, 997f Survival rate with atrioventricular block in relation to pacing mode, 239t with sinus node disease in relation to pacing mode, 238t SVT-VT discrimination, 85-104 algorithms for, measuring performance of, 104 inappropriate detection/therapy/shocks, 104 quantitative considerations, 104 in dual-chamber and cardiac resynchronization ICDs, 95-96 programming for, 109, 109t dual-chamber discriminators, 109 single-chamber discriminators, 109

1082

Index

SVT-VT discrimination (Continued) range of cycle lengths for, 109 in redetection, 108f during redetection, 103-104 in single-chamber ICDs R-R interval regularity, 88 sudden onset, 88-90 ventricular electrogram morphology, 90 SVT-VT discriminator, 111 Synchronous ventricular activation, 914f Synchrony, 911 Syncope. See also Carotid sinus syncope; Vasovagal syncope AV block with incomplete RBBB, tracings from, 336f cardiac pacing as treatment for, 234 definition of, 361 electrophysiologic study for, 328, 331t Long QT Syndrome and, 383 recurrence with/without pacemaker, 370f closed-loop simulation, 371f in VASIS, 368f in VPS-I, 367f in VPS-II, 368f Syncope Diagnosis and Treatment Study (SYDAT), 368 Systolic function, asynchronous activation effect on, 209-210 Systolic impedance, 168-169

T Table positioning for device implantation importance of, 623f Table. See Implant table; Instrument table Tachyarrhythmia anodal stimulation generating, 23 electromagnetic interference and, 1008 sensing and detection of, 117 Tachyarrhythmia detection building blocks, 89t Tachyarrhythmia therapy, at ICD postimplantation, 379-380 Tachycardia classification of, 99f pseudo-ventricular, 879, 879f Tachycardiac episode, 79-82 Tachycardia discrimination, 98f atrial rate equal to ventricular rate, 96t atrial rate greater than ventricular rate, 97t Tachysystolic stage, of ventricular fibrillation, 40 Talent DDDR, 169-170 Tamponade, lead extraction and, 752 transvenous approach and, 765 Tantalum electrolytic capacitor construction of, 188 cutaway view of, 189f Target rate profile, 147, 148f Task Force on Lead Performance Policies and Guidelines, Heart Rhythm Society (HRS), 1031 Telemetered bipolar ventricular electrogram, 853f Telemetry, 848f definition of, 844 electromagnetic interference and, 1010 of event markers, 849-852 for ICD malfunction, 889-891 for lead impedance, 848 limitations of, 860f measured data, 847f

Tendon of Todaro, 506-507 Tetralogy of Fallot, 797 ICD lead positioning in, 804f Therapeutic current, 179 Therapeutic magnet, electromagnetic interference and, 1013 Thermistor, 146 Third-generation lock stylet, 761, 762f Thoracoscopic approach, for ICD implantation, 495 Thoracotomy, endocardial lead placement during, 487f-488f Thorax, anatomic structures of, 453 Three-position ICHD pacemaker code, 195, 196t, 813 pacing modes described by, 196t Threshold voltage, 7 Thromboembolism atrial/dual-chamber pacing versus ventricular single-chamber pacing, 239 atrial fibrillation risk and, 313-314 occurrence of, 313 pacing mode and mortality, studies on, 239t transseptal LV lead implantation approach and, 517-518 Thrombolytic therapy, 341-343 Thrombosis, lead extraction and, 751-752 Tiered-therapy ICDs, 83 Tilt, 42-43 Tilt-table test, 365 Time-based system performance counter, 858 Timing cycle in biventricular pacing, 837 goals of, 836-837 definition of, 813 diagrammatic representation of, 828f in dual-chamber pacing modes, 836 DDI mode, 835-836 VDD mode, 835, 836f VVT and AAT modes, 836 ICD, pacing algorithms in, 841-842 of implantable devices, 813-843 of sensor-driven pacing, 827 single-chamber pacing and, 813-816 SSI mode, 813 Tissue debridement, 754 Total atrial refractory period (TARP), 61, 823, 824f PVARP and AVI, 826f Total endocardial activation, in heart failure, 208f Total occlusion dilation with short balloon, 652f directed needle catheter for, 636f laser crossing of, 635-639 limitations of, 638 orthogonal view, 639f microdissection of, 634f Frontrunner XP CTO Catheter for, 632, 633f Success, 632 retrograde microdissection of, 634f sites for, 650f without implanted leads, 639-646 without pacing leads to follow, 644f-646f Total QRS activation, in heart failure, 208f Total reactance, 17 Total system performance counter, 855-856 Touhy-Borst valve, wire inserted through, 547f-548f

Traction definition of, 755 direct, 755-756 indirect, 756 Transaortic ICD implant, lead extraction, 753f Transatrial endocardial atrial pacing, in congenital heart disease, 487f Transaxillary retropectoral pacemaker implantation, 485f Transclavicular tunneling, 482 Transcutaneous electrical nerve stimulation (TENS), 67 indications for, 1018 shocks from, 1018 Transcutaneous pacing, endocardial electrode implantation and, 409-410 Transdiaphragmatic approach, for ICD implantation, 495 Transhepatic cannulation, 489 Transhepatic lead implantation, 490f Transient hypotension, vasovagal syncope and, 364-365 Transiliac ICD implantation, 500 leads tunneled in, 501f Transitional cell zone, 323 Transjugular intrahepatic portosystemic shunt set (TIPS needle), 635 Transmember potential after biphasic shock, 48f cellular action potential and, 48 changes in, in cardiac pacing/defibrillation, 17-18 sawtooth model of, 46f Transmember voltage, 9 mechanism of change in, 18 Transmitral pressure gradient, 938 LV inflow velocity pattern changes and, 941f Transseptal activation delay, 913 Transseptal activation time, 206 in heart failure, 208f Transseptal left ventricular lead pacing, 517-518 Transseptal left ventricular lead placement, 700-701, 701f-702f modified Elencwajg-Cardinal femoral approach to, 707f-710f Selectsite snare approach to, 703f-706f Transtelephonic monitoring for CIEDs, 988 of pacing system, 885 of pediatric pacemaker, 415-416 Transthoracic defibrillator implantation, 11 Transthoracic impedance, 146 Transvenous access venography, 801 Transvenous electrode implantation, 410 Transvenous endocardial lead placement. See Endocardial lead placement Transvenous ICD system, high defibrillation thresholds and, 793, 795f-796f Transvenous lead bulk in pocket of, 736f radiographic appearance of, 782f Transvenous lead extraction. See also Lead extraction indications for, 750b Transvenous lead extraction approach complications from, 764-765 cardiac tamponade, 765 wall integrity, loss of, 765



Transvenous lead extraction approach (Continued) through femoral vein, 766-767 through lead vein entry site, 764-765 through remote vein sites, 765-766 through superior vein, 767 Transvenous LV pacing lead, as unipolar or bipolar, 920 Transvenous pacemaker system, in subpectoral position, 772f Transvenous pacing, contraindications for, 485-486 Transvenous permanent pacemaker implantation approach, 453 cephalic venous access for, 456-457 in infants and children, 485-486 subclavian venous access for, 457-459 Transvenous permanent pacemaker lead placement, 464 Treadmill exercise, 153f Treatment refusal, patient’s right to, 1040 Tremulous incoordination stage, of ventricular fibrillation, 40, 41f TRENDS study, 314 Tricuspid annulus, composite illustration with guide at, 545f Tricuspid valve, 507 Trifascicular block, 326-327 Trifascicular conduction system, 203 Triggered pacing mode, VVT and AAT, 836 Triphasic rate-response curve, 147, 147f True atrial undersensing, 968 Truncated exponential biphasic waveform, 42 TRUST trial, 989-992 objective of, 989-990 results for, 992f study design for, 991f Tunneling pacemaker system upgrade and, 477 Penrose drain and lead for, 477f subcutaneous, 484f techniques for, 477-478 transclavicular, 482 Tunnel propagation, 49 T wave, prevention of pacing on, 971 T-wave oversensing, 64, 64f, 69-74, 72f, 86f-87f bipolar signal preventing, 73f classification of, 71, 72f correcting, programmable features for, 73f reduction of, 71-74 rejection of, 74f Twiddler’s syndrome, 501, 729f cause of, 791, 864 lead failure in, 891-892 radiographic view of patient with, 793f Twiddling, 896f Two-dimensional bidomain model, 47f

U Ultrasound energy converter, 437, 438f Ultrasound pacing, 436-437 acoustic window for, 437, 437f investigational equipment of, 436f oscilloscope recording during, 437f transmission and focusing of, 439f Ultrasound technique, for axillary venous access, 462-463, 463f-464f Uncoupling consequences of

Index

Uncoupling (Continued) at atrial level, 911 at atrioventricular level, 911 Underdetection cause of, 109-112 of ventricular fibrillation, 110f Undersensing in atrium, 64f cause of, 58, 109-112, 874b effects of, 56 pacing system malfunction and, 875 of QRS complex, 878f with AF, 875f ventricular, 814 of ventricular fibrillation, 109, 111f VT induction and, 902-904 of VT/VF, 66 Undulatory stage, of ventricular fibrillation, 40, 41f Unidirectional block, 48 Unipolar atrial lead, IEGM from, 869f Unipolar electrode system, 56 spatial/temporal relationships for, 57f Unipolar electrogram, bipolar electrogram versus, 61f Unipolar impedance from right ventricle, 168 Unipolar lead, 127 insulation failure, effect of, 128 stimulation threshold of, 127-128 Unipolar pacing circuit, 128f Unipolar pacing lead, 614f Unipolar pacing system, 16, 728f bipolar pacing versus, 404-405 biventricular sensing and, 840f electrode sensing for, 405f implantation thresholds for, 405f Unipolar split-cathodal configuration, 33 Unipolar stimulation, 23-24 Unipolar ventricular impedance, 168 closed-loop simulation sensor and, 150-151 United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial, 242-243 clinical events in, 242t critical appraisal of, 242-243, 249 intolerance to VVI(R) in, 250f Univentricular pacing, biventricular sensing with, 839 Universal Slitter and guide hub, 582f-583f CPS, 597f Upper limit of vulnerability (ULV) method, 378 Upper rate behavior, 822-823, 823f purpose of, 839-840 Upper rate interval (URI), 824f Upper rate limit, 156 Upper-rate set point, 147 Usable energy density, 178 U.S. Joint Commission on Accreditation of Health Care Organizations, 452 Utilization, of ICD therapy, 259

V Vacco v. Quill, 1041 Vagally mediated AV block, 336 Vasopressor, for vasovagal syncope, 366 Vasovagal syncope bradycardia, evidence for, 365 implantable recorder, 365 loop recordings, 370

1083

Vasovagal syncope (Continued) pacemaker memory, 365 tilt-table test, 365 clinical perspective for, 364 epidemiology, 364f evolving technology for, 370-371 management of, 365t medical therapy for beta-adrenergic blocker, 366 Fludrocortisone acetate, 366 rate drop-responsive pacemaker, 367 RCTs for, 366, 366t selective serotonin reuptake inhibitors, 366 vasodepressors, 366 occurrence of, 361 pacing for, 364, 365t benefits of, 366-369 clinical trials of, 369 guidelines for, 371 observational studies, 367 patient selection for, 369-370 rate drop-responsive, 366t, 367 sensors of transient heart rate decrease, 367 physiology of, 364-365 symptoms and QOL for, 364 transient hypotension and, 364-365 treatment of, 365-366 physical counterpressure maneuvers, 365-366 reassurance and education, 365 salt and fluids, 365 Vasovagal Syncope and Pacing Trial (SYNPACE), 369 outcome of, 369 Vasovagal Syncope International Study (VASIS), 367-368, 368f VDD mode, 836f VDD pacemaker, 347f VDD pacing, 219t timing cycle in, 835 VDD(R) pacing, 347 VDD system electrode placement for, 347 implantation of, 347 pacemaker programming of, 348 radiography of, 787f reliability of, 347 complications versus, 347 VDI pacing mode DDI mode versus, 836 timing cycle in, 836 Vegetation, echocardiography diagnosing, 808, 808f Vein, pacing lead-induced perforation of, 590f Vein laceration, 695 Vein rupture, 695 Vein selector, 516 CS access catheter and deploying through, 568 loading into, 571f definition of, 618 failure to cannulate target vein, 569f functions of, 516 injection system and, 572f removal of, 572 renal-shaped delivery guide with, 528f shape of, 568 in tortuous vein, 570f

1084

Index

Vein selector (Continued) types of, 517f hook, 573f standard versus hook, 576f Velocity time integral (VTI), 947 aortic, pacemaker AVI change effect on, 926 Venography device implantation and, 801-806 device replacement and, 729 indications for, 729 venous occlusion and, 729f Venoplasty, 675f for additional LV lead placement, 666f angioplasty balloon versus inflation pressure for, 623-625 of branch vein, 676f of collaterals between veins, 671-681 contrast injection after with previous cardiac surgery, 685f-686f without previous cardiac surgery, 689f failure of edema or clot formation, 660, 660f lack of guide support, 658f using CS access catheter, 659f Kevlar balloon and, 652f after LV lead displacement, 667f-670f after LV lead implantation, 664 of main coronary sinus, 662-664 after open-heart surgery, 671f phrenic pacing and, 671, 674f push-pull technique, 675f of small/stenotic target vein, 664-671 without open-heart surgery, 672f-673f with stent placement, 681 success of, 659f procedures and techniques ensuring, 660-662 training required to perform, 653-655 venous integrity loss with, 681 Venoplasty balloon, preparation of, 626b Venous access sacrificing lead for, 629-632, 632f of total subclavian occlusion, without leads, 642f-643f Venous angioplasty, endocardial electrode implantation and, 410 Venous occlusion, 729f Venous stenosis, lead extraction and, 751-752 Ventricle loading condition, effects of change in, 938, 940f Ventricular activation, 205 anodal capture effect on, 925f characterization during LBBB using QRS hieroglyphics, 928-929 during lateral cardiac vein pacing, 932f LV only effect on LV strain map and, 934f LVO pacing effect on LV strain map and, 935f during middle cardiac vein pacing, 932f during monochamber LV pacing, 931, 931f reverse volumetric LV remodeling, predicting during CRT, 928f RVA pacing and, 936 during sequential BiV pacing at shortened AVD, 938f Ventricular activation time, 951f

Ventricular activation wavefront fusion achievement/confirmation of, 952 during biventricular pacing, 939f CRT after, 933f CRT during, 927-929, 931, 933f as CRT translational mechanism, 952 incomplete, during simultaneous biventricular pacing, 937f Ventricular antitachycardia pacing atrial proarrythmia caused by, 105f supraventricular tachycardia, effect on, 106f ventricular tachycardia, atrial response to, 106f Ventricular arrhythmia EGM displaying, 890f ICD therapy clinical trials for, 261-264 criteria, comparison groups, and results, 262t population details/mortality results, 262t Ventricular asynchrony, heart failure and, factors contributing to, 914 Ventricular asystole, 211 Ventricular-based timing, 823-825 Ventricular-based timing cycle, 829f DDD mode with, 828f Ventricular blanking period, 813 Ventricular Capture Management feature, 34 Ventricular capture threshold, voltage output and, 925 Ventricular capture verification, 79 Ventricular conduction, atrial tachyarrhythmia with, 971-973 Ventricular conduction block, 952-953 ventricular activation wavefront fusion challenges, 958-959 Ventricular conduction delay asynchronous heart failure caused by, 913-917 mechanical dyssynchrony inducing, 916f Ventricular contraction, 205 Ventricular depolarization, far-field R wave and, 57-58 Ventricular double-counting, 968 elimination of, 979 loss of CRT from, 969f of nonsustained VT in nondedicated CRT-D system, 980f reduction of, 968-970 simultaneous RV and LV sensing causing, 978 during VT on stored EGM in nondedicated CRT-D system, 981f Ventricular electrode, placement of, 470-474, 470f stylet placement/withdraw, 474, 474f suture sleeves to secure, 474, 474f through persistent left superior vena cava, 489f Ventricular electrogram (VEGM) amplitude of, 56 atrioventricular pacing and, 216f current of injury, 58 in heart failure patient, 217f during premature ventricular complex (PVC), 58 recording of, 59f sensing cycle lengths of, 68f sensing occurrence in, 62f, 66-67 Ventricular electrogram morphology for SVT-VT discrimination limitations of, 90-95 steps for, 90-95, 90f types of, 91f

Ventricular electromechanical resynchronization, 927-931 Ventricular escape interval, 813 Ventricular extrasystole, 822f Ventricular fibrillation APD restitution relationship during, 41f in Brugada syndrome, 386f detection duration of, 106-108 detection of, 79-83 from electrosurgical equipment, 1019f enhancements for, 907t ICD failure, 900f, 906-907, 906t inappropriate, 87f, 114f electrical defibrillation versus, 40 electrogram variability during, 63f mother rotor hypothesis of, 40-41 oversensing and, 72f recording of, 42f recordings/activation time for cycles after, 53f sensing of, 64 evaluation at implantation, 67 shock producing, 377f stages of, 40 underdetection of, 110f undersensing of, 66, 109, 111f ventricular electrogram during, 58 ventricular tachycardia converting to, failure of, 904-905, 905t Ventricular fibrillation detection zone, 88f Ventricular filling, 938, 940f Ventricular fusion, 355 Ventricular ICD SVT-VT discrimination in, 85-104 ventricular sensing in, 64-67 Ventricular interval, counting, 82 Ventricular intracardiac electrogram (IEGM), 870f Ventricular lead attenuation of, 867f lead dislodgment with, 483 radiography of positioning of, 781 Ventricular muscle, action potential of, 9f Ventricular oversensing, 78f, 814, 978-980 intracardiac signal and, 69-74 lead implantation and, 377 recognition/troubleshooting for, 68-79 Ventricular pacing, 64f abnormal contraction during, 206-211 algorithms to minimize, 316-318 AAIsafeR mode, 316-317 managed ventricular pacing, 316 search AV hysteresis, 316 alternative sites for, 218-219, 320 atrial fibrillation and, 314-315, 315f atrial pacing versus, meta-analysis of, 243 atrioventricular block and, 238 auxotonic relaxation and, 209 cardiac structure/function and, 211 deleterious effects of, 316f detrimental effects of, 314-318 dual-chamber pacing versus, 238-243 in defibrillator patients, 247-249 effects of, 211f, 212t on electrocardiogram, 864-865, 864f electromagnetic interference and, 1007-1008 fixed-rate versus rate-adaptive, 234 heart failure and, 239, 315-316, 315f local energetic efficiency, effect on, 207-209 mean frontal plane QRS axis during, 924f



Ventricular pacing (Continued) minimizing, 219 modes for, 317-318 to reduce AF, 317-318 MVP versus DDD(R) mode, 317f pacemaker operations minimizing, 156 pressure-volume diagrams during, 210f rate response, with versus without, 234 with rate response versus dual-chamber pacing, 234-235 rates at rest, 212f reduction of, 78-79 site-specific, in AV block, 350-353 Ventricular pacing lead in RV apex, 784f in RV outflow tract, 786f Ventricular pacing site, 156 Ventricular pacing threshold, 924 Ventricular premature beats, 973 Ventricular proarrhythmia, during LV pacing, 980-981 Ventricular rate atrial rate versus, 95 counting methods for, 82 detection zones for, 83 dual-chamber rhythm classification and, 96f stabilization leading to pacing, 842f Ventricular Rate Regularization (VRR), 972, 975f-976f BiV pacing increase during AT/AF by, 977f ventricular response pacing (VRP) and, 835 Ventricular refractory period, 813 VVI pacing and, 400f VVI pacing mode for, 814f Ventricular remodeling, 211 mechanisms of, 916f Ventricular repolarization, BiV and LV pacing effect on, 983f Ventricular response pacing (VRP), 835f ventricular rate regularization and, 835 Ventricular resynchronization, 917 Ventricular safety pacing, 78, 817-818, 819f resulting from atrial undersensing, 819f Ventricular Sense Response (VSR), 978f conducted AF response, combined effects of, 979f Ventricular sensing, in ventricular ICDs, 64-67 Ventricular septal defect (VSD), heart block and, 394 Ventricular single-chamber pacing atrial/dual-chamber pacing versus, 238-239 atrial synchronized ventricular pacing versus, 235 in sinus node disease, 237-238, 237t Ventricular synchrony maintenance of, 218 role of, 217-219 Ventricular tachycardia (VT). See also Catecholaminergic polymorphic ventricular tachycardia during AAI pacing, 319f antitachycardia pacing and, 904 detection duration before ATP, 106 detection failure for, 95f ICD system, 906-907, 906t

Index

Ventricular tachycardia (Continued) by intradevice interaction, 113f detection of, 79-83, 99f as diagnostic tool, 112-116 enhancements for, 907t inappropriate, 114f EGM morphologies of, 902 inappropriate classification of, 95 Long QT Syndrome and, 903f managed ventricular pacing causing, 352f monitor-only zones for, 83 oversensing and, 72f pacemaker diagnostics for, 112, 113f pacing-induced, 904f post-therapy sinus rhythm, detection failure, 108f during rapidly conducted atrial flutter, 100f site-specific effects of LV/RV pacing on, 982f as slower than programmed detection interval, 111, 112f undersensing and, 66, 902-904 ventricular antitachycardia pacing, atrial response to, 106f ventricular double-counting during, 981f ventricular electrogram during, 58 ventricular fibrillation, failure to convert, 904-905, 905t in ventricular fibrillation detection zone, 88f Ventricular therapy, for SVT, 104 Ventricular timing, noncompetitive atrial pacing algorithm and, 834f Ventricular triple-counting in nondedicated CRT-P system, 981f occurrence of, 978-979 Ventricular uncoupling, 911-915 Ventricular undersensing, 64f, 814 lead implantation and, 377 VVI pacing mode for, 815f Ventriculoatrial (VA) coupling, 911 Ventriculography, 229f Ventriculotomy, 768 Vert, 630f for crossing occlusion, 631f at peripheral/proximal coil, 630f without glide wire, 630f directing glide wire, 628f for crossing occlusion, 629f with no visible opening, 630f Vest Prevention of Early Sudden Death Trial (VEST), 274, 275t VF Zone High Rate Time Out, 103 Video capsule endoscopy, electromagnetic interference and, 1021 Virtual electrode cardiac excitability and, 11 description of, 11 importance of, 11 occurrence of, 11 Virtual electrode effect, 11 cause of, 376 Volt, 176 Voltage, 3 battery longevity, programming for, 35, 35f decay of, 19, 19f

1085

Voltage (Continued) for endocardial stimulation, 13 resistance and delivered capacity, relationship between, 180f Voltage-gated channel neuronal axon conduction and, 6 opening of, 6 Voltage threshold, 399-400 VOO pacing mode, 815, 836 VVI pacing, 814f diagrammatic representation of, 814f ECG tracing of demand rate of 50 bpm, 869f demand rate of 60 bpm, 869f timing cycles and, 813-815 ventricular refractory period after, 400f VVI ventricular hysteresis, 815f VVI ventricular oversensing, 814f VVI ventricular refractory period, 814f VVI ventricular undersensing, 815f VVO pacing mode, 815f VVT pacing mode, 836

W Waist, elimination of, 662f Wall integrity, loss of cardiac tamponade and, 765 treatment mechanisms for, 765 Wand-based remote monitoring, 990f Warburg impedance effect of, 22 pacing configuration of, 19f Warfarin, bolusing dosing of, 725 Waveform duration of, 43f as monophasic or biphasic, 42-45 shock strength and, 45 Wavefront block, 41-42 Waveshape, of electrogram, 57 Wedensky effect (capture hysteresis), 15 Wenckebach block, 323 Wenckebach pacemaker AV block, DDD mode upper rate response, 824f Wenckebach periodicity, 324 Wenckebach sequence, AV nodal block with, 324 Wet pocket, 480 Wire exchanging to augment support, 517, 618 Wireless cardiac simulation (WiCS) development of, 437 intracardiac electrode for, 438f pulse generator for, 438f Wireless communication device, electromagnetic interference and, 1011-1012 Wire-refractory total occlusion, 629 laser crossing of, 638 venogram of, 638f Wolff-Parkinson-White syndrome, 206, 333 Working environment, electromagnetic interference and, 1014 Wound irrigation, for infection prevention, 452-453

Z Zapper, electromagnetic interference and, 1013